BACKGROUND: Candida infections after injury are associated with significant mortality. Death often results from gram negative sepsis. Because antifungal therapy lowers mortality seen with Candida infections, this study was undertaken to determine whether fluconazole (FCZ) augments host response against bacteria, specifically, the bactericidal activity of polymorphonuclear neutrophils (PMN). METHODS: PMN from 23 volunteers were incubated with phosphate-buffered saline or FCZ (20 micrograms/mL or 40 micrograms/mL). Bactericidal activity of these PMN, as well as FCZ alone, was determined using Escherichia coli and a colony forming unit protocol. RESULTS: PMN possess potent bactericidal activity while FCZ possesses minimal inherent bactericidal activity. PMN bactericidal activity is significantly augmented by preincubation with FCZ. This enhanced bactericidal state is greater than the combined individual bactericidal properties of either FCZ concentration and PMN. CONCLUSIONS: FCZ augments PMN bactericidal activity. This augmentation may help to explain the improved survival of critically injured patients receiving FCZ.
BACKGROUND:Candida infections after injury are associated with significant mortality. Death often results from gram negative sepsis. Because antifungal therapy lowers mortality seen with Candida infections, this study was undertaken to determine whether fluconazole (FCZ) augments host response against bacteria, specifically, the bactericidal activity of polymorphonuclear neutrophils (PMN). METHODS: PMN from 23 volunteers were incubated with phosphate-buffered saline or FCZ (20 micrograms/mL or 40 micrograms/mL). Bactericidal activity of these PMN, as well as FCZ alone, was determined using Escherichia coli and a colony forming unit protocol. RESULTS: PMN possess potent bactericidal activity while FCZ possesses minimal inherent bactericidal activity. PMN bactericidal activity is significantly augmented by preincubation with FCZ. This enhanced bactericidal state is greater than the combined individual bactericidal properties of either FCZ concentration and PMN. CONCLUSIONS:FCZ augments PMN bactericidal activity. This augmentation may help to explain the improved survival of critically injured patients receiving FCZ.
Authors: Jordan T Russell; J Lauren Ruoss; Diomel de la Cruz; Nan Li; Catalina Bazacliu; Laura Patton; Kelley Lobean McKinley; Timothy J Garrett; Richard A Polin; Eric W Triplett; Josef Neu Journal: Sci Rep Date: 2021-01-21 Impact factor: 4.379