CLINICAL PHARMACOLOGY OF ANTIBACTERIAL AGENTS

1. CLINICAL PHARMACOLOGY OF ANTIBACTERIALAGENTS (part II)

2. 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 hasalready severely limited therapeutic options in the treatment of life-threatening infections. Therefore, the clinician should first determine whether antimicrobial therapy is warranted for a given patient.

3. Antimicrobial Therapy

4. Choice of Antimicrobial Agent

5. 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).

7. Guiding Antimicrobial Therapy of Established Infections

8. Amoxicillin • Moxifloxacin • Cotrim • Cefuroxime • Azithromycin

9. Post-Antibiotic Effect

10. Bactericidal & Bacteriostatic Activity

15. Dosage Adjustment Needed in Renal Impairment Contraindicated in Renal Impairment Antimicrobial Agents that Require Dosage Adjustment or Are Contraindicated in Patients with Renal or Hepatic Impairment

16. Amprenavir, atazanavir, chloramphenicol, clindamycin, erythromycin, fosamprenavir, indinavir, metronidazole, rimantadine, tigecycline Dosage Adjustment Needed in Hepatic Impairment

17. 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

18. 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

19. Monitoring Serum Concentrations of Antimicrobial Agents

20. Antimicrobial Drug Combinations

21. Rationale for Combination Antimicrobial Therapy (cont’d)

22. Rationale for Combination Antimicrobial Therapy (cont’d)

23. Synergism & Antagonism

24. Synergistic Action

25. Antagonistic Action

26. ANTIMICROBIAL PROPHYLAXIS

27. ANTIMICROBIAL PROPHYLAXIS

28. 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.

29. 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. General principles of antimicrobial surgical prophylaxis