A review of chemoprophylaxis and therapy of bacterial infections in neutropenic patients

Abstract

Gram-negative infections in neutropenic patients frequently originate from the intestinal flora. Attempts to decrease the incidence of these infections include several regimens for gastrointestinal decontamination, some of which have proved to be clinically useful. The orally administered nonabsorbable antibiotics such as aminoglycosides and polymyxins can decrease the incidence of Gram-negative sepsis during neutropenia. However, tolerance of these agents, with the possible exception of netilmicin, is very poor, and patient compliance is low. Cotrimoxazole (trimethoprim/sulfamethoxazole) has been widely used for prophylaxis of infections in neutropenic patients with variable clinical results. Its efficacy is clearly related to epidemiologic patterns of resistance to cotrimoxazole from potential pathogens in the population under study. More recently, the quinolones, which are well tolerated and inhibit most Enterobacteriaceae, have been associated with the virtual eradication of Gram-negative infections in neutropenic patients. These results are paralleled by an increase in the frequency of Gram-positive infections, for which the mortality rate is fortunately much lower than that seen in Gram-negative sepsis. In addition, quinolone antibiotics are absorbed systematically and this might help to explain their efficacy as chemoprophylaxis during neutropenia. Synergy, as demonstrated in vitro, and adequate bactericidal activity in the serum both correlate with improved clinical effectiveness in severe infections that occur during granulocytopenia. Whereas empiric antimicrobial therapy in febrile granulocytopenic cancer patients has become accepted medical practice, controversy still remains as to the optimal therapeutic regimen that should be used.