DRUGS, MICROBES, HOST

Principles of Antimicrobial Therapy

o Are produced naturally or synthetically

Characteristics of the Ideal Antimicrobial Drug

o Selectively toxic to the microbe but nontoxic to host cells
o Microbiocidal rather microbiostatic
o Relatively soluble, functions even when highly diluted in body fluids
o Remains potent long enough to act and is not broken down or
excreted prematurely
o Doesn’t lead to the development of antimicrobial resistance
o Complements or assists the activities of the host’s defences
o Remains active in tissues and body fluids Considerations in Selecting an Antimicrobial Drug
o Readily delivered to the site of infection o Identify the microorganism causing the infection
o Reasonably priced o Test the microorganism’s susceptibility (sensitivity)
o Does not disrupt the host’s healthy by causing allergies or o The overall medical condition of the patient
predisposing the host to other infections
Testing for Drug Susceptibility
Origins of Antibiotic Drugs
o Common metabolic products of aerobic spore-forming bacteria
(Streptomyces & Bacillus) and fungi (Penicillium & Cephalosporium)

Interactions between Drugs

o Antimicrobial Drugs should be selectively toxic
o Mechanism of Drug Action

Microbe-Human Interactions: Infection and Disease

o Inhibition of cell wall synthesis

o Disruption of cell membrane structure or function
o Inhibition of nucleic acid synthesis structure or function
o Inhibition by protein synthesis
o Blocks on key metabolic pathways Therapeutic Index
o The ratio of drug that is toxic to humans as compared to its
Interactions Between Drug and Host minimum effective dose
Major side effects Infection
o Direct damage to tissue due to toxicity of drug o A condition in which the pathogenic microbes invades host’s
o Allergic reactions defences
o Disruption in the balance of normal flora-superinfections possible
Major Factors in the Development of an Infection
o True Pathogens
o Capable of causing disease in healthy persons with normal
immune defences (ex. Influenza virus, Bacillus spp. Causing
plague, malarial protozoan)
o Opportunistic Pathogens
 o Cause disease when the host’s defences are compromised or antitoxins
when they grow in part of the body that is not natural to them Fever Stimulation Usually not Yes
(Pseudomonas spp., Candida albicans) Manner of Release Secreted from live cell Released from cell
wall during lysis
Typical Sources A few Gram- & All Gram- bacteria
Course of Infection
Gram+

Requirement for an Infectious Dose (ID)

o Minimum number of microbes required for infection to proceed

Agent of Infectious Dose Primary Source of

Estimate Infection
Measles 1 virus Respiratory The Process of Infection and Disease
Q fever 1-10 cells Respiratory o Incubation period: time from initial contact to the time of the
Tularemia 10-50 cells Various first symptom (pathogen is multiplying but is insufficient
Smallpox 10-100 viruses Respiratory enough to cause infection)
Brucellosis 10-100 cells Various o Prodromal stage: feelings of discomfort
Viral Encephalitis 10-100 viruses Mosquito bite o Period of invasion: more specific signs (objective observation
Plague 100-500 cells Flea bite of the disease by the observer) and symptoms (such as
Gonorrhoea 1000 cells Sexual contact
nausea, chills, fatigue, etc.), pathogens multiply at high levels
Anthrax 8,000-50,000 spores Respiratory, cutaneous
(pathogens become more established in the body)
Typhoid 10,000 cells Ingestion
o Convalescent period: symptoms decline
Cholera 100,000,000 cells Ingestion
o Several of these agents are considered bioterror pathogens
o Virus with small infectious dose have greater virulence

Attaching to the Host

Principles of Antimicrobial Therapy

o Administer to an infected person a drug that destroys the infective
agent without harming the host’ cells
o Antimicrobial drugs are produced naturally or synthetically
Causing Disease
Differential Characteristics of bacterial Exotoxins and Endotoxins Terminology of Chemotherapy
Characteristic Exotoxins Endotoxin Chemotherapeutic drug Any chemical used in the treatment, relief,
Toxicity Toxic in minute Toxic in high dose or prophylaxis of a disease
amounts Prophylaxis* Use of a drug to prevent imminent
Effects on the Body Specific to a cell type Systemic: fever, infection of a person at risk
(blood, liver, nerve) inflammation Antimicrobial chemotherapy* The use of chemotherapeutic drugs to
Chemical Small proteins Lipopolysaccharide of control infection
Composition cell wall Antimicrobials All-inclusive term for any antimicrobial
Heat Denaturation at Unstable Stable drug, regardless of its origin
60°C Antibiotics* Substances produced by the natural
Toxoid Formation Can be converted to Cannot be converted metabolic processes of some
toxoid* to toxoid microorganisms that can inhibit or destroy
Immune Response Stimulate antitoxins** Does not stimulate microorganisms
Semisynthetic drugs Drugs which are chemically modified in the
laboratory after being isolated from natural
sources
Synthetic drugs The use of chemical reaction to synthesize
antimicrobial compounds in the laboratory
Narrow spectrum (limited Antimicrobials effectiveness against a
spectrum) limited array of microbial types- for
example, a drug effective mainly on gram+
bacteria
Broad spectrum (extended Antimicrobials effective against a wide
spectrum) variety of microbial types- for example, a
drug effective against both gram-positive
and gram-negative bacteria
 Prophylaxis (a process that prevents infection or disease in a
person at risk)

Origins of Antibitiotic Drugs
o Antibiotics are common metabolic products of aerobic spore-
forming bacteria and fungi
o Bacteria in genera Streptomyces and Bacillus
o Molds in genera Penicillium and Cephalosporium
o By inhibiting the other microbes in the same habitat, antibiotic
producers have less competition for nutrients and space
Interaction between Drug and Microbe
o Antimicrobial drugs should be selectively toxic: drugs should kill or
inhibit microbial cells simultaneously damaging host tissues
o As the characteristics of the infectious agent become more similar
to the vertebrate host cell, complete selective toxicity becomes
more difficult to achieve and more side effects are seen
Mechanism of Drug Action
1. Inhibition of cell wall synthesis
2. Disruption of cell membrane structure or function
3. Inhibition of nucleic acid synthesis, structure or function
4. Inhibition of protein synthesis
5. Blocks on key metabolic pathways
The Spectrum of an Antimicrobial Drug
o Spectrum – range of activity of a drug
o Narrow spectrum: effective on a small range of microbes
 Target a specific cell component that is found only in
certain microbes
o Broad spectrum: greatest range of activity
 Target cell components common to most pathogens
Antimicrobial Drugs that Affect the Bacterial Cell Wall
o Most bacterial cell walls contain peptidoglycan
o Penicillins and cephalosporins block synthesis of peptidoglycan,
causing the cell wall to lyse
o Active on young, growing cells
o Penicillins do not penetrate the outer membrane and are less
effective against Gram-negative bacteria
o Broad spectrum penicillins and cepahalosporins can cross the cell
walls of Gram-negative bacteria
Antimicrobial Drugs that Disrupt Cell Membrane Function
o A cell with a damage membrane dies from disruption in metabolism
or lysis
o These drugs have specificity for a particular microbial group, based
on differences in types of lipids in their cell membranes
o Polymyxins interact with phospholipids and cause leakage,
particularly in Gram-negative bacteria
o Amphotericin B and nystatin form complexes with sterols on fungal
membranes which cause leakage
Drugs that Inhibit Nucleic Acid Synthesis
o May block synthesis of nucleotides, inhibit replication, or stop
transcription
o Chloroquine binds and cross-links the double helix; quilonones
inhibit DNA helicase
o Antiviral drugs that are analogs of purines and pyrimidines
insert in viral nucleic acid, preventing replication
Drugs that Block Protein Synthesis
o Ribosomes of eukaryotes differ in size and structure from
prokaryotes; antimicrobics usually have a selective action against
prokaryotes; can also damage the eukaryotic mitochondria
o Aminoglycosides (streptomycin, gentamycin) insert on sites on the
30S subunit and cause misreading of mRNA
o Tetracyclines block attachment of tRNA on the A acceptor and stop
further synthesis
Drugs that Affect Metabolic Pathways
o Sulfonamides and trimethoprim block enzymes required for
tetrahydrofolate synthesis needed for DNA and RNA synthesis
o Competitive inhibition
o Drug competes with normal substrate for enzyme’s active site
o Synergistic effect
o An additive effect, achieved by multiple drugs working
together, requiring a lower dose of each
Survey of Major Antimicrobial Drug Groups
o Antibacterial Drugs (antibiotics, synthetic drugs)
o Antifungal drugs
o Antiprotozoan drugs
o Antiviral drugs
o About 260 different antimicrobial drugs are classified in 20
drug families

I. Penicillin and Its Relatives
o Large diverse group of compounds
o Could be synthesized in the laboratory (through microbial
fermentation and semi-synthetic modification)
o More economical to obtain natural penicillin through microbial
fermentation and modify it to semi-synthetic forms
o Penicillium chrysogenum – major source
o All consist of 3 parts
o Thiazolidine ring
o Beta-lactam ring
o Variable side chain dictating microbial activity
o Beta-lactam antimicrobials – all contain a highly reactive 3
carbon, 1 nitrogen ring
o Primary mode of action is to interfere with cell wall synthesis
o Greater than ½ of all antimicrobic drugs are beta-lactams
o Penicillins and cephalosporins most prominent beta-lactams
Subgroups and Uses of Penicillins
o Penicillins G and V most important natural forms
o Penicillin in the drug of choice for Gram-positive cocci
(streptococci) and some Gram-negative bacteria
(meningococci and syphilis spirochete)
o Semisynthetic penicillins – ampicillin, carbenicillin, and
amoxicillin have broader spectra ; Gram-negative rods
o Penicillinase-resistant- methicillin, nafcillin, cloxacillin
o Primary problems – allergies and resistant strains of bacteria
II. Cephalosporin
o Account for majority of all antibiotics administered
o Isolated from Cephalosporium acremonium mold
o Synthetically altered beta-lactam structure
o Relatively broad-spectrum, resistant to most penicillinases, & cause
fewer allergic reactions
o Some are given orally; many must be administered parentally
o Generic names have root: - cef, ceph, or kef
o 4 generations exist: each group more effective against Gram-
negatives that the one before with improved dosing schedule and
fewer side effects
o First generation: cephalothin, cefazolin – most effective against
Gram-positive cocci and few Gram-negative
o Second generation: cefaclor, cefonacid – more effective
against Gram-negative bacteria
o Third generation: cephalexin, ceftriaxone – broad-spectrum
activity against enteric bacteria with beta-lactamases
o Fourth generation: cefepime – widest range; both Gram
positive and Gram-negative
Additional Beta-lactam Drugs
o Carbapenems
- Imipenem: broad-spectrum drug for infections with
aerobic and anaerobic pathogens; low dose,
administered orally with few side effects
o Monobactams
- Aztreonam: newer narrow-spectrum drug for infections
by Gram-negative aerobic bacilli; may be used by people
allergic to penicillin
III. Drugs that Interfere with Protein Synthesis
o Aminoglycosides
- Composed of 2 or more amino sugars and an aminocyclitol
(6C) ring; binds ribosomal subunit
o Products of various species of soil actinomycetes in genera
Streptomyces and Micromonospora
o Broad-spectrum, inhibit protein synthesis, especially useful against
aerobic Gram-negative rods ad certain Gram-positive bacteria
- Streptomycin: bubonic plague, tularemia, TB
- Gentamicin: less toxin, used against Gram-negative rods
- Newer: tobramycin and amikacin Gram-negative bacteria
IV. Non Beta-Lactam Cell Wall Inhibitors
o Vancomycin
- Narrow-spectrum, most effective in treatment of Staphylococcal
infections in cases of penicillin and methicillin resistance, or if
patient is allergic to penicillin;
- toxic and hard to administer; restricted use
o Bacitracin
- Narrow-spectrum produced by a strain of Bacillus subtilis; used
topically in ointment
o Isoniazid (INH)
- Works by interfering with mycolic acid synthesis
- Used to treat infections with Mycobacterium tuberculosis
- oral dose in combination with other antimicrobials such as
rifampin, ethambutol
V. Tetracycline Antibiotics
o Broad-spectrum, block protein synthesis by binding ribosomes
o Aureomycin, terramycin, tetracycline, doxycycline, minocycline:
low-cost oral drugs are a concern
o Treatment forSTDs, rocky mountain, spotted fever, lyme disease,
typus, acne, and protozoa
VI. Chloramphenicol
o Isolated from Streptomyces venezuela; no longer derived from
natural source
o Potent broad-spectrum drug with unique nitrobenzene structure
o Blocks peptide bond formation
o Very toxic,restricted uses, can cause irreversible damage to bone
marrow
o Typhoid fever, brain abscesses, rickettsial and chlamydial infections
VII. Macrolides and Related Antibiotics
o Erythromycin
 - Large lactone ring with sugars; attaches to ribosomal 50s d) Flucytosine: analog of cytosine; cutaneous mycoses or in
subunit combination with amphotericin B for systemic mycoses
o Broad-spectrum, fairly low toxicity e) Echinocandins: damage of cell walls; capsofungin
o Taken orally for Mycoplasma pneumonia, legionellosis, Chlamydia,
pertussis, diphtheria, and as a prophylactic prior to intestinal surgery XI. Antiparasitic Chemotherapy
o For penicillin-resistant : gonococci, syphilis, acne o Antimalarial drugs: quinine, chloroquinine, primaquine, mefloquine
o Newer semi-synthetic macrolides: clarithromycin, azithromycin o Antiprotozoan drugs: metronidazole (Flagyl), quinicrine,
sulphonamides, tetracyclines
VIII. Related Macrolides o Antihelminthic drugs: immobilize, disintegrate, or inhibit
o Clindamycin metabolism
- Broad spectrum - Mebendazole, thiabendazole: broad-spectrum; inhibit function of
- Serious abdominal anaerobic infections; adverse reactions microtubules, interferes wjth glucose utilization and disables
o Ketolides them
- Telitromycin (Ketek), new drug with different ring structure from - Pyrantel, piperazine: paralyze muscles
Erythromycin - Niclosamide: destroys scolex
- Used for infection when resistant to macrolides
o Oxazolidinones XII. Antiviral Chemotherapeutic Agents
- Linezolid (Zyrox) o Selective toxicity is almost impossible due to obligate intracellular
- Synthetic antimicrobial that blocks the interaction of mRNA and parasitic nature of viruses
ribosome o Block penetration into host cell
 Used to treat methicillin resistant Staphylococcus aureus o Block transcription or translation of viral genetic material
(MRSA) and vancomycin resistant Enterococcus (VRE) - Nucleotide analogs
 Acyclovir: herpesvirus
VI. Drugs that Block Metabolic Pathways  Ribavirin: a guanine analog – RSV, hemorrhagic fevers
o Most are synthetic  AZT – thymine analog – HIV
o Most important are the sulphonamides, or sulfa drugs – first o Prevent maturation of viral particles
antimicrobic drugs - Protease inhibitors: HIV
o Narrow-spectrum
o Block the synthesis of folic acid by bacteria XIII. Drugs for Treating Influenza
- Sulfisoxazole: shigellosis, UTI, protozoan infections o Amantadine, rimantidine – restricted almost exclusively to
- Silver sulfadiazine: burns, eye infection influenza A viral infections; prevent fusion of virus with cell
- Trimethoprim: given in combination with sulfamethoxazole – UTI, membrane
PCP o Relenza and Tamiflu – slightly broader spectrum; blocks
neuraminidase in influenza A and B
IX. Newly Developed Classes of Antimicrobials
o Formulated from pre-existing drug classes XIV. Antiherpes Drugs
o Three new drug types o Many antiviral agents act as nucleotide analogs and are
- Fosfomycin trimethamine: phosphoric acid effective as incorporated into the growing viral DNA chain; replication ends
alternate treatment for UTI; inhibits cell wall synthesis - Acyclovir: Zovirax
- Synercid: effective against Staphylococcus and Enterococcus - Valacyclovir: Valtrex
that cause endocarditis and surgical infections; used when - Famiciclovir: Famvir
bacteria is resistant to other durgs; inhibits protein synthesis - Peniciclovir: Denavir
- Daptomycin: directed mainly against Gram-positive; disrupts o Oral and topical treatments for oral and genital herpes, chickenpox,
membrane functions and shingles

X. Agents to Treat Fungal Infections XV. Drugs for Treating HIV Infections and AIDS
o Fungal cells are eukaryotic o Retrovirus offers 2 targets for chemotherapy
o A drug that is toxic to fungal cells are also toxic to human cells - Interferes with viral DNA synthesis from viral RNA using
o Five antifungal drug groups: nucleotide reverse transcriptase inhibitors (nucleotide analogs)
a) Macrolide polyene - Interference with synthesis of DNA using nonnucleotide reverse
 Amphotericin B: mimic lipids, most versatile and effective, transcriptase inhibitors
topical and systemic treatments - Azidothymidine (AZT) – thymine analog
 Nystatin: topical treatment
b) Griseofulvin: stubborn cases of dermatophyte infections, XVI. Interferons (INF)
nephrotoxic o Human-based glycoprotein produced primarily by fibroblasts
c) Synthetic azoles: broad-specturum; ketoconazole, and leukocytes
clotrimazole, miconazole o Therapeutic benefits include:
- Reduces healing time and some complications of infections
 - Prevents or reduces symptoms of cold and papillomavirus
…………………….
- Other 2 benefits
Acquisition of Drug Resistance
o Adaptive response in which microorganisms begin to tolerate an
amount of drug that would ordinarily be inhibitory; due to
genetic versatility or variation; intrinsic and acquired
o Acquired resistance
- Spontaneous mutations in critical chromosomal genes
Mechanisms for Drug Resistance
o Drug inactivation by acquired enzymatic activity – penicillinases
o Decreased permeability to drug or increased elimination of drug
from cell- acquired mutation
o Change in drug receptors – mutation or acquisition
o Change in metabolic patterns – mutation of original enzyme
Strategies to Limit Drug Resistance by Microorganisms
Drug Usage
Physician here have the responsibility for making an
accurate diagnosis and prescribing the correct drug
therapy
Patients must comply with and carefully follow the
physician’s guidelines. It is important for the patient
to take the correct dosage, by the best route, for
the appropriate period. This diminishes the
selection for mutants for low drug levels, and
ensures elimination of pathogens.
Administration of two or more drugs together
increases the chance that at least one of the drugs
will be effective and that a resistant strain of either
drug will not be able to persist. The success of
combined therapy depends on carefully choosing
drugs that have different metabolic targets and do
not interfere with one another. It is unlikely that a
microbe would process resistance to multiple drugs
with distinct targets simultaneously
Drug research
Research focus on developing shorter-term, higher-
dose antimicrobials that are more effective, less
expensive, and have fewer side effects
Pharmaceutical companies continue to seek new
antimicrobial drugs with structures that are readily
inactivated by microbial enzymes or drugs with
modes of action that are not readily circumvented
Longterm
strategies Proposals to reduce the abuse of antibiotics range
have educational programs for health workers to
requiring justification for prescribing certain types
of antibiotics
Especially valuable antimicrobial activity may be
restricted in their use to only one or two types of
infection
The addition of antimicrobials to animal feeds must
be curtailed worldwide
Government programs that make effective available
to low-income populations should be increased
Vaccines should be used whenever possible to
provide alternative protection
Interactions between drugs and host
- Estimate that 5% of all persons taking antimicrobials will
experience a serious reaction to the drug – side effects
1. Direct damage tissue
2. Allergic reaction
3. Distract balance of normal flora, resulting to superinfection
Considerations in Selecting an Antimicrobial Drug
o Identify the microorganism causing the infection
o Test the microorganism’s susceptibility (sensitivity) to various
drugs in vitro when indicated
o The overall medical condition of the patient\

Identifying the Agent

o Identification of infectious agent should be attempted as soon
as possible
o Specimens should be taken before antimicrobials are initiated

Testing
o Essential for groups of bacteria commonly showing resistance
o Kirby-Bauer disk diffusion test
o E-test diffusion test
o Dilution test – minimum inhibitory concentration (MIC):
smallest concentration of drug that visibly inhibits growth
o Provide profile of drug sensitivity – antibiogram which guides
the choice of a suitable drug

The MIC and Therapeutic Index

o In vitro activity of a drug is not always correlated with in vivo
effect
- If therapy fails, a different drug combination or different
administration must be considered
o Best to choose a drug with highest level of selectivity but
lowest level toxicity- measured by therapeutic index
o High index is desirable
 3. Micro-culture
Medical Mycology 4. Histopathology
- Is the science that deals with the study of pathogenic fungi 5. Woods light
that produce diseases 6. Indirect methods of diagnosis
Mycoses
- Infections/ diseases caused by fungal pathogens Fungi (longer incubation period)

Mode of Transmission Fungal Skin Test

o Respiratory tract (air borne infection) o Mainly used for epidemiological study
o Gastrointestinal tract (food and water borne infection) o Observed by formation of induration and swelling due to
o Blood stream infection reaction between the injected fungal antigen and T cells
o Skin (direct contact) o Ex. histoplasmin, Candidin, Tricophytin tests
o
Steps of Infection Skin test – ineffective for diagnosis (active vs. latent)
1. Adherence
- By adhesion (ex. Candida spp.) but filamentous fungi have no Antifungal Therapy
adherence Topical antifungals
2. Invasion - Polyenes (ex. nystastin, fungizone)
- Mechanical trauma to skin or mucosal surface is an essential - Azoles (ex. miconazole, ketoconazole, econazole, clotrimazole)
step in fungal infection, because most of the infective element - Miscellaneous (ex. tolanftate, allylamine, iodine)
in fungi is the spore Systemic antifungals:
4. Phagocytic interaction - Polyenes (ex. amphotericin-B)
5. Incubation period (asymptomatic period – initial contact to - 5-flucytosine
appearance of first symptom) - Azoles (ex. Itraconazole)
- Terbinafine
Human Mycosis Terminology - Griseofulvin
A. Anatomical (according to the site of infection) - Iodine
o Dermatoccytosis - New antifungal
- Fungal infection of the skin - Echinocandins (ex. Caspofungin)
o Pulmonary mycosis - New triazole (ex. voriconazole)
- Fungal infection of the lungs
o Cardiovascular mycosis Mechanism of Action of Antifungals
- Fungal infection of the cardiovascular system o Polyenes
- Bind to ergosterol in the fungal cell membrane  altered
B. Mycological Terminology permeability  leakage of K+, Mg2+, sugar  cell death
o Candidiasis/ Candidiosis - Hepatoxic and nephrotic
- Fungal infection by Candida spp.
o Aspergillosis o Azole
- Fungal infection caused by Aspergillus spp. - Inhibits ergosterol biosynthesis via binding to cytochrome p-
o Cryptococcosis 450 dependent enzyme 14a demethylase-accumulation of
- Fungal infection caused by Cryptococcus spp. 14a sterol  depletes sterols
o Histoplasmosis - Hepatotoxic, spermatogenesis inhibitor so its usage restricted
- Fungal infection caused by Histoplasm spp.
o Azole
- Exact mechanism is unknown
- Inhibit nucleic acid synthesis
- Have antimitotic activity by inhibiting microtubules assembly

o 5-flucytosin
- Deaminated in cell to 5-fluorouracil, which replace uracil base
in RNA  disruption of protein synthesis

How to Determine Proper Antifungal Drug

- Susceptibility testing through broth dilution method and agar
diffusion method
Diagnosis of Fungal Infections
1. Direct microscopic preparation
2. Culture for isolation of fungi
 2. Trichophyton (ex. T. rubrum)
3. Microsporum (ex. M. canis)

Epidemiology
According to the source of infection
1. Anthroprophilic
- From human to human
- Epidermohyton flocosum
Dermatophytic Fungal Infections
Diseases caused by fungi include superficial infections of the skin by 2. Zoonotic
dermatophytes in the Microsporum, Tricophyton, or Epidermophyton - From animals to humans
genera. - Ex. Microsporum canis
3. Geophilic
- Spores found in soil
- Ex. Microsporum gypseum
Most prevalent agent of taenia catitis (cats and dogs)

Pathogenesis
Superficial Fungal Infection
1. Infective stage is arthrospore of fungus or keratinous material
A. Ring worm fungi
containing fungus element
Common clinical types
2. Needs direct or indirect contact (indirect by the use of the
1. Tinea corporis
same items of the patient)
- Dermatophyte infection of the glaborous skin (trunk, bank,
3. Requires slight trauma
dorsum of the hand)
4. Active infection restricted to the use of the basal keratinocytes
of the epidermis
Treatment
A. Systemic agents (oral)
Griseofolvin (drug of choice)
Itraconazole
Allylamine (Lamisil)
Ketoconazole (not used now)

B. Topical agents
White field
Clotrimazole (Canesten)
2. Tinea capitis Miconazole
Fungal infection of the skin of the scalp and hair
Three forms of hair involvement Prophylaxis against Tinea pedis:
a. Endothrix – dermatophyte infection of the hair that - Keep feet dry
invade the hair shaft and internalize into the hair cell - Rub between toes by dry piece of gauze & alcohol
b. Ectothrix – infection remained confined in the hair surface
c. Favictype
Candidal Infection
Clinical manifestation of diseases caused by Candida

a. Mucocutaneous infection
Oral thrush: in the mouth (cheesy covering layer), mouth
angles: (stomatitis), at the lips (cheilitis).
Vaginitis: white-milky discharge and itching

Pathogenesis
Causative fungus b. Cutaneous infection
Dermatophytes include 3 genera:
1. Epidermophyton (ex. E. flocusom)
 Skin: napkin area in baby, axilla, groin, submammary folds, Lipid preparation; liposomal amphotericin B
characterized by satellite lesions, redness, itching, and red
follicles Subcutaneous Mycosis
Nails: onychia and paronychia

A. Mycetoma (Madura foot = Maduromycosis)

- Chronic granulomatous infection, which produce tumor-like
Laboratory Diagnosis of Candidiasis:
infection
1. Direct
Etiology
a. Microscopic examination:
1. Bacterial:
Unstained preparation or stained preparation (KOH) lactophenol-cotton
Actinomycotic (Actinomadura, Nocardia, Streptomyces)
blue stains
The granules contain very fine delicate filaments
b. Culture
Usually the pyogenic abscess has one tract
o On SDA medium. The suspected growth is identified by:
Macroscopic appearance of the colonies after 24 – 48 hours are white,
2. Fungal(eumycotic)
smooth, creamy, and have characteristic yeast odor
Most saprophytic fungi can produce mycetoma

o Microculture. Rice agar tween plates for demonstration of

Mycetoma (Madura foot = x)
chlamydospores (in C. albicans)

Diagnosis:
 The suspected growth is identified by:
KOH preparation:
- Biochemical reactions
If bacterial: fine branching filament
- Germ tube formation
Eumycotic: coarse septated hyphae
- Chlamydospores formation on Potato Carrot Bile (PCB)
medium (in C. albicans)
Treatment:
For bacterial (Actinomycotic): antibacterial antibiotic
For eumycotic:
- Amputation of the attached part
- Antifungal agents can be used to prevent the amputation or to
minimize it (ex. itraconazole, Amphotericin B)

Systemic Mycosis
2. Indirect Histoplasma capsulatum
Skin test: no value in diagnosis Pathogenesis: infection of reticulo-endothelial system
Epidemiology:
Serological Test: - Restricted geographical distribution
Ag detection: important in immunocompromised patients - Source of infection: soil containing bird or bat droppings
- No case-to-case transmission
3. Histopathology:
Diagnostic element is yeast cell & pseudohyphae

4. New sets for diagnosis

Detection of B-glucan antigen
D-arabinol marker
Diagnosis:
 Histological examination of bone marrow
Treatment
 Culture
1. Superficial:
 Serology: skin test – histoplasmin test; of epidemiological value
Topical polyene, nystatin & amphotericin B
only
Topical imidazole as micnazole, clotrimazole
2. Deep systemic infection
Cryptococcus neoformans
Amphotericin B
Morphology:
Fluconazole, itraconazole
Capsulated yeast
Caspofungin
 Urease positive

 Infection occurs by inhalation of spores of Cryptoccoccus which

lead to pulmonary infection

Treatment:
Amphotericin B, followed by itraconazole

Mycotoxicosis
 Introduction to Parasitology
- Trace historical development of parasitology
- Know and understand the life cycle, nutrition, and mode of
reproduction of different types of parasites
- Define the terms used in parasitology
Terms to remember:
Parasitic (parasitikos, from parasitos (person) eating at another’s table;
17th century
o Endoparasites: a parasite that lives in the internal organs of the
host
o Ectoparasites: a parasite that lives on the external surface of
the host
Taxonomic Classification of Parasitic Organisms
 no universally accepted system
 comprises some 800, 000 identified species categorized into 33
phyla
 of importance for human health; eukaryotes
 2 sub-kingdom: protozoa (unicellular) and metazoan (multicellular)
 Genus starts with a capital letter and species is always written in
italics
Life Cycle of Parasites

Infestation: refers to parasitic diseases caused by animals such as

arthropods (mites, ticks, and lice) and worms, but excluding conditions
caused by protozoa, fungi, bacteria, and viruses

Host (definitive, intermediate)

- Definitive host: the one that harbors the adult parasite and
where the parasite reproduces sexually
- Intermediate host: the one which harbors the larval stage or
the asexual forms of the parasite
- Few parasites require two different intermediate hosts in
addition to definitive host
Vectors: Trophozoite Stage
- living organism that transmits an infectious agent from an - Stage in protozoan
infected animal to a human or another animal such as - Infected individual contaminates soil with feces containing
arthropods, such as mosquitoes, ticks, flies, fleas, and lice helminth eggs. Eggs develop in the soil
- Other individuals are infected by the eggs; ingested through
Epidemiology lived or from dirty hands, or by larvae penetrating the skin
 majority occur in tropical regions - An infected individual eggs or larvae develop into adult
 often entire communities may be infected with multiple, worms, which produce eggs
different organisms which remains untreated - Cycle continues
 effective prevention and control requires “mass intervention
strategies” and intense community education Important Groups of Animal Parasites
- general improved sanitation
- vector control (insecticide)
- mass screening and drug administration programs

Some major parasitic infections

- Classified according to morphology and locomotion

- Phylum Sarcomastigophora & Apicomplexa mostly infects humans
Phylum Sarcomastigophora  Cyclospora cyatenensis
- Parasites in small intestine; may cause diarrhea for several
weeks
 Balantidium coli
- Large, multicellular parasite that lives on colons of pigs,
humans, and rodents
- Can lead to colonic ulceration
 Enterocytozoan bienusi
- Microsporidian that parasitizes the small intestine
Phylum Apicomplexa - More common in immunocompromised patients
 Tissue parasites
- Alternating sexual and asexual generations
Detected in the Blood
 Plasmodium
- 4 species that infect man are P. falciparum, P. vivax, P. ovale, &
P. malariae
 Toxoplasma gondhi
- Transmitted via or infection from cat’s feces
- Infection can lead to ocular problems and can cause neonatal
toxoplasmosis
 Leishmania
- Transmitted via sandflies
 Trypanosoma
Phylum Microsporidia
- Hemoflagellates that can cause African sleeping sickness
- Minute intracellular parasites
- Transmitted by tsetse fly
- Rarely cause disease; can be observe in immunocompromised
- Tsaga’s disease caused by rhidovid bug in America
patients

Helminths

Phylum Ciliophora

Phylum Platyhelminthes
 Flatworms
 Hermaphrodites
 Intestinal (tapeworms)
- Taenia saginata: occurs worldwide; ingestion of contaminated
- Presence of cilia on cell of parasite
or uncooked beef; common infection but minimal symptoms
- Taenia solium: occurs worldwide; ingestion of contaminated
Intestinal Protozoa (transmitted via fecal/ oral way; causes diarrhea)
meat; cysticerosis that can lead to epilepsy that affects brain
 Giardia lambia:
and muscles
- worldwide distribution, lives in small intestine, causes
 Systemic
malabsorption of the nutrients of host’s tissues
- Echinococcus granulosus (dog tapeworm);
 Entamoeba histolytica:
- Echinococcus multicularis (rodent tapeworm)
- may invade the colon & may cause bloody diarrhea, amoebic
- Disease occurs if the larval stage is ingested that may live on
dysentery, amoebic liver abscess
the human host; and may cause space occupying lesions in
 Cryptosporidium parvum
several organs such as liver and brain
- Prevalent in immunocompromised patients
  120M people infected in >80 countries in Africa, the Pacific islands,
and South and Central America

Phylum Nematoda
 Roundworms Feces
 Intestinal
- Trichuris: whipworm, soil-transmitted helminths prevalent in
warm and humid conditions; can cause diarrhea, rectal
prolapse, and anemia
- Ancylostoma and Necator (hookworm): major cause of anemia
in tropics  Water, undigested and ingestible remnants of food
- Strongyloides: inhabits the small bowel & infection is more  Products of the digestive tract
severe in immunocompromised pesons  Epithelial cells from walls of the intestine
- Enterobius (pinworm or threadworm): prevalent in cold and  Bacteria
temperate climates and rare in tropics; commonly infects
children Biochemical/ Metabolic Contributions of Intestinal Microorganisms
- Ascaris (roundworm): found worldwide w/ area with poor Process Product
hygiens; can be transmitted in oral/ fecal way; adult worms Vitamin synthesis Thiamine, riboflavin, pyridoxine,
tend to live in small intestine & may cause eosinophilia B12, K
 Systemic Gas production CO2, CH4, H2
Odor production H2S, NH3, amines, indole, skatole,
- Onchocerca volvulus
butyric acid
- Wuchereria bancrofti
Organic acid production Acetic, propionic, butytric acids
- Brugia malayi Glycosidase reactions B-Glucoronidase, B-galactosidase,
- Toxocara B-glucosidase, a-glucosidase, a-
galactosidase
Class Nematoda Steroid metabolism (bile acids) Esterified, dehydroxylated,
 Flukes oxidized, or reduced steroids
 Intestinal
- Fasciolopsis buski  Enteroliths
- Fasciola hepatica - Hard solid masses in the intestines
- Clonorchis sinensis - Also known as mineral concretions
- Paragonimus westermani - Rare
- Schistosoma haematobium, S. mansoni, & S. japanicum  Three kinds of intestinal concretions
- Round, heavy stone like masses
- Irregular light porous
- From continuous use of medicine (benzatones)

 Intestinal sand – minute sandy particles (calcium and magnesium

phosphate, calcium carbonate, and organic matter)
Phylum Acanthocephala  Cholelithiasis – formation of gallstones
 Intestinal parasites

Other materials in feces may include:

 Curds – abundant in stools of infants (ether/ Sudan dye 3)
 Thorny-headed worms  Foreign materials – kernels of nuts and fruits, tea leaves
 Digestive tract is absent  Blood – gastric canceer, gastric dysentery

Phylum Arthropoda Blood

 White blood cells
- Inflammatory conditions of the intestines
- PMN + macrophages
 Red blood cell
- Rarely seen
Adaptations to Parasitism - Secretions, excretions or other products of the parasite
 Pre-adaptation/ Evolutionary Changes - Invasion and destruction of host’s tissue
- Nature of increased resistance to the enzymatic activities of
the host  Genetic constitution of the host (ex. sickle cell)
- Loss of enzymes or enzyme system  Diet or nutritional status of the host
 Morphologic adaptations - High P diet: unfavourable for intestinal protozoa
- Organs not necessary to parasitic existence are frequently lost - Low Carb Diet: unfavourable for certain tapeworms
 Biochemical changes
- Loss of certain metabolic pathwaays Epidemiology
- Streamlining  Majority occur in tropical regions
 Entrance to body  Often entire communities may be infected with multiple, different
- Special mechanisms absent in other microorganisms organisms which remain untreated
 Overcoming host’s immune response  Effective prevention and control requires “mass intervention strategies”
 Increased reproductive capacity and intense community educations:
- Involvement of an intermediate host - General improved sanitation
- Vector control
Host’s Immune Response - Mass screening and drug administration programs
An immune response must:
 Recognize – foreign (non-self) as distinct from self (afferent limb)
 Respond – production of specific antibodies and specific
lymphocytes
 Mediate the elimination (efferent limb)
 Immunogen – an agent which evolves an immune response
 Antigen – reacts with antibody

Immunglobulin
 Glycoproteins present in the serum and cells of the immune system
 IgE

- Least common serum Ig

- Involved in allergic reactions
- Plays a role in the parasitic helminths diseases

Effects of the Parasites on Host

 Number of worms present
 Nutritional status of the host

 Parasites stimulate resistance while still in the body

 Injury to the Host