Targeted Short-Term Fluconazole Prophylaxis Among Very Low Birth Weight and Extremely Low Birth Weight Infants

Uko, Smart E.; Soghier, Lamia; Vega, Mario; Marsh, Jeremy; Reinersman, G T; Herring, Lucille; Dave, Viral A.; Nafday, Suhas; Brion, Luc P.

doi:10.1542/peds.2005-1969

Cited by 103 publications

(67 citation statements)

References 54 publications

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“…7,[9][10][11][12]14,15,18 In solid organ and bone marrow transplant patients, antifungal prophylaxis with fluconazole has been successfully used for years to prevent colonization and infection due to Candida species and markedly reduced the need for empiric amphotericin B therapy. 19,20 However, because of the lack of larger multicenter randomized trials and data on long-term Fluconazole prophylaxis for highest risk infants J-H Weitkamp et al neurodevelopmental outcomes as well as concerns about unwanted side effects and development of Candida resistance, fluconazole prophylaxis in high-risk infants remains controversial.…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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

et al. 2008

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“…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.…”

Section: Fluconazole Prophylaxismentioning

confidence: 99%

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

2013

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The definition of neonatal sepsis is complicated by the frequent presence of noninfectious conditions that resemble those of sepsis, especially in very low-birth-weight (VLBW) preterm infants and by the absence of optimal diagnostic tests. Although growth of an organism from a sterile site is the "gold standard" for definitive diagnosis, it is not always possible to isolate a causative pathogen. Invasive infections can occur in seemingly asymptomatic neonates. Therefore, assessment of history and risk factors in combination with diagnostic tests are used to identify neonates who are more likely to be infected.The definitions of early onset sepsis (EOS) and late onset sepsis (LOS) are subject to subspecialist variation. Many investigators, including those who participate in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Network and the Vermont Oxford Network, define EOS by the onset of signs/symptoms and an associated positive culture at or before 72 hours of life. LOS is characterized by the onset of symptoms consistent with sepsis at greater than 72 hours of life. These classifications of EOS and LOS reflect the differing etiologies and proposed pathophysiology of pathogens commonly associated with the timing of Keywords ► neonatal sepsis ► invasive candidiasis ► epidemiology ► management AbstractIdentifying neonates with sepsis is complicated by variability in clinical presentation. The incidence of early onset sepsis (EOS) resulting from invasive group B streptococcal (GBS) infections has been notably reduced by the widespread delivery of intrapartum antibiotic prophylaxis. Rates of EOS attributable to non-GBS etiologies have remained constant, and ampicillin-resistant Escherichia coli has become more prevalent. Lateonset sepsis (LOS) attributable to gram-positive organisms including coagulase-negative Staphylococci and Staphylococcus aureus is associated with increased morbidity and mortality among premature infants. Invasive candidiasis is an emerging cause of LOS, especially among infants who receive broad-spectrum antimicrobial agents. Prophylactic fluconazole administration to very low-birth-weight (VLBW) neonates during the first 6 weeks of life prevents invasive candidiasis in neonatal intensive care units (NICU) with high rates of fungal infections. Targeted fluconazole prophylaxis may be beneficial in VLBW neonates who receive care in NICUs with lower rates of invasive fungal infections. Assessment of immune function, neutrophil markers, acute phase reactants, and utilization of sepsis screening scores may contribute to the management of sepsis. Maternal decolonization, antimicrobial stewardship, early enteral feeding, and optimal infection control practices are potential practical strategies for reducing the burden of neonatal sepsis.

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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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Targeted Short-Term Fluconazole Prophylaxis Among Very Low Birth Weight and Extremely Low Birth Weight Infants

Abstract: This study suggests that targeted short-course fluconazole prophylaxis in very low birth weight and ELBW infants may be efficacious and cost effective.

Cited by 103 publications

References 54 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

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

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

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