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Antimicrobial Agents and Chemotherapy, April 2007, p. 1240-1245, Vol. 51, No. 4
0066-4804/07/$08.00+0     doi:10.1128/AAC.01298-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Neonatal Coinfection Model of Coagulase-Negative Staphylococcus (Staphylococcus epidermidis) and Candida albicans: Fluconazole Prophylaxis Enhances Survival and Growth{triangledown}

Mohan Pammi Venkatesh,1* Don Pham,1,{dagger} Mindy Fein,1,{ddagger} Lingkun Kong,1 and Leonard E. Weisman2

Baylor College of Medicine and Texas Children's Hospital, MC: WT 6-104, 6621, Fannin, Houston, Texas 77030,1 Perinatal Health Center, Texas Children's Hospital, Houston, Texas 770302

Received 18 October 2006/ Returned for modification 6 January 2007/ Accepted 17 January 2007

Coagulase-negative staphylococci (CoNS) and Candida 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 and Candida) and evaluated its effects on mortality and morbidity and the impact of antifungal prophylaxis with fluconazole. Neonatal Wistar rats were infected with Candida albicans and/or Staphylococcus epidermidis with doses of 2 x 108 and 2 x 106 CFU subcutaneously in different combinations and were monitored for mortality, weight gain, and bacteremia. The in vitro sensitivity of C. 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 the Candida 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 with Candida 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.

* Corresponding author. Mailing address: Baylor College of Medicine and Texas Children's Hospital, MC: WT 6-104, 6621, Fannin, Houston, TX 77030. Phone: (832) 826-1380. Fax: (832) 825-3204. E-mail: mohanv{at}bcm.edu

{triangledown} Published ahead of print on 29 January 2007.

{dagger} Present address: Creighton University, School of Medicine, 2500 California Plaza, Omaha, NE 68178.

{ddagger} Present address: University of Texas Health Science Center at San Antonio, Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78284-7701.

Antimicrobial Agents and Chemotherapy, April 2007, p. 1240-1245, Vol. 51, No. 4
0066-4804/07/$08.00+0     doi:10.1128/AAC.01298-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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