Evolution of antibiotic therapy for infection in neutropenic patients: studies at M. D. Anderson Hospital

Abstract

The prompt administration of antibiotics as therapy for fever in neutropenic patients has become an accepted principle. Combinations of an aminoglycoside plus a broad-spectrum beta-lactam agent have been used most extensively, producing response rates of 65%-70% at M. D. Anderson Cancer Center, Houston, Texas. We found that in neutropenic patients aminoglycosides alone were not effective, even against infections caused by susceptible gram-negative bacilli. Among patients with neutrophil counts of less than 100/mm3, only approximately 25% responded. The first studies of combinations of a penicillin plus a cephalosporin were initiated at this institution. Carbenicillin plus cephalothin was as effective as carbenicillin plus kanamycin (57% vs. 56%), and moxalactam plus ticarcillin was as effective as moxalactam plus tobramycin (63% vs. 53%). Monotherapy with broad-spectrum beta-lactam agents has also been effective, even for the treatment of gram-negative bacillary infections, with response rates of 73%-100%. Recent prospective, randomized trials indicate that agents such as ceftazidime and aztreonam are as effective alone as in combination with an aminoglycoside or another beta-lactam antibiotic. Because of the changing spectrum of infecting organisms, of new approaches to therapy for malignant diseases that alter patients' susceptibility to infection, and of the availability of new antimicrobial agents, antibiotic therapy for fever in neutropenic patients will continue to be a subject for clinical investigation.