Microbiology Made Ludicrously Simpler

(Jarrod’s key for MOD and USMLE)

***YOU NEED TO LOOK AT PICTURES OF ALL THIS STUFF ALONG WITH THIS
DOCUMENT!!!! YOU WILL NOT DO WELL IF YOU’RE NOT LOOKING AT PICTURES!!!***
Chapter 1
Gram Stain – separates bact into two major groups
 Procedure = crystal violet stain  wash with water  flood with iodine  wash with water  decolorize with alcohol  counter
stain with safranin
o Gram-positive – holds crystal violet and appear blue
o Gram-negative – crystal violet washed away by alcohol. Cells absorb safranin (red)

Bacterial cell membrane/cell wall

 Peptidoglycan layer = cell wall - layer outside plasma membrane. Present in G+ and G-
o Transpeptidase (penicillin binding protein)  cross linkages in peptidoglycan layer
 Target of penicillin
o G+ - cell wall is thick with extensive cross-linking
 Contains teichoic acid = antigenic determinant helpful in ID of many G+ species
 NO ENDOTOXIN (exception = Listeria monocytogenes = TQ)
o G- - cell wall is thin with simple cross-linking. NO teichoic acid
 G- cell wall – 3 layers. From inside to out, they are:
o Plasma membrane –
 Periplasmic space b/w plasma membrane and peptidoglycan layer
o Thin peptidoglycan layer – murein lipoprotein links this layer to the outer PM
o Outer cell membrane – contains LPS. Protects cell wall from some abx (e.g. pcn)
 LPS – three components
 O-antigen – outer component. Antigenic determinant.
 Core polysaccharide
 Lipid A = Endotoxin. All G- possess.
o Lysing of bact by immune system and/or abx  release of lipid A  fever, diarrhea,
shock (septic shock)

Bacterial Morphology
 Cocci – spherical
 Bacilli – rods (short rods are called coccobacilli)
 Spiral forms – comma, ‘S’ or spiral shaped
 Pleomorphic – no distinct shape

G+ bacteria assoc with human dz (only 6)

 Streptococcus – strips of cocci
 Staphylococcus – clusters of cocci
 Spore formers
o Bacillus
o Clostridium
 Non-spore formers
o Corynebacterium
o Listeria

G-
 Diplococcus (Neisseria) is the only G- coccus
 All other gram negative organisms are rods or pleomorphs

Others
 Mycobacteria – acid-fast stain (bugs that cause tuberculosis and leprosy)
 Spirochetes – gram negative, but too small to be seen with light microscopy. Can be seen via dark field microscopy
 Mycoplasma – no cell wall – neither G+ nor G-

Bacterial ribosomes – 70S.  Subunits 30S (inhibited by tetracyclines) and 50S (inhibited by erythromycin)

Oxygen and Carbon Source

 Macrophages produce oxyradicals to destroy bacteria
 How do bacteria deal with oxyradicals (oxidative stress)?
o Catalase – 2H2O2  H2O + O2
o Peroxidase – also metabolizes hydrogen peroxide
o Superoxide dismutase (SOD)  O2- + O2- + 2H+  H2O2 + O2
 Breaks down superoxide radical
 Obligate Aerobes – use glycolysis, TCA and ETC. Possess catalase, peroxidase and SOD.
 Facultative anaerobes – use oxygen as final electron acceptor. Make catalase and SOD. Can grow in absence of oxygen
(fermentation)
 Microaerophilic (aerotolerant anaerobes) – no ETC, use only fermentation. Can tolerate small amts of O2 because they
synthesize SOD (no catalase)
 Obligate anaerobes – oxygen haters. Harbor no enzymes to protect from oxidative stress
 Chemoheterotrophs – all clinically important bugs. They use organic compounds (e.g. glucose) for energy
 Obligate intracellular organisms – (Chlamydia and Rickettsia) must steal ATP from host (via a special cell membrane transport
system). Thus, they live in their host cell, or they’d die

Chapter 2
Virulence – degree of pathogenicity
 Flagella – confers motility and allows for chemotaxis. Increase virulence. Connected to bacteria by basal body. Basal body spans
entire cell wall, binding to inner and outer membrane in G-, and inner membrane in G+ (don't have outer membrane)
o Bacteria can have a single polar flagellum (i.e. vibrio cholera), many peritrichous flagella (i.e. E. coli), or none (i.e.
Shigella)
o Spirochetes have specialized flagella called periplasmic flagella, where axial flagella come out of the ends of its
cell wall, but their flagella run sideways
 Pili – (aka fimbriae) – can serve as adherence factors, called adhesins.
 Capsules – macrophages and neutrophils are unable to phagocytize encapsulated organisms
o Usually made of sugar residues except Bacillus anthracis, which has aa capsule
o India ink stain – stain is not take up by capsule, but capsule appears as a transparent halo around cell e.g.
cryptococcus
o Quellung reaction – bacteria mixed with Abs that bind to capsule. Capsule swells with water and can be visualized
o Opsonization – Abs against capsule antigens can coat organism and facilitate phagocytosis
o Pneumovax – 23 capsule Ags injected  stimulate immune system to make Abs against Ags  Abs act as
opsonins in cases of infection
 Endospores (Bacillus and Clostridium). Metabolically dormant and resistant to heat
o Form during times of nutrient shortage. Becomes active when nutrients are again available
o Autoclaving destroys spores (15 min, 15 psi, 121C)
 Biofilms. An extracellular polysaccharide network that forms a mechanism scaffold around bacteria.
o Allows bacteria to bind to prosthetic devices. i.e. Staph. epidermidis forms biofilms on intravascular catheters and
leaches out to cause bacteremia and catheter related sepsis
o Best way to get rid of infection is to remove prosthetic

Facultative intracellular organisms – inhibit phagosome-lysosome fusion. To be covered individually later.

 Listeria monocytogenes
 Salmonella typhi
 Yersinia
 Francisella tularensis
 Brucella
 Mycobacterium
 Legionella
 Listen Sally Yer Friend Bruce Must Leave (Listeria, Salmonella, Yersinia, Francisella, Brucella, Legionella, Mycobacterium)

Toxins
 Exotoxins – released by G+ and G- organisms. All G+, except Listeria, release. Many have two polypeptide sub-units where the
Subunit involved in binding its target is called ‘B’ or ‘H’, and the subunit exerting its toxic effect is called ‘A’ or ‘L’
o Neurotoxins – e.g. tetanus and botulinum toxins (discussed later)
o Enterotoxins – usu cause diarrhea by way of inhibiting NaCl resorption, activating NaCl secretion (osmosis)
 Infectious diarrhea – bacteria colonize and bind to GI tract, continuously releasing their enterotoxins.
Vibrio cholera, E. coli, Campylobacter jejuni, and Shigella dysenteriae
 Food poisoning – ingest preformed toxin  diarrhea and vomiting ensue  usu resolves within 24h (i.e.
Bacillus cereus and Staph. aureus)
o Pyrogenic exotoxins – release cytokines  rash, fever, or toxic shock syndrome
 o Tissue invasive exotoxins – destroy/tunnel through tissues (destroy DNA, collagen, fibrin, NAD, RBCs and WBCs)

 Endotoxin – again = lipid A. Not a protein secreted from cells, but a lipid that is continually shed by G- organisms and Listeria,
esp during cell lysis
o Septic shock – number one cause of death in ICU. Aka endotoxic shock.
o Bacteremia – bacteria in the bloodstream
o Sepsis – refers to bacteremia that causes a systemic immune response to the infection
 High temp, increased WBCs, tachycardia, tachypnea
o Septic shock – dangerous drops in BP and associated organ dysfunction (e.g. acute renal failure). Aka endotoxic
shock.
 Spread of localized infection  bacteremia release of exotoxin or endotoxin  stimulation of immune
cells (macs and neuts)  release of endogenous mediators of shock response
 TNF – aka cachectin. Key endogenous mediator of sepsis. Causes wasting in cancer pts (cachexia)
 IL-1 and other cytokines and PGs  vasodilation, hypotension, organ system dysfunction
o Systemic vasodilation, myocardial depression, acute renal failure, ARDS, hepatic
failure, encephalopathy, DIC
 Tx – find site of infection and start broad spectrum abx  find bug responsible and then specifically tailor
abx to target culprit organism
 Maintain BP with fluids and NE or dopamine
 Maintain oxygenation (intubation and ventilation is often necessary.

Chapter 3
Bacterial Genetics – bacterial chromosome is circular dsDNA. One copy per cell = haploid state.

 Transformation – DNA released during cell lysis binds to cell wall of neighboring competent (same species) bacterium and is
taken up and incorporated into recipient’s genome.
o Griffith 1928 – classic experiment with two strains of pneumococci (the little bastard that causes pneumonia)
o Smooth encapsulated colonies = virulent  inject into mice  mice die
o Rough nonencapsulated colonies = nonvirulent  inject into mice  no effect
o Heat killed smooth + live rough  inject into mice  mice die  live smooth cultured from animals (rough
transformed into sm)
o The experiments illustrated that the rough bacteria were somehow “transformed” by some component of the dead
smooth bugs.

 Transduction – process by which a bacteriophage carries a piece of bact DNA from one organism to another
o Phage – nucleic acid genome surrounded by a protein coat (capsid). Phage binds to bacterium (adsorption) and
undergoes penetration. Phage genome is then injected into bacterial host.
o Virulent phage – infects  reproduces  lysis (kills bacterium).
 Generalized transduction = adsorption  penetration  destruction of bacterium’s DNA  some
residual bacterial DNA fragments remain and are randomly packaged into viral capsids, which aren’t
infective (i.e. contain no viral genome). The phage capsids containing bact DNA adsorp and penetrate other
bacteria, but there is no infection, only DNA transfer (i.e. transduction).
o Temperate phage – infects  incorporated (as an integrated prophage) into host’s genome  can become
activated and virulent at a later date.
 Specialized transduction – when an integrated prophage becomes active, it is sometimes erroneously
spliced out of bact genome. The result is that bacterial DNA that was flanking the integrated provirus is
carried with the provirus. The provirus/bacterial DNA is packaged and transferred to another bacterium
upon infection.
 Lysogenic conversion – transfer of gene from one bacterium to another via specialized
transduction.
o Biotin gene – carried by lambda phage from one E coli to another
o Diptheria exotoxin – obtained by lysogenic conversion (TQ)
o Lysogenic immunity – ability of integrated prophage to block infection by a similar phage. Integrated prophage
accomplishes this via production of a repressor protein

 Conjugation – major mechanism for transfer of antibiotic resistance (TQ)

o F plasmid – encodes enzymes and proteins for sex pilus
o F+ organism passes F plasmid, through pilus, to F- organism into its cytoplasm. The F- organism becomes F+ and
forms a pilus. The cycle goes on and on. It’s a good thing this doesn’t happen in humans!
 o Hfr cell. Rarely, the F plasmid becomes integrated into the bacterial chromosome, called an Hfr cell (high
frequency of chromosomal recombinants). This integration can result in two mechanisms of DNA transfer:
 F plasmid is in the entire bacterial circular DNA and is transferred from Hfr cell to recipient cell
 Integrated F plasmid may be excised at a different site from that of integration. This results in F plasmid
that now also contains a segment of chromosomal DNA  this plasmid is called F’ plasmid

 Transposons – mobile genetic elements, which can insert themselves into a donor chromosome without having DNA homology.
This is a mechanism for passage of antibiotic resistant genes from one species to another.

Chapter 4
Streptococci – strips of cocci. Catalase negative. Five strains cause human dz

Hemolysis – classified based on ability to lyse red blood cells

o Beta-hemolytic – complete lysis of RBCs, leaving a clear zone around colony
o Alpha-hemolytic – partial lysis of RBCs, leaving greenish discoloration around colony
o Gamma-hemolytic – unable to hemolyze RBCs. Aka non-hemolytic

 Lancefield antigens – classification based on the antigenic characteristics of the C carbohydrate.

o Groups A, B and D are clinically significant
o Strep pneumoniae and Strep viridans have no Lancefield antigens

 Streptococcus pyogenes: Group A Beta hemolytic strep. It will be called S. pyogenes on the exam.
o M protein – major virulence factor for Group A strep. Inhibits the activation of CoMplement (thus, prevents
phagocytosis).
o Streptolysin O – oxygen labile toxin (meaning inactivated by oxygen). Destroys red and white blood cells.
Mechanism of beta hemolytic activity. ASO (anti-streptolysin O) antibodies develop in response to infection with
strep. ASO titer can be used to confirm infection with Group A strep.
o Streptolysin S – oxygen stable toxin. Also mediates beta hemolysis, but is not antigenic
o Pyrogenic exotoxin – aka erythrogenic toxin. Found in a few strains that cz Scarlet fever. Acquired by lysogenic
conversion.
o Other virulence factors = streptokinase, hyaluronidase, DNases, anti-C5a peptidase
o Is inhibited by bacitracin!
o Dz mediated by local invasion or exotoxin release
 Pharyngitis – classic strep throat with red, swollen tonsils and pharynx. Purulent exudate on the tonsils,
fever, lymphadenopathy. Pcn is curative.
 Skin infections
 Folliculitis – infection of hair follicles
 Pyoderma – a pustule, usually on face
 Erysipelas – only found on superficial skin, dermis only, appearance is raised, bright red rash
with a sharp border (rarely caused by staph. Aureus)
 Cellulitis – deep skin infection  rubor, tumor, calor, dolor
 Impetigo – vesicular, blistered eruption. Crusty and flaky and frequently perioral. Most common
in kids.
 Necrotizing fasciitis (flesh eating strep) – strep enter through lesion on skin  spread along
fascial planes  rubor, tumor and calor  skin changes from red to blue  bullae form. May
include myositis. Must be dx early. Surg followed by abx is required. Mortality is high. Give
Penicillin G
o Fournier’s gangrene – a form of necrotizing fasciitis involving male genital area and
perineum
 Scarlet fever – pyrogenic exotoxin/erythrogenic toxin. Scarlet red rash begins on trunk and neck, then
spreads to extremities. Spares the face. Skin may peel off during healing
 Streptococcal Toxic shock syndrome – mediated by pyrogenic exotoxin also. Similar to S aureus toxic
shock (see later). Tx: high dose penicillin and clindamycin (sensitive to penicillin, and clindamycin inhibits
bacterial ribosomes)

o Delayed antibody-mediated disease

 Rheumatic fever – usu in kids 5-15. Follows untreated pharyngitis, but NOT skin infections
 Fever and Myocarditis – inflammation of the heart  chest pain, arrhythmias, and occasional
heart failure
 o This is antibody-mediated!! Abs against strep cross react with heart antigens (molecular
mimicry), causing the myocarditis
o Recurrent infections  permanent valvular damage. Mitral valve is most common
(aortic second most common)
o There is an initial myocarditis, and many years later rheumatic valvular heart disease
develops
o Once damaged, valves are susceptible to damage by other bacteria. Consequently,
prophylactic amoxicillin is often administered before minor surgical or dental procedures
performed in patients with hx of rheumatic fever.
 Joint swelling – acute migratory polyarthritis (does not cause permanent damage)
 Chorea - uncontrolled dance-like movements, also called Sydenham’s chorea or St. Vitus dance
 Subcutaneous nodules – rubbery nodules under the skin
 Erythema marginatum – rash with red margin that spreads from center
 Acute post-streptococcal glomerulonephritis – occurs one week after pharyngitis OR skin infection
 Streptococcal antigens complex with antibodies formed during immune response  deposition of
AgAb complexes in glomerular basement membrane  activation of complement cascade 
glomerular destruction  fluid retention
o Type III hypersensitivity rxn: immune complex disease
 Kids will present with cola colored urine (hematuria), puffy face (fluid retention), and high BP.
However, prognosis is good

 Streptococcus agalactiae : Group B Beta hemolytic (baby) Strep. Women carry vaginally – baby acquires during delivery.
o major cause of neonatal meningitis, pneumonia, and sepsis
 neonatal meningitis does not cause stiff neck, like in adults
o Group B strep > E. coli > Listeria monocytogenes = 3 most common causes of meningitis in neonates (TQ)
o Two bacteria that cause meningitis later in life  Neisseria meningitides and Haemophilus influenza

 Enterococcus Faecalis: Group D strep – alpha-hemolytic, beta, or gamma

o Enterococcus – (E. faecalis and E. faecium) normal bowel flora. Grow in bile and 6.5% NaCl (halophilic).
  Cause urinary, biliary tract and blood infections and SBE [extracellular dextran helps bind to heart valve
(see Viridans).
 Again, these bugs are normal flora. They are a major cause of nosocomial infection (originate from
hospital)
 Many strains are resistant to ampicillin. Some are even resistant to vancomycin.
o Non-enterococci – (S. bovis and S. equines). Normal GI flora. Glow in bile but NOT in 6.5% NaCl.
 S. bovis in the blood correlates with cancer in the bowel (TQ)

 Streptococcus Mutans: Viridans Group Strep (no Lancefield Ag) – alpha-hemolytic (viridans = green = partial hemolysis).
Optochin resistant*.
o Normal flora in GI tract, nasopharynx, and gingival crevices. Causes 3 main infections:
o Dental infections – S. mutans – causes dental caries (ferments sugars into destructive acids)  cavities
o Endocarditis – dental manipulations send these bugs into bloodstream  implantation on previously damaged heart
valves (e.g. from S.pyogenes rheumatic fever)  Cause subacute bacterial endocarditis (SBE), a slow growth of
bacteria on heart valves (staph. aureus causes acute bacterial endocarditis, which is fast growth and worse)
 SBE – caused by S. viridans or Group D strep. Slow development of fever, fatigue, anemia, and murmurs
 Differs from acute bact endocarditis – usu caused by S. aureus. Common in IVDA. Acute onset
of chills, spiking fevers and rapid valve destruction
o Abscesses – S. intermedius/Anginosus. Microaerophilic group (part of normal GI flora) that are often found alone or
in combination with anaerobes in abscesses (e.g. in brain or GI tract)
 If S. intermedius is cultured from the blood, look for an abscess in an organ as the source.
 Streptococcus InterMeDius and AnginoSus  IMeDiately ASsess for ABSCESS

 Streptococcus pneumoniae (no Lancefield antigen) – alpha-hemolytic. Affects adults (unlike group B which affects babies). Aka
pneumococcus. Optochin sensitive, can’t grow in bile.
o Lancet-shaped G+ diplococcus
o Polysaccharide capsule is major virulence factor. 84 serotypes!!
o Most common cause on pneumonia in adults (typical pneumonia)
 Sudden onset of shaking chills, fever, chest pain, and dyspnea
 Consolidations evident of CXR
 Patient coughs up yellow-green phlegm (tasty) bearing G+ diplococci
o **Most common cause of pediatric otitis media
o Most common cause of bacterial meningitis in adults (pneumococcus is for parents what StrepB is for babies)
o Pneumovax – contains 25 of most common capsular Ags  promotes formation of anticapsule Abs  opsonization
of organisms in event of infection.
 Should be given to immunocompromised, elderly, and asplenic patients (asplenic patients are highly
susceptible to infection by encapsulated organisms)
o Some strains are resistant to pcns. Resistance to other abx is becoming a problem
Fusobacterium is also a Gram+ coccus, but talked about in Chapter 9 of the Enterics

Chapter 5
Staphylococci – clusters of cocci. Catalase positive. 3 pathogenic species.

Differentiating staph from strep

o Gram stain – staph in clusters, strep in chains (strips)
o Catalase – all staph are catalase positive. All strep are catalase negative
o Culture – Staph aureus is beta hemolytic (like group A and group B strep); however, it elaborates a golden (aureus)
pigment on sheep blood agar
 Staph aureus is coagulase positive. Other important Staph are coagulase negative (epidermitis and
saprophyticus)
 Coagulase  stimulates prothrombin  clotting

 Staph aureus – Jarrod’s microorganism classification schema = this bug is a bad-ass son-of-a-bitch
o Proteins that jack up host’s immune defenses
 Protein A – has Fc binding sites for IgG  protects organism from opsonization
 Coagulase  fibrin formation around organism  protects from phagocytosis
 Hemolysins – destroy RBCs, neuts, macs, and platelets
 Leukocidins – destroy WBCs
 Penicillinase – secreted form of beta-lactamase  disrupts pcn molecule
 Novel PBP – aka transpeptidase, target of pcn. The novel form is resistant to pcn
o Tunneling proteins
 Hyaluronidase – spreading factor – lyses proteoglycans in CT
 Staphylokinase – lyses clots
 Lipase – degrades fats and oils. Facilitates colonization of sebaceous glands
 Protease – destroys tissue proteins
o Exotoxins
 Exfoliatin toxin A and B – causes skin to slough - scalded skin syndrome
 Usu affects neonates with recently severed umbilicus or older kids with skin infections
o Cleavage of the middle epidermis  fine sheets of skin peel off  red moist skin
revealed.
o Healing is rapid and mortality low
o Can mimic drug allergy, which must be ruled out
 Enterotoxins – (heat stable) cause food poisoning (gastroenteritis)
 Organisms grow in food and release exotoxin. Host ingests pre-formed toxin  peristalsis,
diarrhea, vomiting, and abd pain. 12-24h course. (esp in mayonnaise, potato salad)
 Toxic shock syndrome toxin (TSST-1) – similar to group A strep’s pyrogenic toxin, but worse. Note:
please change tampons regularly. Tampons that stay in too long cause this toxin to be released
 Toxin is superantigen that binds to MHC II on APCs  massive T-cell response  huge surge of
cytokine release  fever, vomiting, watery diarrhea, septic shock, desquamation of palms and
soles, diffuse red rash
 Toxin stimulates TNF and IL-1 release
  Abortions, childbirth, infected surgical sutures = also implicated in TSST-1 release.
o Pneumonia – aureus is a common cause of nosocomial pneumonia. Usu follows flu virus
 Abrupt onset of chills, fever, consolidation of lung, rapid destruction of pulmonary parenchyma 
cavitations (holes in the lungs). Empyema – pus in the pleural space
o Meningitis, cerebritis, brain abscess
o Osteomyelitis – hematogenous spread of infection to bone. Most common in boys < 12.
 Warm swollen tissue overlying affected bones. Fever and shakes.
o Acute endocarditis – high fever, chills, myalgias. Often no hx of valvular dz. Vegetations (organisms) grow
quickly on valves  embolize (brain if left heart; lungs if right heart). Rapid valve degeneration
 IVDA – tricuspid valve endocarditis (TQ). May present with pneumonia – embolization of fragments from
tricuspid valve  seeding of lungs with organisms
 Much more fulminant than SBE caused by group D strep or Viridans.
o Septic arthritis – acutely painful, red, swollen joint with ↓ROM. Closed infxn of joint cavity
 Aureus is the most common cz of septic arthritis in pediatric pts and pts over 50
 Aspiration of synovial fluid required for dx. Synovial aspirate is yellow, turbid and laden with neuts.
o Skin infections – minor skin infections are nearly exclusively caused by group A strep (pyogenes)) or Staph aureus.
Clinically impossible to distinguish between the two.
 Strep sensitive to pen G, staph are often resistant to pen G. As a result, tx should be with penicillinase-
resistant pcn.
 Scratching spreads the infection
 Impetigo – infection on face (esp perioral). Vesicles  pustules  honey-colored, wet, flaky crust (TQ)
 Cellulitis – hot, red, shiny, swollen tissue. Represents a deeper infection.
 Abscess – collection of puss
 Furuncle – folliculitis  deep penetration into subcutaneous tissue
 Carbuncles – multiple, communicating, painful, subcutaneous lesions
 Wounds – any wound can become infected with aureus. If surgical wounds become infected, they must be
re-opened and allowed to heal by secondary intention (from the bottom of wound outward)
o Blood and catheter infections – aureus can migrate from skin and colonize central venous lines  bacteremia,
sepsis and septic shock. Can also  endocarditis
o MRSA – usu develop nosocomially. These bugs are resistant to penicillinase-resistant pcns. Vancomycin is the drug
of choice for these critters.

 Staph epidermidis – G+, Catalase+, Coagulase Negative, novobiocin sensitive. Normal skin flora.
o Compromised hospital patients with Foley urine catheters (UTIs) or IV lines can become infected (TQ)
 Organism migrates from skin along the tubing of the catheter
o Epidermidis often contaminates blood culture samples drawn through skin
o Causes infections of prosthetic devices (TQ) – heart valves, prosthetic joints, peritoneal dialysis catheters, etc.
Organism has a polysaccharide capsule that forms a protective biofilm that adheres to prosthetic material, protecting
it from abx and immune syst

 Staph saprophyticus – second most common cause of UTIs in sexually active young women (E. coli is number one).
o G+, Catalase positive, Coagulase negative, novobiocin resistance
Overview of Streptococci and Staphylococci

Staphylococci of medical importance

Catalase Coagulase Typical

Species Important features
production production hemolysis
Staphylococcus
positive positive beta ferments mannitol
aureus
Staphylococcus
positive negative none sensitive to novobiocin
epidermis
Staphylococcus
positive negative none resistant to novobiocin
saprophyticus

Streptococci of medical importance

Catalase Lancefield Typical

Species Diagnostic features
production group hemolysis
Streptococcus
negative A beta bacitracin-sensitive 
pyogenes
Streptococcus
negative B beta bacitracin-resistant; hippurate hydrolyzed 
agalactiae
Streptococcus
faecalies alpha or beta or
negative C growth in 6,5% NaCl 
(Enterococcus none
faecalis)
Streptococcus alpha or beta or
negative D no growth in 6,5% NaCl
bovis none 
Streptococcus
negative - alpha  bile-soluble; inhibited by optochin 
pneumoniae
Streptococcus
negative - alpha  not bile-solube; not inhibited by optochin 
viridans
Chapter 6
Bacillus and Clostridium – Spore Forming Rods

Bacillus (aerobic, spore-forming G+ rods)

 Bacillus anthracis – unique protein capsule (poly-D-glutamic acid)  prevents phagocytosis. Non-motile. Causes anthrax, which
usu affects herbivores, e.g. cows and sheep. Humans are exposed to spores during contact with animals or animal products (hides,
wool, drums, rugs). Human to human transmission hasn’t been reported. Pcn = tx
o Spores – resistant to heat, UV, disinfectants. Spores germinate when they contact lungs, intestines or skin wounds.
Spores are small (1-2 µm) and can enter alveoli. Spores only activate once in the host (so elevated temps and incr
CO2 levels)
 Spores are phagocytized by macs, germinate into G+ rods, reproduce in lymphatic syst, leave macs, and
enter bloodstream
o Pulmonary anthrax – Aka wool sorter’s dz. Spores germinate within macs in the hilar and mediastinal nodes where
they germinate. This explains the mediastinal widening (DT hemorrhage) on CXR. Usually Fatal
o Cutaneous anthrax – most common mode of entry. Release of potent exotoxin  local tissue necrosis = painless,
round, black lesion with edematous rim = “malignant pustule”
 Abx (penicillin) are curative. Without tx, organisms can enter bloodstream. Skin lesion usually resolves
spontaneously
o GI anthrax – usu fatal. Rare. Usu contracted from contaminated meat. Presentation = bloody diarrhea, abd pain,
vomiting. Exotoxin causes necrotic lesion within the intestine
o Exotoxin – encoded by genes on plasmid “pXO1”. Three components
 Edema factor (EF) – ‘A’ subunit of exotoxin. This protein is a calmodulin dependent adenylate cyclase 
↑cAMP  which impairs neutrophil fnxn and causes edema (disruption of fluid balance)
 Protective antigen (PA) – ‘B’ subunit of exotoxin. Promotes entry of EF into phagocytes
 Lethal Factor (LF) – a zinc metalloprotease that inactivates protein kinase. Stimulates macs to release
TNF-alpha and IL-1 beta, which contribute to mortality in anthrax
o pXO2 – plasmid w/ 3 genes encode ply-glutamyl capsule, which inhibits phagocytosis. Both plasmids are required
for virulence.

 Bacillus cereus – gram+, spore forming, aerobic, motile, non-encapsulated, pcn resistant. Causes food poisoning.
o Spores survive the cooking process  spores germinate in cooked food  release 2 types of Enterotoxins:
 Heat-labile toxin – similar to cholera toxin and LT toxin from E. coli (incr cAMP levels, which increase
NaCl in intestinal lumen, so water follows in to lumen). Causes nausea, abdominal pains, diarrhea, and lasts
12-24 hrs
 Heat-stable toxin – produces syndrome similar to S. aureus food poisoning (increases GI motility); short
incub. period followed by severe nausea and vomiting, limited diarrhea
o No abx are necessary because syndrome is caused by preformed toxins. Thus, it won’t alter the course of symptoms
o Rice is a common source of B. cereus food poisoning (Chinese buffet in HPI)

Clostridium (anaerobic, spore-forming G+ rods)

 Clostridium botulinum – causes a rapidly fatal food poisoning by release of a neurotoxin that blocks release of Ach from
presynaptic terminals causing a flaccid paralysis
o Adult Botulism – smoked fish or home canned veggies are common culprits.
  If foods are improperly cooked, spores may survive  germinate in anaerobic environment (e.g. sealed
cans or zip bags)  release neurotoxin into the food and pt when opens jar will be ingesting potent
neurotoxin.
 Presentation = bilateral cranial nn palsies, diplopia, dysphagia, weakness, resp paralysis. Ventilatory
support often needed. Antitoxin is given.
o Infant Botulism – honey-containing spores is often the culprit.
 C. Botulinum colonizes infant intestinal tract. Spores germinate and Botulism Toxin is released from
intestinal tract
 Presentation = Constipation for 2-3days  dysphagia and mm weakness  floppy baby
 Antitoxin usu not necessary. Hospitalization required – No fever in either cases.
o Wound Botulism – least common. Associated with puncture wound infection (likely from soil and environment)
and similar to adult botulism w/out GI symptoms. Pt have Fever

 Clostridium tetani – drumstick shape. G+, anaerobic follows skin trauma by object contaminated with spores, puncture wound
with rusty nail (usu found in soil and animal feces). Spores germinate in anaerobic environment (Ex: deep skin wound)  release
of its exotoxin tetanospasmin (tetanus toxin)  toxin inhibits inhibitory neurons in the CNS (e.g. Renshaw cells) by↓the release
of GABA and glycine  results in hyperstimulation of skeletal mm.  tetanic contraction = paralysis
o Presentation – spasms, trismus (lockjaw), risus sardonicus (grinning expression)
o Mortality high if trismus (lock jaw) is present  respo mm paralysis
o Prophylaxis – formalin-inactivated toxin (tetanus toxoid)  stimulates formation of Abs against tetanus toxin.
Boosters given every ten years or following trauma.
 Tetanus toxoid - component of DPT shot
 If trauma patient hasn’t been immunized, human tetanus immunoglobulins must be given in addition to
tetanus toxoid injection. – note: Pcn helps clear any residual toxin producing organisms

 Clostridium perfringens – spores found in soil, non-motile (only non-motile clostridium!). Germinate in anaerobic environment.
Spores into deep wounds  gas gangrene. 3 classes of infection:
o Cellulitis/wound infection– necrotic skin is anaerobic environment for growth. Palpation reveals tissue pockets of gas =
crepitus
 o Myonecrosis – mm destruction. Pockets of gas evident in mm on CT. Thin, blackish fluid exudes from skin as mm are
degraded. Tx = Hyperbaric O2, pcn, and excision of necrotic tissue.
o Diarrheal (food poisoning) illness – spores can germinate in food, ingestion of toxin produces watery diarrhea and can
lead to hemorrhagic necrosis of the jejunum. (rare in U

 Clostridium difficile – cause of pseudomembranous colitis (can follow use of broad spectrum abx that wipe out GI flora).
o Exotoxins
o Toxin A = diarrhea;
o Toxin B = cytotoxic to colonic mucosa
o A newer binary toxin CDT produces 20x more toxin
o Presentation = diarrhea, abd cramping, fever. Red inflamed colonic mucosa w/ white exudate (pseudomembranes) seen
on colonoscopy.
o Dx – made by identification of toxin in the stool (can’t do a stool culture because it is normal flora)
o Tx – metronidazole or vancomycin (both drugs stay in GI tract and don’t enter the bloodstream. (Ideal for treating C.
difficile.)

____________________________________________________________________________________________________________

Chapter 7
Corynebacterium and Listeria: Non-Spore Forming Rods  both infect pediatric age group

Corynebacterium diptheriae (G+, Bacilli, non-spore forming, non-motile, club-shape (pleomorphic)) “appears as Chinese letters
under microscope”.
 C. diptheriae – colonizes pharynx  forms grayish pseudomembrane (fibrin, leukocytes, necrotic epithelial cells  releases
exotoxin into bloodstream  damages by interfering w/ protein synthesis in the heart and neural cells
o In heart: AV block and myocarditis
o In brain: peripheral nn palsies, ascending paralysis (guillain bare syndrome), cranial neuropathies
 o Pseudomembrane is darker/thicker exudate than strep and should not be scraped because bleeding can facilitate systemic
absorption of lethal exotoxin
o Cultured on potassium tellurite agar (they are gray/black) and Loeffler’s coagulated blood serum
o Tx – antitoxin (neutralizes circulating toxin), Pcn or erythromycin, DPT vaccine (contains formalin inactivated diptheria
toxin)
o TQ –Not all c. diptheriae release exotoxin; exotoxin is acquired via lysogenic conversion (thus, needs a bacteriophage)
o Exotoxin – has two subunits: B subunit binds target cell. A subunit inhibits elongation factor (EF 2), which results in
inhibition of protein synthesis in humans – because of this it’s called a “human antibiotic”. Interferes with translation.

Listeria monocytogenes (G+, Bacilli, non-spore forming, facultative anaerobe, (tumbling) motility, beta hemolytic) – divides in
the cytoplasm*
 L. monocytogenes –often cultured at 10*C (cold enrichment) to differentiate it from other bacteria.
o Major Virulence Factor: Listeriolysin O (LLO) - which allows it to escape the phagolysomes of macrophages to
avoid intracellular killing
 Listeria is the ONLY GRAM + bacteria w/ Endotoxin (LPS) (for the third time). Facultative intracellular
pathogen (thus, it NEEDS a host to survive!)
o Tropism for nervous tissue causes meningitis in neonates and the immunocompromised (third most common cz of
meningitis in babies < 3mos, next to group B strep and E. coli)
o These groups have compromised cell-mediated immunity, which is required to fight off facultative
intracellular pathogens
o Can affect pregnant women – infection usu occurs in 3rd trimester, may have meningitis or be asymptomatic carriers.
Avoid soft cheese and cold cuts, so to prevent baby from getting infected and die
o Elderly and immunocompromised at risk for Listeria meningitis – 2nd most common cause >50 years of age.
o Clinical Pearl for meningitis (talked before, just saying it again!!): 3 bacteria responsible for causing meningitis in
neonatal (<3 months): listeria monocytogenes, E. coli, and Group B Strep. 2 bacteria responsible for causing meningitis
later in life: Neisseria meningitides and Haemophilus influenza
o Dx: lumbar puncture shows CSF with increased neutrophils, high protein, low glucose, and Gram+ rods

Chapter 8
Neisseria – the only pathogenic Gram Negative Coccus (diplococcus)
 These are mutual characteristics

Neisseria Meningitidis (G neg, Diplococci, maltose and glucose oxidizer) “remember: MeninGitis ferments Maltose and Glucose”
 N. meningitidis – causes meningitis and meningococcemia. Aka meningococcus.
Virulence Factors: (no exotoxins)
o Capsule – polysaccharide capsule is anti-phagocytic unless antibodies opsonize the bacterium. Meningitis is caused
by strains with capsule serotypes A, B and C
o Endotoxin (LPS)– released via blebs of endotoxin that causes blood vessel destruction and sepsis. Responsible for
classic clue to invasive meningococcal infection – petechial rash. Mediates adrenal hemorrhage.
o IgA1 protease – only found in pathogenic Neisseria. IgA1 protease cleaves IgA in half (IgA found in mucus 
nasopharyngeal location, or mucus locations)
o Pili- allows attachment to human nasopharyngeal cells and undergo antigenic variation to avoid immune attack.

o N. menigitidis is usually present as normal nasopharyngeal flora

o High risk groups = infants 6mos-2yrs when antimeningococcal IgG is low and Army Recruits and College Freshmen
 Spreads via respiratory secretions

Mengiococcal Diseases
o Meningococcemia – spiking fever, chills, arthralgias, myalgia, petechial rash (DT LPS causing endothelial damage)
o Fulminant meningococcemia – (Waterhouse-Friderichsen Syndrome) – septic shock = hypotension, tachycardia
and DIC, Petechial skin lesion with adrenal insuff.
 Bilateral adrenal hemorrhage  adrenal insuff. Death occurs rapidly. Petechial rash usu present.
o Meningitis – signs incl bulging open anterior fontanelle in neonates (usu no nuchal rigidity). Older kids may present
with nuchal rigidity, Kernig’s and Brudzinski’s signs.
 (NOTE: infants will NOT have nuchal rigidity)

o Dx – G stain and culture on chocolate agar or VCN media

 Thayer Martin VCN media
 Vancomycin – kills G+ organisms
 Colistin – kills all G-neg organisms except Neisseria
 Nystatin - kills fungi
 Meningiditis can produce acid from maltose. Gonorrhoeae cannot (gonorrhea is only glucose)
o Tx – pen G or ceftriaxone. Contacts should receive prophylactic rifampin.
Neisseria gonorrhoeae (Gram Neg, diplococcic, only oxidizes glucose) “Gonorrhoeae only ferments Glucose”
 N. gonorrhoeae – second most common STD (next to Chlamydia). Aka gonococcus. No exotoxins
o Specialized Pili – involved in adherence to host cells. Hypervariable amino acid seq, so no vaccine is avail.
 Allows attachment to mucosal surface, antigenic variation and prevents phagocytosis
o Outer membrane protein porins (Protein 1)– PorA and PorB appear to promote invasion into epithelial cells.
o Opa Proteins (Protein II) – outer membrane proteins that increase adherence and invasion into epi cells – resulting
in opaque colonies
o IgA1 protease (since it’s mucous membranes) and endotoxin (LPS)
o Mechanism:
 Pili, Porins and Opa proteins allow gonococci to bind fallopian tube cell, endotoxin LPS destroys the cilia
on neighboring cells, the gonococcus is taken up by endocytosis and transported into the endocytotic
vacuole were it multiplies and is released into subepithelial space causing systemic infections.

N.gonorrhoeae cont.
o Men - urethritis – painful urination with purulent discharge.
 Complications include: epididymitis, prostatitis, urethral strictures
 Some affected men are asymptomatic, but can still transmit to partners -- Sex w/ Men results in rectal
gonococcal infection.
 Ceftriaxone – curative

o Women - urethritis more likely to be asymp in women. Cervix is reddened and friable
 Symptoms – dyspareunia, lower abd pain, purulent vaginal discharge
 Can progress to PID (Pelvic Inflammatory Disease) = infection of uterus (endometritis), fallopian tubes
(salpingitis), and/or ovaries (oophoritis).
 Presentation = fever, cervical motion tenderness, abnormal menstruation (menstrual spreads bug to
upper GU)
o Sterility – usually caused by scarring of fallopian tubes
o Ectopic pregnancy – salpingitis greatly increases risk. Scarring of tubes impedes
transport of conceptus down the GU tract.
o Abscesses, peritonitis
 Perihepatitis – (Fitz-Hugh-Curtis Syndrome) – gonococcal infection of liver capsule.
o Presentation = RUQ pain and tenderness. Also seen with Chlamydial infections.
Presentation in both men and women
o Gonococcal bacteremia – fever, arthralgias, skin lesions. Pericarditis, endocarditis, meningitis can occur
o Septic arthritis – gonococcus is the most common cz in young sexually active individuals
 Red, swollen, hot joint – synovial aspirate reveals ↑WBCs and G stain reveals G- diplococci within
WBCS.

o Infants – opthalmia neonatorum can be acquired during delivery if mother has gonococcal infection. This can cause
blindness if left untreated. Erythromycin (TQ) is used to cover both gonococcus and Chlamydia.

o Dx – Gram stain of urethral pus, culture on chocolate agar or selective VCN media.
o Tx – gonorrhea is treated with ceftriaxone. If patient is allergic to cephalosporins, spectinomycin or ciprofloxacin
can be used. Doxycycline or azithromycin is often also given to cover Chlamydia (50% of pts will be concurrently
infected with Chlamydia)
Moraxella
 Moraxella Branhamella catarrhalis – normal respiratory flora, Gram (-), non-motile, causes otitis media and respiratory
infections esp in those with COPD. Produces beta-lactamase.
o Catarro = “cough” in Spanish
o Bacteria that cause Ear infections
 Strep. Pneumo
 H. Influenzae
 Moraxella

 Kingella Kingae – most common pathogen of kingella genera. Causes septic arthritis and osteomyelitis in children.

o HACEK group causes endocarditis: (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella) TQ**

Chapter 9
The Enterics – for USMLE, you must know which organisms are motile, ferment lac and prod H2S

Biochemical stuff – E. coli ferments lactose. Shigella, Salmonella and Pseudomonas do NOT ferment lactose.
 EMB agar – lactose fermenters are deep purple to black. E. coli have green metallic sheen
 MacConkey agar – lactose fermenters develop pink-purple coloration
 O antigen – Outermost external component of LPS
 K antigen – Capsule antigen
 H antigen – Flagella antigen

Escherichia coli (Gram Neg, bacilli, Fast Lactose Fermenter, Indole pos, Beta hemolytic) Enterobacteriaceae
E. coli – normal flora that can undergo DNA change (conjugation, etc.)  gain virulence factors  cause disease.
 Diarrhea – 5 mil. kids die of E. coli diarrhea per year worldwide. Traveler’s diarrhea (Montezuma’s revenge) affects those visiting
developing countries.
o EnteroToxigenic E. coli (ETEC) – causes travelers diarrhea
 Has pili (colonization factor) that attach the E.coli to the intestinal epithelial cells allowing it to release
toxins similar to cholera exotoxins  inhibit Na and Cl resorption  osmotic diarrhea (H2O and electrolyte
loss). No fever
 LT – heat labile toxin, similar to cholera toxin - cAMP
 ST – heat stable toxin - cGMP
 Stool looks like rice water, just like cholera, but not as severe. No blood.

o Enterohemorrhagic E. coli (EHEC)

 Has pili that are colonization factor but differ in that they secretes shiga-like toxin (veratoxin)  inhibits
60S ribosome  intestinal epithelial cell death and endothelial cells  bloody diarrhea (RBCs only) and
severe abd cramps, called hemorrhagic colitis
 Hemolytic uremic syndrome (HUS) – anemia, thrombocytopenia and renal failure
 E. coli 0157:H7 is cause (TQ). Inhibits 60S ribosome (from bad hamburger meat)
 o Enteroinvasive E. coli (EIEC) – same dz as that caused by Shigella
 Plasmid shared b/w E. coli and Shigella  Shiga toxin  inhibits 60S ribosome
 Bacteria invade intestinal epithelial cells  inflamm. rxn  fever
 Diarrhea (inflamed mucosa can’t resorb) is bloody with WBCs, like shigellosis
o Diarrhea symptoms for EHEC, EIEC, and ETEC
 EHEC  bloody with no invasion
 EIEC  bloody with invasion
 ETEC  watery (Traveler’s diarrhea/Monetezuma’s revenge)
 UTIs – pili gives organism ability to travel up urethra  cystitis, pyelonephritis, etc.
o E. coli is most common cz of UTIs : Sx = dysuria, frequency, urgency, fullness
o Second most common cause of neonatal meningitis (remember others?? listeria monocytogenes, E. coli, and
Group B Strep)
o Most common cause of gram negative sepsis and a common cz of nosocomial pneumonia

Proteus mirabilis – very motile. Common cause of UTIs and nosocomial infections. Does NOT ferment lactose.
 Urea splitting (urease) – organisms splits urea to CO2 and NH3  increases pH of urine  promotes microbial growth
 UTI and sepsis
 Dx: cultures: colonies swarm over entire plate, exam shows high pH (from splitting urine into NH3)
 Weil-Felix test: Ab vs strains of prteus to dx rickets adz.

Enterobacter – highly motile. Normal flora. Can cz nosocomial infections

Serratia – produces a bright red pigment. Czes UTIs, wound infections and pneumonia

Klebsiella pneumonia (Gram Neg, Rods, lactose fast fermenter)

K. pneumoniae – encapsulated (has K antigen), non-motile  thus, no H antigen
o Second most common cause of gram negative sepsis
o Causes pneumonia w/ significant lung necrosis and bloody sputum in alcoholics and hospitalized pts.
o Sputum looks like red currant jelly (TQ)
Shigella dysenteriae– Non-motile. NO lactose fermentation. NO H2S production. Never normal flora, always pathogen.
 Humans are the only host – and it is passed via fecal-oral transmission
 Affects young kids and the elderly most commonly
Virulence
 Invades submucosa of intestinal tract but not the lamina propria.
 Non-motile therefore it doesn’t have H-antigen bc there’s no flagella.
 Shiga toxin – B subunit for binding, A subunit inhibits 60S ribosome preventing prot synthesis and killing intestinal epi
cells (like EIEC)
 Dx: stool culture : shigella is never part of the normal intestinal flora
 Presentation=Induces fever. Presentation and course identical to EIEC w/ bloody diarrhea and mucus and pus (fecal
WBCs)

Salmonella – Motile, NO lactose fermentation. H2S production. Never normal flora.

 Spread via contamination of food or H2O with animal feces (except S. typhi, which is only carried by humans).
 Capsule: Vi Ag instead of K Ag. protects from intracellular killing
 Pet birds and reptiles (pet turtles - TQ), chickens, eggs are common sources

Salmonella diseases:
 Typhoid fever (S. typhi) – aka enteric fever. Transmitted via fecal-oral route
o Invasion of intestinal epithelium  spread to regional nodes  seeding of organs  organisms
phagocytized  facultative intracellular phase.
o Presentation – 1-3wks post exposure – fever, headache, abd pain over RLQ mimicking appendicitis.
Splenic enlargement and rose spot rash on stomach may occur
o Tx – ceftriaxone or ciprofloxacin
o Carrier state – in some recovered individuals, organisms are harbored in gall bladder and continuously
shed in feces

 Sepsis (S. choleraesuis) – doesn’t involve GI tract. Salmonella are encapsulated (Vi Ag) - organisms must be opsonized
(coated with Abs) and phagocytosed by cells in the splenic reticulo-endothelial system. Bugs can infect bone, brain or
lungs.
o Asplenic pts (trauma or Sickle-cell dz) – cannot effectively remove encapsulated bugs from bloodstream.
o Osteomyelitis – Sickle-cell pts are susceptible to Salmonella osteomyelitis.
  Diarrhea (S. enteriditis) – most common type of Salmonella infection. Usu watery, but may have trace blood. Tx – fluid
and lyte replacement. Lasts only a few days.

Yersinia enterocolitica – transmitted in contaminated foods (e.g. milk or feces contam H2O). Organism can grow in the cold. Motile,
non-lactose fermenting. Virulence factors are temp. sensitive.
 Acute gastroenteritis: Fever, diarrhea, abd pain (RLQ  pseudoappendicitis, TQ)
 Can be invasive (see S. typhi)
 Enterotoxin similar to ST of ETEC (increase cGMP levels)

Family Vibrinaceae
Vibrio cholera - same dz as ETEC, but more severe. No epith invasion. Rice water stool, isotonic fluid loss  diminished pulses,
sunken eyes, poor skin turgor  death by dehydration. From contaminated water
 Choleragen = cholera toxin – B subunits bind to GM1 ganglioside  A subunit activates G protein  activation of
membrane bound adenylate cyclase  ↑cAMP (TQ) ↑Na and Cl secretion and ↓Na and Cl resorption  fluid enters
intestinal lumen via osmosis  diarrhea  1 L fluid loss per hour
 Motile, curved G- rod
 Oxidase +
 Non-lactose fermenting
 Needs special media!
 Tx – supportive. Doxycycline can shorten duration of illness

Vibrio Vulnificus – Gulf of Mexico, gets in wound and causes PRIMARY SEPSISEMIA (fever,shock) in pts w/ liver dz.

Vibrio parahaemolyticus – gastroenteritis following ingestion of raw seafood. Leading cz of diarrhea in Japan
Campylobacter jejuni – C. jejuni, rotavirus and ETEC are the most common czes of diarrhea worldwide
 Prodrome of fever and headache  cramps and bloody/secretory diarrhea
 Can be invasive like S. typhi and Y. enterocolitica
 Has LT like toxin and the ability to destroy intestinal epithelial cells. Organism is zoonotic like S. enteriditis
 Selective media with antibiotics at 42C (special media!)
 Zoonotic: unpasteurized milk and poultry. G- rod, oxidase +.

Helicobacter pylori – most common cz of duodenal ulcer and chronic gastritis. Second most common cz of gastric ulcers. Urease +
 protection against gastric acidity. Pepto bismol (bismuth salts) inhibit growth.

Family Bacteroidaceae
Bacterioides fragilis – no Endotoxin. Encapsulated. Anaerobic. Normal GI flora becomes a problem in cases of intestinal trauma or
surgical perforation of the intestines (problem when bowel becomes perforated)
 Trauma  bacteria release into peritoneal cavity  abscess formation  requires surgical drainage
 Prophylaxis – antibiotics that cover anaerobes are given following abdominal surgery
  OB/Gyn – septic abortion, PID, IUDs can  abscess formation

Bacterioides melaninogenicus – produces black pigment when grown on blood agar. Lives in mouth, vagina and intestine.
 Involved in necrotizing anaerobic pneumonias czed by aspiration of sputum (e.g. seizures or intoxication). Also czes periodontal
dz.

Fusobacterium – like melaninogenicus, these bugs are involved in aspiration pneumonia and periodontal dz
Anaerobic G+ cocci – Peptostreptococcus – normal flora of mouth, vagina, and intestine. Found in aspiration pneumonias and
abscesses, often along with other anaerobes
____________________________________________________________________________________________________________

Chapter 10
Hospital Acquired Gram (-)

Hospital acquired infections include pneumonia, UTIs, wound infections, and bloodstream infections (assoc. w/ intravenous lines).
Remember the 4 W’s: wind (pneumonia), water (UTIs), wound, and wires (intravenous lines)

Pseudomonas aeruginosa – infects, sick immunocompromised pts (not healthy people). Obligate aerobe, NO lactose fermentation,
produces green (pyoverdin) and blue (pyocyanin) pigments on colonies and wound dressings, gives off sweet grape-like scent
(TQ). Urea splitter
 Exotoxin A – same mechanism of action as diptheria toxin (inhibition of protein synthesis)
 Pneumonia – cystic fibrosis and immunocompromised pts
 Osteomyelitis
o Diabetic foot ulcers – inhabited by organisms  penetrate into bone  osteomyelitis
o IVDAs (intravenous drug abuser) – introduce organisms with dirty needle  osteomyelitis of vertebrae or
clavicle
o Kids – puncture wound of foot  organisms penetrate bone
 Burn wound infections – can lead to sepsis (pseudomonas sepsis is bad news)
 UTIs, pyelonephritis – nursing homes and hospitals. Associated with chronic placement of Foley catheter
 Endocarditis – pseudomonas can cz rt heart endocarditis in IVDAs, but S aureus is more common
 Malignant external otitis – elderly diabetic pts. Tx = anti pseudomonal pcn + aminoglycoside
 Corneal infections – in contact lens wearers
 BE PSEUDO
o Burns
o Endocarditis
o Pneumonia
o Sepsis
o External malignant otitis media
o UTI
o Diabetic Osteomyelitis

Burkholderia cepacia – oxidase +, aerobic gram negative, rod. infects hospitalized burn pts, ventilated pts, and cystic fibrosis pts.
Stenotrophomonas maltophilia – part of normal respiratory flora, but can cause disease in immunocompromised pts. Infections
include pneumonia and line-related bacteremia

Acinetobacter baumannii – similar to pseudomonas: aerobic gram negative bacteria found in soil and water. Frequent cause of
hospital-acquired pneumonia, line-related bacteremias, burn infections, and foley-catheter-associated UTIs.

Chapter 11
Haemophilus, Bordetella, and Legionella  all acquired through the respiratory tract

Haemophilus influenzae – means “blood loving,” obligate human parasite. Transmitted via respiratory secretions. G- rod. Need
special media (chocolate agar)
 Nonencapsulated strains – cz otitis media in kids and resp dz in adults with preexisting lung dz (smokers). COPD pts get
recurring H. influenzae infections
 H. influenzae type b (Hib)– type b capsule most commonly associated with invasive dz. (6 types of capsules: a, b, c, d, e, f. b is
bad)
o Meningitis – main cz of meningitis in kids 6mos – 3yrs before advent of Hib vaccine. Remember, no nuchal rigidity
in this age group. When Tx with antibiotics, LPS is released resulting in a violent immune response, give steroids
before abx Tx
o Acute epiglottitis – following sore throat and fever  wheezing (stridor) and inability to swallow (as evidenced by
saliva oozing from mouth). Epiglottis looks like a large bright red cherry at the base of the tongue. Examination of
larynx is dangerous and can result in laryngeal spasm
o Septic arthritis – Hib is the major cz of septic arthritis in kids 6mos – 3yrs. Synovial fluid contains G- pleomorphic
rods
o Sepsis – kids 6mos – 3yrs with constitutional symptoms and no evidence of localized dz may be affected.
 Most common in kids with absent or non-functioning spleens (inability to fight off encapsulated organisms).
Prompt ID and tx will prevent invasion  epiglottis, joint, meninges.
o Tx – third generation cephalosporin
o Vax – consists of type b capsule plus diptheria toxin, which activates T-cells and facilitates the production of Abs
against the Hib capsule. (DTaP for kids in 5 installments; Tdap as boosters for adults every 10 yrs)

Haemophilus ducreyi – G- coccobacillus causes painful chancroid (STD). Tx = erythromycin or TMP/SMX. Characterized by
painful chancre and unilateral painful inguinal lymphadenopathy. LN drain pus. DDx includes:
 Syphilis (Treponema) – adenopathy is usu bilateral and lesion is painless
 Herpes (HSV-2) – usu has associated systemic symptoms like myalgia and fever (absent in chancroid)
 Lymphogranuloma venereum (Chlamydia) – Painless matted suppurative inguinal lymph nodes, adenopathy develops slowly and
doesn’t coexist with skin lesion (in chancroid, the primary lesion and adenopathy occur simultaneously, but this is not the case
here).

Remember the bacteria that are slow growing and cause endocarditis?!?!
HACEK group causes endocarditis: (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella)

Gardnerella vaginalis – in conjunction with vaginal anaerobes, this bug czes bacterial vaginitis.
 Vaginal pruritis, dysuria, copious foul-smelling (fishy odor) vaginal discharge. Tx = metronidazole
 Clue cells in vaginal discharge are diagnostic. Clue cells = vaginal epithelial cells with small, pleomorphic bacilli in their
cytoplasm
 He’s smells like a GARDen. There’s something FISHY about this. This must be a CLUE of why he smells like this.
o Gardnerella  fishy odor and clue cells

Bordatella pertussis – causes whooping cough. Organisms attach to ciliated epithelium (not invasive)
 Pertussis toxin – B subunit binds. A subunit increases cAMP resulting in: Incr sensi to histamine and incr insulin release and
lymphocytosis
 Extra cytoplasmic adenylate cyclase – released by organism  taken up by host immune cells  ↑cAMP inside immune
cells  impaired chemotaxis and oxyradical production
 Filamentous hemagglutinin (FHA) – helps organisms attach to ciliated epithelial cells
 Tracheal cytotoxin – destroys ciliated epithelial cells
 Unimmunized infants under 1yr are most susceptible
 Whooping cough stages: catarrhal stage  paroxysmal stage  convalescent stage
o Catarrhal stage: URI (upper resp. infection) prodrome, pt very contagious. Erythromycin tx here may prevent
dz
o Paroxysmal stage: bursts of non-productive cough can  cyanosis and hypoxemia, creates a lymphocytosis!!
o Convalescent stage: recovery, not contagious. Contacts should be treated with erythromycin.
 Culture – posterior pharynx is swabbed with calcium alginate swab (organisms won’t grow on cotton) grow on Bordet-
Gengou medium
 Vax – heat-killed organisms, pertussis toxin, FHA and adenylate cyclase (component of DPT shot)

Legionella pneumophila – ubiquitous in water environments. Aerosolized contaminated H2O (air conditioning and cooling towers) is
source of transmission. Not transmitted from person to person.
 Facultative intracellular parasite – inhibits phagosome-lysosome fusion and proliferates intracellularly. Can enter a low
metabolic state and survive in a biofilm. Needs special media!! (fastidious)
 Pontiac fever – flu-like illness that resolves in less than one week (fever, chills, muscle aches, fatigue)
 Legionnaire’s dz – high fever and severe pneumonia (lobar consolidation with high fever, low HR) may also see elevated
CPK (muscle breakdown from rhabdomyolysis) and AST/ALT (liver enzymes)
o One of the most common czes of community acquired pneumonia
 o Should be suspected in all pts over 50, esp in smokers
o Sputum G stain reveals neuts and very few organisms
o Tx = erythromycin

Chapter 12
Zoonotic facultative intracellular organisms

Yersinia pestis (Bubonic Plague) – rats harbor and fleas are the vector. Squirrels and prairie dogs in the SW US carry organism.
 F1 – capsular Ag, anti-phagocytic
 V and W Ags – unique to Y. pestis. Unknown actions
 Bipolar staining – ends of rod take up more stain than the middle
 Bact invade skin  phagocytosed by macs  multiply intracellularly  move to nodes (usu inguinal)  nodes swell like
eggs, becoming hot, red and painful  fever and headache  bact invade bloodstream, liver, lungs and other organs 
subcutaneous hemorrhages give black discoloration (“Black Death”). During epidemics, can spread via aerosolized droplets.
Buboes.
 Fatal without tx = aminoglycoside or doxycycline
 Pneumonic plague – pneumonia, person to person transmission via aerosol. During epidemics.
 Sepsis: bacteria survive in macrophages and spread to the blood
 Epidemics – controlled by killing rodents and fleas (if only rodents are killed, fleas seek out humans)

Yersinian enterocolitica – Gram (-) rod, motile, transmitted through flea bite, pigs, can survive cold, can invade lymph nodes and
blood, symptoms are enterotoxin = diarrhea, fever, appendicitis-like abdominal pain

Francisella tularensis – (tularemia) most commonly acquired from handling rabbits or from bite from tick or deerfly. Like Yersinia,
organisms can invade any area of contact. High infectivity!
 Ulceroglandular tularemia – contact with rabbit or deerfly/tick bite  development of well demarcated hole in the skin
with a black base  course and sx mimic plague exactly. Skin lesion differentiates from Yersinia. Much less fatal than
plague
 Pneumonic tularemia – aerosolization during skinning and evisceration of rabbit or hematogenous spread from skin to lungs.
Be careful when eviscerating road kill in your kitchen.
 Oculoglandular (eyes) and typhoidal (GI tract) varieties occur
 Skin test similar to PPD used for dx. Culturing is dangerous since just 10 organisms can cz dz.
Brucella (Brucellosis) – acquired from direct contact with infected meat, aborted animal placentas, tainted milk products. (goats,
cows, dogs, pigs)
 B. melitensis  goats
 B. abortus  causes abortion in cows
 B. suis  pigs (pig sooo-eeeyy  suis)
 B. canis  dogs
 Usually affects meat-packers, veterinarians, farmers, travelers
 Neither buboes nor a primary skin ulcer appear. Penetration (skin, conjunctiva, lungs, GI)  lymphatic spread  intracellular
growth in macs  blood and organ invasion
o Causes undulant fever = Systemic sxs where Fever peaks in evening and is normal by morning
o Dx – made by culture of organism from blood or ↑anti-Brucella Ab titer

Pasteurella multocida – NOT facultative intracellular organism. Normal flora of cats and dogs! Can also cause disease in birds
 Usu assoc with cat or dog bite (or scratch). Such wounds shouldn’t be closed with sutures. Closed wounds may promote invasion
of local joints and bones by organisms.
Chapter 13: Chlamydia, Rickettsia and Friends
Chlamydia – obligate intracellular parasite. Must get ATP from host cell. No peptidoglycan layer (insensitive to pcns and cephalos).
Very tiny organisms. Fond of columnar cells, so causes conjunctivitis, cervicitis and pneumonia. Replicates in endosomes
(inclusions). Requires living media.
 Life cycle – Elementary Body (EB), the infecting agent/metabolically inert, enters host cell  EB inhibits phagosome-lysosome
fusion  grows (RNA synth) into initial body (IB)  IB synthesizes protein, DNA and RNA  IB transforms back into EB 
host cell liberates EBs  infection of more host cells
 Tx – erythromycin or tetracycline will zap Chlamydia

 Chlamydia trachomatis – affects eyes and genital tract

o Serotypes A, B and C – leading cause of preventable blindness in the world
 Trachoma Dz: conjunctival infxn causes scarring. Scar traction  entropion  lashes scar cornea and
conjunctiva  after several years, blindness ensues. Tetracycline will prevent
 Tx – all babies born in US get erythromycin drops (covers gonococcus and C. trachomatis)

o Serotypes D through K – cause inclusion conjunctivitis in newborns, infant pneumonia and urethritis (STD) in
adults
 Inclusion conjunctivitis – baby gets C. trachomatis from mother’s birth canal, purulent discharge from eyes
 Dx – intracytoplasmic inclusions (collections of IBs) in cells obtained via conjunctival scraping.
Erythromycin drops prevent as infection usu lags behind birth by 5-14 days
 Infant pneumonia – baby’s passage through infected birth canal can also lead to pneumonia: rapid
breathing, cough, respo distress (4-11 weeks after delivery). Oral erythromycin is curative
 Urethritis – most common STD = NGU. NGU usu czed by C. trachomatis or Ureaplasma urealyticum.
Many pts are asymptomatic. Some have mucoid discharge and dysuria. Mixed infection (gonococcus and
C. trachomatis or Ureaplasma) is common – tx with ceftriaxone and doxycycline or azithromycin will
cover all organisms
 If G stain of urethral discharge reveals no diplococci, dx is probably NGU
 PCR is available for detecting Chlamydial DNA in vaginal swabs or urethral discharge.
 Cervicitis and PID
 – abn uterine bleeding, dyspareunia, nausea, vomiting, fever. Most common sx is lower abd pain. Pts may
be asymptomatic, but risk for infertility is still eminent.
 Chandelier sign – cervical motion tenderness
 PID can  infertility, ectopic pregnancy, chronic pain
 Tx – ceftriaxone + doxycycline
 Epididymitis – unilateral scrotal swelling, tenderness and pain
 Reiter syndrome – arthritis, urethritis and conjunctivitis
 Fitz-Hugh-Curtis syndrome – infection of the liver capsule with RUQ pain. Can be czed by either C.
trachomatis or gonococcus.

o Serotypes L1, L2, and L3 – cause lymphogranuloma venereum

 Painless papule or ulceration on genitals  heals  organisms spread to regional nodes  nodes enlarge
over a few months and become tender. Nodes may break open and drain pus. Has a late development of
ulcers, fistula, and genital elephantiasis
Overview of serotypes
o Serotypes A-C: ocular trachoma in endemic countries (blindness)
o Serotypes D-K: genital-tract infections, conjunctivitis
o Serotypes L1, L2, L3: lymphogranuloma biovar, associated with lymphogranuloma venereum, an inguinal
adenopathy

 Chlamydia psittaci – affects bird handlers (parrots)  results in atypical pneumonia called psittacosis
 Atypical pneumonia – pneumonias czed by C. pneumoniae, C. psittaci, Mycoplasma, and viruses.
o Fever, headache, dry hacking cough without production of yellow sputum
o Patches or streaks of infiltrate on CXR (no consolidations)
Rickettsia – small G- ATP pirate like Chlamydia, but these bugs require arthropod vectors. Ricketsia replicate in the cytoplasm
(Chlamydia in endosome). Require living media
 Tropism for endothelial cells. Replicates in cytoplasm. Some species share Ags with Proteus strains OX-2, OX-19, OX-K.
o Weil-Felix reaction – mix serum of pt suspected of having Rickettsial inf with Proteus Ags attached to latex beads.
If anti-Rickettsial Abs are present, beads will agglutinate.
o Tx – doxycycline and chloramphenicol

 Rickettsia rickettsii – carried by Dermacentor ticks (dog or wood ticks)  Rocky Mountain spotted fever = fever, conjunctival
redness, severe headache. Rash on wrists, ankles, soles, and palms spreads to trunk
o More common in Appalachian’s than in the Rocky Mts
o Organisms replicates in endothelium of small blood vessels and capillaries  small hemorrhages seen as the
wrist/ankle rash
o Early discovery and removal of ticks may prevent infection with R. rickettsia

 Rickettsia akari – (Rickettsialpox) transmitted to humans by mites that live on mice. Doxycycline = tx
o Mite bite (red papule)  blister  fever, headache  vesicles over body like chickenpox. Self-limiting.

 Rickettsia prowazekii – (Epidemic typhus) flying squirrels are reservoir in southern US, vector = louse (TQ)
o Common in overcrowding and unsanitary conditions. Human body louse is vector.
 o Transmitted from squirrels to humans via louse of flea bites
o Abrupt fever and headache  2wk incub  small pink macules on upper trunk  spread over body (spares palms,
soles and face, unlike R. rickettsii). Can be fatal if untreated. Can also get gangrene.
o Brill-Zinsser Dz – pts that recover from epi typhus without abx harbor organism in latent state. Reactivation 
milder sx (no skin rash) and ↑IgG instead of IgM, which signifies first time inf.

 Rickettsia typhi – (Endemic or murine typhus) not as severe as epidemic typhus. Rodents are reservoir and rat flea is vector.
Rodent and flea population control  prevention.
o 10 day incubation  fever and headache  flat, bumpy maculopapular rash
o Tx – doxycycline or chloramphenicol

 Rickettsia tsutsugamushi – Scrub typhus Asia and southwest Pacific. Larvae of mites (chiggers) spread to humans.
o 2wk incub  fever and headache  scab at original bite  flat, bumpy maculopapular rash
 Bartonella quintana – (Trench Fever) louse-borne febrile illness. NOT an intracellular parasite
o Fever, rash, headache, back and leg pain  relapses every five days (quintana)
o Filth and lice (conditions similar in epidemic typhus)  trench fever

 Bartonella henslae – (Cat scratch fever) cat bite or scratch  lymph node swelling  low grade fever and malaise  dz
resolves within a few months
o Bacillary angiomatosis – czed by B henslae. Proliferation of small blood vessels in the skin and organs of AIDS
pts (Putthoff loves to ask Qs relating to HIV/AIDS)

 Coxiella burnetti – (Q fever) has an endospore form. No arthropod vector. Organism grown in ticks and cattle. Only rickettsial
dz that czes pneumonia and NO rash.
o Spores present in tick feces on cattle hides  aerosolization  inhaled by humans  mild pneumonia often
develops (similar presentation to Mycoplasma pneumonia) along with abrupt onset of fever and sweats.
 Ehrlichia canis and chaffeensis
o canis – dz of dogs. Dogs get it from ticks
o chaffeensis – dz of humans (similar to Rocky Mt spotted fever) czed by ticks

Chapter 14: Spirochetes

Spirochetes – corkscrew-shaped w/ endoflagella called axial filaments. Have an additional phospholipid-rich outer membrane with
few exposed proteins, which helps protect them from immune recognition. Dark-field microscopy and silver stain are required to
visualize very small organisms. Need special media! Produces no toxins, dz caused by host’s own immune response.

 Treponema pallidum – cz of Syphilis. Black ♂ and ♀ in urban areas at greatest risk. Organism penetrates mucous membranes or
epithelial abrasions. Skin contact with infected ulcer = transmission
o Primary syphilis – painless chancre and regional lymph node swelling. Highly infectious
o Secondary syphilis – organisms spread in the blood. Widespread rash (small red, flat lesions) over palms, soles
and mucous membranes of oral cavity (rash eventually becomes popular) and generalized lymphadenopathy.
Condyloma lata – painless, wart-like lesion over vulva or scrotum (extremely contagious – filled with spirochetes).
May also see hairloss with lesions. MOST INFECTIOUS STAGE, because of more concentrated spirochetes.
 Progresses to noninfectious (over 4 years), but can still be infectious to fetus!
o Latent syphilis – asymptomatic. Relapses to secondary skin manifestations can occur. 1/3 progress to tertiary
syphilis. Non-infxous
o Tertiary syphilis – many years after primary chancre
 Gummatous syphilis – granulomatous lesions found in skin (painless) and bone (deep gnawing pain).
Resolve with abx.
 Cardiovascular syphilis – at least 10 yrs after primary. Aneurysm of ascending aorta or aortic arch. Chronic
inflamm of vasa vasorum  tunica media necrosis  dissection  sometimes aortic insuff and coronary
occlusion occur
 Neurosyphilis
 Asymptomatic – CSF tests positive, but no sx
 Subacute meningitis - ↑lymphs, ↑protein and ↓glucose in CSF (Syphilis and TB are only bact to
cause subacute meningitis). Bacteria usu cause acute form = ↑neuts, ↑protein, ↓glucose in CSF.
 Meningovascular syphilis – BVs of brain and meninges affected  CNS infarctions and
corresponding focal neural deficits.
 Tabes dorsalis – posterior columns and dorsal roots affected  impaired vibratory sensation and
proprioception  ataxia. Loss of dorsal root ganglia = loss of temp and pain, along with DTRs
 General paresis (of the insane)
 Argyll-Robertson pupil – occurs in tabes dorsalis and general paresis. Pupil constricts during
accommodation, but doesn’t react to light (prostitute’s pupil)

o Syphilis – 6 axial filaments  6 week incubation  6 wks for chancre to heal  6 wks later, secondary syphilis
develops  6 wks for secondary to resolve  66% resolve (no tertiary)  6 yrs to develop tertiary

o Congenital syphilis – organism crosses placenta  infects fetus

 Early congenital syphilis – like severe secondary in adults. Nasal mucous membrane involvement 
snuffles (runny nose). Lymph node, liver, spleen enlargement. Bone infection.
 Late congenital syphilis – like adult tertiary, except no cardiovascular involvement
 Neurosyphilis – same as adults. Eighth nerve deafness is common
 Saddle nose (inflammation destroys nasal septum), saber shins (inflammation, tibial bowing),
Hutchinson’s teeth (central incisors are widely spaced with a notch in each tooth), mulberry
molars (too many cusps).
 Corneal inflammation
  Treating mother with abx prior to 4 months gestation can prevent congenital syphilis

o VDLR and RPR – detect anti lipoidal Abs (e.g. anti-cardiolipin and anti-lecithin). Non-specific. 1% of pop without
syphilis also have these Abs.  screening tests!
o FTA-ABS – specific test that detects anti-Treponema Abs. (TQ) if
 Both VDLR and FTA-ABS are + = active syphilis infxn.
 Only VLDR is positive = a false positive (preggo women).
 VLDR is neg but FTA-ABS is + = a treated syphilis infxn.
 Both are - = probs not a syphilis infnx, or person is immunocompromised, or person was very recently
infected

o Tx – pcn. Pcn will cross placenta and cure fetus as well. If allergic to pcn, give erythromycin or doxycycline
(erythromycin in pregnancy because doxycycline is toxic to the fetus)
 Following tx, VDLR and RPR will return to negative levels, but FTA-ABS will remain elevated for life.
 Jarisch-Herxheimer rxn– acute worsening of sx immediately after abx are started. Sx include fever, chills,
headache, malaise, myalgia. Thought to be result of killed organisms releasing a pyrogen. Occurs with most
spirochetes

 Treponema pallidum subspecies – like syphilis – primary skin papule  secondary stage with widespread skin lesions  tertiary
stage with gummas of the skin and bones. Non-venereal treponemes do not involve heart or CNS
o Subspecies endemicum (endemic syphilis: Bejel) – African and Middle Eastern deserts. Spread via sharing eating
utensils. Lesions in oral mucosa. Gummas in tertiary stage.
o Subspecies pertenue (Yaws) – tropics. Spread via contact with open ulcers. Mother yaw = initial lesion (growing,
wart-like papule). Disfigures face. Gummas in tertiary stage.
o Subspecies carateum (Pinta) – rural Latin America. Spread by direct contact. Papule that slowly expands 
secondary eruption of numerous red lesions  turn blue in the sun  depigmentation of lesions (white) no
gummas!
 Borrelia burgdorferi (Lyme dz) – most common reported tick-borne illness in the US. 24 attachment of tick required for infection
(early removal of tick  prevention)
o White footed mouse and white-tailed deer = reservoirs; Ixodes tick
o Early localized stage – 10 days after tick bit, erythema chronicum migrans develops = flat, red, round rash with red
margins and clearing center (center may necrose) , it is a painless skin lesion
o Early disseminated stage – diss to skin, nervous system (variety of PNS and CNS effects, Bell’s palsy common),
heart (AV block and myocarditis) and joints (arthritis)
o Late stage – chronic arthritis that can last for more than a year (HLA-DR 1+4). Also chronic neuro damage.
o Dx – anti Borrelia Abs. Tx – doxycycline or pcn. Vax – ImuLyme or LYMErix

 Borrelia recurrentis –(Relapsing fever) t-mitted to humans via the body louse (many other Borrelia species can cause relapsing
fever and are t-mitted by the Orithodoros tick). Ticks feed on sleeping camper is the western US, esp in rustic mountain cabins.
o Bact disseminate in the blood  fever, chills, headaches, myalgias  rash and meningeal involvement may follow
 fever resolves with drenching sweats after 3-6 days  afebrile for about 8 days  relapses (3-6 day periods)
 Antigenic variation of surface proteins responsible for relapsing nature of illness

 Leptospira interrogans – organisms have ‘ice tongs” appearance. Found in urine of animals. Can penetrate abraded skin and
mucous membranes
o Leptospiremic phase – bact invade bloodstream and CSF  spiking fever, headache, malaise, severe muscle aches.
Conjunctiva are red and pt experiences photophobia
o Second (immune) phase – appearance of IgM. Meningismus may develop. ↑WBC in CSF.
o Weil’s dz (more severe illness czed by serogroup icterohaemorrhagiae) – infectious jaundice = renal failure
(proteinuria), hepatitis with jaundice (↑liver enzymes), mental status changes and hemorrhage into many organs
o Dx – culture from CSF or blood. Tx – pcn or doxycycline. Needs special media!

Chapter 15
Acid-Fast Bacteria – thin rods with high lipid content –stain acid fast (lipids stained with carbolfuchsin aren’t washed away with acid
alcohol)
 Mycobacterium tuberculosis ; TB – on the rise. Catalase +, aerobic. Type IV hypersensitivity rxn with CD4 T cells, Usu affects
elderly, AIDS pts and urban poor (ppl with poor cell-mediated immunity). Obligate aerobe, grows slowly, facultatively
intracellular, colonies lump together (hydrophobic bugs) in culture. Only infects humans. A great imitator.
o Virulence – mycosides, lipids specific to Mycobacterium.
 Mycolic acid – a large fatty acid
 Mycoside – mycolic acid bound to carbohydrate = glycolipid
 Cord factor – 2 mycolic acids bridged by a disaccharide – inhibits neut migration and damages
mitochondria. Only found in virulent strains of tuberculosis. Cause TNF release
 Sulfatides – inhibit phagosome-lysosome fusion  facilitative intracellular growth
 Wax D – adjuvant – thought to activate cell-mediated immunity in host
o Facultative intracellular growth – local infiltration of neuts and macs. Phagocytized bact aren’t destroyed,
survives and lives in the macrophage phagosomes–(prevents fusion of the degrading lysosome) (TQ) 
lymphatogenous dissemination

o Cell-mediated immunity – some macs break up bugs  present Ags to T-helper cells  sensitized helper cells
encounter Ag  release lymphokines  recruitment and activation of macs  attack on infected target  tissue
damage  foci of caseous necrosis (soft caseous center surrounded by macs, multinucleate giant cells, fibroblasts
and collagen deposits. Calcification present = TQ)

o PPD skin test – intradermal injection of purified protein derivative  localized swelling and redness. Positive =
area of induration > 10 mm in diam. 48 hrs after injection (indicates DTH reaction)
 Positive PPD often precedes sx. Treatment at this stage can prevent lung damage, etc.
 False positive – people who have received BCG (bacillus Calmette-Guerin) vaccine overseas.
 False negative – pts are anergic due to steroid use, malnutrition or AIDS.
 no response to injection mumps or candida can confirm false anergy

o **Primary tuberculosis – sub-clinical lung infxn. transmitted via aerosol  inhaled droplets land in mid to lower
lung zones (where ventilation is the greatest)  small patch of pneumonitis with neuts and edema  bacteria enter
macs  lymphatogenous dissemination to regional nodes, other areas of lungs and distant organs
 Asymptomatic primary infection – bact walled off in caseous granulomas  heal with fibrosis,
calcification and scarring.
 Tubercles – granulomas on CXR. A calcified tubercle in mid or lower lung zone is called a
Ghon focus. A ghon focus + perihilar node calcified granuloma = Ghon complex (**TQ**).
Ghon complex is PRIMARY tuberculosis!
o When a Ghon complex becomes calcified, it’s called a Ranke complex. But this
happens in secondary reactivation TB!!!!
 Symptomatic primary infection – less frequent than asymp. Occurs in kids, elderly and
immunocompromised.
 Large caseous granulomas – necrosing material liquefies, extrudes and leaves cavitary lesions
behind  air-fluid levels on CXR. Enlargement of mediastinal or hilar lymph nodes and
lower/middle lung infiltrates
o **Secondary or reactivation tuberculosis – can occur in any organ system seeded during primary infection.
Temporary weakening of immunity may precipitate. “great imitator”
 Pulmonary TB – occurs in apical areas around clavicles (high O2 tension due to low perfusion). Fever,
night sweats, weight loss, productive cough with red snappers (organisms in sputum)
 Pleural or pericardial infection - infectious effusions
 Lymph node infection – most common extrapulmonary manifestation of tubercles, called Scrofula
 Kidney – sterile pyuria and hematuria (RBCs and WBCs in urine)
 Skeletal – infection of thoracic and lumbar spine vertebrae and intervertebral discs (Pott’s Dz)
 Joints – arthritis
 CNS – subacute meningitis or granulomas in the brain
 Military TB: tiny millet-seed sized tubercles (granulomas) are disseminated all over the body. Usu occurs
in elderly and children
BIG PICTURE: TB is usu a chronic disease; it presents slowly with wt. loss, low-grade fever, and symptoms related to the
organ system infected. Because of its slow course, it may be confused with cancer. Whenever you have an infection of any
organ system, TB will be somewhere on the Dx list. It is one of the great imitators!!
 Mycobacterium avium-intracellulare (MAI) – usu only infects birds. Infects AIDS patients (TQ). Harbinger of death – only
attacks when CD4 count is extremely low. MAI  chronic wasting with organisms disseminated to spleen, liver, bone marrow
and intestines (chronic watery diarrhea)

 Mycobacterium leprae - Leprosy (Hansen’s Dz) – catalase +, phenolase +, non-motile, facultative intracellular growth, can’t
culture. Must grow in animal e.g. armadillo. Most common in India, Mexico, Pacific Islands and Africa. Transmitted via resp
secretions. Bact grow better at lower temp close to body surface. Lepromin test = skin test similar to PPD, tests for ability to
mount a cell-mediated immune response.

o Lepromatous leprosy – most severe form. Pts CANNOT mount a cell-mediated response. Defective T-suppressor
cells block CD4 response. Negative lepromin test. Death ensues if untreated
 Organisms are found everywhere throughout pt’s body. Multiple lesions.
 Damage occurs mostly in skin, eyes, peripheral nerves, and testes (cooler areas)
 Leonine facies, saddlenose deformity, infertility (testicular involvement)
 Peripheral nn are thickened  sensory loss in glove and stocking distribution

o Tuberculoid leprosy – pts CAN mount a cell-mediated response  less severe and sometimes self-limiting.
Positive lepromin test.
 Usually one or two skin lesions – hypopigmented, elevated, hairless blotches with diminished sensation.
 Enlarged peripheral nn can be palpated near the skin (greater auricular, ulnar, posterior tibial,
peroneal)

Chapter 16
Mycoplasma – NO CELL WALL: lack peptidoglycan layer (insensitive to pcns and cephalos). Sensitive to erythromycin and
tetracycline. Pleomorphic organisms. Smallest bacteria capable of self-replication outside a host cell
 Mycoplasma pneumoniae – number one cz of atypical pneumonia in teens and young adults. Motile
 o transmitted via resp aerosol. P1 adhesin (virulence factor) allows organisms to attach to resp epithelial cells.
o Fever, sore throat, malaise, dry hacking cough = walking pneumonia (pts not very sick). Illness is self-limiting, but
erythromycin or tetracycline will shorten course of the illness.
o CXR  streaky infiltrate (atypical pneumonia!) along with the dry, unproductive cough.
o Cold agglutinins (TQ) – Abs to Mycoplasma Ags that are identical to Ags on RBCs. These Abs will agglutinate
RBCs at 4oC.
 This is a presumptive diagnosis! Not a confirmation test.
 This test is not specific for M. pneumoniae. Mononucleosis influenza can have the same response
o Complement fixation, sputum culture and DNA probe – other dxic tests
 Sputum culture must be done on special media filled with lots of cholesterol!  colonies have a round,
bumpy appearance (mulberry)

 Ureaplasma urealyticum – Urease positive. T-strain mycoplasma – forms Tiny colonies in culture. Part of normal flora
o Causes NGUrethritis. Tx = erythromycin or tetracycline
o Normal GU flora in many healthy sexually active women

HYMB Buzz Words:

Gram Positive – Cocci Gram Positive – Baccili Others
Staph aureus Catalase+, coagulase + / TSS Bacillus Spore forming, motile, food Chlamydia Obligate intracel parasite
(tampons), SSS, mayo food poison, cereus poison due to rice// LT (cAMP) Psittaci = /inclusion bodies/Giemsa
IV users, septic shock osteomyelitis and ST (cGMP) toxins  1st psittacosis stain/Birds
enemic then 2nd diahrrea
symptoms
Staph Catalase+,Coagulase -/ Forms Bacillus Spore forming – Poly D- Chlamydia Infects Eyes+Genitals/ ATP
epidermidis Biofilm on prostetics/sepsis, also anthracis Glugamic capsule, black skin trachomatis = parasite/ MCSTD/ no
IV user, endocarditis pustules/wool Urethritis/PID peptidoglycan layer
soorters”medialstinal widening”
Staph Novobiocin resist/ virgins get UTI Clostridium Lock jaw, “drumstick” spore Rickettsia Peripheral rash that spreads to
saprophyticu bc new to sex- “Honey mooners” tetani = forming anaerobe, on rusty nails, rickettsia = trunk, fever/ dog tick / Weil-
s Tetanus Tatanospasmn= decrease Rocky Mt. SF Felix+
GABA+Glycine
Strep Beta Hemolytic, Strep throat, Clostridum Spore frm, anerobic, motile cz Rickettsia Epidemic typhus/ rash starts
pyogenes = Rehmatic fever and dark urine due botulinum food poisoning in adults and prowazekii @ trunk and spreads outwards
group A strep to M protein// Scarlet Fever! ASO+ floppy baby in infants. Blocks (R. typii is
Ach release. “Canned” endemic)
Strep Catalase -, Beta hemolytic, Clostridium Only non-motile member, Treponema Spirochetes/endoflagellum /
agalactiae = bacitracin resistanct // MCc Baby = perfringens = military wound that would get gas pallidum= STD rules of 6/1*painless
group B strep Pneumonia, meningitis and sepsis gas gangrene under skin that crackles (crepitus), syphilis chancre/2*hand,foot rash,
found in soil latent, 3* Gummas/Jarisch
Herxheimer rxn
Strep alpha-hemolytic, Lancet diplococci, Clostridum Pseudomembrane colitis due to Borrelia Ixodes tick/1* Erythema
pneumonia MCc for pneumo in adults- “rusty difficile = Abx, Toxin A (diarrhea) and B burgdorferi = chronicum migrans rash w/ bk
sputum”, Cc for osteo media in PMC (pseudomem), do not culture bc Lyme dz necrotic center2* bells
kids, high risk if asplenic its normal flora, palsy3*arthritis
Strep Mutans Dental carries, can cause Corynebacteri Chinese letters, grow on Borrelia VMP antigen cuases recurrent
Normal flora SBEndocarditis after mouth sx um diptheriae Potassium tellurite and Loefflers recurrentis fever
= AB toxin media, grey - pseudomembrane in
blocks EF2 throat, vaccine
Listeria Only G+ w/ Endotoxin ; LLO Mycobacteriu Acid fast staining due to
monocyogene toxin/ “tumbling motility” / m tuberculosis Mycolic acid cell wall/ PPD+/
s neonate meningitis = tuberculosis
Mycobacteriu Acid fast/ inflammatory
m leprae= damage at skin, sensory loss
leprosy aka:
Hansen dz
Mycoplasma No cell wall, B-lactamase, no
pneumonia = gram stain, agglutinating RBC
walking at 4*C
pneumo

Gram Negative – Cocci Gram Negative Baccili Gram Negative - pleomorphic

Neisseria MC in college, army and infants: Klebsiella Pneumonia and nosocomial UTIs, Haemophilus Epiglottistis “thumb pring”
meningitides petechial rash, fever, nuchal pneumoniase red currant jelly sputum , A’s: influenza type use chocolate agar, IgA
rigidity (except infants: budging Alcoholics and abscesses B protease, 2nd MCc Otitis
fanteals) media
Neisseria Purulent (pus) yellow discharge / Escherichia Normal flora gets virulence: Bordetella Whooping cough, FHA
gonorrheae PID that can ascend upwards, VCN coli types- pertussis antigen, Bordet-Gengou
media ETEC: LT+ST no blood media, pertussis toxin “off-
Pink on EHEC: O157:H7 SLT w/ blood Bacteria but off”, ↓Gi, ↑cAMP causing
McConk but noninvasive – HUS(kidney czs lymphocytosis, DTaP vaccine
Black on dz) lymphocytosis
Moraxella Exacerbated in COPD patients , EMB EIEC: invasive SLT, blood and Legionella Grow on charcoal yeast agar,
catarrhalis beta-lactamse producing – Otitis pus w/ leukocytes seen pneumonia cz walking atypical pnuemo in
media Old Smokers, visualize w
MCc of female UTI’s Silver Stain*
Proteus UTI, “swarming” growth and Yersinia pestis Capsular f1 antigen, Bipolar
mirabilis urease + (splits ureaNH3) “bubonic staining*flea vector,
causes alkaline ph of urine plague” cutaneous necrosis “black
death”
Shigella “NON-Shigella” : non-lactose, Brucella Undulating fever,
dysenteriae non-motile, non-cat, non-oxidase, species contaminated animals,
non-H2S, Dysentery, small brucellergin Positive skin test
inoculum, Shiga toxin inhibits
60S ribosome
Salmonella Motile and H2S producing: Francisella Talaremia cz by Rabbits –
typhi antigen is Vi capsule , not K tularensis ulcer w black base and
antigen* Typhoid fever regional lymphadenopathy
Salmonella Turtles and food – motile, Bartonella Cat scratch fever,
enteritidis produces H2S, gastroentertitis, Vi henselae
capsule
Vibrio cholera Comma shaped, rice water Pasteurella Oxidase and catalase positive,
diahreea, secretes cholera (AB5) multocida cellulitis after Cat or
toxin “on-on” ↑Gs, ↑cAMP, Pasteurella
secretes cl and na canis Dog Bite
Campylobacte Curved s-shaped, urease neg, Bacteroides Most Common species
r jejuni Unpasturized milk, Culture at fragilis amoung normal Gut (GI) flora
42*C, ill smelling poop, G-Barre , Strict anaerobe – cz dz if gut
syndrome trauma
Helicobacter Urease + breath test, Duodenal
pylori ulcer, acute gastritis
Yersinia Enertocolitis and manifests
enterocolitica different at different ages >5
appendix pain ; adult arthritis --
ST toxin
Pseudomonas Non-glucose nor lactose ferm,
aeruginosa oxidase+, pneumonia in CF pts,
Burn sepsis – blue/green colonies
and fruity odor

MOA – mechanism of action. U - uses. SE – side effects. Tox – toxicities. Int – interactions. Contra – contraindications. DOC – drug of choice
PCN family ABX – bacteriacidal. Aka beta-lactam abx. Only effective against organisms with cell wall.
 MOA – competitively inhibit transpeptidase (aka pcn binding protein), the enzyme that catalyzes cross-linking in the
peptidoglycan cell wall.
 Resistance to pcns –
o G- organisms have porins in their outer plasma membranes through which some beta-lactam abx can pass. Altering
porins is one mechanism of resistance
o Beta-lactamase – enzyme that destroys beta-lactam ring in pcns
 G+ - secreted form (called penicillinase)
 G- - harbor beta-lactamase in the periplasmic space
o Altered transpeptidase – this is how MRSA defends itself from all pcn family drugs (TQ)
 SE – IgE mediated allergic rxn can  urticaria, bronchospasm, anaphylaxis; however, usually just a rash occurs several days to
weeks later. Diarrhea via wiping out normal GI flora.
 Pen G – given IM or IV. Sensitive to beta-lactamase
o U – Streptococcus pneumoniae pneumonia
 Pen V = oral form used for group A strep pharyngitis
 Ampicillin and Amoxicillin – broader spectrum, killing more G- bugs (better penetration through outer membrane). Sensitive to
beta-lactamase. Given p.o.
o U – E. coli and other enterics, G+ enterococcus. Amoxicillin commonly given for bronchitis, UTI, sinusitis.
 IV amp – given in combo with gentamicin for broad G- coverage (e.g. serious UTI)
 Methicillin, nafcillin, and oxacillin – penicillinase resistant pcns that kill S. aureus. Given IV
o U – nafcillin = DOC for S aureus (cellulites, endocarditis, sepsis). NOT good for G- bugs. PRIMARILY used for
penicillinase producing G+s.
 Skin infections – czed by S aureus or group A strep. These drugs will cover both
o Cloxacillin and dicloxacillin – p.o. forms
o SE – methicillin  interstitial nephritis
 Ticarcillin, carbenicillin, piperacillin - Anti-Pseudomonal pcns. Expanded G- rod coverage. Also active against anaerobes
o U – pseudomonal sepsis and pneumonia. These agents are commonly combined with gentamicin for increased anti-
pseudomonal power
o SE – carbenicillin requires high doses, which can  high sodium load, platelet dysfcn, hypokalemia. Therefore,
ticarcillin is usu used.
 Clavulanic acid, sulbactam, tazobactam – inhibitors of beta-lactamase. Usu combined with pcns to produce a beta-lactamase
resistant combination, e.g. amoxicillin + clavulanic acid.
 Cephalosporins – much more resistant to beta-lactamase. Each new generation has ↑G- coverage and ↓G+ coverage. NOTE:
MRSA and G+ enterococci are resistant to all cephalos.
o First generation – most contain “ph” in their names, e.g. cephalexin. Good G+ coverage, poor G- coverage.
 U – staph and strep when pcn can’t be tolerated. Given preoperatively to prevent skin infection
o Second generation – most contain “f” followed by a vowel. Moderate coverage of G- and G+.
 U – cefuroxime – good coverage against S. pneumoniae and H. influenzae; therefore, an ideal agent for
community acquired pneumonia when sputum is negative
o Third generation – most contain “ceft” in their names. Good G- coverage, poor G+ coverage.
 U – multi-drug resistant G- nosocomial infections
 Ceftriaxone – DOC for meningitis and for gonorrhea (TQ)
 Ceftazidime and cefoperazone – effective against Pseudomonas
o Fourth generation – cefepime – good coverage of G+ and G-
 U – same as third, but more kick against G+s. Effective against Pseudomonas.
o SE – ten percent of pts with pcn allergy will also be allergic to cephalosporins
 Imipenem – broad spectrum agent that kills G-, G+ and anaerobes. MRSA and some Pseudomonads are resistant. Ineffective
against Mycoplasma – no peptidoglycan layer
o Cilastin – inhibitor of enzyme (renal dihydropeptidase) that breaks down imipenem. Given with imipinem to
increase half-life
o SE – allergy similar to pcn. Decreases seizure threshold, so don’t give to epileptics.
o Meropenem – not broken down by dihydropeptidase, so cilastin isn’t needed
 Aztreonam – highly effective against G- aerobes. Ineffective against G+, its monolactam ring only binds to transpeptidase of G-s.
o U – nosocomially acquired G-, incl pseudomonads.
 Often used in conjunction with an agent that kills G+ bugs, e.g. vancomycin
o CAN be used in pts with pcn allergy

Anti-ribosomal abx – bacteriostatic

 Chloramphenicol – kills most bacteria, even anaerobes
o MOA – inhibits 50S ribosomal sub-unit
o U – meningitis in pt with beta lactam allergy(incl cephalos). Good penetration into CSF and wide spectrum make
chloramphenicol ideal in such situations. DOC in young kids and pregos with RMSF (can’t be treated with
tetracyclines).
o SE/tox – aplastic anemia. Gray baby syndrome = neonates cannot metabolize drug, so high concentrations exist 
vasomotor collapse, abdominal distention and cyanosis (ashen gray color)
 Clindamycin – not effective against gram negatives
o MOA – inhibits 50S ribosomal sub-unit
o U – anaerobic infections
 Surgeons use clindamycin (covers anaerobes) + aminoglycoside (covers G-) for penetrating wound
infections of the abdomen (perforation of the GI tract)
 Septic abortions, bacterial vaginosis.
 Topically for acne vulgaris and rosacea
o SE/tox – pseudomembranous colitis = normal flora of GI tract destroyed. Clostridium difficile, if resistant to
clindamycin, will proliferate and secrete exotoxin  epithelial cell death and colonic ulcerations  severe diarrhea.
Dx – stool culture or toxin titer in the stool.
 Tx for pseudomem colitis = oral vancomycin or metronidazole (less expensive and preferred due to risk
of increasing resistance to vancomycin)
 Most cases now caused by pcns (prescribed more often)
 Linezolid – new agent that is last resort tx for vancomycin resistant enterococcus. Inhibits 50S sub-unit
 Erythromycin – inactive against most G- bugs. Covers Chlamydia and Legionella (the atypicals)
o MOA – inhibits 50S ribosomal sub-unit
o U
 DOC for community acquired pneumonia (S. pneumoniae, Mycoplasma pneumoniae, Chlamydia
trachomatis)
 Strep and staph – in pcn allergy pts
 DOC for Legionnaire’s dz
o SE/tox – abdominal pain, cholestatic hepatitis
o Clarithromycin, azithromycin, roxithromycin
 Azithromycin – alternative to doxycycline in NGU. Also used to tx community acquired pneumonia
 Tetracycline/doxycycline – dox is better absorbed orally
o MOA – inhibit 30S ribosomal sub-unit
o U – Chlamydia trachomatis, Mycoplasma pneumoniae, Brucella, Rickettsia, acne
o SE/tox – GI irritation, phototoxic dermatitis (e.g. tanning while on dox), renal and hepatic toxicity (rare), discolored
teeth and depressed bone growth in babies and kids under 7
 Don’t give to pregos or baby’s teeth may be affected
 Aminoglycosides – must diffuse across cell wall to work; therefore often given with pcn to facilitate action. Must be given IV.
Streptomycin, gentamicin, tobramycin, amikacin, neomycin, netilmicin
o MOA – inhibit 30S ribosomal sub-unit
o U – kill aerobic, G-, enteric organisms including Pseudomonads
 Tobramycin – good against Pseudomonas aeruginosa
 Neomycin – very broad coverage. Given topically for skin infections.
 Netilmicin – preoperative coverage before GI surgery. Given po and not absorbed  high concentration in
GI tract
o SE/tox – eighth cranial nerve toxicity, vertigo, hearing loss (irreversible) - TQ
 Renal toxicity – always follow BUN and creatinine
 Neuromuscular junction blockade – rare
 Spectinomycin – given IM. Not an aminoglycoside
o MOA – inhibits 30S ribosomal sub-unit
o U – gonorrhea if ceftriaxone is contraindicated (e.g. allergy)
o SE – infrequent and minor

Anti-TB and Anti-Leprosy Abx

 Tx of active tb – presentation with dyspnea, fever, productive cough (sputum with red snappers), night sweats, upper lobe
consolidation on CXR
o 6 month regimen – 2 months of isoniazid, rifampin and pyrazinamide  followed by 4 months of isoniazid and
rifampin
o 9 month regimen – 9 months of isoniazid and rifampin
 Tx of PPD reactors
o Isoniazid – alone for 6-12 mos OR
o Rifampin + pyrazinamide – 2 months
o Decision to tx – risk of developing reactivation should outweigh the risk of liver injury
 Isoniazid hepatitis – risk near zero if < 35yoa. Risk increases with age after 35
 Risk of reactivation tb – size of PPD, immune status, CXR and exposure status are all used to assess for tx

 Specific tb drugs – all cz hepatotoxicity, most taken orally, all penetrate into most tissues and can thus reach areas of caseous
necrosis. Freq of use: Isoniazid > rifampin > pyrazinamide > ethambutol > streptomycin
o Isoniazid – first line tx. Bacteriacidal
 MOA – interferes with mycolic acid synthesis
 SE/tox – hepatotoxicity. ↑urinary excretion of B6 can deficiency  peripheral neuropathy, seborrheic
dermatitis, cheilosis, glossitis, convulsions. NOTE: give B6 supplements with isoniazid to circumvent.
Book uses term ‘pellagra’, which should be reserved for niacin deficiency. Also, pellagra is defined
improperly (periph neuropathy, rash and anemia). The usual accepted components of the syndrome are:
dermatitis, diarrhea, dementia (the “three Ds” according to Robbins)
 Contra – alcohol  ↑metabolism of isoniazid  ↓efficacy and ↑risk for hepatitis
 Resistance – if sputum culture is still positive after 2 mos tx, suspect resistance
 4 or more first line drugs should be used
 when adding agents, add 2  prevents development of new resistant strain
o Rifampin
 MOA – inhibits prokaryotic RNA polymerase
 SE/tox – body fluids turn bright red-orange. Hepatitis
 ↑cyt p450 enzyme system  ↓half-life of other drugs: coumadin, OCTs, hypoglycemics,
corticosteroids, anticonvulsants (phenytoin)
o Rifabutin – similar to rifampin in structure
 MOA – same as rifampin
 U – MAI (common in HIV)
 SE/tox – same as rifampin
o Pyrazinamide – MOA unknown. Very hepatotoxic. Use only 2 mos. Contra in pregos.
o Ethambutol – dose-dependent, reversible ocular toxicity can occur
 ↓ visual acuity with central scotoma
 loss of color vision
 Contra – young kids that can’t report visual SE
o Streptomycin – an aminoglycoside. Given IM or IV.
 MOA – inhibits 30S ribosomal sub-unit
 SE/tox – ototoxicity and nephrotoxicity
 Contra – prego (can cz congenital deafness)

 Treatment of leprosy
o Severe cases – rifampin, dapsone and clofazimine for minimum of 2 yrs and until pt is acid-fast bacilli negative.
o Less severe cases – rifampin and dapsone for 6 months
o Clofazimine – MOA – binds to M leprae DNA. Also has anti-inflamm action
 SE – turns conjunctiva and skin a reddish color. Leprosy lesions will be tan to blk
o Leprosy reactions
 Type 1 – only occurs in borderline cases
 Skin lesions swell and sometimes ulcerate. Neuritis can occur. DTH reaction to dead bacilli
 Do not withdraw anti-leprosy meds if reaction occurs.
 Corticosteroids or clofazimine can be used to ↓inflamm reaction
 Type 2 – (erythema nodosum leprosum) – assoc with borderline leprosy and lepromatous leprosy
 Painful, nodular rash. Neuritis, orchitis, arthritis, iritis and adenopathy can also occur.
 Thalidomide is indicated (teratogen, not used for anything else)

Other Abx
 Fluroquinolones – the “floxacins”. Excreted renally, concentrated in urine. Penetrate well into bone and prostate
o MOA – inhibit DNA gyrase
o SE/tox – GI irritability, cartilage damage in kids, Achilles tendonitis and rupture (rare), headache, restlessness,
insomnia
  Ciprofloxacin – seems to inhibit GABA and cz seizures in pts with renal insuff
o U – poor G+ and anaerobe coverage. GOOD aerobic G- coverage
 to cover Pseudomonas in cystic fibrosis pts
 Enteric coverage – can prevent traveler’s diarrhea
 Complicated UTIs – psuedomonads, enterics. Also used in epididymitis and prostatitis (penetrates prostate
well)
 G- facultative intracellular bugs (drug achieves high intracellular concentration)
 Legionella, Brucella, Salmonella, Mycobacterium
 Chronic osteomyelitis czed by G+ S aureus (high drug concentration in bone)
 Atypicals – Chlamydia, Mycoplasma, Legionella – good choice for community acquired pneumonia

 Vancomycin – kills all G+ bugs, even MRSA, enterococcus and resistant S. epidermidis in indwelling caths.
o MOA – complexes with D-alanine D-alanine  inhibits transpeptidation. Acts synergistically with aminoglycosides
o SE – red man syndrome = rapid infusion  nonimmunologic release of histamine  flushing. Can be avoided by
infusing slowly.
o Not absorbed orally – used po to treat pseudomembranous colitis b/c it stays in GI tract

 Synercid and Linezolid – newer bad ass abx that can kill multi-resistant bugs.
 TMP/SMX – trimethoprim sulfamethoxazole – broad spectrum G+ and G- coverage. Excreted in the urine – good for UTIs.
o MOA
 TMP – binds to a reversibly inhibits dihydrofolate reductase in bacteria
 SMX – PABA analogue – competes with PABA and ↓tetrahydrofolate synth
o SE/tox – nausea, vomiting, diarrhea, rash (rare)
 AIDS pts – half will have skin rashes and marrow suppression (not good when your CD-4 cells are already
jacked up), but we give it anyway (see later)
o Int – TMP/SMX  ↑warfarin concentration  ↑risk for bleeding
o U - bact
 Resp inf – covers S pneumoniae and H influenzae –bronchitis, otitis media, sinusitis, pneumonia
 GI inf – Shigella, Salmonella, E. coli - diarrhea
 GU inf – Enterics – UTIs, prostatitis, urethritis
o U - protozoans
 PCP in AIDS pts with really low CD-4 counts
 Toxoplasma and Isospora

Fungi – ergosterol is essential sterol in the cell membrane (target of many anti-fungal meds). Cell wall composed of carbs  potent
antigenicity. Capsule – polysaccharide Ag. Cryptococcus. India Ink stain
 Terminology
o Yeast – unicellular form of fungi. Long chains = pseudohyphae
o Hyphae – threadlike, branching tubules of fungal cells
o Molds – multicellular colonies of intertwined, branching hyphae
o Spores – reproducing bodies of molds
o Dimorphic fungi – grow as yeast or molds
o Saprophytes – feed on dead organic matter

 Superficial infections
o Pityriasis versicolor (aka tinea versicolor) - hypo or hyper pigmented patches. Skin around patches will tan, but
patches won’t. Malassezia furfur = cz. Asymptomatic
o Tinea nigra – dark brown to black painless patches in volar distribution. Exophiala werneckii = cz
o Dx – skin scrapings in KOH  hyphae and spherical yeast. M. furfur looks like spaghetti (hyphae) and meatballs
(spherical yeast)
o Tx – dandruff shampoo (selenium sulfide) can be rubbed on skin. Imidazoles can be used.

 Cutaneous infections of skin, hair and nails – czed by many species. Fungi infect dead, horny layer of skin. Fungi secrete
keratinase.
o Tinea corporis – aka ringworm. Ring shaped lesion with red, raised border.
o Tinea cruris – aka jock itch. Itchy red patches on groin and scrotum
o Tinea capitis – scaly red lesions; loss of hair. Usu affects kids. Microsporum (often czes)
o Tinea unguium – thickened, discolored, brittle nails
 o Dx – skin scrapings in KOH  branched hyphae
 Wood’s light (UV – 365 nm)  Microsporum will fluoresce green
o Tx – topical imidazoles. Oral Griseofulvin for capitis and unguium.

 Subcutaneous fungal infections – follow trauma to skin

o Sporothrix schenckii – dimorphic. Rose thorns and splinters. Gardeners at risk.
 Pathogenesis - subcutaneous nodule in finger  becomes necrotic and ulcerates  heals  new nodules
along lymphatic tracts up the arm
 Micro – budding yeast (culture 37C  yeast; culture 25C  branching hyphae)
 Tx – Potassium iodide or amphotericin B
o Phialophora and Cladosporium – chromoblastomycosis – copper colored soil saprophytes in rotting wood.
 Pathogenesis – puncture wound  small, violet, wart-like lesion  clusters resembling cauliflower.
 Skin scrapings with KOH  copper-colored sclerotic bodies.
 Tx – itraconazole and local excision

 Systemic fungal infections – czed by 3 dimorphic fungi that grow as mycelia (molds) in soil and release spores. All grow as yeast
cells at 37C. Histoplasma capsulatum, Blastomyces dermatidis, Coccidioides immitis.
o Histo and Blasto – endemic to areas that drain into the Mississippi River.
o Cocc – endemic to SW US
o Pathogenesis – spores are released into the air  inhaled by humans  local infection in lung  hematogenous
dissemination  fungi destroyed via cell-mediated immunity
o Coccicioidin and histoplasmin = antigenic preparations similar to PPD for tb
o Three major clinical presentations – similar to tb, but no person to person t-mission
 Asymptomatic
 Pneumonia – fever, cough, CXR infiltrates. Granulomas with calcifications. Some get severe pneumonia.
Fewer get cavitary pneumonia marked by wt loss, night sweats, fever like chronic tb.
 Disseminated – rare. Bone lytic granulomas, meningitis, skin granulomas. Most common in
immunocompromised pts
 Tissue is the issue – skin tests aren’t useful for dx because many people have been exposed previously.
o Tx – acute histo and cocc usu DON’T require tx. Chronic or disseminated histo or cocc – amphotericin B or
itraconazole
 All blasto – aggressive tx with amphotericin B or itraconazole
o Histo – nonencapsulated, found in bird and bat droppings (chicken coops and spelunking)
o Blasto – most cases present as chronic disseminated dz
o Cocc – mild pneumonia in normal individuals in SW US. common opportunistic infection in AIDS pts in SW (very
common in AIDS pts in AZ)

 Cryptococcus neoformans – polysaccharide encapsulated yeast

o Inhaled into lungs  usu asymptomatic  major manifestation is meningoencephalitis (not pneumonia)
o Pigeon droppings
o Most cases occur in the immunocompromised – nearly 10% of AIDS pts develop
o Subacute to chronic meningitis – headache, nausea, confusion, staggering gait, CN deficits. Without tx, cerebral
edema and death can ensue
o Dx – lumbar puncture. India ink stain of CSF – capsule appears as halo surrounding yeast cells. Cryptococcal
antigen test is also used.
o Tx – flucytosine and amphotericin B. Tx required for as long as 6 mos (required for life in AIDS pts)

 Candida albicans
o Oral thrush – patches of creamy white exudate with reddish base cover mucous membranes of mouth. Swish and
spit preps of nystatin or amphotericin provide effective tx.
o Vaginitis – abx, OCTs, menses, pregnancy all  ↑risk. Thick, copious vaginal secretions.
 Speculum exam – inflamed vaginal mucosa. Cottage cheese appearing white clumps affixed to vaginal
wall
o Diaper rash – affects warm moist areas. Red, macerated skin in affected area
o In immunocompromised pts
 Esophagitis – burning substernal pain, worse with swallowing. Doesn’t affect immunocompetent
individuals
 Disseminated – candida is normal flora, so can be cultured from urine, sputum, etc. HOWEVER, isolation
from blood is ALWAYS ABNORMAL
  Tx – amphotericin B or fluconazole for systemic infections
 Aspergillus flavus – type I hypersensitivity reaction with bronchospasm, ↑IgE, eosinophilia
o Lung cavitations  aspergilloma (fungal ball)  surgical removal required
o Immunocompromised hosts – bloody sputum may occur due to blood vessel wall invasion by hyphae
o Aflatoxin (a mycotoxin) – contaminates peanuts, grains and rice. Major cz of liver cancer in Sub-Saharan Africa

 Actinomycetes israelii – prokaryotic. Grow in form of mycelia. G+ and anaerobic. Normal flora in mouth and GI tract
o Czes abscesses following trauma to mucous membranes of the mouth or GI tract
o Pus from abscesses reveals yellow granules (sulfur granules) = microcolonies of Actinomycetes
o Tx – pcn G

 Nocardia asteroides – acid-fast, beaded branching thin filaments. Prokaryotic. NOT normal flora.
o Same dz process as tb. Frequently misdiagnosed as tb
o Most common in immunocompromised (esp those taking steroids).
o Tx – TMP/SMX

Antifungal drugs – ergosterol is common target of these agents

 Serious systemic infections – amphotericin B (iv or intrathecally), itraconazole (po)
 Less serious systemic infections – oral azole drugs (ketoconazole, fluconazole, itraconazole)
 Superficial fungal infections – griseofulvin (po), topical agents – nystatin, clotrimazole and miconazole)
 Amphotericin B – DOC for most serious fungal infections
o MOA – binds to ergosterol in fungal membrane
o U – systemic candida; Cryptococcal meningitis (in combo with flucytosine); extrapulmonary blast, histo, and cocc;
invasive aspergillosis; invasive sporotrichosis, Mucormycosis
o SE – numerous and common
 dose dependent azotemia in most pts (reversible). Check BUN and creatinine daily. Hydration and lyte
replacement sometimes required. Addition of lipid to drug prep  ↓nephrotoxicity
 acute febrile reaction following IV infusion. Acetaminophen given prophylactically.
 anemia
 phlebitis at IV site
 Flucytosine – rarely used alone due to resistance
o MOA – inhibits DNA/RNA synthesis, targets rapidly dividing cells
o U – partner of amphotericin B
o SE/ tox – bone marrow depression, nausea, vomiting, diarrhea
 Azoles
o MOA – inhibit p450 system, which is involved in ergosterol synth
o Imidazoles – ketoconazole, miconazole (topical infections only) and clotrimazole (topical infections only)
 Ketoconazole – DOC for chronic mucocutaneous candidiasis. Not used for systemic infections
 SE – GI – nausea, vomiting, anorexia. Hepatotoxicity. Inhibition of testosterone synthesis
o Triazoles – fluconazole, itraconazole, voriconazole (flu and itra for systemic infections)
 Fluconazole – less toxic and broader coverage than ketoconazole.
 U – second line agent behind amph B for systemic candidiasis and cryptococcal meningitis
o AIDS pts with cryptococcal meningitis – prevents relapses
o Kills candida very well – single dose cures candida vaginitis
 Itraconazole – poor oral absorption
 U – first-line for chromoblastomycosis, histoplasmosis, coccicioidomycosis, blastomycosis and
invasive aspergillosis
 Voriconazole – used for invasive aspergillosis that doesn’t respond to amph B or itraconazole
 Nystatin – swish and swallow
o MOA – binds to ergosterol  cell lysis
o U – too toxic to be given iv. Useful in GI fungal infections (oral or esophageal). Given po (not absorbed orally, so
systemic SE are avoided)
 Given topically for candidal vaginitis
 Griseofulvin
o MOA – prevents mitosis (disrupts spindle formation)
 Deposits in keratin precursor cells of skin, hair and nails  inhibits growth of fungi in those cells
 Static, not cidal
o SE – uncommon, but include: headache, nausea, vomiting, photosensitivity, mental confusion, marrow suppression
 Potassium iodide – U –sporotrichosis. If infection  systemic, use amph B or itraconazole
 Terbinafine – blocks ergosterol synth. Tends to accumulate in nails; useful for tinea unguium.
o Other U – tinea pedis, tinea capitis, tinea corporis
Viruses
 RNA viruses – most are ss, enveloped, helical, and replicate in the cytoplasm. Exceptions:
o Reo – ds
o CPR – calici, picorna, reo = naked (do mouth-to-mouth, then get naked, sounds fun)
o Icosahedral - reo, picorna, toga, flavi calici
o Rhabdo – rabies, bullet-shaped
o Replication in the nucleus – retro and orthomyxo
o Segmented – Bunya, orthomyxo, arena, rhabdo (imagine a segmented BOAR – aka a striped pig)
o +RNA – can be translated directly into protein by host ribosomes (like mRNA)
o –RNA – must 1st be t-scribed into plus. Virus must carry RNA dependent RNA pol.
o RNA retroviruses – t-scribed into DNA by reverse transcriptase (RT)

 DNA viruses – most ds, icosahedral, and replicate in nucleus. Exceptions:

o Parvo – ssDNA
o Pox – (in a box) replicates in cytoplasm
o Positive DNA strand – used as a template for template for transcription into RNA
o HHAPPPy – herpes, hepadna, adeno, papova, parvo, pox
o PAP – papova, adeno, parvo are naked (get naked for a pap smear)

 Capsids – icosahedral = 20 triangles on surface. Helical = protein capsomers bound to RNA (only RNA viruses have helical
symmetry)
 Envelope – lipid membrane = enveloped. No membrane = naked
 Replication - Viruses block synthesis of host DNA, RNA and proteins
o Adsorption and penetration – viral encoded protein binds to host cell membrane receptor  internalization occurs
by endocytosis or fusion of virion envelope with host cell membrane
o Uncoating – nucleic acid released
o Transcription, translation, replication – cytoplasm for RNA viruses, nucleus for DNA viruses
o DNA virus Immediate early and early genes – encode enzymes and proteins needed for DNA replication and t-
scription of late mRNA
o DNA virus late genes – usu t-scribed after viral DNA replication has begun (e.g. capsid proteins)
o Assembly and release – structural proteins + genome assemble  virion release
 Naked virions – released by lysis or Exocytosis
 Enveloped virions – bud through Golgi, nuclear membrane, or cytoplasmic membrane

 Host cell outcome – death or transformation (infection can activate oncogenes  uncontrolled, uninhibited cell growth
o Latent infection – virus survives in a dormant state
o Chronic slow infection – dz after long period of infection

Orthomyxo and paramyxo viruses

 Orthomyxo – spherical virions with 8 segments of –RNA. Helical capsid with outer membrane studded with HA and NA
o HA – hemagglutinin (Czes agglutination when mixed with RBCs) – attaches to sialic acid receptors (present on
upper resp tract cells)  binding  fusion  viral genome dumped into cytosol.
o NA – neuraminidase – cleaves neuraminic acid  disrupts mucin barrier  exposes sialic acid. Abs against NA are
protective
o M-proteins - anchor HA and NA
o Three types of influenza –
 Type A – infects humans, other mammals and birds
 Types B and C – only isolated from humans
 Epidemics – antigenic drift = mutations in HA or NA  changes in antigenic nature  resulting strains
only partially attacked by immune system
 Pandemics – antigenic shift = complete change of HA, NA or both. Only with type A – mechanism =
trading RNA segments between animal and human strains
  2 types coinfect same cell  RNA fragments are mispackaged
 complications of flu - elderly and immunocompromised suffer more serious illness as virus spreads to lwr
resp tract.
 Host defenses against bacteria are lowered – Staph and Strep pneumonia common.
 Reye syndrome – liver and brain dz in kids given asa for flu or Varicella
 Dx – culture, detection of viral proteins, PCR, serological dx
 Tx and control – virus grown in chick embryos  inactivated and purified  used as vaccines. Elderly,
immunocompromised and healthcare workers should receive.
 Amantadine and rimantidine – prevent uncoating of influenza A
 Sanamavir and oseltamivir – NA inhibitors – shorten course of flu B and C

 Paramyxo - -RNA, ss. HA and NA are part of same protein spike. ‘F’ (fusion) protein  host cells form multinucleate giant cells.
All adsorb and replicate in the upper resp tract. Most occur in kids. Viremia common  dissemination to distant sites e.g. mumps
– parotitis and orchitis
o Parainfluenza virus – URI in adults. LRI in elderly, kids and immunocompromised
 Croup (laryngotracheobronchitis) – occurs in kids. Narrowing of airway  stridor (seal bark)
o RSV – multinucleate syncytial cells. Number one cz of pneumonia in young kids (esp < 6mos).
 Prevention – palivizumab = monoclonal Ab against RSV. Serum RSV immune globulin (risk of blood-
borne infection)
 Immunity – previous infection does not confer immunity, but subsequent infections are usu limited to UR
tract

o Mumps virus – replicates upper resp tract and regional nodes  spread via blood  distant organs
 3weeks after initial exposure, parotid gland swells and becomes painful. Testes frequently infected.
Meningitis and encephalitis can also occur.
 Prevention – live, attenuated vaccine (part of MMR)

o Measles (rubeola virus) – highly contagious via nasopharyngeal secretions

 Multiplies in resp mucous membranes and conjunctival membranes
 Incubation for 2 weeks  rash
 Prodrome – conjunctivitis, swelling of eyelids, photophobia, fever, hacking cough, rhinitis and malaise
 Koplik’s spots – day or two before rash – red-based lesions with blue-white centers I the mouth
 Rash – red, flat to slightly bumpy (maculopapular). Spreads out from forehead to face, neck and torso 
feet by third day. As rash spreads downward, initial rash on head and shoulders coalesces.
 Complications – pneumonia, eye damage, myocarditis, encephalitis (most feared)
 Infection in prego assoc with spontaneous abortion and premature delivery. Fetal death often
occurs.
 Subacute sclerosing panencephalitis (SSPE) – slow form of encephalitis caused by measles
virus.
 Prevention – MMR – contains live attenuated virus.

Hepatitis viruses – You must know serology for the boards!!!!!!!!!!!!!!!!!!!!!!!!!!

 Hep B – the only DNA virus, all others are RNA

 Hep E and Hep A – fEcAl to oral transmission. Others parenteral t-mission

 Acute viral hepatitis – flu-like, fever, myalgia, arthralgias, cough, rhinorrhea, pharyngitis. May develop jaundice
o ↑liver enzymes – AST, ALT, GGT and alkaline phosphatase
o 2 weeks into illness – jaundice, enlarged liver, high levels of liver-function enzymes

 Chronic viral hepatitis – difficult dx. Often asymptomatic with only enlarged, tender liver. Mildly elevated LFTs

 LFTs – ALT, AST usu very elevated. GGT, alk phos and bilirubin usu only mildly elevated
o Note – gallstone yields exactly the opposite pattern
o Hepatocytes produce AST and ALT. AST and ALT released early upon hepatocyte rupture
o Cells that line canaliculi produce alk phos and GGT – rise later as infection worsens
o Canaliculi carry bilirubin – rises later in course

 HAV – naked, icosahedral, +ssRNA. Picornavirus family.

 o 15-40 day incubation  pt develops acute hepatitis
o young kids most frequently affected – milder course than in adults
o very small percentage develop fulminant hepatitis
o Serology – active infection – anti-HAV IgM. Anti-HAV IgG indicates old infection and no active disease. IgG is
indefinitely protective
o Tx – pooled immune globulin  prevent or decrease severity. Vaccine currently available for kids (2 doses
required). Once infection is established, tx is only supportive.

 HBV – virus lives in all body fluids. Enveloped, icosahedral capsid, circular dsDNA  Dane particle – intact virus
o Pathogenesis
 Fulminant hepatitis – severe acute with rapid liver destruction
 Chronic hepatitis
 Asymp carrier – never develops anti-HbsAg
 Chronic persistent – low-grade, smoldering hepatitis
 Chronic active – acute state that continues without recovery
 Co-infection with HDV (see later)
 Complications – primary hepatocellular carcinoma – chronic infection  HBV DNA incorp into
hepatocyte  malignant growth. HBV carriers – 200x ↑ risk for hepatocellular carcinoma
 Cirrhosis – permanent liver scarring and loss of hepatocytes
o Serology
 HBsAg – surface antigen. Presence indicates live virus present
 Anti-HBsAg – patient protected when this antibody is present
 HBcAg – IgM anti-HBcAg = new infection. IgG anti-HBcAg = old infection
 Antibodies to core Ag are NOT protective
 HBeAg – presence = high infectivity and active dz. Pregos with HBeAg in blood will often transmit virus
to fetus.
 Anti-HBeAg – low infectivity
 Window period - IgM anti-HBcAg present. Know this for Cunningham and boards!!
o Tx – test donor blood to prevent virus from entering donor pool. Active immunization (HBsAg cloned in yeast = no
risk vaccine). All infants and healthcare workers get vaccinated.
 Lamuvidine – anti HIV agent (suppresses HBV DNA) and Interferon alpha – suppresses HBeAg and
HBV DNA. Prevents cirrhosis.
 HDV – can only replicate with the help of HBV. Uses HBV’s envelope (HBsAg) – can only cz infection with HBsAg coat.
o Co-infection – both viruses are t-mitted together
o Superinfection – HDV infects a person who has chronic HBV infection  acute hepatitis in pt already chronically
infected with HBV
 Often severe and can  fulminant hepatitis, cirrhosis, ↑mortality
 Pt with chronic HBV cannot make anti-HBsAg, so remains chronically infected with HBV and HDV
o Tx – none. Must control HBV to prevent HDV.
 HCV – enveloped, icosahedral RNA virus. Hepatitis Cirrhosis virus
o Czes acute and chronic hepatitis similar to HBV
o Half infected develop chronic hepatitis
o Hepatocellular carcinoma – in pts with chronic active HCV infection and cirrhosis
o Tx – alpha interferon may reduce liver inflamm
 HEV – acquired from fecally contaminated water during monsoon flooding. Asia, India, Africa, Central America
 HGV – RNA Flavivirus. Parenteral transmission. May not cz liver dz??

Retroviruses – contain RT (RNA dependent DNA polymerase). Viral DNA (made by RT) has sticky ends and incorporates into host
genome
 Oncogenes – some retros carry oncogenes
o Src – rous sarcoma virus oncogene that encodes t-membrane protein that phosphorylates tyrosine residues (at an
accelerated rate)  activation of cell cycle, etc.

 Retroviruses can activate proto-oncogenes in host

 Oncogenesis – loss of contact inhibition  uncontrolled proliferation  cancer

 Acute transforming viruses – carry intact oncogenes which integrate into the host’s DNA
o Source of oncogenes – during viral infection  mistake in splicing  virus captures proto-oncogene  becomes
an oncogene in the virus
  If oncogene sequence is long, virus loses RNA required for viral replication = defective acute transforming
virus that requires co-infecting virus to cz cancer
 Rous sarcoma virus – non-defective acute transforming virus

 Non-acute t-forming viruses – activate host proto-oncogenes by integrating into key regulatory area. These viruses don’t carry
oncogenes.
 HTLV-1 – tropical spastic paraparesis (TQ). T-cell leukemia in Caribbean and Japan.
 HTLV-2 – czes T-cell variant of hairy cell leukemia.

 Epidemic of 1980 – AIDS

o Agent present in filtered blood (something small)
o Delayed onset – lag time for integration, etc.
o Destruction of T-helper cells
o HTLV-1 and 2 were known to be T-cell tropic
o HIV-1 was discovered to be the cause of AIDS
o HIV-2 – czes similar dz in western Africa. Sequence homology with HIV-1.

 HIV-1 (high-yield) – spherical, enveloped, central cylindrical nucleocapsid, 2 identical ssRNA pcs
o Nucleocapsid proteins, protease, RT and integrase are packaged with genome
o Caspid protein p24 = can be measured in serum and used as means of early detection (TQ)
o gp120 and gp 41 – surface glycoproteins

o LTRs – flank viral genome

 Sticky ends – recognized by integrase – involved in insertion into host DNA
 Promoter/enhancer function

o gag (group Ag) – codes for major structural proteins that are antigenic

o pol – encodes protease, integrase and RT enzymes

 protease – post-translational modification of gag and pol
 protease inhibitors – block viral core formation  ↓ HIV levels and ↑CD4 count
 RT – undergoes frequent mutations

o env – gp 120 forms head and gp 41 forms stalk. Together – gp 160

 hypervariability in region encoding gp120 – mutations, insertions, deletions (codon reading frame is
preserved, but antigenicity is changed = chicanery).

o tat – transactivator protein – binds viral genome and activates transcription

o rev – revs shit up. Binds to env gene  ↓splicing  ↑reading of gag, pol and env  ↑production of virions
o Vaccine and drug development are difficult due to variable nature of gp120 and RT.

HIV Transmission - parenteral

o Western world – most cases are in homosexual men and IV drug users – more infected men than women
o Developing areas – spread is heterosexual with men and women affected equally
o Sexual activity – women 20x more likely than men to acquire infection during vaginal intercourse (prolonged
exposure of vagina and cervix to seminal fluid)
 STDs – increase the risk of transmission (mucosal erosions, etc.)
o Blood products – blood is screened for anti HIV Abs and for p24
o Needle sharing
o Transplacental spread
o Needle stick acquired by healthcare professional – 0.3% chance of getting infected

o Infection of CD4 cells – gp120 and gp 41 bind to CD4 receptor  viral envelope fuses with the infected host cell
 capsid entry  viral RNA is RTd into DNA  DNA t-ported to nucleus  integrated into host DNA  latency
or viral replication (certain other infections may promote viral replication within T-cells)  virions bud through
host membrane  T-cell dies
 2 cell surface proteins: fusin and CKR5 – if CKR5 is produced at low levels, individual appears to be
resistant to HIV infection
o Acute viral illness – like mononucleosis – fever, malaise, lymphadenopathy, pharyngitis 1 mo after init exposure
 Immune response - ↓viremia and resolution of sx.

o Clinical latency – (around 8yrs) – dramatic gen lymphadenopathy results aggressive immune attack of virus in
nodes
 Steady destruction of CD4 TH cells

o AIDS – usu culminates in death within 2 yrs – definition = CD4 count < 200 cells/ml blood
 Constitutional illness – night sweats, fever, adenopathy, severe wt loss, wasting syndrome
 Neurologic dz – virus carried to CNS by mon/mac cells. Brain can suffer diffuse damage and progressive
cognitive decline (AIDS dementia)
 Myelopathy and neuropathy can also occur

 Malignancies – B-cell lymphoma often presents as a brain mass, many contain EBV
 HHV-8 – Kaposi’s Sarcoma (TQ) – red to purple plaques or nodules arise on skin. Can spread to
nodes, GI tract and lungs

 Opportunistic infections
 Bacteria
o S. aureus or S epidermidis if pt has indwelling lines
o ↓humoral immunity  ↓opsonization  ↑infections by encapsulated organisms (H.flu, S.
pneumoniae)
o Tb and MAI
 MAC – smoldering, wasting dz with fever, night sweats, wt loss, diarrhea,
↑LFTs
 Fungi
o Candida – oral thrush and esophagitis (scraping  bleeding base)
o Cryptococcus – meningitis (fever, nausea, vomiting prodrome). Without intact immunity,
meningeal inflammation may not be present (neg Kernig’s and Brudzinski’s signs, no
headache, etc.)
 Always do lumbar puncture and CSF testing in AIDS pts with fever
o Histoplasma and Coccidioides – disseminated dz in AIDS pts.
 Viruses
o Zoster – may be nondermatomal (disseminated)
o EBV – oral hairy leukoplakia (OHL) – white hairlike projections from the side of tongue.
Different from candidal thrush (OHL won’t scrape off with a tongue blade)
o HSV – severe oral and genital outbreaks
o CMV – chorioretinitis and blindness, esophagitis, diarrhea
 Protozoans
o PCP – most common opportunistic infection – cough and hypoxia. Nearly all AIDS pts
will develop PCP without prophylactic TMP-SMX.
o Toxoplasma gondii – contrast-enhancing masses in the brain. Fever, headache, focal
neurologic deficits
o Cryptosporidium, Microsporidia, Isospora – chronic diarrhea

o Progression – CD4 count declines by approx 60 cells/ml/yr. count is best predictor of risk for opportunistic
infections. (CD4 count approx 1000 at time of infection)
 200-400 – constitutional sx = wt loss, fever, night sweats, adenopathy, skin infections (tinea pedis, oral
thrush, zoster, etc). Tb becomes more common
 <200 – PCP pneumonia, Cryptococcus neoformans meningitis, Toxoplasma gondii
 <50 – Mycobacterium avium-intracellulare, CMV infections. Disseminated infections prevail

 viral load - ↑viral RNA  ↑risk for opportunistic infections, progression and death. More importantly,
viral load tells you how fast the dz is progressing.

Progression (cont)
 Mechanism of T-cell death – CD4 receptor is involved because helper cells are affected the most
dramatically
  Gp160 is integrated into host membrane  virion buds at gp160 and binds to adjacent CD4
receptors  tears helper cell membrane
 Gp160 also binds to CD4 on adjacent cells  cell: cell fusion
o Multinucleate giant cells – virus can pass between fused T-cells and is protected from
circulating Abs.
 Gp160 may be trigger for destruction of CD4 cell by CD8 cells
 Polyclonal activation of B-cells  outpouring of Igs  immune complex formation and auto-Ab
production  ↓ability to mount Ab response against new Ag.

 Monos and macs – also CD4+, but CD4 isn’t as dense (so these cell types aren’t affected as adversely as
T-helper cells) – monos and macs serve as reservoirs for HIV, thus protecting it from circulating Abs, etc.

o Dx – p24 detected in blood within weeks of infection. ELISA (screening test - many false positives). Western blot
(confirmation test).
 HIV should be expected when at risk individuals develop a constitutional illness or suffers recurrent
bacterial infections
 AIDS dx made when CD4 is < 200 and serologic evidence is present (+ELISA or Western)

o Prevention – education and screening of blood products

o Vaccine – rapid mutations in V3 loop of gp 120 and RT enzyme. Cell to cell t-mission allows virus to evade humoral
immunity. NO good animal model of HIV. Conclusion – vaccine development is very challenging.

o Tx – triple drug therapies to target HIV infection(see later). Opportunistic infections must also be treated:
 PCP – proph with TMP-SMX
 Toxoplasmosis – pyrimethamine/sulfadiazine will cz brain lesions to shrink. If it doesn’t, B-cell lymphoma
should be considered
 MAI – proph with azithromycin or clarithromycin
 TB – see section on TB treatment
 CMV – foscarnet or ganciclovir will prevent vision loss
 HSV and VZV – acyclovir
 Candida – clotrimazole, nystatin or fluconazole for thrush or esophagitis. Amphotericin B or fluconazole
for systemic infections.
 Bacteria – appropriate abx (see previous sections on antibacterial agents)

Herpes viruses – latent state, cell-mediated immune response counters virus

 Latency – primary infection  virus migrates up nerves to sensory ganglia  virus rests until reactivated during by stressor
(menstruation, sunlight, anxiety, etc.)

 Cytopathic effect – HSV 1 and 2 and VZ – destruction and separation of epithelial cells  blisters
 Multinucleated giant cells and intranuclear inclusions (areas of viral assembly) evident on scraping or skin biopsy
 CMV and EBV exhibit less cytopathic effect

 HSV-1 – most adults harbor anti-HSV-1 Abs.

 Gingivostomatitis – swollen gums and mucous membranes with vesicles
 Reactivation – during stressed states. AIDS pts may present with severe HSV-1 reactivation.
 Herpetic keratitis – most common infectious cz of corneal blindness in the US
 Encephalitis – HSV-1 is most common cz of viral encephalitis in the US. Sudden onset of fever and focal neurologic
deficits

 HSV-2 – commonly czes genital dz. Can cz oral/skin/eye dz. Tx is same for HSV-1 and HSV-2
 Vesicles on vagina, cervix, vulva, perineum, glans, shaft. Vesicles are painful, with burning and itching (often assoc with
urination)

 Neonatal Herpes – transplacental viral transfer  congenital defects or intrauterine death.

 Can be acquired during delivery if mother has active genital infection
 TORCHES pathogens can cross blood-placental barrier:
o TO: toxoplasmosis
o R: rubella
 o C: CMV
o HE: herpes, HIV
o S: Syphilis

 VZV – cz of Varicella and Zoster

 Varicella – dz of kids  resolution  latency  reactivation late in life  zoster (stressors or impaired cell-mediated
immunity
o Highly contagious. Epidemics in winter and spring
o Virus infects resp tract  2wk incubation  viremia  fever, malaise, headache  rash (starts on face and
trunk, spread to body, including mucous membranes). Skin vesicles have “dew on a rose petal” appearance.
Vesicles rupture and scab over
 Tx – vaccine for kids

 Zoster – (shingles) dz of elderly or immunocompromised individuals with hx of previous Varicella infection. Stress 
reactivation via migration along sensory nerves  vesicles similar to those in chicken pox (Varicella)
o Children may get chickenpox from exposure to zoster lesions
o Tx – in elderly and immunocompromised, zoster immune globulin can be given to prevent progression to
pneumonia and encephalitis. IV acyclovir can be given early on to decrease duration and severity of illness.

 CMV – infected cells become swollen

o Asymptomatic infection – most adults have anti-CMV Abs
o Congenital dz – most common viral cz if mental retardation.
 Also czes microcephaly, deafness, seizures, and other birth defects
o CMV mononucleosis – similar to EBV mononucleosis
o Reactivation in immunocompromised – retinitis (blindness), pneumonia, disseminated infection
 AIDS pts – typically develop CMV viremia  retinitis and colitis
 Bone marrow t-plant pts – high risk for developing CMV pneumonia, which can cz death
o Invades WBCs – higher culture yield if buffy coat of centrifuged blood is cultured

 EBV – mononucleosis and Burkitt’s lymphoma. Nasopharyngeal carcinoma and B-cell lymphoma in AIDS pts (brain
mass).
o Transformation and malignant potential – in mono, EBV infects B-cells (binds to complement C3d
receptor). Transformed cells pass on copies of EBV DNA to progeny. EBV is latent in some cells and active
and proliferative in others. Interestingly, malignant cells suddenly disappear with resolution of mono illness.
EBV czes Burkitt’s lymphoma (a B-cell lymphoma) in kids in Central Africa.
o Mononucleosis – dz of young adults, aka kissing dz.
 Fever, chills, sweats, headache, very painful pharyngitis, enlarged lymph nodes and enlarged spleens
 ↑WBC count, atypical lymphs on smear (lg activated T-lymphocytes)
 heterophile Ab = anti EBV Ab  agglutinates sheep RBCs = monospot test
 HHV-8 – Kaposi’s sarcoma

Poxviridae – pox in a box morphology. Cz of smallpox (only infects humans)

 Smallpox
 Last case of smallpox in Somalia in 1977
 Spread via resp tract  pox skin lesions and death
 Vaccine contained vaccinia virus (avirulent form of pox virus). No animal reservoir, so smallpox is though to be
eradicated.

 Molluscum contagiosum – small, white bumps with central umbilications. Similar to warts. Common in AIDS
 Papilloma virus – tropism for squamous epithelial cells. Cz of warts (benign hyperproliferated squamous epithelia). Papilloma
warts resolve within a year or two.
 Cervical CA – HPV type 16 and 18 (TQ). BTW: type 31 also common cz of cervical CA

 Polyoma virus
 BK virus – mild, asymptomatic infection in children
 JC virus – progressive, multifocal leukoencephalopathy (PML) = dz in CNS of AIDS pts that results in white matter
damage (TQ on PML)

 Adenovirus – URIs in kids. All adults show serological evidence of previous exposure
  Rhinitis, cough, sore throat, conjunctivitis

 Parvovirus – ssDNA icosahedral virus. Cz of erythema infectiosum (Fifth disease) = fever and slapped face rash on cheeks (TQ)

Arboviruses – all are t-mitted by blood sucking arthropods and cz fever and encephalitis
 Togaviruses
 Alpha – mosquito-borne. Encephalitis, headache, altered consciousness, focal neurologic deficits
o WEE – Western equine encephalitis
o EEE – Eastern equine encephalitis
o VEE – Venezuelan equine encephalitis

 Rubivirus – rubella (aka German measles) one of TORCHES pathogens

o Not an arbovirus – humans are only species infected
o Causes terrible congenital defects, eps in 1st trimester (heart, eye, CNS defects)
o Measles like illness spread via resp secretions
 Prodrome of flu sx and fever
 Red maculopapular rash that spreads from face to torso to extremities. Lasts 3 days – “3-day measles”
 Pts are less sick than Measles pts and May cause self-limiting arthritis in women
 Encephalitis does not occur as a complication
o Vaccine – live, attenuated rubella virus given to all young kids
o Pregos are screened and immunized after delivery if anti-Rubella Abs aren’t detected
 Flaviviruses
 Yellow fever – t-mitted by mosquitoes
o 1 week incubation  hepatitis with jaundice, fever, headache, backache, nausea, vomiting
 Dengue fever – mosquito-borne. Occurs in tropics. Painful backache, myalgia, arthralgias, severe headache.
o Severe variant – hemorrhage and shock in children

 Bunyaviruses – California encephalitis and Rift Valley fever – both fever and encephalitis
 Hantavirus pulmonary syndrome – four corners area. Flu-like illness with resp failure  death.
o High fever,. myalgia, cough, nausea, vomiting, tachycardia, tachypnea, leukocytosis, ↑RBC count
o Pulmonary edema – intubation and ventilation often necessary.
o Death within 10 days
o Consider in young adults with flu-like sx and pulmonary edema.
o Tx = ribavirin
 Hemorrhagic fever with renal failure – seen in Asia and Europe. Deer mouse reservoir – droppings cz human infection

 Picornaviruses – polio, coxsackie, echo, hep A = entero (fecal oral r-mission). Rhinoviruses - cold
 Polio – infects Peyer’s patches, motor neurons. Cz of paralytic poliomyelitis
o Kids have fewer paralytic complications than do adults
 As sanitation improved, fewer people were exposed as children  more adults affected  more
paralytic complications
o Virus replicates in tonsils (virus can spread by resp secretions while replicating in tonsils) and Peyer’s patches
 blood  across BBB  CNS  anterior horn of spinal cord  3 possible dz manifestations
 Mild illness – most common form. Often asymptomatic.
 Aseptic meningitis – fever and meningismus. Recovery in one week
 Paralytic poliomyelitis – destruction of presynaptic motor neurons in ant horn and post synaptic
neurons leaving horn  UMN and LMN lesions
 Atrophy and loss of reflexes, but no sensory deficits.
o Vaccines – inactivated polio (formalin-killed viruses) given sc. Attenuated poliovirus given orally.
 Oral route and full replication  formation of IgA and IgG
 Attenuated virus is spread to contacts  immunity
 Vaccine associated paralytic poliomyelitis – persons with immunodeficiencies should not receive
vaccine.

 Coxsackie A and B, Echovirus, New Enteroviruses – all cz mild febrile infections, resp sx, rashes, aseptic meningitis
(enteroviruses are most common cz of aseptic meningitis in the US)
 Coxsackie A – herpangina – self-limiting. Fever, sore throat, small red-based vesicles over the back of throat.
 Coxsackie B
o Pleurodynia – fever, headache, severe lower thoracic pain on breathing
 o Myocarditis, pericarditis – self-limited chest pain to severe arrhythmias, cardiomyopathy, heart failure. Cox B
implicated in half of cases

 Cold – rhinoviruses and coronaviruses both cause the common cold.

 Viral diarrhea
 Calciviridae – young kids and infants. Indistinguishable from rotavirus (diarrhea vomiting, fever).
 Norwalk virus – can occur in adults
 Rotavirus – a reovirus. Most common cz of acute infectious diarrhea. Major cz of infant mortality worldwide.
 Tx for all is ORT (oral rehydration therapy)

 Rhabdovirus – rabies. Bullet-shaped, enveloped, helical. Infects all warm-blooded animals. Dogs, cats, coyotes, foxes, raccoons,
bats = reservoir.
 Infected creatures – develop encephalitis and become fearless, aggressive and disoriented
 Human is bitten  local replication  migrates up axons to CNS  fatal encephalitis
 Brain cells contain Negri bodies (collections of virions in the cytoplasm)
 Incubation period following animal bite = 1 week to years. Once sx develop  death within 2 weeks
 Prodrome – fever, headache, sore throat, fatigue, nausea, painfully sensitive nerves around bite (note: Muscles around
bite may fasciculate)
 Acute encephalitis – confusion, meningismus, seizures
 Classic brainstem encephalitis – CN dysfcn, painful contractions of pharyngeal muscles with swallowing liquid
(hydrophobia)  foaming at the mouth
 Death – resp center dysfcn
 Vaccination of dogs and cats – very effective against reducing incidence in humans
 Tx – wash bite sites with soap and water. Human rabies immunoglobulin (5 injections)

 Filoviruses – Ebola and Marburg viruses

 Fever, diarrhea, weakness, dysphagia, hiccups, bleeding from mucous membranes
 Viral hemorrhagic fever ; Filamentous shaped RNA virus ; Transmitted via body fluids ; Airborne t-mission is unlikely
in humans
 Reuse of unsterile needles causative in outbreak in Zaire epidemic
 Control – barrier precautions, sterile needles, proper disposal of corpses, incineration of laundry and equipment. Tx –
supportive.

Anti Herpesviridae meds

 Acyclovir and ganciclovir are guanine analogues.
o Acyclovir – must be phosphorylated by virus thymidine kinase. Human cells don’t have this enzyme, but herpes
viruses do  limited toxicity to human cells
 CMV lack thymidine kinase, so acyclovir doesn’t work as well
 U – not indicated for self-limiting HSV and VZV infections
 Reserved for serious shit like herpes simplex encephalitis in immunocompetent hosts.
 Approved for tx of genital herpes infections
 Used for most herpes infections in the immunocompromised host
 Not used for CMV or EBV
o Famciclovir and valacyclovir – same MOA as acyclovir, but better oral absorption.
 U – zoster and recurrent genital herpes in immunocompetent hosts.
o Ganciclovir – need not be phosphorylated, so it kills all herpesviridae
 SE – neutropenia and thrombocytopenia
 U – because of SE, only used in immunocompromised pts
 AIDS – CMV retinits, pneumonitis, esophagitis
 Bone marrow t-plant pts – CMV pneumonitis and CMV prophylaxis
o Foscarnet – pyrophosphate analogue
 MOA – inhibits DNA pol and RT
 U – AIDS pts with CMV retinits and acyclovir resistant herpesviridae
 SE – reversible nephrotoxicity and decreased seizure threshold

Basic HIV pharmacology – three drug combination of two nucleoside RT inhibitors and a protease inhibitor is 1st line standard of
care
 If CD4 counts drop, viral load increases, opportunistic dz develops, SE develop  change therapy
 Nucleoside reverse Transcriptase Inhibitors (NRTIs) – Zidovudine (ZDV or AZT)
o Reduce mortality and opportunistic infections in pts with CD4 count <200
o Delay progression to clinical dx of AIDS
o Reduces maternal to infant transmission of HIV
o SE – anemia and neutropenia
o Other NRTIs = didanosine (ddI), zalcitabine (ddC), stavudine (d4T), lamivudine (3TC)
 Reduce viral load, ↑CD4 count, slow progression to AIDS
 Prevent emergence of AZT resistance
 AZT + lamivudine + protease inhibitor or a NNRTI = 1st line therapy
 Lamuvidine + AZT = combivir (combination therapy aimed at increasing compliance)
 Lamuvidine – well tolerated, used in comb with IFN alpha in tx of HBV
 Didanosine – purine nucleoside analogue. Unstable in acid (formulated with buffer and taken on
empty stomach). SE = pancreatitis
 Zalcitabine – good oral absorption, pancreatitis less common than with didanosine. SE – severe
oral ulcers
 Stavudine – SE - ↓LFTs
 Abacavir – synthetic carbocylic NRTI. SE – hypersensitivity rxns – rash + constitutional sx. Once
withdrawn for hypersensitivity, reinstitution can result in death
 ddI, ddC, d4T – all cz peripheral neuropathy (reversible)

 NNRTIs – bind directly and noncompetitively to RT  conf change  disruption of active site of enzyme. Unlike NRTIs, these
drugs need not be phosphorylated to become active.
o Resistance emerges rapidly - resistance to one agent often confers cross-resistance to other NNRTIs
o Nevirapine – induces cytochrome p450 CYP3A system. Avoid with other drugs metabolized through cyt p450
CYP3A.
o Delaviridine – metabolized by cytochrome p450. Inhibits CYP450 activity  increases plasma levels of other
drugs metabolized through CYP450.
o Efavirenz – central nervous sx in half of pts = dreams, insomnia, dizziness, impaired concentration, somnolence.
 Inhibits CYP450
o Rash and Stevens-Johnson Syndrome have been reported with all of these agents

 Protease inhibitors – “navirs”

o Saquinavir – minimally absorbed when taken orally (taken with meals to increase absorption). SE – GI
o Indinavir – rapidly absorbed in fasting state. Absorption reduced if given with food.
 SE – GI, nephrolithiasis (used cautiously in pts with renal dysfcn; all pts on this agent should drink 1.5L
H2O per day)
o Ritonavir – poorly tolerated. GI SE
o Nelfinavir – diarrhea in about a third of pts
o Amprenavir – GI SE
o Interleukin-2 infusion – IL-2 regulates proliferation of CD4 T-lymphs. Infusion  ↑CD4 count.

 Post exposure prophylaxis – exposed healthcare workers get triple therapy with AZT, 3TC and indinavir for 4 weeks.

Tx of Influenzae
Amantadine – inhibits uncoating of influenza A. if given early  ↓severity and duration of influenza illness
 Given prophylactically in nursing home outbreaks
Rimantidine – as effective as amantadine. Fewer CNS SE than amantadine. No dosage adjustment necessary in renal dysfcn/failure –
good for use in older pts.
NA inhibitors – active against inf A and B. Indicated for uncomplicated illness. ↓ illness duration by 1-2 days.
 Oseltamivir – oral tablet started within 2 days of onset of flu sx
 Zanamavir – intranasal spray and oral inhaler initiated within 2 days of onset of flu sx
o Contra - COPD or asthma pts
o SE – nosebleed

Ribavirin – wide spectrum against RNA and DNA viruses. Teratogenic in small animals.
 U – severe RSV, Lassa fever, Hantavirus pulmonary syndrome
o Oral form available for tx of HCV - ↓LFTS but doesn’t lower viral level in blood
Interferon – cytokine that promotes cellular anti-viral state
 IFN alpha – used in HBV and HCV
 More than half of pts relapse when interferon is discontinued
 IFN alpha + ribavirin = most promising tx for chronic HCV(albeit not very effective)

Protozoans – watch for a matching section at the end of Putthoff’s exam over these critters!
 Intestinal protozoa
o Entamoeba histolytica – moves via pseudopodia
 Most infections are asymptomatic
 Fecal-oral t-mission. Homosexual men are often asymptomatic carriers
 Trophozoite – motile feeding form. Cruises along intestinal wall.
 Converts to precyst (2 nuclei and chromatoid bodies, which are food vacuoles)  matures to
tetranucleated cyst (eaten by others)
 Trophozoite can invade intestinal mucosa  abdominal pain, loose stools with flecks of blood and
mucus. Voluminous bloody diarrhea may result.
o Penetration of portal circulation  hepatic abscesses  spread through diaphragm into
lung  pulmonary abscesses
 Dx – stool is examined for cysts.
 Trophozoites with RBCs in cytoplasm suggests active dz.
 No RBCs in trophozoites suggests asymptomatic carrier state.
 Tx – metronidazole
 Contra – EtOH
 SE – metallic taste in mouth

o Giardia lamblia – cyst form and mature, motile trophozoite that looks like a kite.
 Many adults harbor asymptomatically
 Outbreaks result contamination of drinking water with sewage
 Harbored by rodents and beavers (TQ)  campers acquire infection from drinking from clear mt streams
 Organism coats SI  inhibits fat absorption  steatorrhea with pungent odor (greasy, frothy diarrhea),
cramps and flatulence. NO blood in stool
 Dx – cysts or trophozoites in stool; immunoassay for Giardia Ags in stool
 Tx – metronidazole

o Cryptosporidium – many Americans have serological evidence of previous exposure

 Infants in daycare centers. Contaminated municipal water can be the etiology.
 round oocyst, containing 4 motile sporozoites, is ingested  life cycle in intestinal epithelial cells 
diarrhea and abd pain  self-limiting in immunocompetent hosts
 Severe, protracted diarrhea in AIDS pts

o Isospora and microsporidia – severe diarrhea in immunocompromised. Fecal-oral t-mission

 Tx – TMP/SMX for Isospora and albendazole for Microsporidia

 Sexually t-mitted protozoan

o Trichomonas vaginalis – flagellated
 Females - itching, burning on urination, copious vaginal discharge
 Thin, watery, frothy, malodorous discharge in vag vault on speculum exam
 Microscopic examination of vaginal discharge reveals flagellated organisms. Organisms may also
be present in the urine
 Males – usu asymptomatic
 Tx – metronidazole – provide enough for sexual partners
 Meningitis causing free-living protozoans – Naegleria fowleri and Acanthamoeba.
o Live in fresh water and moist soils
o Summer months – people swim in freshwater lakes
o Organisms penetrate nasal mucosa  through cribiform plate  into brain and CSF
 o Naegleria fowleri – 95% mortality within 1 week (immunocompetent pts). Enjoy Putthoff’s story about autopsies on
individuals that contracted this organism while swimming in Lake Worth.
 Fever, headache, stiff neck, nausea, vomiting with hx of swimming 1 week earlier
 CSF – high neuts, low glucose, high protein – just like bacterial meningitis
 G stain and culture  NO bacteria
 Tx – intrathecal amphotericin B (but, it doesn’t work)

o Acanthamoeba – chronic, granulomatous, brain infection in immunocompromised pts

 CSF and brain parenchyma reveal organisms
 Tx – multiple antifungal agents with pentamidine
 Organism may infect the cornea (immunocompetent pts) when contact lenses are not cleaned properly.

 Toxoplasma gondii – undercooked meats (pork) and household cat feces. Jacks up brain and eyes in fetuses and AIDS pts.
o Organism undergoes sexual division in cats  excreted as infectious cyst in feces
o Reactivation in immunocompromised pts or a primary infection in prego  transplacental infection of fetus.
o Toxoplasma encephalitis is most common CNS infection in AIDS pts.
 Growing mass, headache, focal neuro deficits. Will see ring enhancing lesions!!
 Chorioretinitis is also common
 Retina reveals white, fluffy, patches
o One or TORCHES organisms
 Congenital toxoplasmosis – doesn’t occur in pregos with serologic evidence of previous exposure
 Chorioretinitis, seizures, mental retardation, microcephaly, encephalitis, blindness
 Can result in stillbirth if infection is acquired early in gestation
 Pregos should avoid cats – case for kitten punting (One of Dan’s favorite pastimes)
o Dx – CT  contrast enhancing mass. Retinal exam reveals inflamm. ↑Ig titers
o Tx – Sulfadiazine/pyrimethamine

 Pneumocystis carinii – flying-saucer shaped fungus. Invades lungs in all individuals and persists in latent state. Most kids have
had a bout with PC by age 4.
o PCP – in immunocompromised hosts. Most common opportunistic infection in AIDS pts
 Silver staining alveolar secretions
 Most AIDS pts will develop in their lifetime without prophylactic TMP/SMX.

 Malaria – organisms grow in liver, spread to RBCs to reproduce. RBCs fill with protozoa  burst synchronously  protozoa in
bloodstream  immune response (fever). Regular, cyclic patterns.
o Vivax and ovale – burst every 48 hours  2 day cycle of chills and fever (tertian malaria)
 Produce dormant forms (hypnozoites)  relapsing malaria
o Malariae – bursts every 72 hours  3 day cycle of chills and fever followed by sweats (quartan malaria)
o Falciparum – most common and most deadly. Red cells burst more irregularly (every 36-48 hours)
o Plasmodia undergo sexual division in the anopheles mosquito  asexual division in the human liver and RBCs
 pre-erythrocytic cycle
 Sporozoites swim out of mosquito’s sucker  enter human bloodstream  burrow into liver
 Sporozoite rounds into ball in the liver = trophozoite
 Trophozoite undergoes nuclear division thousands of new nuclei = schizont  cytoplasmic
membranes form around nuclei forming merozoites
 Liver cell overloaded with merozoites bursts  merozoites rel into bloodstream
o exoerythrocytic cycle - some merozoites will re-infect liver cells (process repeats itself)
o erythrocytic cycle – merozoite rounds in RBC to become trophozoite (shaped like a
diamond ring  nuclear division forms a lg multinucleated schizont  cytoplasmic
membranes form around nuclei forming merozoites within late schizont  RBC lysis
with release of merozoites  immune response (fever, chills, etc.)
o merozoites continue to infect other RBCs  cycling
o Some merozoites will form male and female gametocytes  taken up by biting
mosquito  t-mitted to other hosts

o The dz – periodic episodes of chills and high fever

 Anemia
 Sticky RBCs  plug up post-capillary venules  renal failure, lung edema, coma
 Most deaths occur in children who often develop cerebral malaria (impaired consciousness and seizures
 coma)
  Hepatomegaly and splenomegaly – fixed phagocytes pick up debris from destroyed RBCs

Malaria cont.
o Resistance – many African-blacks and African-Americans are resistant
 Absence of RBC Ags Duffy a and b (used by vivax for binding)
 Sickle cell trait – protects RBCs from invasion by falciparum.
o Dx – trophozoites and schizonts in RBCs on smear. Fluorescent Abs can be used to ID species
o Control – eliminate vector. Use insect repellants
o Prophylaxis for travelers –chloroquine. Mefloquine or doxycycline in chloroquine resistant areas.
 Pyrimethamine/sulfadoxine starter pack for breakthrough infection, esp if using dox for prophylaxis.
o Tx – chloroquine kills malariae, vivax and ovale. However, vivax and ovale have exoerythrocytic cycles –
primaquine used to kill organisms in the liver (chloroquine won’t kill organisms in liver)
 Falciparum – use chloroquine since falciparum has no exo-erythrocytic cycle
 Chloroquine resistant areas – use quinine or quinidine; artemether; or pyrimethamine/sulfadoxine
 All drugs for malaria can be taken po
 SE – GI upset (all drugs). “–quines” cz hemolysis in G6PD deficiency
 “-quines” and pyr/sulf are safe in pregos

 Babesiosis – similar to malaria. T-mitted by ticks, not mosquitoes. Fever and hemolysis. Organisms can be seen in RBCs
o Over 100 species of Babesia
o Do not affect liver cells
o Northeastern coastal US (Eastern seaboard)
o Ixodes tick picks up organism from white-footed mouse  t-mits to humans
o Sporozoites leave tick’s salivary glands  invade erythrocytes  form pear or ring-shaped trophozoites, which
asexually bud into 4 merozoites (X-shaped tetrads = Maltese cross)
o Asplenic pts are unable to clear organisms
o Tx – quinine and clindamycin

 Leishmaniasis – t-mitted to humans by sandfly (S. America, Middle East, Africa). Tx of all varieties = stibogluconate (arsenic
containing compound).
o Promastigote invades macs  t-forms into nonmotile amastigote  multiplies in phagocytes in nodes, spleen,
marrow and liver
o Cutaneous leishmaniasis – at site of fly bite, skin ulcer develops (oriental sore)  ulcer heals a year later leaving
depigmented scar.
 Cell-mediated immunity  attack of skin (ulceration)  clearance of infection
o Diffuse cutaneous leishmaniasis – chronic form in immunocompromised individuals in Ethiopia and Venezuela
 Nodular skin lesion that doesn’t ulcerate (defective cell-mediated immunity)
 Numerous nodular lesions over body (often concentrated near nose)
 Promastigotes spread  diffuse nodularities
o Mucocutaneous leishmaniasis – dermal ulcer. Site of bite heals. Months to years later, ulcers in mucous
membranes of nose and mouth arise.
o Visceral leishmaniasis – most commonly occurs in malnourished kids
 Abdominal discomfort, distention, fever, anorexia, wt loss, hepatomegaly, massive splenomegaly, anemia,
↓WBC
 Fatal if untreated
 Dx – liver or spleen biopsy. Skin test is negative because cell-mediated immunity is deficient.

 African sleeping sickness (Trypanosoma brucei) – t-mitted by tsetse fly bite

o Motile, flagellated trypomastigote spreads through bloodstream  nodes and CNS
o Hard, red, painful skin ulcer that heals within 2 weeks.
o Fever, headache, dizziness, lymphadenopathy with systemic spread
o Episodic fever can occur for months.
 Due to variable surface glycoproteins (VSG)
 When host develops antibodies and fever, the trypanosome produces progeny with a new VSG coat.
 Similar to Borrelia recurrentis (relapsing fever)
 o CNS sx eventually develop – daytime drowsiness, slurred speech, gait and behavioral abnormalities  coma and
death
o Dx – trypomastigotes in blood, nodes, CSF
o Tx – suramin (doesn’t penetrate BBB). Melarsoprol penetrates BBB.

 Chagas’ dz (Trypanosoma cruzi) – southern US down into S America. Wild animal reservoirs. Reduviid bug is vector
o Reduviid feeds on sleeping humans. Bug defecates on human. Feces contains trypomastigotes, which tunnel into
human host.
o Trypomastigote  amastigote  multiplies  invades local skin, macs, nodes  spreads to distant organs
o Acute Chagas’ – hardened, red chagoma forms  spread with fever, malaise, swollen nodes  heart and CNS
affected
 Heart – tachycardia and ECG changes
 CNS – severe meningoencephalitis
o Intermediate phase – no sx, but low levels of parasite in blood. Most persons remain in this phase for life.
o Chronic Chagas’ – heart, colon, esophagus affected
 Heart – AV block, V-tach, dilated cardiomyopathy
 Colon and esophagus – megadz. Dilated, poorly functioning esophagus  regurgitation of food.
Megacolon  constipation and abdominal pain (weeks without bowel movements)
o Dx – motile trypomastigotes in blood
o Tx – nifurtimox and benznidazole for acute cases. No tx for chronic

 Balantidium coli – water contaminated with pig feces.

o Cysts are ingested  mature into ciliated trophozoites  dig into intestinal wall  consume native bacteria 
asymptomatic or diarrheal illness
o Dx – ciliated trophozoites or cysts in stool
o Tx – tetracycline

Helminths – roundworms (nematodes), flatworms (platyhelminthes). No immune reaction to living worms. Response is to dead
worms or eggs. Eosinophilia is common with worm infections.

Nematodes
 Ascaris lumbricoides – tropics and mountainous areas of southern US. T-mitted via food contaminated with eggs
o Larvae penetrate intestinal wall  hematogenous spread to lungs  larvae grow in alveoli  coughed up and
swallowed  larvae mature in SI  adult lays 200K eggs/day  excreted in feces
o Cough, pulmonary infiltrate on CXR
o Dx – eggs in feces. Sputum may reveal larvae. Eosinophilia.
o Tx – “-bendazoles”  paralyze roundworms  corpses passed in stool. Pyrantel pamoate = alternative agent for
Enterobius, Necator, Ascaris

 Necator americanus – (TQ) – larvae live in soil  filariform larvae penetrate human skin (between the toes)  travel to alveoli 
coughed up and swallowed  adults develop as they reach SI  attach by mouth to intestinal wall and suck blood  worms
copulate and release fertilized eggs
o Fe deficiency anemia
o Itching and rash between toes at site of bite and penetration
o Pulmonary sx and eosinophilia
o Dx – eggs in fresh fecal sample
o Tx – mebendazole. Also tx Fe deficiency anemia

 Strongyloides stercoralis – same as Necator, but eggs aren’t passed in stool.

o Autoinfection – penetrate intestine and move to lung
o Direct cycle – larvae pass from feces to soil  infect another human
o Indirect cycle – larvae passed in stool  develop and mate in the soil  lay fertilized eggs that hatch and reinfect a
human
o Vomiting, diarrhea, anemia, wt loss
o Pruritic rash, lung sx
o Dx - sputum may reveal larvae, eosinophilia
o Tx – thiabendazole
 Trichinella spiralis – ingestion of encysted larvae in raw pork
o Cysts travel to SI  larvae mature into mating adults  adult males are passed in feces  females penetrate
intestinal mucosa  produce larvae  larvae enter bloodstream  spread to skeletal mm and encyst (sometimes for
decades). Heart mm and brain are invaded in severe cases
o Initial infection usu asymptomatic – abd pain, diarrhea and fever may occur
o Dx – muscle biopsy reveals encysted larvae. Eosinophilia and ↑CPK
o Tx – “-bendazoles” have little effect on encysted larvae

 Trichuris trichiura – (whipworm) – no tissue invasion, so no eosinophilia

o Ingestion of food contaminated with eggs  hatch in GI tract  migrate to cecum and ascending LI  mature
adults produce eggs for about a year
o Abdominal pain and diarrhea
o Dx – eggs in feces. Eggs look like footballs with humps at each end
o Tx – mebendazole

 Enterobius vermicularis – ingestion of eggs  mature in the cecum  female migrates to perianal area (usu at night)  lays eggs
 severe perianal itching  host scratches his or her ass and reinfects him or herself and others
o Dx – scotch tape on the bunghole will pick up eggs, which can be seen via microscopy
 Adult female can sometimes be seen crawling across perianal area
 No tissue invasion, so no eosinophilia
o Tx – mebendazole or pyrantel pamoate, avoid scratching, change sheets daily

 Onchocerca Volvulus – humans are bitten by infected black flies  microfilariae mature into adults, which are found coiled up in
fibrous nodules in skin. Adults produce microfilariae  pruritic skin rash with darkened pigmentation  papular lesions
(intraepithelial granulomas)
o Skin may be dry, scaly and thick (lizard skin)
o Microfilariae may migrate to the eye  river blindness
o Dx – microfilariae in skin biopsies or adults in nodule. Microfilariae can be seen in cornea and anterior chamber via
slit lamp examination
o Tx – ivermectin

 Wuchereria bancrofti and Brugia malayi – chronic leg swelling. Wuchereria in Pacific Islands and Africa. Brugia in Malay
peninsula and SE Asia.
o Humans are bitten by infected mosquitoes  transmitted microfilariae mature in lymphatic vessels and nodes of
genitals and LEs
o Frequent infections in endemic areas  febrile episodes with headache and swollen inguinal nodes  repeated
exposure  fibrous tissue formation around dead microfilariae plugs lymphatic system  swelling of legs and
genitals, which become covered with thick, scaly skin (pachydermatous) = elephantiasis. One might actually have
to use a wheelbarrow to haul around his scrotum (you can find pics on the web)
o Dx – nocturnal periodicity – organisms circulate during nighttime (blood drawn at night)
o Tx – diethylcarbamazine

 Dracunculus medinensis – t-mitted via drinking water contaminated with microscopic crustaceans
o Larvae penetrate intestine  move to subcutaneous tissue  adults develop and mate  female grows to 100cm 
she migrates to skin and a loop of her body pokes out. When she contacts water, she releases thousands of motile
larvae (exactly why you shouldn’t let Brandon Zinn swim at your house)
o Nausea, vomiting, hives, breathlessness during larvae release

 Cutaneous larval migrans – creeping eruption

o Intensely pruritic migratory skin infection
o Larvae of dog and cat hookworms penetrate skin  migrate beneath epidermis  raised, red, itchy rash moves with
advancing larvae.
o Dog hookworm – Ancylostoma braziliense
o Other organisms can cz
o Dx – biopsy advancing edge of rash

Platyhelminthes (flatworms)
 Trematodes (flukes)
 o Schistosoma (blood fluke) – penetrate exposed skin  invade venous system  mate and lay eggs  eggs must
reach freshwater to hatch (cannot multiply in humans)
 Larvae emerge  find freshwater snail  mature within snail  cercariae (mature larvae) released 
infect humans via skin penetration  move to intrahepatic portal system  mature and mate
 Eggs may enter lumen of bladder or intestine  excreted in urine or feces
 Adult worms release eggs for years (worms are not killed by immune system)
 Molecular mimicry (schistosomes incorporate host Ags on their surface, thus they evade the host’s
immune system)
 Swimmer’s itch – dermatitis assoc with cercariae penetrating skin
 Katamaya fever – fever, hives, headache, wt loss, and cough
 Chronic fibrosis – some eggs deposit in liver, lung or brain  walled off as granulomas
 May cz portal HTN
 Hematuria, abd pain, diarrhea, CNS injury, pulmonary HTN are not uncommon
 S. haematobium = most common cz of squamous cell carcinoma of the bladder (Sudan and Egypt)
 Dx – eggs in stool or urine
 Tx – praziquantel. Immediate exacerbation of sx not uncommon – immune response assoc with
schistosomal death.

 Cestodes (tapeworms) – all can be treated with praziquantel or niclosamide

o Taenia solium – (pork tapeworm) – undercooked pork infected with larvae. Cysticercus is larval from in animal’s
mm tissue.
 Worm attaches to intestine via its scolex  eggs released into feces
 Sx are minimal
 Cysticercosis – human plays the role of the pig (human ingests eggs rather that larvae)
 Eggs hatch in SI  larvae migrate throughout body  penetrate and encyst in tissues 
commonly in brain and skel mm
 Neurocysticercosis – seizures, obstructive hydrocephalus, focal neuro deficits. Cysts grow slowly
o In endemic areas, cysticersosis is most common cz of seizures (Mexico, Central and
South America, Philippines, SE Asia)
o Dx – CT or biopsy of brain – calcified cysticerci. Eosinophilia.
o Tx – dibendazole or praziquantel

o Taenia saginata (beef tapeworm) – exact same life cycle as solium, except humans do NOT develop cysticerci.
 Source = undercooked beef mm containing larval cysticerci
 Adult tapeworm develops and adheres to intestinal mucosa  can grow to 10meters
 Pts usu asymptomatic, but may exhibit malnutrition and wt loss (signs)
 Dx – eggs in feces

o Diphyllobothrium latum (fish tapeworm) – can grow to 45 meters. Ingested of raw freshwater fish contaminated
with larvae  human infection.
 Crustacean and a fish are required for life cycle
 Can cz B12 deficiency
 Dx - Eggs in feces
o Hymenolepis nana (dwarf tapeworm)– humans ingest eggs  grow into adults  pass eggs in feces  ingested
by other humans
 Abd discomfort, nausea, vomiting
 Dx – eggs in fecal sample

o Echinicoccus granulosus and multilocularis (Hydatid dz, an extra-intestinal tapeworm infection) –

 Granulosus similar to Taenia solium – human ingest eggs  hatch in intestine  larvae  disseminate 
most harbored in liver. May also infect brain, kidney and lungs
 Early larva  hydatid cyst  cyst undergo asexual budding  daughter cysts  each cyst may compress
organ around it producing sx.
 If cyst bursts  allergic reaction may be fatal
 Granulosus grows larger and only spreads upon rupture
 Multilocularis spread and can be misdiagnosed as a tumor
 Dx – CT and tissue biopsy
 Dogs and sheep perpetuate the life cycle
 Dogs shouldn’t be fed undercooked meat in relevant countries
 Periodic treatment of dogs with niclosamide helps
Prions – microscopic spongiform changes and accumulation of prion protein (PrP)
 Infectious agent and etiology – protein-only hypothesis is most widely accepted theory
o PrP – encoded by endogenous gene (chrom 20 in humans, Putthoff loves to ask stuff like this)
 Two conformational isoforms
 PrPC – cellular isoform = constitutive form normally expressed in animals
 PrPSc – scrapie isoform (sheep scrapie is source of name) = disease associated isoform.
o Small amt of PrPSc  chain reaction  conformational change of PrPC into PrPSc
 Transmission and epidemiology
 Creutzfeldt-Jakob disease – disease resulting endogenous protein gone awry
 Bovine spongiform encephalopathy – results feeding cattle meat and bone meal
 Kuru epidemic – probably t-mitted through ritualistic cannibalism (rite of mourning the
deceased)
 Iatrogenic Creutzfeldt-Jakob disease – contaminated neurosurgical instruments, dural and
corneal grafts, administration of cadaveric pituitary hormones.
o Clinical presentation – rapidly progressive dementia, psychiatric sx, cerebellar sx, involuntary movements,
ultimately fatal
o Dx – gold std = histopathological staining for PrPSc
 Serial EEG – period sharp wave complexes in most pts
o Tx – no curative treatment.