Chemoprophylaxis of gram-negative infections in neutropenic patients

Gram-negative infections in neutropenic patients originate frequently from the gut flora. Attempts to decrease the incidence of these infections have utilized several regimens for gastrointestinal decontamination, of which some have proven to be clinically useful. Orally administered nonabsorbable antibiotics (aminoglycosides, polymyxins) can decrease the incidence of gram-negative sepsis during neutropenia, but, with the possible exception of netilmicin, tolerance to these agents is generally poor, and compliance is low. Trimethoprim-sulfamethoxazole has been used widely for the prophylaxis of infections in neutropenic patients. Clinical results with this agent have been conflicting, as its efficacy is clearly related to epidemiological patterns of resistance of the pathogens in the population under study. More recently, the quinolones, which are well tolerated by patients and are presently active on most strains of Enterobacteriaceae, have been associated with a virtual eradication of gram-negative infections in neutropenic patients. These results have been paralleled by an increase in the frequency of gram-positive infections, which, fortunately, cause an incidence of mortality that is much lower than that seen in gram-negative sepsis. The fact that the quinolones are absorbed systemically might help to explain their efficacy in chemoprophylaxis during neutropenia. This paper discusses the chemoprophylaxis of gram-negative infection during neutropenia in the light of theoretical concepts such as 'colonization resistance', 'selective decontamination', and 'bacterial translocation'.