Antifungal Susceptibility and Clinical Outcome in Neonatal Candidiasis

Background: Invasive candidiasis is an important cause of sepsis in extremely low birth weight infants (ELBW, < 1000 g), is often fatal, and frequently results in neurodevelopmental impairment (NDI) among survivors. We sought to assess the antifungal minimum inhibitory concentration (MIC) distribution for Candida in ELBW infants and evaluate the association between antifungal resistance and death or NDI. Methods: This was a secondary analysis of a National Institute of Child Health and Human Development Neonatal Research Network study. MIC values were determined for fluconazole, amphotericin B and micafungin. NDI was assessed at 18–22 months adjusted age using the Bayley Scales of Infant Development. An infant was defined as having a resistant Candida isolate if ≥ 1 positive cultures from normally sterile sites (blood, cerebrospinal fluid, or urine) were resistant to ≥ 1 antifungal agent. In addition to resistance status, we categorized fungal isolates according to MIC values (low and high). The association between death/ NDI and MIC level was determined using logistic regression, controlling for gestational age and Bayley Scales of Infant Development (II or III). Results: Among 137 ELBW infants with IC, MICs were determined for 308 isolates from 110 (80%) infants. Three Candida isolates from 3 infants were resistant to fluconazole. None were resistant to amphotericin B or micafungin. No significant difference in death, NDI, or death/NDI between groups with low and high MICs was observed. Conclusions: Antifungal resistance was rare among infecting Candida isolates, and MIC level was not associated with increased risk of death or NDI in this cohort of ELBW infants.