Fluconazole for Prophylaxis Against Candidal Rectal Colonization in the Very Low Birth Weight Infant

Kicklighter, Stephen D.; Springer, Shelley C.; Cox, Toby H; Hulsey, Thomas C.; Turner, Ronald B.

doi:10.1542/peds.107.2.293

Cited by 228 publications

(190 citation statements)

References 25 publications

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“…Most of the data comes from the growing body of literature assessing fluconazole prophylaxis in this population. Five randomized controlled trials addressing this question also looked at the effect of fluconazole on liver function tests [52,[65][66][67][68]. These five studies included 726 infants in the NICU and two found statistically though not clinically significant increases in aspartate aminotransferase (AST) and alanine aminotransferase (ALT).…”

Section: Toxicities Side Effects and Drug Interactionsmentioning

confidence: 99%

“…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%

“…The first of the RCT's was performed by Kicklighter, et al [67] and found that rectal colonization was significantly lower in VLBW infants receiving fluconazole 6 mg/kg/d versus placebo [15 vs. 46%, p<0.001].…”

Section: Neonatal Clinical Studiesmentioning

confidence: 99%

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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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Section: Toxicities Side Effects and Drug Interactionsmentioning

confidence: 99%

Section: Neonatal Clinical Studiesmentioning

confidence: 99%

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

Watt¹,

Manzoni²,

Cohen‐Wolkowiez³

et al. 2013

Current Drug Metabolism

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“…Colonization at multiple sites and CVC colonization have been reported as independent risk factors for candidal BSI [100]. The use of fluconazole prophylaxis seems to be effective against fungal colonization as well as to prevent candidal BSI [91][92][93][94][95][101][102][103]. None of the prophylaxis studies has reported changes in the fluconazole susceptibility of the Candida strains.…”

Section: Bloodstream Infectionsmentioning

confidence: 99%

“…Prophylaxis studies conducted in NICUs [91,94,[101][102][103] have shown no signs of fluconazole resistance or reduced susceptibility regarding C. parapsilosis isolates. Some have hypothesized that this phenomenon is due to the low total fluconazole doses received [91].…”

Section: Emergence Of Fluconazole Resistance In C Parapsilosis (Iii)mentioning

confidence: 99%

314 Healthcare-Associated Infections in Pediatrics

SpringerReference

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Helsinki 2008 P u b l i c a t i o n s o f t h e N a t i o n a l P u b l i c H e a l t h I n s t i t u t e K T L A 1 1 / 2 0 0 8 Dr. Alexander Langmuir, 1963 Emmi Sarvikivi, Healthcare-associated infections in pediatrics Publications of the National Public Health Institute, A11/2008, 93 Pages ISBN 978-951-740-803-5; 978-951-740-804-2 (pdf-version) ISSN 0359-3584; 1458-6290 (pdf-version) http://www.ktl.fi/portal/4043 ABSTRACT Background and aims. Healthcare-associated infections (HAIs) are known to increase the risk for patient morbidity and mortality in different healthcare settings and thereby to cause additional costs. HAIs typically affect patients with severe underlying conditions, such as patients treated in intensive care units, or patients who have undergone medical procedures, e.g., surgery. HAIs are prevalent also among pediatric patients, but the distribution of the types of infection and the causative agents differ from those detected in adults. The aim of this study was to obtain information on pediatric HAIs in Finland through an assessment of the surveillance of bloodstream infections (BSIs), through two outbreak investigations in a neonatal intensive care unit (NICU), and through a study of postoperative HAIs after open-heart surgery.Methods. The Hospital for Children and Adolescents of the Helsinki University Central Hospital has participated in the BSI surveillance of the Finnish Hospital Infection Program since 1999. These data were utilized in all studies. The epidemiological features of pediatric BSIs were assessed. For the outbreak investigations, case definitions were set and data collected from microbiological and clinical records. The antimicrobial susceptibilities of the Serratia marcescens and the Candida parapsilosis isolates were determined. The S. marcescens isolates were genotyped with pulsed-field gel electrophoresis and the C. parapsilosis blood culture isolates (obtained between the years 1990 and 2002) with Southern blot hybridization by use of a DNA fingerprinting probe. Patient charts were reviewed for the case-control and cohort studies during the outbreak investigations, as well as for those patients who acquired surgical site infections (SSIs) after having undergone open-heart surgery. Also a prospective postdischarge study was conducted to detect postoperative HAIs after open-heart surgery.Results. During 1999During -2006, the overall annual BSI rate was 1.6/1,000 patient-days (range by year, 1.2-2.1). High rates (average, 4.9 and 3.2 BSIs/1,000 patient-days) were detected in hematology and neonatology units. Coagulase-negative staphylococci were the most common pathogens both hospital-wide and in each patient group. The overall mortality was 5%. The genotyping of the 15 S. marcescens isolates revealed three independent clusters. All of the 26 C. parapsilosis isolates studied proved to be indistinguishable. No common source was identified for either of the outbreaks, but the NICU was overcrowded during the S. marcescens clusters. In both investigations, low birth we...

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Effect of Fluconazole Prophylaxis on Candidiasis and Mortality in Premature Infants

Benjamin

Hudak

Duara

et al. 2014

JAMA

113

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IMPORTANCE Invasive candidiasis in premature infants causes mortality and neurodevelopmental impairment. Fluconazole prophylaxis reduces candidiasis, but its effect on mortality and the safety of fluconazole is unknown. OBJECTIVE To evaluate the efficacy and safety of fluconazole in preventing death or invasive candidiasis in extremely low-birth-weight infants. DESIGN, SETTING, AND PATIENTS This study was a randomized, blinded, placebo-controlled trial of fluconazole in premature infants. Infants weighing less than 750 g at birth (N = 361) from 32 neonatal intensive care units (NICUs) in the United States were randomly assigned to receive either fluconazole or placebo twice weekly for 42 days. Surviving infants were evaluated at 18 to 22 months corrected age for neurodevelopmental outcomes. The study was conducted between November 2008 and February 2013. INTERVENTIONS Fluconazole (6 mg/kg of body weight) or placebo. MAIN OUTCOMES AND MEASURES The primary end point was a composite of death or definite or probable invasive candidiasis prior to study day 49 (1 week after completion of study drug). Secondary and safety outcomes included invasive candidiasis, liver function, bacterial infection, length of stay, intracranial hemorrhage, periventricular leukomalacia, chronic lung disease, patent ductus arteriosus requiring surgery, retinopathy of prematurity requiring surgery, necrotizing enterocolitis, spontaneous intestinal perforation, and neurodevelopmental outcomes—defined as a Bayley-III cognition composite score of less than 70, blindness, deafness, or cerebral palsy at 18–22-months corrected age. RESULTS Among infants receiving fluconazole, the composite primary end point of death or invasive candidiasis was 16% (95% CI, 11%–22%) vs 21% in the placebo group (95% CI, 15%–28%; odds ratio 0.73 [95% CI 0.43–1.23]; P=.24; treatment difference −5% [95% CI, −13%–3%]). Invasive candidiasis occurred less frequently in the fluconazole group (3% [95% CI, 1%–6%] vs the placebo group (9% [95% CI, 5%–14%]; P=.02; treatment difference −6% [95% CI, −11%–−1%]). The cumulative incidences of other secondary outcomes were not statistically different between groups. Neurodevelopmental impairment did not differ between the groups (fluconazole 31% [95% CI, 21–41%] vs placebo, 27% [95% CI, 18–37%]; P=.60; treatment difference 4% [95% CI, −10–17%]). CONCLUSIONS AND RELEVANCE Among infants with a birth weight of less 750 g, 42 days of fluconazole prophylaxis compared with placebo did not result in a lower incidence of the composite of death or invasive candidiasis. These findings do not support the universal use of prophylactic fluconazole in extremely-low-birth-weight infants. TRIAL REGISTRATION ClinicalTrials.gov number NCT00734539

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Fluconazole for Prophylaxis Against Candidal Rectal Colonization in the Very Low Birth Weight Infant

Cited by 228 publications

References 25 publications

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

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

314 Healthcare-Associated Infections in Pediatrics

Effect of Fluconazole Prophylaxis on Candidiasis and Mortality in Premature Infants

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