Candida is the second leading cause of sepsis related death in the neonatal intensive care unit (NICU). Using the C. parapsilosis paradigm, the endogenous and exogenous routes of infection were simulated in order to enhance prevention among neonates at highest risk. A deterministic model was constructed with transmission parameters calculated from the basic reproductive number ( ), derived from the mean serial interval from two published outbreaks. Uncertainty and sensitivity analyses were performed via Latin hypercube sampling. Prevention measure effects were ascertained by incorporating percent coverage and efficacies into the existing model. The colonized and infected neonatal prevalence peaked at 17.4% and 39.4%, respectively, and reduction was achieved by compartmental replacement with susceptibles. Containment of greater than 60% of the cohort had minimal effect on the effective reproductive number ( ) unless hand hygiene compliance dropped below 40% at a fixed ratio of nurses to neonates. Antifungal prophylaxis in combination with hand hygiene and cohorting extinguished an outbreak 14 days sooner than baseline. The critical proportion ( ) requiring prophylaxis in order to stop an outbreak increases, as rises, and the prophylaxis efficacies decrease. Internal and external sources of Candida lead to invasive disease in neonates differentially. Optimal prevention is dependent upon understanding the dynamics of this disease process under diverse circumstances. 1. Introduction Candida species are commensals of the human gastrointestinal tract and skin but can become pathogenic, being the fourth leading cause of bloodstream infections in the United States [1]. Candida parapsilosis is an “emerging fungal pathogen,” with infection incidences increasing globally [2]. According to data from the ARTEMIS DISK Surveillance Program (1997–2005), C. parapsilosis was the fourth most common yeast isolated with an estimated prevalence of 4%–7% and the second most common yeast associated with bloodstream infections [3, 4]. C. parapsilosis candidemia prevalence is 4%–34%, depending upon the time period, location, and host factors [5]. In particular, neonates—defined as infants whose age is within 30 days following birth—are especially vulnerable to this infection. Though attributable mortality is 10% over 10 years in neonates despite therapy—lower than that due to other Candida species, overall, the genus is the second leading cause of death from sepsis in the neonatal intensive care unit (NICU) [6, 7]. Colonization precedes infection. The gastrointestinal tracts of
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