A Multicenter, Randomized Trial of Prophylactic Fluconazole in Preterm Neonates

Manzoni, Paolo; Stolfi, Ilaria; Pugni, Lorenza; Decembrino, Lidia; Magnani, Corrado; Vetrano, Gennaro; Tridapalli, Elisabetta; Corona, Giuseppina; Giovannozzi, C.; Farina, Daniele; Arisio, Riccardo; Merletti, Franco; Maule, Milena; Mosca, Fabio; Pedicino, Roberto; Stronati, Mauro; Mostert, M.; Gomirato, G

doi:10.1056/nejmoa065733

Cited by 322 publications

(219 citation statements)

References 34 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%

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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: Discussionmentioning

confidence: 99%

“…10,11 In contrast, many other studies did not find a difference in overall mortality, 7,9,12-14 including a recent multicenter trial. 15 Concerns about development of azole resistance and unwanted drug side effects remain. One study reported an association between fluconazole use and a higher incidence of cholestasis.…”

Section: Introductionmentioning

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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“…In this trial, having two or more sites positive in a single day was associated with an odd ratio of 8.2. Recently, Manzoni et al [11] showed a significant decrease of invasive candidiasis with fluconazole prophylaxis, although this was in neonates; no effect on mortality was observed.…”

Section: Prophylactic Antifungal Treatment In the Icumentioning

confidence: 99%

Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: Part II. Treatment

et al. 2008

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Background: Invasive candidiasis and candidemia are frequently encountered in the nosocomial setting particularly in the intensive care unit (ICU). Objective and methods: To review the current management of invasive candidiasis and candidemia in non-neutropenic adult ICU patients based on a review of the literature and an European expert panel discussion. Results and conclusions: Empiric and directed treatment for invasive candidiasis are predicated on the hemodynamic status of the patient. Unstable patients may benefit from broad-spectrum antifungal agents, which can be narrowed once the patient has stabilized and the identity of the infecting species is established. In stable patients, a more classical approach using fluconazole may be satisfactory provided that the patient is not colonized Intensive Care Med

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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%

“…The attack rate of invasive Candida infections over the past two decades has ranged from 3% to 17% among VLBW infants, and from 6% to 20% among extremely low birth weight infants (≤1,000 g), with a case-fatality of around 30% [10,[86][87][88][89][90][91][92][93][94][95]. The main causative agents causing candidemias in the VLBW infant population have been Candida albicans and Candida parapsilosis, and a shift towards the latter has occurred gradually [86,96,97].…”

Section: Bloodstream Infectionsmentioning

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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A Multicenter, Randomized Trial of Prophylactic Fluconazole in Preterm Neonates

Abstract: Prophylactic fluconazole reduces the incidence of colonization and invasive candida infection in neonates weighing less than 1500 g at birth. The benefit of treating candida colonization is unclear. (Current Controlled Trials number, ISRCTN85753869 [controlled-trials.com]).

Cited by 322 publications

References 34 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

Management of invasive candidiasis and candidemia in adult non-neutropenic intensive care unit patients: Part II. Treatment

314 Healthcare-Associated Infections in Pediatrics

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