Evaluation and management of neonatal candidiasis.
Review morbidity and mortality associated with invasive candidiasis; provide recommendations for prevention, diagnosis, empirical therapy, and treatment of neonatal candidiasis.
Invasive candidiasis (IC) is common in premature infants, occurring in up to 6% of infants <1000 g birth weight. IC in premature infants is associated with significant mortality and morbidity. Death occurs in up to 34% of affected infants and neurodevelopmental impairment occurs in up to 63% of survivors. IC is also associated with increased hospital stay, hospital costs, severe retinopathy of prematurity, and bronchopulmonary dysplasia. Although the overall incidence of invasive candidiasis has recently decreased, prevention and appropriate management of this disease leads to reduced morbidity and mortality.
MAJOR RECOMMENDATIONS: PREVENTION
Prevention of IC is paramount. Methods to prevent IC are centered around minimization of risk factors that promote colonization of mucosal surfaces, disrupt anatomic barriers, or weaken the host immune response. Preventive efforts should focus on the judicious use of broad-spectrum antibiotics, early removal of central venous catheters, early initiation of enteral feeds, and infection control practices to prevent horizontal transmission. In addition, fluconazole prophylaxis is safe and effective, and should be used at moderate- to high-incidence centers and in high-risk infants <1000 g birth weight.
Several randomized controlled trials have demonstrated safety and efficacy of fluconazole prophylaxis for the prevention of IC in premature infants. However, in the largest trial of infants <750 g birth weight, there was no difference in death or IC for those who received 6 mg/kg of fluconazole twice weekly for 42 days compared to those who received placebo (odds ratio [OR]: 0.73; 95% CI 0.43–1.23). Centers included in this trial had low incidence of IC compared to previous trials conducted in high-incidence centers. Based on available evidence, we recommend fluconazole prophylaxis (6 mg/kg twice weekly for 42 days) in infants who are <1000 g birth weight and admitted to moderate- or high-incidence centers (>5–10% incidence of IC).
IMPLEMENTATION OF GUIDELINE
DESCRIPTION OF IMPLEMENTATION STRATEGY
Recommend written guidelines for prevention of IC and implementation of prophylactic therapy; written guidelines for prevention should include identification of triggers for central line removal and protocols for attainment of oral feeds. Guidance on antibiotic stewardship should also be included.
Adherence to guidelines; incidence of IC; need for replacement of central lines after early removal.
MAJOR RECOMMENDATIONS: DIAGNOSIS AND EMPIRICAL THERAPY
Isolation of Candida from sterile body fluid is the current gold standard for diagnosis of IC. Once IC is identified, providers should initiate evaluation for disseminated infection. Empirical therapy may be helpful but has not been evaluated in well-powered, randomized trials of infants.
Large-volume blood cultures may be positive in as few as 29% of cases of IC in adults. The smaller volume (0.5–1 mL) of cultures obtained from infants is likely to have even lower sensitivity. Further, diagnosis of IC by culture is time intensive, often requiring days for growth of the organism, speciation, and sensitivity testing. New techniques, including detection of Candida DNA by polymerase chain reaction, matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS), and mannan, D-arabinitol/L-arabinitol, and 1,3-β-D-glucan antigen assays, are promising methods that may improve sensitivity and decrease time to diagnosis and speciation. However, these methods have not been systematically validated in infants.
IC can affect any organ system, most commonly ...