Comparative review of combination therapy: two beta-lactams versus beta-lactam plus aminoglycoside

Febrile neutropenic patients are usually treated with a combination of a beta-lactam and an aminoglycoside. Since Pseudomonas aeruginosa is an important pathogen in these patients, the empiric use of possibly synergistic combinations against that organism has been traditionally recommended. The recent appearance of beta-lactams more active against P. aeruginosa and the well-known nephrotoxicity of aminoglycosides have led some to advocate the use of beta-lactam combinations for empiric treatment of fever in neutropenic cancer patients. This article reviews the available literature on the controlled use of combinations of beta-lactams in the treatment of febrile neutropenic patients as compared with that of combinations of beta-lactams and aminoglycosides. The review includes comparison of overall response, response in patients with septicemia or other infections, response associated with different pathogens, the effect of profound neutropenia, and an evaluation of the toxicities encountered. Overall, these results show that response rates with a combination of two beta-lactams are similar to those obtained with the combinations of a beta-lactam and an aminoglycoside for infections in patients with serious underlying disease and compromised mechanisms of defense. They also suggest that the steady emergence of resistance of pathogens to beta-lactams has often been overcome by the use of newer drugs in regard to infections caused by the Enterobacteriaceae but much less effectively in regard to P. aeruginosa. There are still important theoretic reasons for preferring an aminoglycoside-containing combination as empiric therapy in febrile neutropenic patients, and our overall conclusion is that it would be appropriate to conduct a large-scale trial comparing beta-lactam combinations with the traditional beta-lactam plus aminoglycoside regimens in that setting.