Transcript CLINICAL PHARMACOLOGY OF ANTIBACTERIAL AGENTS

CLINICAL PHARMACOLOGY OF
ANTIBACTERIAL AGENTS
(part II)
Clinical Use of Antimicrobial Agents
• The development of antimicrobial drugs represents one of the
most important advances in therapeutics, both in the control or
cure of serious infections and in the prevention and treatment of
infectious complications of other therapeutic modalities such as
cancer chemotherapy and surgery. However, evidence is
overwhelming that antimicrobial agents are vastly overprescribed
in outpatient settings, and the availability of antimicrobial agents
without prescription in many developing countries has already
severely limited therapeutic options in the treatment of lifethreatening infections. Therefore, the clinician should first
determine whether antimicrobial therapy is warranted for a given
patient.
Antimicrobial Therapy
Choice of Antimicrobial Agent
Choice of Antimicrobial Agent
• Selection from among several drugs depends on host
factors that include the following: (1) concomitant
disease states (eg, AIDS, neutropenia due to the use of
cytotoxic chemotherapy; severe chronic liver or kidney
disease) or the use of immunosuppressive medications;
(2) prior adverse drug effects; (3) impaired elimination
or detoxification of the drug (may be genetically
predetermined but more frequently is associated with
impaired renal or hepatic function due to underlying
disease); (4) age of the patient; (5) pregnancy status;
and (6) epidemiologic exposure (eg, exposure to a sick
family member or pet, recent hospitalization, recent
travel, occupational exposure, or new sexual partner).
Guiding Antimicrobial Therapy of Established
Infections
•
•
•
•
•
Amoxicillin
Moxifloxacin
Cotrim
Cefuroxime
Azithromycin
Post-Antibiotic Effect
Bactericidal & Bacteriostatic
Activity
Antimicrobial Agents that Require Dosage Adjustment or
Are Contraindicated in Patients with Renal or Hepatic
Impairment
• Dosage Adjustment
Needed in Renal
Impairment
• Contraindicated in
Renal Impairment
Dosage Adjustment Needed in
Hepatic Impairment
• Amprenavir,
atazanavir,
chloramphenicol,
clindamycin,
erythromycin,
fosamprenavir,
indinavir,
metronidazole,
rimantadine,
tigecycline
Drug Concentrations in Body Fluids
• Most antimicrobial agents are well
distributed to most body tissues and fluids.
Penetration into the cerebrospinal fluid is an
exception. Most do not penetrate
uninflamed meninges to an appreciable
extent. In the presence of meningitis,
however, the cerebrospinal fluid
concentrations of many antimicrobials
increase
Drug Concentrations in Body Fluids
• Most antimicrobial agents are
well distributed to most body
tissues and fluids. Penetration
into the cerebrospinal fluid is an
exception. Most do not
penetrate uninflamed meninges
to an appreciable extent. In the
presence of meningitis,
however, the cerebrospinal fluid
concentrations of many
antimicrobials increase
Monitoring Serum Concentrations of
Antimicrobial Agents
Antimicrobial Drug Combinations
Rationale for Combination
Antimicrobial Therapy (cont’d)
Rationale for Combination
Antimicrobial Therapy (cont’d)
Synergism & Antagonism
Synergistic Action
Antagonistic Action
ANTIMICROBIAL
PROPHYLAXIS
ANTIMICROBIAL PROPHYLAXIS
General principles of antimicrobial surgical
prophylaxis
• The antibiotic should be active against common surgical
wound pathogens; unnecessarily broad coverage should be
avoided.
• The antibiotic should have proved efficacy in clinical trials.
General principles of antimicrobial surgical
prophylaxis
• The antibiotic must
achieve concentrations
greater than the MIC of
suspected pathogens, and
these concentrations must
be present at the time of
incision.
• The shortest possible
course—ideally a single
dose—of the most
effective and least toxic
antibiotic should be used.