Neonatal Candidiasis Among Extremely Low Birth Weight Infants: Risk Factors, Mortality Rates, and Neurodevelopmental Outcomes at 18 to 22 Months

Benjamin, Daniel K.; Stoll, Barbara J.; Fanaroff, A.A.; McDonald, Scott A.; Oh, William; Higgins, Rosemary D.; Duara, Shahnaz; Poole, Kenneth; Laptook, Abbot R.; Goldberg, Ronald N.

doi:10.1542/peds.2004-2292

Cited by 604 publications

(592 citation statements)

References 16 publications

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“…10 In a recent multi-center study, 5% (14/293) of candidemic infants had Candida meningitis. 1 In our study of infants receiving an LP, 9% (7/77) of candidemic infants had evidence of Candida meningitis. Further, the majority (63%, 12/19) of infants with Candida meningitis had negative blood cultures for Candida.…”

Section: Discussionmentioning

confidence: 59%

“…1,12 We observed 13% mortality (8/61) of candidemic infants and only 6% (3/51) in those infants with candidemia and culture-negative CSF for Candida. However, 41% (7/17) of infants with culture-positive Candida meningitis and 71% (5/7) of the infants with both positive blood and CSF cultures for Candida died.…”

Section: Discussionmentioning

confidence: 75%

“…A high proportion (48%, 13/27) of negative blood cultures was also observed in a recent multi-center study examining blood culture results from infants with Candida meningitis. 1 Blood culture sensitivity for candidemia is low in adults 11 and may be even lower in infants where blood culture vials are inoculated with as little as 0.5 ml of blood.…”

Section: Discussionmentioning

confidence: 99%

“…Candida meningitis complicates invasive candidiasis more often in infants than older patients. 1 Definitive diagnosis of Candida meningitis is determined by isolation of the organism in the cerebrospinal fluid (CSF). However, lumbar punctures (LP) in infants are often delayed until after institution of empirical anti-fungal therapy or until blood culture results are known to be positive, because of the delicate medical conditions of some infants, absence of specific clinical findings or assumptions of low risk of meningitis.…”

Section: Introductionmentioning

confidence: 99%

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Neonatal Candida meningitis: significance of cerebrospinal fluid parameters and blood cultures

et al. 2006

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Objective: The purpose of this study was to examine the frequency of normal cerebrospinal fluid (CSF) parameters in Candida meningitis and the proportion of candidemia associated with Candida meningitis. Study design:We evaluated the initial lumbar puncture results from infants discharged from 150 Neonatal Intensive Care Units between 1997 and 2004. Candida meningitis was diagnosed by a positive CSF culture or positive Gram stain for yeast. We calculated two-tailed P-values using non-parametric testing, Mann-Whitney, Kruskal-Wallis or Fisher's exact tests where appropriate.Results: Twenty infants had culture-positive Candida meningitis. Normal CSF parameters were found in 43% (3/7) of the infants with Candida meningitis and only 37% (7/19) of them had positive blood cultures for Candida. Conclusion:Normal CSF parameters do not exclude the diagnosis of neonatal Candida meningitis. The majority of infants in this cohort with Candida meningitis did not have evidence of candidemia at the time of diagnosis.

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Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Neonatal Candida meningitis: significance of cerebrospinal fluid parameters and blood cultures

et al. 2006

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“…However, this organism has increased in prevalence in recent years. C. parapsilosis is a common cause of bloodstream infection in neonates [3-5], and has overtaken C. albicans in frequency of hospital-acquired infection in some hospitals worldwide [4, 6, 7]. Recent studies have identified the importance of secreted lipase in the virulence of this organism and have documented its ability to damage tissue in vitro [8, 9].…”

Section: Introductionmentioning

confidence: 99%

High efficiency opsonin-independent phagocytosis of Candida parapsilosis by human neutrophils

et al. 2009

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Candida species are associated with invasive fungal infections, and C. parapsilosis has become increasingly prevalent. As key antifungal effector cells, the function of human neutrophils confronting C. parapsilosis was investigated. We hypothesized that interaction between neutrophils and Candida species may not be uniform. Opsonins were omitted from these studies to understand the antifungal mechanisms at their most basic level. Human neutrophils underwent phagocytosis of C. parapsilosis with much higher efficiency than C. albicans. Immunofluorescence assays with β-glucan specific antibody detected more surface exposed β-glucan on C. parapsilosis than C. albicans. However, blockade of the β-glucan receptor, Dectin-1, reduced phagocytosis of C. albicans but not C. parapsilosis. Inclusion of excess β-glucan, mannan, or chitin also had no effect on phagocytosis of C. parapsilosis. Consistent with the difference in phagocytosis, neutrophils mediated damage to C. parapsilosis but not C. albicans in assays of residual metabolic activity. C. parapsilosis was more sensitive to oxidative stress, and inclusion of antioxidant in toxicity assays decreased neutrophil mediated damage, suggesting that generation of reactive oxygen species contributes to the mechanism of toxicity. These data suggest that the interaction between neutrophils and Candida species is not uniform and may partially account for differences observed in the epidemiology and natural history of infections caused by these species.

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Effect of Fluconazole Prophylaxis on Candidiasis and Mortality in Premature Infants

Benjamin

Hudak

Duara

et al. 2014

JAMA

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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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Neonatal Candidiasis Among Extremely Low Birth Weight Infants: Risk Factors, Mortality Rates, and Neurodevelopmental Outcomes at 18 to 22 Months

Abstract: Blood cultures were negative for approximately one half of the infants with Candida meningitis. Persistent candidiasis was common. Delayed catheter removal was associated with increased death and NDI rates.

Cited by 604 publications

References 16 publications

Neonatal Candida meningitis: significance of cerebrospinal fluid parameters and blood cultures

Neonatal Candida meningitis: significance of cerebrospinal fluid parameters and blood cultures

High efficiency opsonin-independent phagocytosis of Candida parapsilosis by human neutrophils

Effect of Fluconazole Prophylaxis on Candidiasis and Mortality in Premature Infants

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