Chapter 18. Principles of Antimicrobial Therapy

1. Antibiotic therapy should be based on the infection site, host defenses, antibiotic toxicity, antibiotic pharmacokinetics and pharmacodynamics, and the regional resistance organisms and antibiotic susceptibility patterns.

2. Methicillin-resistant Staphylococcus aureus, which is generally spread by contact, has become a major cause of serious hospital-associated infections and ensuing morbidity despite the development of newer effective antibiotics.

3. The term catheter-associated infection is used for surveillance and is a diagnosis of exclusion based on the presence of a catheter within 48 hours of a bloodstream infection and no other identifiable source.

4. Ventilator-associated pneumonia typically arises as an extension of upper airway bacteria and is related to duration of intubation. Several "bundles" are recommended for prevention, although their efficacy is controversial.

5. Most guidelines recommend avoiding central venous catheters when possible, removal as soon as it is no longer needed, and placement using full sterile procedures with barrier precautions.

6. Intra-abdominal infections are often associated with mixed flora and generally require anaerobic as well as aerobic antibiotic treatment.

7. Recommended surgical prophylaxis for infective endocarditis is evolving. In contrast with past guidelines, it is currently recommended for only a few conditions.

In general, antimicrobial drugs may be used in 3 different modes: therapeutic, prophylactic, and preemptive. In the therapeutic mode, they are prescribed to treat established clinical infection. This requires prompt diagnosis of clinical infection and a clear understanding of the pharmacologic principles governing treatment of such infections. In the prophylactic mode, antimicrobials are prescribed to all members of a given population before an event (eg, surgery) to prevent infection. Successful prophylactic programs require that the antimicrobial therapy be sufficiently nontoxic, inexpensive, and efficacious to justify the intervention. Finally, in the preemptive mode, antimicrobial therapy is administered to a subgroup of individuals based on either laboratory markers or clinical epidemiologic characteristics that place them at significant risk of a serious clinical infection (eg, patients undergoing organ transplants).1 Effective preemptive therapy requires the careful delineation of the factors that justify antimicrobial intervention at a point when clinical disease is not yet manifest.2-4 Clearly, there is some overlap between prophylactic and preemptive modes.

The purpose of this chapter is to present the pharmacologic and clinical principles that underlie all 3 forms of antimicrobial use, distinguishing between what is known, what is suggested by consensus but lacks definitive evidence, and what needs further study. The focus is primarily on antibiotics rather than antifungal and antiviral drugs. Specific information on newer antibiotics such as cyclic lipopeptides, glycylcyclines, ketolides, oxazolidinones, streptogramins, and newer fluoroquinolones can be found in review articles5-8 and newer textbooks such as Mandell et al.9 Aside from the specifics of a particular antibiotic, it is important to recognize the different characteristics among the various antibiotic classes. For example, some antibiotic classes such as tetracyclines are bacteriostatic in contrast to bacteriocidal antibiotics which directly kill bacteria, bacteriostatic antibiotics prevent bacteria from growing but generally require leukocytes to kill them. Another important difference among antibiotic classes is their mechanisms ...