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A number of studies have evaluated the efficacy of the new fluoroquinolones for therapy of bacterial enteric diseases and for prevention of gram-negative sepsis in granulocytopenic patients. The success of the quinolones in these settings is related to several special features of these agents, including their spectrum of activity and high fecal levels, which are in turn reflected in their effect on the gastrointestinal flora. Other factors that are important, particularly for invasive disease such as typhoid fever and shigellosis, include good intracellular and bowel wall penetration, and lymph node and systemic drug concentrations many times higher than the MICs of the causative organisms. This article reviews the factors that contribute to the changes in fecal flora, and the results of clinical studies in patients with diarrhea, granulocytopenic patients, and patients with selected other infections of, or related to, the gastrointestinal tract.

A purified human granulocyte colony-stimulating factor (hG-CSF) was studied for its protective effect on the induction of neutropenia and enhanced susceptibility to microbial infections in mice receiving cyclophosphamide (CPA). A severe reduction in peripheral blood neutrophils was induced 4 days after injection with 200 mg of CPA per kg although the level normalized rapidly thereafter. When mice were injected subcutaneously once a day with 2.5 micrograms of hG-CSF beginning on the day after CPA injection, the reduction was prevented markedly, even 4 days later. On the other hand, in mice receiving CPA 4 days prior to infection, a weakened resistance to intraperitoneal challenge with a strain of Pseudomonas aeruginosa was induced. This weakened resistance was dose-dependently restored to normal by four daily injections with hG-CSF. A daily dose of 1.0 microgram was required for complete restoration, although hG-CSF did not directly inhibit bacterial growth in vitro. In hG-CSF-treated mice, morphologically mature neutrophils migrated rapidly into the peritoneal cavities where bacteria were inoculated, followed by a rapid elimination of bacteria from the locality as compared with controls. In addition, the same treatment with hG-CSF was able to protect significantly against systemic infections caused by Serratia marcescens, Escherichia coli, Staphylococcus aureus, and Candida albicans. These data show the possibility that prophylactic therapy with hG-CSF may augment the resistance of immunocompromised patients to infections.