Clinical strategies for serious infection: a North American perspective

In the United States, as in Europe, clinical strategies for serious infection are being increasingly driven by growing numbers of cephalosporin-resistant and multiresistant gram-negative bacilli. In a survey of nearly 400 hospital intensive care units in North America, resistance rates of Klebsiella to third-generation cephalosporins increased (from 3.6 to 14.4%) between 1990 and 1993. Resistance rates in Enterobacter are even higher, approaching 40%. Much of this resistance, which is due mainly to production of type-1 and extended spectrum beta-lactamases, appears to have arisen through overuse of third-generation cephalosporins and from poor hand-washing practices. In some American cities, a major reservoir of resistant organisms are nursing homes, where there is evidence of overuse of oral antibiotics. Currently, the most reliable agents available for the treatment of resistant gram-negative pathogens are the carbapenems, imipenem/cilastatin and meropenem, and the aminoglycoside, amikacin. A recent clinical study of meropenem monotherapy in patients with nosocomial pneumonia showed statistically significantly better clinical and microbiologic outcome compared with a standard regimen of ceftazidime plus tobramycin. The enhanced in vitro activity of meropenem against a number of key organisms may have been responsible for the superior results. Although the newer cephalosporins, cefepime and cefpirome, show greater stability to chromosomal type-1 beta-lactamases than ceftazidime, they have variable activity against extended spectrum beta-lactamase producers and can be rendered ineffective by permeability changes which occur in certain organisms. Carbapenems, on the other hand, possess good activity against virtually all of the pathogens which produce the clinically important beta-lactamases, and represent a reliable option for treatment.