Neonatal Candidiasis: Epidemiology, Risk Factors, and Clinical Judgment

Department of Pediatrics, Duke University, Duke Clinical Research Institute, 2400 Pratt St, Durham, NC 27705, USA.
PEDIATRICS (Impact Factor: 5.47). 09/2010; 126(4):e865-73. DOI: 10.1542/peds.2009-3412
Source: PubMed


Invasive candidiasis is a leading cause of infection-related morbidity and mortality in extremely low birth weight (<1000-g) infants. We quantified risk factors that predict infection in premature infants at high risk and compared clinical judgment with a prediction model of invasive candidiasis.
The study involved a prospective observational cohort of infants≤1000 g birth weight at 19 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. At each sepsis evaluation, clinical information was recorded, cultures were obtained, and clinicians prospectively recorded their estimate of the probability of invasive candidiasis. Two models were generated with invasive candidiasis as their outcome: (1) potentially modifiable risk factors; and (2) a clinical model at time of blood culture to predict candidiasis.
Invasive candidiasis occurred in 137 of 1515 (9.0%) infants and was documented by positive culture from ≥1 of these sources: blood (n=96); cerebrospinal fluid (n=9); urine obtained by catheterization (n=52); or other sterile body fluid (n=10). Mortality rate was not different for infants who had positive blood culture compared with those with isolated positive urine culture. Incidence of candida varied from 2% to 28% at the 13 centers that enrolled≥50 infants. Potentially modifiable risk factors included central catheter, broad-spectrum antibiotics (eg, third-generation cephalosporins), intravenous lipid emulsion, endotracheal tube, and antenatal antibiotics. The clinical prediction model had an area under the receiver operating characteristic curve of 0.79 and was superior to clinician judgment (0.70) in predicting subsequent invasive candidiasis.
Previous antibiotics, presence of a central catheter or endotracheal tube, and center were strongly associated with invasive candidiasis. Modeling was more accurate in predicting invasive candidiasis than clinical judgment.

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    • "Thus, of the Candida clade [37] of 19 Candida species reported, nine (47%) had to be renamed, and the name-changes were not only restricted to the Candida species. The “new” (“emerging”) taxons, partly called before “not-Candida albicans Candida,” “not-Candida yeasts,” or “cryptic” pathogens [16–18, 34, 54–58], were already widely present at the beginning of and found throughout the German multicenter studies [49–51]. "
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    ABSTRACT: From 1997 to 2009, 1,862 dermatology, gynaecology, and paediatrics (DGP) associated clinical yeast isolates were analysed for species occurrence, specimen origin and type, (multi-) resistance pattern, and testing period. The top seven of the isolated DGP-associated species remained the same as compared to total medical wards, with Candida albicans (45%) as most frequent pathogen. However, the DGP wards and DGP ICUs showed species-specific profiles; that is, the species distribution is clinic-specific similar and however differs in their percentage from ward to ward. By applying the “one fungus one name” principle, respectively, the appropriate current taxonomic species denominations, it has been shown that no trend to emerging species from 1998 to 2008 could be detected. In particular the frequently isolated non- Candida albicans species isolated in the DGP departments have already been detected in or before 1997. As yeasts are part of the cutaneous microbiota and play an important role as opportunistic pathogens for superficial infections, proper identification of the isolates according to the new nomenclature deems to be essential for specific and calculated antifungal therapy for yeast-like DGP-related infectious agents.
    Full-text · Article · Dec 2013 · International Journal of Microbiology
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    • "Invasive fungal infections in infants and neonates, especially in pediatric ICU settings (PICU), are a problem in clinical treatment as they are accompanied with a high mortality.1,2 Although the overall incidence of candidemia is decreasing from 0.92 to 0.2 infections per 1,000 central IV line days, treatment is still a challenge.3 "
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    ABSTRACT: Invasive fungal infection in pediatric intensive care units (PICU) is a rising challenge. Candida species are the most common microorganisms in these infections. Due to growing resistance against fluconazole, echinocandins are being used for the appropriate therapy. However, the recent IDSA guidelines recommend them only in cases where fluconazole or Amphotericin B cause treatment failure or are contraindicated. In a literature review, the importance of invasive fungal infections in PICU settings and the role of anidulafungin shall be examined. Articles were retrieved form PubMed covering the years 2000-2012. Various search terms were used. Then the articles were clustered in different types like 'review,' 'pharmacokinetics,' 'case reports' and others. From 67 search results, 14 articles were selected. Of these, 7 were related to anidulafungin, while 7 were related to echinocandins or fungal infections in the PICU. Anidulafungin was examined in 4 PK/PD studies where a good safety profile was found. No serious adverse events occurred. The articles reporting risk factors show that central venous catheters, receipt of antibiotics, receipt of parenteral nutrition, and neutropenia are the most important independent risk factors for invasive fungal infections in PICU. Three reviews of antifungal agents show that echinocandins may be useful due to their safety profile; micafungin is the best examined one and further trials are needed. The published literature on invasive fungal infections in PICU settings has grown over the years. There are only a few articles, however, which are directly related to the use of anidulafungin in this setting. A most recent publication showed good PK/PD dynamics and a good safety profile for anidulafungin. So far, no RCT in the area of invasive candidiasis in infants and neonates has been published. A review of currently registered trials at has shown one more trial related to PK/PD and two trials that investigate the use of anidulafungin or anidulafungin in combination with Voriconazole in pediatrics. The small body of existing literature on anidulafungin in infants shows success in treatment, no drug-related adverse events, and good pharmacodynamics. A dosing of 0.75 mg/kg/day or 1.5 mg/kg/day is as effective as 50 mg/day or 100 mg/day in adults. More trials on the use in clinical reality of PICU or NICU should follow.
    Full-text · Article · Feb 2013
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    • "The reported incidence in the survey fits within the range reported by other studies [28], although methodologies in data collection differ and direct comparison with incidence data is not possible. Incidence rates of fungal infection differ between studies, from 2,6 to 9% [29,30]. A large part of the variation in rates is due to the number of extremely low birth weight infants admitted at each NICU [31,32], but may also reflect differences in clinical practices [33]. "
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    ABSTRACT: Background Treatment and prophylaxis of sepsis in very low birth weight neonates is a matter of concern and research is being undertaken with the aim to give rise to shared approaches based on solid evidence. As part of a European initiative, a survey was set up to describe the use of two drugs in this area. The Italian national practices concerning neonatal sepsis, as well as calls for related guidance, are described. Methods A standardized and previously tested questionnaire was submitted online to all Italian level III NICUs. A 5-point Likert scale was used to analyze attitudinal replies. Categorical variables were compared by χ2 analysis and 2-tailed P-values are reported. Results Data was provided by 38 Italian NICUs (36% of the country’s level III centers), 53% of which have 1–10 cases of bacterial sepsis monthly and 90% a prevalence of <1% fungal infections. Ciprofloxacin and fluconazole treatment for neonatal sepsis are scantly used in Italian NICUs (13% and 45%, respectively). Major concerns are related to the safety of ciprofloxacin and the efficacy of fluconazole. On the contrary, prophylaxis of fungal infections is a routine approach in many Italian NICUs. The use of both ciprofloxacin and fluconazole is characterized by a large inter-NICU variability in dose and scheme of use. The lack of adequate, shared evidence is a common consideration made by the survey participants. Conclusions Common approaches are needed to standardize and update a national drug strategy for the prevention and treatment of sepsis in very low birth weight newborns. This can be achieved through collaborative initiatives aimed at setting up guidelines, based on available data, and multicenter trials to produce new evidence that will address the knowledge gaps.
    Full-text · Article · Jan 2013 · BMC Pediatrics
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Questions & Answers about this publication

  • Mary C R Wilson added an answer in Nursing Care:
    What is the recent Research related to Humidity in prematurity and Nursing care?

    what is the recent EBP in nursing care with humidity in premature babies ?

    Mary C R Wilson

    Hello Rima

    This looks relevant but is from 2006:

    Ågren, J., Sjörs, G., & Sedin, G. (2006). Ambient humidity influences the rate of skin barrier maturation in extremely preterm infants. The Journal of pediatrics, 148(5), 613-617.

    Fujii, K., Sugama, J., Okuwa, M., Sanada, H., & Mizokami, Y. (2010). Incidence and risk factors of pressure ulcers in seven neonatal intensive care units in Japan: a multisite prospective cohort study. International wound journal, 7(5), 323-328.

    I have the full text to the above paper if you are unable to access it.

    Benjamin, D. K., Stoll, B. J., Gantz, M. G., Walsh, M. C., Sánchez, P. J., Das, A., ... & Walsh, T. J. (2010). Neonatal candidiasis: epidemiology, risk factors, and clinical judgment. Pediatrics, 126(4), e865-e873.

    Knobel, R. B. (2014). Thermal stability of the premature infant in Neonatal Intensive Care. Newborn and Infant Nursing Reviews, 14(2), 72-76.

    I have the full text to the above paper if you are unable to access it.

    Unfortunately, I could not access the full texts of these papers:

    Fox, M. (2011). Wound care in the neonatal intensive care unit. Neonatal Network, 30(5), 291-303.

    Deguines, C., Dégrugilliers, L., Ghyselen, L., Chardon, K., Bach, V., & Tourneux, P. (2013). Impact of nursing care on temperature environment in preterm newborns nursed in closed convective incubators. Acta Paediatrica, 102(3), e96-e101.

    Very best wishes


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      ABSTRACT: To test the hypothesis that the level of relative humidity (RH) in which preterm infants are nursed might influence their postnatal skin maturation. In 22 preterm infants (GA 23-27 weeks), transepidermal water loss (TEWL) was determined at postnatal ages (PNA) of 0, 3, 7, 14, and 28 days. At a PNA of 7 days, the infants were randomized to care at either 50% or 75% RH. TEWL decreased at a slower rate in infants nursed at the higher RH. At a PNA of 28 days, TEWL was about twice as high in infants nursed at 75% RH (22 +/- 2 g/m2 h) than in those nursed at 50% RH (13 +/- 1 g/m2 h; P < .001). The results indicate that the level of RH influences skin barrier development, with more rapid barrier formation in infants nursed at a lower RH. The findings have an impact on strategies for promoting skin barrier integrity in extremely preterm infants.
      Full-text · Article · May 2006 · Journal of Pediatrics

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