Chapter 39

### PRINCIPLES OF ANTIMICROBIAL THERAPY

Antimicrobial therapy of infections is arguably the most important scientific development of 20th-century medicine. It contributes significantly to the quality of life of many people and reduces the morbidity and mortality due to infectious disease. The remarkable success of antimicrobial therapy has been achieved with comparatively little toxicity and expense. The relative ease of administration and the widespread availability of these drugs have led many to adopt a philosophy of broad-spectrum empiric antimicrobial therapy for many common infections.

Unfortunately this era of cheap, safe, and reliable therapy is being limited by the increasing frequency of antimicrobial resistance in previously susceptible microorganisms. The problem of antimicrobial resistance is not new—resistance was recognized for sulfonamides and penicillins shortly after their introduction. What is new is the worldwide dissemination of resistant clones of microorganisms, such as Streptococcus pneumoniae and Staphylococcus aureus, which are more virulent and commonly cause serious infections, not only among hospitalized patients, but also among outpatients.

Until recently the recognition of new resistant clones was balanced by the promise of newer and more potent antimicrobial agents. Today, because fewer new agents are under development, clinicians are beginning to encounter limitations in their ability to treat some serious bacterial infections. Many factors contribute to the selection of resistant clones. Our success in treating chronic diseases and immune-compromising conditions, which has resulted in additional years of life for patients, has increased opportunities for selection of resistant strains in inpatient units and chronic care facilities. Overuse of antimicrobial agents also contributes to the selection of resistant strains. Examples include antimicrobial treatment of mildly ill patients with self-limited conditions, such as viral infections, and administration of broad-spectrum antimicrobials to patients whose conditions could be treated with narrow-spectrum agents. Similarly, failure to document infection with cultures obtained prior to starting therapy limits our willingness to stop or narrow the spectrum of antimicrobials. Insufficient research has been conducted to determine the optimal duration of therapy for many infections, with the result that we probably often treat longer than is necessary. Prophylactic strategies, as used for prevention of recurrent otitis media or urinary tract infection (UTI), create a selection pressure for antibiotic resistance.

The decision-making process for choosing an appropriate antimicrobial agent is summarized in Table 39–1. Accurate clinical diagnosis is based on the history, physical examination, and initial laboratory tests. The clinical diagnosis then leads to a consideration of the organisms most commonly associated with the clinical condition, the usual pattern of antimicrobial susceptibility of these organisms, and past experience with successful treatment regimens.

Table 39–1.Steps in decision making for use of antimicrobial agents.

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