Fluconazole prophylaxis in extremely low birth weight infants: association with cholestasis

Aghai, Zubair H.; Mudduluru, Manjula; Nakhla, Tarek; Amendolia, Barbara; Longo, Daniela; Kemble, Nicole; Kaki, Shiny; Sutsko, Ronald P.; Saslow, Judy; Stahl, Gary E.

doi:10.1038/sj.jp.7211570

Cited by 88 publications

(64 citation statements)

References 19 publications

(45 reference statements)

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“…26 Fluconazole has an excellent safety profile in children 27 and we did not observe any untoward side effects in the fluconazole prophylaxis group, such as increases in conjugated bilirubin. This is in contrast to a study by Aghai et al 16 who found a transient but significant increase in conjugated hyperbilirubinemia in the fluconazole prophylaxis group. One explanation for this difference could be that we used a twice weekly dosing protocol in contrast to the more frequent dosing protocol used by Aghai et al Additionally, our study was not powered to detect statistically significant differences in this specific outcome.…”

Section: Discussioncontrasting

confidence: 99%

“…A recent study suggests that fluconazole prophylaxis may be associated with a higher risk for cholestasis in preterm infants <1000 g. 16 As part of our protocol, hepatic function tests (AST, ALT, total bilirubin and conjugated bilirubin), serum creatinine, BUN, platelets and complete blood count with differential were ordered weekly for patients receiving fluconazole prophylaxis. We compared the no-prophylaxis and prophylaxis groups to identify unwanted side effects associated with fluconazole prophylaxis and found no differences (Figures 1 and 2).…”

Section: Evaluation Of Undesired Side Effectsmentioning

confidence: 99%

“…One study reported an association between fluconazole use and a higher incidence of cholestasis. 16 Based on the 2004/2005 microbiology data from our own institution, the incidence of invasive Candida infections was 10% in ELBW infants with an incidence of 6.8% for candidemia. All infected ELBW infants in that year were <26 weeks gestational age and/or <750 g birth weight.…”

Section: Introductionmentioning

confidence: 99%

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Fluconazole prophylaxis for prevention of invasive fungal infections in targeted highest risk preterm infants limits drug exposure

et al. 2008

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Objective: Previous reports suggest a benefit of fluconazole prophylaxis in extremely low birth weight (ELBW) infants <1000 g. Our aim was to evaluate if limiting fluconazole prophylaxis to targeted highest risk infants effectively prevents invasive fungal infections, has no undesired side effects and limits unnecessary drug exposure.Study Design: This nonrandomized retrospective pre-post intervention study compared two groups of infants: (1) Infants <26 weeks gestation and/or <750 g birth weight, requiring central vascular access and admitted to the Monroe Carell Jr Children's Hospital at Vanderbilt neonatal intensive care unit (NICU) prior to 5 days of age, who received fluconazole prophylaxis and (2) a matched control group from the year prior to prophylaxis. This target population was selected for fluconazole prophylaxis based on prior infection control data from our institution and a number needed to treat of <15 to prevent one episode of fungemia. Following implementation and integration through the institution's computerized physician order entry (CPOE) system, provider adherence to the protocol was assessed during the prophylaxis period.Result: A total of 86 patients were included in the study, 44 in the no-prophylaxis group and 42 in the prophylaxis group. In the targeted prophylaxis group, no invasive fungal infections were observed as compared to nine infants with invasive infections in the no-prophylaxis group (P ¼ 0.004). No significant adverse effects were recorded. Targeting the highest risk infants reduced the number of infants <1000 g requiring prophylaxis from 80 to 42 (48% reduction) with no preventable infection missed. Provider compliance was 91% following implementation of this protocol through the CPOE system using a standardized order set. Conclusion:Targeting the highest risk infants for fluconazole prophylaxis through CPOE can effectively prevent invasive fungal infections and limit drug exposure with no unwanted side effects.

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Section: Discussioncontrasting

confidence: 99%

Section: Evaluation Of Undesired Side Effectsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Fluconazole prophylaxis for prevention of invasive fungal infections in targeted highest risk preterm infants limits drug exposure

et al. 2008

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“…To date there have been five randomized controlled trials (RCTs) [52,[65][66][67][68], eight retrospective reviews [19,20,[73][74][75][76][77][78], and a Cochrane review [79] examining fluconazole prophylaxis in neonates.…”

Section: Neonatal Clinical Studiesmentioning

confidence: 99%

Triazole Use in the Nursery: Fluconazole, Voriconazole, Posaconazole, and Ravuconazole

Watt¹,

Manzoni²,

Cohen‐Wolkowiez³

et al. 2013

Current Drug Metabolism

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Invasive fungal infections in infants admitted to the neonatal intensive care unit are common and often fatal. The mainstay of therapy against invasive fungal infections is antifungal agents. Over the last two decades, the development and approval of these drugs evolved tremendously, and the azole class emerged as important agents in the treatment and prevention of invasive fungal infections. Among the azoles, fluconazole has been used extensively due to its favorable pharmacokinetics, excellent activity against Candida spp, and safety profile. This drug has been well studied in children but data for its use in infants are largely limited to Candida prophylaxis studies. Voriconazole, a second generation triazole, has excellent activity against Candida and Aspergillus spp. However, data on its use in neonates are extremely limited. Posaconazole and Ravuconazole are the newest agents of the triazole family. The antimicrobial spectrum of posaconazole is similar to voriconazole, but with additional activity against zygomycetes. Experience with posaconazole in children is very limited, and there are no reports of its use in infants. Ravuconazole is not approved for use by the FDA but studies in animals and humans show that it is often fungicidal and has favorable pharmacokinetics. In conclusion, the management of invasive fungal infections has progressed greatly over the last two decades with the azole antifungals playing a significant role. Related to this class, future research is needed in order to better assess dosing, safety, schedules and areas of use of these agents in infants admitted to the neonatal intensive care unit.

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“…17 In previous studies, an association between FP and a higher incidence of cholestasis, as well as reversible elevations in liver enzymes and bilirubin levels have been reported. 13,18 Healy et al 19 had also described a shift of invasive candidiasis to older, more mature infants after implementation of FP for extremely low birth weight infants. On a careful evaluation of laboratory results over the initial 6 weeks, FP was not independently associated with elevated direct jaundice, liver enzymes, thrombocytopenia or elevated serum creatinine.…”

Section: Targeted Fluconazole Prophylaxis In Preterm Infantsmentioning

confidence: 99%

Impact of ‘targeted’ fluconazole prophylaxis for preterm neonates: efficacy of a highly selective approach?

et al. 2011

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Objective: The objective of this study was to evaluate the efficacy of targeted intermittent fluconazole prophylaxis (FP) to high-risk preterm (PT) infants.Study Design: Observational pre-post cohort study (n ¼ 524). Targeted FP (3 mg kg À1 ) was administered to PT infants (birth weights <1500 g and <6 weeks of age) who received broad-spectrum antibiotics for more than 2 days and had at least one additional risk factor for invasive candidiasis during the antibiotic administration period.Result: Invasive candidiasis decreased significantly from 15.3 to 6.2% during the FP period. Duration of parenteral nutrition (15.5 vs 19.2 days), central line (12.7 vs 15.8 days) and necrotizing enterocolitis rates (7 vs 9.5%) were significantly higher in the FP period. FP was administered to 89 (31.3%) infants; the median (range) number of doses was four (1 to 24) and duration was 7 (1 to 38) days.Conclusion: In the current study, targeted intermittent FP to a selected population of PT infants was efficacious in reducing the rate of invasive candidiasis, compared with historical controls.

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Fluconazole prophylaxis in extremely low birth weight infants: association with cholestasis

Cited by 88 publications

References 19 publications

Fluconazole prophylaxis for prevention of invasive fungal infections in targeted highest risk preterm infants limits drug exposure

Fluconazole prophylaxis for prevention of invasive fungal infections in targeted highest risk preterm infants limits drug exposure

Triazole Use in the Nursery: Fluconazole, Voriconazole, Posaconazole, and Ravuconazole

Impact of ‘targeted’ fluconazole prophylaxis for preterm neonates: efficacy of a highly selective approach?

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