Challenging issues in neonatal candidiasis

Abstract

In an era of quality improvement and 'getting to zero (infections and/or related mortality),' neonatal candidiasis is ripe for evidence-based initiatives. Knowledge of each institution's invasive Candida infection (ICI) incidence and infection-related mortality is critical to evaluate disease burden and effective interventions. Evidenced-based interventions include: antifungal prophylaxis, starting with appropriate dosing, and prompt removal of central venous catheters (CVC). There is A-I evidence supporting antifungal prophylaxis with fluconazole, and it should be considered in every neonatal intensive care unit (NICU). The literature supports targeting infants51000 g and/or 27 weeks, because this group has high infection-related mortality and neurodevelopmental impairment in 57% of survivors. Antifungal prophylaxis has been shown to nearly eliminate infection-related mortality. Interventions start with prenatal initiatives, with women being treated for vaginal candidiasis, especially with preterm labor or complications. Targeting modifiable risk factors, including restriction policies for use of third-and fourth-generation cephalosporins, carbapenems, H2-antagonists, proton pump inhibitors, and postnatal steroids; guidelines for CVC care and removal; and feeding practices, with promotion of early feedings and breast milk, may also reduce risk. A few studies have emerged on empiric antifungal therapy with sepsis evaluations for preterm infants 51500 g and other high-risk patients that have shown favorable effects of eliminating mortality, but these have not been compared to appropriate antifungal therapy and central line removal. Further study of empiric therapy, prospective treatment studies with higher targeted dosing of amphotericin B preparations, fluconazole, and new antifungals with prompt CVC removal may contribute to a 100% survival rate for those infants41000 g and 28 weeks not receiving antifungal prophylaxis. Evaluation of ICI incidence and mortality by gestational age and birth week should be followed in each NICU, to evaluate infection control and prevention.

Recent Developments and Current Issues in the Epidemiology, Diagnosis, and Management of Bacterial and Fungal Neonatal Sepsis

“…25 A single center was able to decrease invasive candidiasis mortality with fluconazole prophylaxis administered to highrisk neonates. 92 Results from over 14 trials at multiple institutions with 3,100 neonates suggest that fluconazole prophylaxis decreases colonization of the urine, gastrointestinal tract, and integument, without promoting the development of resistance and without adverse effects.…”

“…23,24 Approximately 2.5% of all bloodstream infections in VLBW neonates are estimated to be due to fungal etiologies. 25 The risk for fungal sepsis is increased by colonization acquired vertically from maternal sources as well as horizontally from the NICU environment. A positive correlation exists between multiple sites of colonization and risk for invasive candidiasis.…”

“…95 Of note, enterally administered fluconazole does not appear to provide protection against CVC-associated candidiasis. 25 Both the Infectious Diseases Society of America and the American Academy of Pediatrics support the administration of prophylactic fluconazole to preterm infants. 73,88 Based on an annual U.S. preterm birth cohort of approximately 30,000 VLBW, it has been estimated that fluconazole prophylaxis could prevent about 2,000 to 3,000 cases of invasive candidiasis, about 200 to 300 deaths, and the adverse neurodevelopmental outcomes of invasive candidiasis in approximately 400 to 500 infants per year.…”

“…Fluconazole pharmacokinetics demonstrates that doses between 6 and 12 mg/kg per day achieve serum concentrations adequate for treatment of neonatal candidiasis. 25,78,79 The echinocandins, semisynthetic lipopeptides produced via chemical modification of natural products of fungi, have excellent efficacy against most species of Candida and have a comparatively benign safety profile. 80,81 They have excellent soft tissue and bone penetration, with application in hepatosplenic candidiasis and osteomyelitis.…”

“…92 Results from over 14 trials at multiple institutions with 3,100 neonates suggest that fluconazole prophylaxis decreases colonization of the urine, gastrointestinal tract, and integument, without promoting the development of resistance and without adverse effects. 25,[91][92][93][94][95][96][97] Targeted therapy of 3 mg/kg of intravenous fluconazole initiated before 48 hours of life to neonates < 1,000 g and continued for the duration of intravenous access is a regimen that has been adopted by some NICUs with high baseline rates of candidiasis. 95 Of note, enterally administered fluconazole does not appear to provide protection against CVC-associated candidiasis.…”