Management of Febrile Episodes in Neutropenic Patients: Defining the Role of Meropenem
Harriet M. Lamb
Karen L. Goa
Neutropenic patients with cancer are at risk of serious infection, particularly if neutropenia is severe or prolonged. Because patients with neutropenia have a diminished inflammatory response, fever is sometimes the first, and only, sign of infection. Prompt empirical antibacterial therapy is imperative in neutropenic patients with fever, as minor localised infections can progress rapidly to bacteraemia. An antipseudomonal beta-lactam agent plus an aminoglycoside, 2 beta-lactam agents or monotherapy with an appropriate cephalosporin or carbapenem are all currently recommended as first-line empirical treatment in this patient group by the Infectious Diseases Society of America. Addition of a glycopeptide should be considered only in patients at high risk of Gram-positive infection. The empirical regimen may be modified as appropriate after 72 to 96 hours. It may be possible to discharge selected patients at low risk of complications on oral or parenteral outpatient therapy. Meropenem, a parenteral carbapenem, has excellent activity against all Gram-negative and Gram-positive anaerobic pathogens, and slightly more variable activity against Gram-positive aerobic organisms. In 8 clinical trials, meropenem 3 g/day consistently demonstrated similar efficacy to other regimens (imipenem/ cilastatin, ceftazidime with or without amikacin) commonly used in the empirical treatment of neutropenic patients with febrile episodes. Response rates with meropenem at treatment end ranged from 37 to 59% compared with 36 to 62% for comparator regimens (modification of the empirical regimen was considered a treatment failure). Meropenem is generally well tolerated; diarrhoea, nausea and vomiting, rash and pruritus are the most commonly reported adverse events. Seizures occur infrequently (0.24% overall incidence) and have not, to date, been reported in trials of patients with febrile neutropenia. Meropenem can be used effectively as monotherapy in the first-line empirical treatment of febrile episodes in neutropenic patients. It offers better activity against many Gram-negative pathogens and stability against a broader spectrum of beta-lactamases than the third generation and extended spectrum cephalosporins, with possibly fewer gastrointestinal and CNS tolerability problems than imipenem/cilastatin. Therefore, meropenem is likely to be an important first-line agent particularly at institutions where resistant Gram-negative pathogens are problematic. It may also be useful as a second-line agent in infections unresponsive to other regimens. Although meropenem is administered 3 times daily, it can be given as a bolus without the need for monitoring of plasma concentrations and so may have a potential place in the outpatient management of febrile neutropenia.
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