‫أ‪.‬د‪ .

‬أحمد عبد السالم‬

Once a specific cause of infection is identified based
upon specific microbial tests, the following questions
should be considered:
1. If a specific microbial pathogen is identified, can a
narrower spectrum agent be substituted for the initial
empirical therapy?
2. Is one agent or a combination of agents necessary?
3. What is the optimal dose, route of administration, and
duration of therapy?
4. What adjunctive measures can be undertaken to
eradicate the infection? For example is surgery feasible for
removal of devitalized tissue or foreign body or drainage of
an abscess- into which antimicrobial agents may be unable
to penetrate?
Choice of antimicrobial agent depends upon
I. Host factors:
History of allergy- renal and hepatic function-
resistance to infection (ie whether immuno-
compromised)- ability to tolerate drugs by mouth-
severity of illness- age- and if female whether
pregnant, breast-feeding or taking oral contraceptive.
Patients with AIDS have an unacceptably high risk of
allergic and toxic reactions to many antimicrobial
agents.
Patients with severe liver disease have an unacceptably
high risk of developing non-oliguric renal failure with
aminoglycosides.
Prior adverse effects and impaired elimination or
detoxification of the drug- this may be genetically pre-
determined or due to underlying renal or hepatic
disease.
The age of the patient at times may provide
important additional clues to the likely organism
or may affect the choice of the antimicrobial:
In meningitis, neonates are usually infected with
group B streptococcus or enteric organisms.
In children younger than 2 years, H.influenza is
common but S. pneumoniae and Neisseria
meningitidis also occur. The last two organisms
are the most common pathogens in adults.
The duration of therapy, dosage and route of
administration depend on site, type and severity
of infection and response.
The dose varies according to a number of factors
including age, weight, renal function and
severity of infection.
II. Pharmacologic factors:
. The kinetics of absorption, distribution and elimination.
. The ability of the drug to be delivered to the site of
infection.
. The potential toxicity of an agent.
. The pharmacokinetic or pharmcodynamic interaction with
other drug.
Pharmacokinetic differences among agents with similar
antimicrobial spectrum may be exploited to decrease the
frequency of dosing (e.g. ceftriaxone may be conveniently
given every 24 hours).

III. Lastly, increasing consideration is being given to cost

of antimicrobial therapy especially when multiple agents
with comparable efficacy are available for a specific
infection.
Interpretation of culture results
 Properly obtained and processed specimens for culture
frequently yield reliable information. The lack of a
confirmatory microbial diagnosis may be due to:
1. Sample error, e.g. obtaining culture after antimicrobial
agents have been administered.
2. Non-cultivable or slowly growing organisms, where
cultures are discarded before sufficient growth.
3. Requesting bacterial cultures when the infection is due
to other organisms.
4. Not recognizing the need for special media or isolation
techniques.
Susceptibility testing
Testing bacterial pathogens in vitro for their
susceptibility, ideally to a narrow-spectrum,
non-toxic antimicrobial drug.
Tests measure the concentration of drug
required to inhibit growth of the organism
(MIC) or kill the organism (MBC). The results
can be correlated to known drug concentration
in various body compartments.
Only MICs are routinely measured in most
infections, where in infections in which
bactericidal therapy is required for irradication
(e.g. meningitis, endocarditis, sepsis in the
granulocytopenic patient), MBC measurements
may be useful.
Clinical failure of antimicrobial therapy
. Errors in susceptibility testing are rare, but the original
results should be confirmed by repeated testing.
. Drug dosing and absorption should be scrutinized and
tested directly using serum measurements. Pill counting or
directly observed therapy.
. The clinical data should be reviewed to determine whether
the patient’s immune system is adequate, and if not, what
can be done to maximize it. For example, are adequate
number of granulocytes present and are HIV infection,
malnutrition, or underlying malignancy present?
. The presence of abscesses or foreign bodies should also
be considered.
. Culture and susceptibility testing should be repeated to
determine if superinfection has occurred with another
organism- or if the original organism becomes resistant.
Antimicrobial Pharmacodynamics

Pharmacodynamic factors include

1. pathogen susceptibility testing
2. Drug bactericidal versus bacteriostatic activiy
3. Drug synergism or antagonism
4. Post-antibiotic effect
Together with pharmacokinetics, pharmaco-
dynamic information permits the selection of
antimicrobial dosage regimens.
Bacterioststic versus bactericidal activity
. This classification has limitations: Some agents that are
considered bacteriostatic may be bactericidal against
selected microorganisms. For example chloramphenicol
is often bactericidal against pneumococci, meningococci,
and H.influenza. On the other hand, enterococci are
inhibited, but not killed, by vancomycin, penicillin or
ampicillin, used as single drugs.

. Static and cidal agents are equivalent for treatment of

most infections in immunocompetent host. Cidal agents
should be selected over static ones when local or systemic
host defenses are impaired. Cidal agents are required for
treatmnt of meningitis, endocarditis and other
endovascular infections and infections in neutropenic
cancer patients.
Bactericidal agents can be divided into two groups:

1. Agents that exhibit concentration-dependent killing

(e.g. aminoglycosides, quinolones) with which the rate
and extent of killing increase with increasing drug
concentration, i.e. increasing concentrations kill an
increasing proportion of bacteria and at a more rapid
rate.
Maximizing peak serum concentration of such drugs
results in increased efficacy and decreased selection of
resistant bacteria.
Concentration dependent killing is one of the
pharmacodynamic factors responsible for the efficacy of
once-daily dosing of aminoglycosides.
2. Agents that exhibit time-dependent killing (e.g. Beta
lactams and vancomycin) do not exhibit increasing
killing with increasing concentraion above MBC.
Antibacterial activity is directly related to time above
MBC and becomes independent of concentration once
the MBC has been exceeded. Bactericidal activity
continues so long as serum concentrations are greater
than MBC.

Drug concentration of time-dependent killing agents that

lack a post-antibiotic effect should be maintained above
the MBC for the entire dosage interval.
Antibiotic Pharmacodynamic Categories
• Time-Dependent (with minimal or no PAE)
Beta-lactams
Vancomycin
• Concentration-Dependent (with PAE)
Aminoglycosides
Daptomycin
Fluoroquinolones
Metronidazole
Azithromycin

• Time-Dependent, Concentration-Enhanced (with PAE)

Clarithromycin
Clindamycin
Erythromycin
Linezolid
Streptogramins (Quinupristin-dalfopristin)
Tetracyclines
Tigecycline
• The time-dependent antibiotics exert optimal bactericidal effect
when drug concentrations are maintained above the minimum
inhibitory concentration (MIC). Typically, concentrations are
maintained at 2 to 4 times the MIC throughout the dosing
interval. For these agents, higher concentrations do not result in
greater kill of organisms. Furthermore, they tend to have minimal
to no postantibiotic effect (PAE).
• Concentration-dependent antibiotics achieve increasing bacterial
kill with increasing levels of drug. In addition, these agents have
an associated concentration-dependent PAE in which bactericidal
action continues for a period of time after the antibiotic level falls
below the MIC. The peak concentration and area under the
concentration curve (AUC) determine efficacy of these
antibiotics. For this group of drugs, concentrations of at least 10
times the MIC are needed for optimal bactericidal effect.[3]
• The third PD category consists mainly of bacteriostatic antibiotics
that have prolonged PAEs. Some of these agents have been
classified elsewhere as time-dependent; however, because of the
presence of PAE, they also have concentration-dependent
features. Efficacy of this group is determined by the 24-hour
AUC to MIC ratio (AUC/MIC).
Postantibiotic effect “PAE”
It is the persistent suppression of bacterial growth after
limited exposure to an antimicrobial agent, ie.
Antimicrobial activity persists beyond the time that
measurable drug is present. It is expressed
mathematically as follows: PAE = T – C
T= time required for the viable count in the test (in vitro)
culture to increase tenfold above the count observed
immediately before drug removal.
C= time required for the count in untreated culture to
increase tenfold above the count observed immediately
after completion of the same procedure used in the test
culture.
The PAE reflects the time required for bacteria to return
to logarithmic growth. It may represent an extension of
the lag phase of bacterial growth.
Proposed mechanisms of PAE:
1. Recovery after reversible non-lethal damage to cell
structures.
2. Persistence of drug at a binding site or within periplasmic
space.
3. The need to synthesize new enzymes before growth.
4. In-vivo PAE is thought to be due to postantibiotic
leukocyte enhancement (PALE).

Most antimicrobials possess in vitro PAE (> 1.5 h) against

susceptible gram positive cocci. Antimicrobials with
significant PAE against susceptible gram negative bacilli
are limited to carbapenems, and agents that inhibit
protein or DNA synthesis.
Antimicrobials with in vitro PAE > 1.5 h

Against gram positive cocci:

Aminoglycosides, carbapenems, cephalosporins,
chloramphenicol, clindamycin, macrolides,
oxazolidinones, penicillins, quinolones,
rifampicin, sulphonamides, tetracyclines,
trimethoprim, vancomycin.

Against gram negative bacilli:

Aminoglycosides, carbapenems,
chloramphenicol, qinolones, rifampicin,
tetracyclines
In-vivo PAEs are usually much longer than in vitro PAEs.
This may be due to postantibiotic leucocyte enhancement
(PALE) and exposure of bacteria to subinhibitory antibiotic
concentrations.
PALE reflects the increased susceptibility of bacteria to the
phagocytic and bactericidal action of neutrophils.
Subinhibitory drug concentrations result in altered bacterial
morphology and decreased rate of growth.

The lowest drug concentration required to induce

morphologic changes is known as the minimal antibacterial
concentration.
Clinical relevance of PAE:
Aminoglycosides have significant PAE that can reach
several hours.
Aminoglycosides and quinolones possess concentration
dependent PAEs; thus high doses of aminoglycosides
given once daily result in enhanced bactericidal activity
and extended PAEs. These pharmacodynamic effects
allow amioglycoside serum concentrations that are below
the MICs of target organisms to remain effective for
extended periods of time.
Aminoglycoside toxicity is both time- and concentration-
dependent. Toxicity is unlikely to occur until a certain
threshold concentration is achieved, but once it is
achieved the time above this threshold becomes critical.
At clinically relevant doses the time above the threshold
is greater with multiple smaller doses than with a single
large dose.
Advantages of once-daily dosing:
1. A single daily dose of aminoglycosides is just as
effective and no more (often less) toxic than multiple
smaller doses.
2. Avoidance of adaptive resistance, a phenomenon in
which reduced bactericidal activity occurs following a
second antibiotic exposure. It is probably caused by a
reduction in energy-dependent aminoglycoside uptake
into bacteria.
3. Lower monitoring cost than conventional dosing. No
need to obtain serum concentrations unless the
intention is to administer aminoglycosides for more
than 4-5 days.
N.B. The use of once-daily dosing does not eliminate
careful monitoring and dose adjustment to minimize
toxicity (accoding to creatinine clearance).
Pharmacokinetic considerations
Route of administration
In critically ill patients oral or IM absorption is unreliable.
The IV route is preferred in such patients. IV therapy is
also preferred in bacterial meningitis or endocarditis.
Parenteral therapy should be selected in patients with
nausea, vomiting, gastrectomy or diseases that affect GI
absorption. This route is also preferred for drugs such as
vancomycin and antipsudomonas penicillin which are
poorly absorbed from GIT.
However, many antimicrobials have similar
pharmacokinetic properties when given orally or
parenterally (tetracycline, cotrimoxazole, quinolones,
chloramphenicol, metronidazole, clindamycin, rifampin,
fluconazole). In most cases, oral therapy with these drugs is
equally effective, less costly and with fewer complications.
Conditions that alter antimicrobial pharmacokinetics
Various diseases and physiologic states alter the
pharmacokinetics of antimicrobial drugs.
Impairment of renal or hepatic function may result in
decreased elimination. Dosage adjustment is necessary
in these situations to avoid toxicity.
Conversely patients with burns, cystic fibrosis, or
trauma may have increased dosage requirements for
selected agents.
The pharmacokinetics of antimicrobialsare also altered
in the eldely, in neonates and in pregnancy.

Dosage adjustment needed in hepatic impairment:

Chloramphenicol, clindamycin, erythromycin,
amprenavir, indinavir, rimantadine, metronidazole.
Dosage adjustment needed in renal impairment
Acyclovir, amantadine, aminoglycosides, aztreonam,
cephalosporins (except cefoperazone and ceftriaxone),
clathromycin, cycloserine, didanosine, ethambutol,
famciclovir, fluconazole, flucytosine, foscarnet,
ganciclovir, imipenem, lamivudine, meropenem,
penicillins (except antistaph, e.g. nafcillin and
dicloxacillin), quinolones, rimantadine, atavudine,
terbenafine, cotrimoxazole, valacyclovir, vancomycin,
zalcitabine, zidovudine.

Antimicrobials contraindicated in renal impairment:

Cidovovir, methenamine, nalidixic acid, nitrofurantoin,
sulfonamides (long acting), tetracyclines (except
doxycycline and possibly minocycline).
Drug concentrations in body fluids:
Most antimicrobial agents are well distributed to most
body tissues and fluids. Penetration into the CSF is one
important exception; clindamycin, aminoglycosides and
first and some second generation cephalosporins
penetrate poorly.
Many antibiotics do not penetrate uninflamed meninges
to an appreciable extent. In the presence of meningitis,
however the CSF concentration of many antibiotics
increase.
Two other sites of poor penetration are the prostate and
the obstructed biliary tree.
The pH of the site of infection may affect antibiotic
activity: Aminoglycosides are much more effective at
physiologic pH (7.4) than in acid environment (e.g
abscess). In pus or sputum, an acid pH may alter the
activity of these antibiotics.
CSF penetration of selected antimicrobials (percent of
serm concentration):
Antimicrobial uninflamed inflamed meninges
Ampicillin 2-3 2-100
Aztreonam 2 5
Cefotaxime 22.5 27-36
Ceftazidime 0.7 20-40
Ceftriaxone 0.8-1.6 16
Cefuroxime 20 17-88
Ciprofloxacin 6-27 26-37
Imipenem 3.1 11-41
Meropenem 0-7 1-52
Nafcillin 2-15 5-27
Penicillin-G 1-2 8-18
Sulphamethoxazole 40 12-47
Trimethoprim <41 12-69
Vancomycin 0 1-53
Pregnancy and Lactation:
Certain drugs may pose special problems (e.g. the
tetracycline which may cause hepatotoxicity to the
mother and dentition problems in the infant).
Placental transfer of antibiotics:
Whenever possible, pregnant women should avoid all
drugs because of the risk of fetal toxicity:
. Antibiotics considered safe in pregnancy include the
penicillins, cephalosporins, erythromycin base and
probably aztreonam
. Antibiotics to be used with caution include the
aminoglycosides, vancomycin, clindamycin, imipenem-
cilastatin, trimethoprim and nitrofurantoin.
. Antibiotics contraindicated in pregnancy include
chloramphenicol, erythromycin estolate, tetracycline,
fluoroquinolnes, cotrimozazole, metronidazole and
sulfonamides.
Placental transfer of antibiotics (infant-maternal serum
concentration):

50-100% :
Ampicillin, carbenicillin, chloramphenicol, methicillin,
nitrofurantoin, penicillin-G, sulphonamides,
tetracyclines, trimethoprim.

30-50% :
Amphotericin-B, cefamandole, cephalothin, clindamycin,
gentamycin, kanamycin, streptomycin.

0-30% :
Amikacin, cefazolin, ceftriaxone, dicloxacillin,
erythromycin, nafcillin, oxacillin, tobramycin
Antibiotics in breast milk:
Minimal data are available regarding adverse effects in
nursing neonates.

If possible nursing mothers should avoid all drugs.

The total daily dose a nursing baby receives is often

probably not toxicologically significant.

As in pregnancy, chloramphenicol, tetracycline,

sulphonamides and metronidazole should be avoided.
Until further data are available, it is suggested to avoid
the use of fluoroquinolones.
Maternal milk Antibiotic milk conc
Plasma conc (ug/ml)
50-100% Ampicillin NA
Chloramphenicol* 16-25
Clindamycin NA
Erythromycin 0.4-1.6
Isoniazid 6-12
Metronidazole* NA
Sulfapyridne* 30-130
Tetracycline* 0.5-2.6
Cotrimoxazole NA
<30% Cefotaxime NA
Cefazolin 1.5
Kanamycin* 18.4
Nalidixic scid* 4
Oxacillin 0.2
Penicillin-G 0.01-0.04
Streptomycin* 0.3-1.3
--------------------------------------------------------------------------------
*Potential toxicity to the mother NA= not available
Monitoring serum concentration of antimicrobial agent

For most antimicrobial agents, the relationship between dose

and therapeutic outcome is well established and serum
concentration monitoring is unnecessary for these drugs.

In clinical practice, serum concentration monitoring is

routinely performed on patients receiving aminoglycosides.

Despite the lack of supporting evidence for its utility or

need, serum vancomycin concentration monitoring is also
performed.

Flucytosine serum concentration monitoring has been

shown to reduce toxicity when doses are adjusted to
maintain peak concentration below 100ug/ml.
Antimicrobial combination
Although indications for combination therapy exists,
antimicrobial combinations are often overused in
clinical practice.
Current indications:
1. To provide broad spectrum empirical therapy in
seriously ill patients.
2. To treat polymicrobial infections such as
intrabdominal sepsis or pelvic abscess.
3. Limiting or preventing the emergence of resistant
strains as in tuberculosis.
4. Synergism: Mechanisms:
a) Blockade of sequential steps in a metabolic
sequence, eg. Cotrimoxazole.
b) Inhibition of enzymatic activation.
c) Enhancement of antimicrobial uptake, e.g. cell wall
active agents increase the uptake of aminoglycosides.
Commonly used antimicrobial combinations:
1. Penicillin and gentamycin are synergistic against S.
especially S.viridans and enterococci.
2. Antipseudomonas penicillins and aminoglycosides are
synergistic.
3. Cephalosporins and aminoglycosides are synergistic
against K. pneumoniae.
4. Sulfamethoxazole and trimethoprim are synergistic
against some gram positive and negative organisms.
5. Penicillins and cephalosporins are synergistic with beta-
lactamase inhibitorsas clavulanic acid and sulbactam.
6. Flucytosine and Amphotericin-B in cryptococcal
meningitis to reduce the dose of amphotericin-B.
7. Unique dug combination; imipenem-cilastatin. The
enzyme inhibitor cilastatin prevents metabolic
breakdown of imipenem by the kidney.
Disadvantages of multiple antibiotics:
1. An increased risk of drug sensitivities or toxicity.
2. Increased cost.
3. False sense of security: The use of multiple agents to
cover all possible organisms is often not possible,
practical or necessary and may be associated with
significant complications.
4. An increased risk of colonization with a resistant
organism may occur. If superinfection develops, this
organism is difficult to treat.
5. Possibility of antagonism:
The most striking example was reported in a study of
patients with pneumococcal meningitis who were
treated with a combination of penicillin and
chlortetracycline. The mortality rate was 79% versus
21% in patients who received penicillin monotherapy.
Mechanisms of antagonistic action:
1. Inhibition of cidal activity by static action:
a) Tetracycline and chloramphenicol can antagonize
the action of bactericidal of cell wall active agents
(beta-lactam antibiotics) whose action requires that
the bacteria be actively growing and dividing.
b) Tetracycline and chloramphenicaol can also
antagonize the bactericidal action of
aminoglycosides by inhibition of active
aminoglycoside uptake by susceptible organisms.
2. Induction of enzymatic activation:
Some gram negative bacilli possess inducible beta-
lactamases. Beta-lactam antibiotics as imipenem,
cefoxitin and ampicillin are potent inducers of beta-
lactamase production. If an inducing agent is
combined with hydrolyzable beta-lactam, such as
piperacillin, antagonism may occur.
 Selecting Appropriate Antibiotic Therapy

When faced with a severely ill patient in whom you

suspect an infection, it's important to try to:
• initiate antimicrobial therapy as quickly as possible
• consider risk factors for infection with multidrug-
resistant organisms
• one of the most important factors to consider is
previous antibiotic therapy
• give antibiotic therapy that is most likely to cover
multidrug-resistant organisms based on your local
antibiotic resistance patterns.
• take advantage of combination therapy in order to
maximize coverage
• stop antibiotic therapy once the patient has improved
and to reduce total antibiotic usage by de-escalating as
quickly as possible and giving as short a duration of
therapy as possible.
 The epidemiology of antibiotic resistance

• First: antibiotic resistance continues to increase

• Second: antibiotic resistance often leads to worse
patient outcomes.
• Third, based on the well-described epidemiology of
antibiotic resistance in hospitals, there are several
control measures: to review these
• first-hand, hygiene, particularly with an alcohol-based
hand rub
• second, isolation precautions for patients who are
known to be infected or colonized
• third is proper antimicrobial use
• the fourth is preventing device-related infections, as
vascular catheter infections or similar recommendations
to prevent the ventilator-associated pneumonia and
urinary catheter-associated infections.
• the fifth is the need to ensure adequate environmental
cleaning in the hospital.
 Factors That Affect Emergence of Resistant
Organisms
• Overuse and inappropriate use of antibiotics
• Breaks in infection control
• Bacterial factors
• Antibiotic factors
• Patient characteristics
Bacterial and antibiotic factors:
• Some bacteria become resistant more quickly than
others; Pseudomonas can become resistant very quickly
to a lot of different antibiotics, and yet group A Strep
continues to be kind of somewhat susceptible despite
70 years of penicillin G exposure.
Potential for Emergence of Resistance: Antibiotic
Factors: there might be some differences in antibiotics
in their ability to select resistant mutants, their ability to
induce resistance, and their ability to remain active
against resistant organisms.
 Factors That Affect Emergence of Resistant
Organisms
• Effects of Active Antimicrobials: probably one of the
most important aspects of antibiotic therapy (and
whether or not an antibiotic will select out resistance) is
whether or not it has activity against anaerobes and
whether or not you have high concentrations in the
bowel.

Pathogenesis
• what we think happens, is that you're colonized in the
bowel with a variety of different organisms, and when
exposed to an antibiotic those organisms are selected
out. And because of the intestinal colonization, the
environment becomes colonized with these organisms,
as are the skin of the patient and the hands of the
healthcare workers, thus, ultimately leading to infection
in some of the people who are colonized.
 Factors That Affect Emergence of Resistant
Organisms
Nosocomial Infections That Colonize the Intestinal
Tract: pathogens that we know colonize the
gastrointestinal tract -- the resistant organisms are
vancomycin-resistant enterococci, antibiotic-resistant
gram-negative bacilli, Candida, and Clostridium
difficile.
Antimicrobial Impact on Balance of Intestinal
Colonization
• antibiotics that have anaerobic activity and achieve
high concentrations in the bowel eliminate some of the
obligate anaerobes, allowing the facultative organisms
-- such as multidrug-resistant organisms -- to overtake
the bowel, and we think that that's one of the major
characteristics of antibiotics that select multidrug-
resistant organisms.
Most Common Outpatient Department (OPD)
Bacterial Infections and Treatment
Considerations
The most common outpatient bacterial
infections
• urinary tract infections, particularly cystitis
• skin and soft-tissue infections, particularly
cellulitis with abscess
• upper respiratory tract infections, particularly
pharyngitis
• lower respiratory tract infections, particularly
community-acquired pneumonia.
 Urinary Tract Infections (UTIs)

The common syndromes are cystitis and then tissue-

based infections, like pyelonephritis or prostatitis.
• Likely pathogens, E coli accounts for the vast majority
of urinary tract infections.
• For patients who've been treated with other antibiotics
or have recurrent infections or complicated infections
due to stones and so forth, gram-negative bacilli other
than E coli may become a problem.
• In pregnant women, coagulase-negative Staph,
particularly Staphylococcus saprophyticus, may be a
problem.
• And in some patients, particularly patients with
diabetes and elderly patients and little kids, group B
streptococci may be a pathogen.
 Urinary Tract Infections (UTIs)

Important historical information

• prior infections and antibiotic use
• any exposure to or symptoms of sexually transmitted diseases,
which can sometimes mimic urinary tract infections -- such as
herpes simplex, general infection can mimic a UTI.

UTI Antibiotic Treatment Commonly Recommended for Cystitis

• The commonly recommended antibiotic treatment regimens for
lower tract disease that is cystitis:
• Years ago, amoxicillin was kind of the knee-jerk drug, but most E
coli have become resistant to amoxicillin even in the community,
and so there are now really 4 groups of drugs that are
recommended:
• trimethoprim-sulfamethoxazole
• fluoroquinolones, specifically ciprofloxacin or levofloxacin for
urinary tract infections
• nitrofurantoin
• or amoxicillin-clavulanate.
 Urinary Tract Infections (UTIs)

Treatment durations for uncomplicated cystitis are usually:

• 3 days for trimethoprim-sulfamethoxazole or for fluoroquinolones
• 7 days for nitrofurantoin or amoxicillin-clavulanate
• and also for older women -- women over the age of 50 -- 7 days is
usually recommended rather than 3 days.

Now how do you decide among these various antibiotics?

• Usually trimethoprim-sulfamethoxazole is the generally
recommended antibiotic unless the patient has some allergies.
• But you have to move to the next drug on the list potentially based
on empiric evidence of antibiotic susceptibility patterns in your
community.
• So, as a kind of a general rule, when resistance has reached the
10% to 15% rate for a drug, you usually discard that drug and
move to the next drug.
• In addition for patients who have repeat or complicated infections,
cultures are obtained and susceptibilities from cultures can be
used.
 Skin & Soft-Tissue Infections

• The common syndromes for skin and

soft-tissue infections are cellulitis,
impetigo, erysipelas, furuncles,
carbuncles, and abscesses.
• Likely pathogens -- Staphylococcus
aureus and group A beta-hemolytic Strep
or Strep pyogenes -- are the
overwhelmingly most common
pathogens, and for diabetic patients,
particularly group B streptococci, may
cause skin and soft-tissue infections.
 Skin & Soft-Tissue Infections
Important historical items
• prior infections and prior treatment
• risk factors for community-associated methicillin-resistant Staph
aureus - particularly athletes, people who have recently been
incarcerated either in jail or in prison, day care centers, and
children. So the commonality among these groups is the risk of
person-to-person transmission.
• animal bite and any sort of animal exposures, swine, exposing
patients to things like erysipelas, and exposure to fish also
exposing patients to unusual pathogens potentially.
• comorbidities -- particularly diabetes mellitus.
• if there are abscesses that can be incised and drained: in patients
without comorbidities, and if the abscess and the skin infection are
less than 5 cm in diameter incision and drainage is often adequate.
In the past we never bothered to culture these infections; we
drained them and put the patient on an oral antibiotic, but now
because of community-acquired methicillin-resistant Staph aureus,
culturing wound infections is increasingly important.
 Skin & Soft-Tissue Infections
Antibiotic Treatment for Cellulitis With Abscess

The drugs that you would use if the patient has a bigger infection or a more
complicated infection or has a comorbidity:
• The first is dicloxacillin, which has great activity against methicillin-susceptible
Staph aureus, but it does have as a gap community-acquired MRSA.
• Many of the community-acquired methicillin-resistant Staph aureus are susceptible
to trimethoprim-sulfamethoxazole, but its gap is group A Strep, so if the patient has
lymphangitis and you're worried about group A Strep as part of the infection, you'd
probably shy away from trimethoprim-sulfamethoxazole.
• Clindamycin has superb activity against methicillin-susceptible and methicillin-
resistant Staph aureus as well as group A streptococci. There's a test called the D
test, which labs now do to assess whether there's inducible antimicrobial resistance
among methicillin-resistant Staph aureus that would affect clindamycin.
• The fourth group are doxycycline or minocycline; there's less experience with
MRSA than with some of the other drugs, and you wouldn't use these for children
because of the potential for staining teeth.
• The fifth drug is linezolid (Zyvox), which is a newer drug that's more costly and has
bone marrow suppression as one of its side effects so that prolonged courses that are
more than 2 weeks, you have to be very careful to measure and monitor platelets
and other bone marrow elements.
• And then finally, some people use combination therapy -- fluoroquinolones and
rifampin; neither of these agents would you use alone because of the emergence of
resistance, particularly among Staph aureus, but they can be used together.
 Respiratory Tract Infections
Common Syndromes, & Likely Pathogens:
The most likely pathogen for colds, that is, common colds,
are viral pathogens, and so common colds should not be
treated with antibiotics.
• Pharyngitis is either usually a viral infection or group A
streptococci
• Otitis media is usually viral or pneumococci,
Streptococcus pneumoniae
• Sinusitis is often viral or Streptococcus pneumoniae.
This is obviously a simplification, but these are the
major pathogens.
• The lower respiratory tract -- acute bronchitis -- the vast
majority of these are viral, and randomized controlled
trials show no benefit of antibiotics for acute bronchitis,
so antibiotics should not be used for acute bronchitis.
• Acute exacerbations of chronic bronchitis are more
likely to be bacterial and community-acquired
pneumonia bacterial as well as viral.
 Respiratory Tract Infections

Important Historical Information

• Prior illnesses and antibiotic exposures.
• We want to know about STD [sexually transmitted disease]
exposures and HIV risk factors. And I think a lot of people feel
that patients with community-acquired pneumonia should be
routinely screened for HIV because of the association of those
illnesses.
• Sick contacts is important, as people have been exposed to
anybody with pertussis or tuberculosis, basically people who've
had prolonged coughs.
• Pet or animal exposure, psittacine birds, psittacosis. And then
there's Q fever associated with a variety of animal exposures.
• Occupations are useful to ask about, particularly, people who are
exposed to dust or other environmental contaminants who may
have hypersensitivity pneumonitis.
• And, finally, [there are] TB [tuberculosis] risk factors, such as
history of a positive skin test for TB or country of origin.
 Respiratory Tract Infections

Pharyngitis - Treatment Approaches

• There are basically 2 outpatient treatment approaches; they both
are based on a scoring system, that is, you score 1 point for each of
the following: fever; a tonsillar exudate; tender anterior cervical
adenopathy; absence of cough. Each one of those gets 1 point.
• If you score 0-1 the 2 treatment approaches would be not to test
and not to treat, so 0-1 you generally -- unless the patient comes
back sicker -- you assume it's a viral infection and you don't test
the patient or treat.
• With a score of 2, it's recommended that the rapid group A Strep
antigen test be performed, and if positive the patient be treated.
• For patients who have scores 3 or 4, there are 2 options depending
on the group that's recommending it. One is to not test and go
ahead and treat empirically because of high risk of group A Strep
infection, and the second option is to test with a rapid group A
Strep antigen test and only treat those people who are positive.
The treatment is penicillin V; there's been some debate about
whether oral cephalosporins have higher cure rates and lower rates
of relapse: That's somewhat debated. And some people prefer
amoxicillin to penicillin V for absorption reasons.
 Respiratory Tract Infections
Community-Acquired Pneumonia: OPD Treatment Approaches
• There are 2 major questions that you have to consider when you're
deciding on treatment; the first is do you hospitalize the patient, and the
second is what empiric antibiotics do you give?
• The decision to hospitalize is based on potentially a number of
prognostic models, one is called CURB-65: basically you look for:
• Confusion
• uremia defined as a BUN [blood urea nitrogen] > 20 mg/dL
• respiratory rate that's increased defined as > 30 respirations per minute
• a low blood pressure that's defined as either a systolic lower than 90 or a
diastolic lower than 60
• age > 65
• there's the pneumonic CURB-65:
• if you have 0-1 of those factors, it's safe to be treated generally as an
outpatient
• if you have 2 of those factors, hospitalization is often recommended
• and if you have 3 or more of those factors, intensive care in the hospital is
often recommended. So those are generalizations for decisions to
hospitalize.
 Respiratory Tract Infections
The empiric antibiotic regimens ‘’3 considerations’”:
• The first is whether the patient was previously healthy
with no prior antibiotic use, at least not in the last 3
months; for those patients doxycycline or macrolide
seem to be reasonable.
• The second consideration is: Does the patient have
comorbidities -- any chronic heart, lung, liver, kidney
disease; diabetes; alcoholism; a malignancy; lack of a
spleen; or any other immunosuppression or recent
antibiotic use? If any of those comorbidities are
present, then the recommendation is either a respiratory
fluoroquinolone (levofloxacin, moxifloxacin,
gemifloxacin) or amoxicillin-clavulanate.
• And then the third consideration is areas that have
increased macrolide-resistant Streptococcus
pneumoniae, avoid the macrolides; so those areas you
would not use erythromycin, clindamycin, or
azithromycin.