Open AccessNeonatal Coinfection Model of Coagulase-Negative Staphylococcus ( Staphylococcus epidermidis ) and Candida albicans : Fluconazole Prophylaxis Enhances Survival and Growth
Author(s) -
Mohan Pammi Venkatesh,
Don Pham,
Mindy Fein,
Lingkun Kong,
Leonard E. Weisman
Publication year - 2007
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.01298-06
Subject(s) - coinfection , fluconazole , candida albicans , staphylococcus epidermidis , corpus albicans , medicine , mortality rate , microbiology and biotechnology , biology , staphylococcus aureus , immunology , antifungal , virus , genetics , bacteria
Coagulase-negative staphylococci (CoNS) andCandida are among the most common causes of single infections and coinfections in neonates after 72 h of age. In neonates, coinfection increases the rate of mortality threefold and results in significantly greater morbidity compared to those that result from single infections. In an effort to better understand this phenomenon, we developed the first neonatal animal model of coinfection (with CoNS andCandida ) and evaluated its effects on mortality and morbidity and the impact of antifungal prophylaxis with fluconazole. Neonatal Wistar rats were infected withCandida albicans and/orStaphylococcus epidermidis with doses of 2 × 108 and 2 × 106 CFU subcutaneously in different combinations and were monitored for mortality, weight gain, and bacteremia. The in vitro sensitivity ofC. albicans to fluconazole was evaluated and the MIC was determined. A subset of rats in these experiments received fluconazole at 10 mg/kg of body weight/dose intraperitoneally starting 24 h before infection for 4 days, and the serum trough levels of fluconazole were measured. Coinfection in the suckling rat significantly increased the rate of mortality compared to that after infection with a single species (P < 0.001) and resulted in deaths even at sublethal doses. Coinfection also impaired weight gain significantly in severely infected pups compared to that achieved after infection with a single species (P < 0.001). Fluconazole prophylaxis significantly reduced mortality by 30% in theCandida group and 36% in the coinfection group and improved weight gain in this neonatal model of coinfection (P < 0.001). We developed a neonatal model of coinfection withCandida and CoNS, observed significantly greater mortality and morbidity with coinfection, and found that fluconazole prophylaxis significantly reduced the rates of both mortality and morbidity. Further research on neonatal coinfection is urgently needed to improve clinical outcomes.