OBJECTIVE. Despite the promising preliminary results observed in extremely low birth weight (ELBW) populations, the use of fluconazole to prevent fungal colonization and infection in preterm neonates in the NICU is still an open question and not yet recommended as a standard of care. We have reviewed our 6-year series to assess the effectiveness and safety of this form of prophylaxis.
METHODS. This retrospective study consisted of 465 neonates who weighed <1500 g at birth and were admitted to our NICU in the period 1998–2003. Those who were born between 1998 and 2000 and did not receive fluconazole prophylaxis (group A, n = 240) were compared with those who were born between 2001 and 2003 and treated with fluconazole until the 30th day of life (45th for neonates <1000 g at birth; group B, n = 225). Weekly surveillance cultures were obtained from all patients. Incidence of fungal colonization, incidence of systemic fungal infection (SFI), rate of progression from colonization to infection, and mortality rates attributable to fungi were calculated for both groups and separately for neonates who were <1000 g (ELBW) and were 1001 to 1500 g (NE-VLBW) at birth.
RESULTS. Overall fungal colonization was significantly lower in group B (24.0%) than in group A (43.8%; relative risk [RR]: 0.406; 95% confidence interval [CI]: 0.273–0.605). The same was true of neonates with colonization in multiple sites (2.6% vs 5.8%) and of those with colonization from high-risk sites (5.8% vs 19.2%). SFI incidence was significantly lower in group B (10 of 225 cases; 4.4%) than in group A (40 of 240 cases; 16.7%; RR: 0.233; 95% CI: 0.113–0.447). Reduction of both colonization and SFI in group B was greater in the ELBW neonates and also significant in the NE-VLBW neonates. Rate of progression from colonization to infection was significantly lower in group B (0.17 vs 0.38; RR: 0.369; 95% CI: 0.159–0.815). Crude mortality rate attributable to Candida species was 1.7% (4 of 240) in group A vs 0% (0 of 225) in group B. Overall mortality rate (any cause before hospital discharge) was similar in the two groups (11.2% vs 10.6%), but in colonized infants (n = 159), it was significantly lower in group B (3.7% vs 18.1%; RR: 0.174; 95% CI: 0.039–0.778). The incidence of natively fluconazole-resistant fungal species did not increase over the years, and patterns of sensitivity to fluconazole remained the same. No adverse reaction related to fluconazole occurred.
CONCLUSIONS. Prophylactic fluconazole significantly reduces the incidence of colonization and systemic infection by Candida species in both ELBW and NE-VLBW neonates and decreases the rates of progression from initial colonization to massive colonization and to systemic infection. All VLBW neonates may benefit from fluconazole prophylaxis.
The study by Manzoni et al (1) of 464 babies of <1500g birthweight is of interest. However, it raises the question of differences between neonatal centres, and their significance. I have no interest in Fluconazole fungal prophylaxis, as we have no need for it. In the same issue of your journal, Benjamin et al (2) describe a 7% incidence of Candidiasis in a large cohort of <1000g birthweight babies. In the time period addressed by Manzoni et al (1) (1998 – 2003), our neonatal unit in Brisbane, Australia admitted 1127 babies of <1500g birthweight, with 433 of those being of <1000g birthweight. We grew Candida from the blood stream of only two of those (0.18%), of 520g and 585g birthweight respectively, one in 1998 and the other in 1999. Eleven babies of all birthweights in that time received systemic antifungal medication for this and other indications such as heavy colonisation of endotracheal tube or skin, or growth from the peritoneal cavity. This is a dramatically lower incidence of Candidiasis than that experienced by the authors of either of these reports.
Why is this so? We do use antifungal prophylaxis of oral and topical nystatin for all babies receiving parenteral nutrition (741 of those above), which is delivered by peripherally inserted central venous catheter (731 of those) or umbilical venous line (665 – many had both), but I doubt that fully explains the difference. Is there a fundamental difference in our local flora? Is there a difference in our general management practices that discourages the presence or growth of Candida? The ‘why is it so?’ may be the unanswerable question, but if it were answerable, and our experience was transportable, it would be far better than routine exposure to a systemically delivered powerful antifungal agent.
1. Manzoni P, Arisio R, Mostert M et al. Prophylactic Fluconazole Is Effective in Preventing Fungal Colonization and Fungal Systemic Infections in Preterm Neonates: A Single-Centre, 6-Year, Retrospective Cohort Study. Pediatrics. 2006;117:e22-e32
2. Benjamin DK, Stoll B, Fanaroff A et al. Neonatal Candidiasis Among Extremely Low Birth Weight Infants: Risk Factors, Mortality Rates, and Neurodevelopmental Outcomes at 18 to 22 Months. Pediatrics. 2006;117:84-92
Conflict of Interest:
None declared