EMPIRIC MONOTHERAPY IN NEUTROPENIA - A REALISTIC GOAL

Infection remains the major cause of morbidity and mortality for cance r patients who become granulocytopenic as a result of chemotherapy. Tr eatment is instituted at the first sign of infection and before the id entification of the causative pathogen (empiric treatment). For many y ears, standard empiric treatment has been combination therapy with bet a-lactams and aminoglycosides. The advent of new broad spectrum antibi otics, such as ceftazidime, has introduced the possibility of empiric monotherapy. However, ceftazidime has only modest activity against inf ections due to Gram-positive organisms, which presently account for at least 50% of infections in neutropenic patients, and resistance to ce ftazidime in Gram-negative organisms has been documented. Meropenem is a new carbapenem with a broad antibacterial spectrum with greater in vitro activity than ceftazidime against staphylococci, streptococci an d many Gram-negative bacteria. A comparative study of intravenous mero penem (1 g 8-hourly) and ceftazidime (2 g 8-hourly) in the empiric tre atment of febrile neutropenic patients with haematological malignancie s has been conducted. In an open, randomised trial of the treatment of 338 febrile episodes, all patients survived to 72 hours on both treat ments, and meropenem was found to be at least as clinically effective as ceftazidime in eradicating both Gram-positive and Gram-negative inf ections. Early modification of treatment (48-72 hours) was required fo r approximately 40% of patients but occurred less frequently in patien ts treated with meropenem than with ceftazidime. Tolerability of both treatments was good. Meropenem should be compared with standard combin ation therapy in a large randomised trial before adopting it as empiri c monotherapy for febrile neutropenic patients.