55: Early Onset Neonatal Candidiasis in Preterm Infants: Perinatal Factors, Disease Severity and Outcome

Severe and fatal cases of invasive candidiasis (IC) have been reported in extremely low birth weight (ELBW) infants who develop this disease perinatally. Prospective observational studies of the early onset disease (EOD) variant of IC in ELBW infants are lacking. To describe the clinical pattern of EOD in ELBW infants To determine perinatal factors associated with EOD To determine mortality rate and long term neurodevelopmental outcome in EOD compared to LOD ELBW infants and factors associated with these outcomes. A secondary analysis of the multicentre Paediatric Investigators Collaborative Network on Infections in Canada (PICNIC) prospective case control study of neonatal candidiasis was conducted. ELBW infants with EOD, (onset within first seven days of life) and LOD (onset after seven days of life) and ELBW controls without IC were identified. Factors associated with occurrence and outcome of EOD in ELBW infants were identified using logistic regression. Of 69 cases of neonatal IC in the PICNIC cohort, EOD occurred in 14/45 (31%) of ELBW infants compared to 2/24 (8%) infants ≥1000 g (P=0.039). Among the ELBW cohort, there were 14 cases of EOD, 31 LOD cases and 84 controls. Birth weight <750 g, gestational age <25 weeks, histological presence of chorioamnionitis, and vaginal delivery were all strongly associated with EOD (P<0.01). C. albicans was more likely to cause infection in EOD than in LOD infants, [11 (79%) versus 12 (39%), resp.; (P=0.023)]. Disseminated disease was more common in EOD (93%) than in LOD (42%); P=0.003) as was pulmonary involvement (86% versus 24%; P=0.0002) and cardiovascular disease (75% versus 30%; P=0.044). EOD was associated with a higher mortality rate than LOD or controls (71% versus 32% versus 15%, resp.; P=0.007). Twelve of 14 infants received antifungal therapy, in eight (67%) of whom it was begun within 48 hours of the day of disease onset. Neurodevelopmental impairment (NDI) and mortality combined occurred at a similar rate in EOD and LOD infants (86% versus 72%) but at higher rates than in controls (32%; P=0.007). The early onset variant of IC in ELBW infants has a very poor prognosis; even worse than IC presenting after one week of life. The role of perinatal transmission in the pathogenesis of EOD is supported by its association with histological chorioamnionitis, vaginal delivery and pulmonary infection. Dissemination and cardiovascular involvement is common in early onset perinatally-acquired IC, and affected infants often die. Early empiric treatment should be considered for ELBW infants at high risk, i.e. those with pneumonia, delivered vaginally, whose mothers had an intrauterine foreign body or who have histological evidence of chorioamnionitis.