FLUCONAZOLE INCREASES BACTERICIDAL ACTIVITY OF NEUTROPHILS

Background: Candida infections after injury are associated with signif icant mortality. Death often results from gram negative sepsis. Becaus e antifungal therapy lowers mortality seen with Candida infections, th is study was undertaken to determine whether fluconazole (FCZ) augment s host response against bacteria, specifically, the bactericidal activ ity of polymorphonuclear neutrophils (PMN). Methods: PMN from 23 volun teers were incubated with phosphate-buffered saline of FCZ (20 mu g/mL or 40 mu g/mL). Bactericidal activity of these PMN, as well as FCZ al one was determined using Escherichia coli and a colony forming unit pr otocol. Results: PMN possess potent bactericidal activity while FCZ po ssesses minimal inherent bactericidal activity. PMN bactericidal activ ity is significantly augmented by preincubation with FCZ. This enhance d bactericidal state is greater than the combined individual bacterici dal properties of either FCZ concentration and PMN. Conclusion: FCZ au gments PMN bactericidal activity. This augmentation may help to explai n the improved survival of critically injured patients receiving FCZ.