Modifying Empirical Therapy Based on Cultures and Clinical Response

If a successful clinical response occurs and culture results are available, therapy should be de-escalated. De-escalation refers to decreasing antimicrobial regimen spectrum of activity to provide coverage against specific antimicrobial-sensitive pathogens recovered from culture. The purpose of de-escalation therapy is to minimize the likelihood of secondary infections owing to antimicrobial-resistant organisms. In cases where a specific organism is recovered that has a known preferred agent of choice, therapy might be changed to that specific agent. For example, antistaphylo-coccal penicillins are considered to be the agents of choice for methicillin-susceptible S. aureus owing to their bactericidal activity and narrow-spectrum activity and may be preferable to other antibiotic regimens. In other cases, empirical coverage might be discontinued if a specific suspected pathogen is excluded by culture or an alternative, noninfectious diagnosis is established. In addition, intravenous antimicrobials frequently are more expensive than oral therapy. Therefore, it is desirable to convert therapy to oral antimicrobials with a comparable antimicrobial spectrum or specific

pathogen sensitivity as soon as the patient improves clinically. Failure of Antimicrobial Therapy

While many infections respond readily to antimicrobials, some infections do not. A relatively common question when a patient's condition fails to improve relates to wheth er the antimicrobial therapy has failed? Changing antimicrobials generally is one of the easiest interventions relative to other options. However, it is important to remember that antimicrobial therapy comprises only a portion of the overall disease treatment, and there may be many factors that contribute to a lack of improvement. In general, inadequate diagnosis resulting in poor initial antimicrobial or other non-antibiotic drug selection, poor source control, or the development of a new infection with a resistant organism are relatively common causes of antimicrobial failure. An infection-related diagnosis may be difficult to establish and generally has two components: (a) differentiating infection from noninfection-related disease and (b) providing adequate empirical spectrum of activity if the cause is infectious. Failure of improvement in a patient's condition should warrant broadening the differential diagnosis to include noninfection-related causes, as well as considering other potential infectious sources and/or pathogenic organisms. Another common cause of failure is poor source control. A diagnostic search for unknown sources of infection and removal of indwelling devices in the infected environment or surgical drainage of abscesses should be undertaken if the patient's condition is not improving. Less common but still frequent causes of therapeutic failure include the development of secondary infections. In this case, the patient generally improves, but then develops a new infection caused by an antimicrobial resistant pathogen and relapses. The emergence of resistance to a targeted pathogen while on antimicrobial therapy can be associated with clinical failure but usually is limited to tuberculosis, pseudomonads, or other gramnegative enterics. Drug- and patient-specific factors such as appropriate dosing, patient compliance, and drug interactions can be associated with therapeutic failure and also should be considered. A common assumption is that the correct diagnosis was made, but the patient was not treated long enough with antimicrobials. There are certain types of infections (e.g., endocarditis or osteomyelitis) where the standard of care is to treat for prolonged periods of time (i.e., weeks or months). However, the optimal duration of therapy for many infectious diseases is somewhat subjective. Recently, studies of several infectious processes have suggested that shorter durations of therapy can result in similar clinical outcomes as longer durations of therapy, frequently with


fewer complications or secondary infections. The general trend has been to treat these disease processes with shortened courses of antibiotic therapy. In this period of extensive antimicrobial resistance, clinicians should keep abreast of changing recommendations emphasizing shorter durations of therapy.

FIGURE 69-4. Approach to selection of antimicrobial therapy.

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