History Of Fever And Neutropenia Therapy

In the 1960s and '70s, it was recognized that the most immediate threat came from Gram-negative infections, particularly E. coli, Klebsiella, and Pseudomonas, which could cause rapid overwhelming sepsis.3 Thus, empiric therapy regimens have historically been directed at preventing these Gram-negative infections. The combination of an antipseudomonal beta-lactam and an aminoglycoside has been widely used to achieve synergy against such organisms as Pseudomonas. Concerns about potential toxicity, and the development of third-generation cephalosporins and car-bapenems, have led to a preference for monotherapy at some centers.

As discussed below, there has been a shift in recent years, from predominantly Gram-negative toward Grampositive organisms. Whether or not to include an agent such as vancomycin in the initial regimen has been vigorously debated. The emergence of resistance factors such as extended-spectrum beta-lactamases has also caused alteration in regimens at some centers. In general, growing antimicrobial resistance should prompt frequent reconsideration of empiric antibiotic regimens.4

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