Potential of imipenem as single-agent empiric antibiotic therapy of febrile neutropenic patients with cancer

Abstract

Infection remains a major cause of morbidity and mortality for the patient with cancer who experiences episodes of severe granulocytopenia. The search continues for new antimicrobial agents with improved efficacy and lower incidence of toxicity. Imipenem is a new carbapenem antibiotic which possesses a broad antibacterial spectrum with excellent activity against Pseudomonas aeruginosa and the other commonly recovered enteric gram-negative bacilli that infect the granulocytopenic patient with cancer. The combination of imipenem plus an aminoglycoside has shown in vitro synergy against P. aeruginosa and Staphylococcus aureus whereas the combination of imipenem plus piperacillin or the extended spectrum cephalosporins have frequently shown antagonism when tested against P. aeruginosa and Serratia marcescens. The use of a P. aeruginosa-infected neutropenic rat model has provided an in vivo system to evaluate the activity of new antibiotics or antibiotic combinations. Monotherapy with imipenem is as effective in this model as any of the currently available synergistic antibiotic combinations. This degree of activity has not been found with other broad-spectrum antibiotics when used alone. Imipenem provides serum bactericidal activity well above a 1:8 dilution for the four most commonly isolated pathogens: P. aeruginosa, Escherichia coli, Klebsiella species, and S. aureus. In addition, imipenem's post-antibiotic effect against P. aeruginosa may be pertinent. Imipenem is a unique antibiotic, with properties that make it well suited for study as monotherapy for fever and suspected infection in granulocytopenic patients with cancer. A prospective randomized, double-blind study comparing imipenem with a control regimen of piperacillin plus amikacin as empiric antibiotic therapy of febrile granulocytopenic patients with cancer is currently underway at the University of Maryland Cancer Center.