Neonatal candidemia and end-organ damage: A critical appraisal of the literature using meta-analytic techniques

Objective. Neonatal candidemia is an increasing cause of infant morbidity and mortality. We evaluated the current medical literature in an effort to critique the literature and to document the reported prevalences of end-organ damage after neonatal candidemia. Methods. We analyzed all peer-reviewed articles of neonatal candidemia published in the English language; inclusion criteria included a cohort limited to all neonatal intensive care unit admissions or all episodes of candidemia in neonates. Articles that also incorporated older patients, did not define a numerator and a denominator for at least 1 form of end-organ damage, included patients from other reports, or did not include all episodes of candidemia in the source population were excluded from the analysis. Results. Thirty-four articles reported episodes of candidemia and mortality; 21 articles reported prevalence for at least 1 form of end-organ damage. Only 4 (19%) of 21 articles reported prevalence for >4 forms of end-organ damage from the following list: endophthalmitis, meningitis, brain parenchyma invasion, endocarditis, renal abscesses, positive cultures from other normally sterile body fluids, or hepatosplenic abscesses. The median reported prevalence of endophthalmitis was 3% (interquartile range [IQR]: 0%-17%), of meningitis was 15% (IQR: 3%-23%), of brain abscess or ventriculitis was 4% (IQR: 3%-21%), of endocarditis was 5% (IQR: 0%-13%), of positive renal ultrasound was 5% (IQR: 0%-14%), and of positive urine culture was 61% (IQR: 40%-76%). The medical literature concerning end-organ evaluation after episodes of neonatal candidemia is heterogeneous and consists largely of single-center retrospective studies. Year that the data were collected and prevalence of neonates infected with Candida albicans were associated with observed heterogeneity. Conclusions. Given the heterogeneity of the medical literature, precise estimates of the frequencies of end-organ damage are not possible and a prospective multi-center trial is warranted, but the data from the published literature suggest that the prevalence of neonates with end-organ damage not only is greater than 0 but also is high enough that until such a prospective trial is completed, end-organ studies should be considered before the conclusion of antifungal therapy.