Neonatal Candidiasis: Epidemiology, Risk Factors, and Clinical Judgment

Abstract

OBJECTIVE-Invasive candidiasis is a leading cause of infection-related morbidity and mortality in extremely low-birth-weight (<1000 g) infants. We quantify risk factors predicting infection in high-risk premature infants and compare clinical judgment with a prediction model of invasive candidiasis. METHODS-The study involved a prospective observational cohort of infants <1000 g birth weight at 19 centers of the NICHD Neonatal Research Network. At each sepsis evaluation, clinical information was recorded, cultures 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.RESULTS-Invasive candidiasis occurred in 137/1515 (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 was not different from infants who had positive blood culture compared to those with isolated positive urine culture. Incidence varied from 2-28% at the 13 centers enrolling ≥ 50 infants. Potentially modifiable risk factors (model 1) included central catheter, broad-spectrum antibiotics (e.g., third-generation cephalosporins), intravenous lipid emulsion, endotracheal tube, and antenatal antibiotics. The clinical prediction model (model 2) 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. Performance of clinical judgment did not vary significantly with level of training. CONCLUSION-Priorantibiotics, presence of a central catheter, endotracheal tube, and center were strongly associated with invasive candidiasis. Modeling was more accurate in predicting invasive candidiasis than clinical judgment. KeywordsCandidiasis; premature infant; risk factors In the extremely low-birth-weight (ELBW; <1000g) infant, invasive candidiasis is common, often fatal, and frequently leads to poor neurodevelopmental outcomes. 1,2 Invasive candidiasis (Candida infections of the blood and other sterile body fluids) is the second most common cause of infectious disease-related death in the extremely premature infant. Despite antifungal treatment, 20% of infants who develop invasive candidiasis die, and neurodevelopmental impairment occurs in nearly 60% of survivors. 1,2 Rates of invasive candidiasis vary 10-fold among similar academic tertiary care neonatal intensive care units (NICUs). 3 This variation among nurseries is found throughout the world 4-9 and has not been explained, but exposure to environmental risk factors (e.g., incubator humidity), third-generation cephalosporins, and foreign bodies such as catheters have all been associated with development of disease. 3,10,11 The high morbidity related to invasive candidiasis leads to the consideration of empirical anti...

Risk factors for persistent candidemia infection in a neonatal intensive care unit and its effect on mortality and length of hospitalization

“…8,10 Notably, the site of this study has a low incidence by internal measure (3% for birth weight under 1000 grams); thus, fungal prophylaxis would not be indicated.…”

“…A single center retrospective study with historical controls did note a reduction in mortality after adopting an institutional guideline for initiating antifungal therapy. 9 Benjamin et al 10 identified the following as risk factors for the development of invasive candidiasis: vaginal delivery, lower gestational age at delivery, Candida dermatitis, presence of a central catheter, lack of enteral feeds, increased blood glucose, increased number of antibiotic days and decreased platelet count. From the present study, utilization of a clinical prediction modelFas discussed by Benjamin et al 10 Fcould have resulted in five of the six persistent candidemia patients receiving empiric antifungal therapy, as they had at least three of the risk factors above.…”

“…Broadly speaking, the absence of enteral feeds could be reflective of the severity of illness in those patients rather than a predisposing factor itself. 2,3,10,11 The limitations of this study include the retrospective design and the size of the study population. Other authors on this topic have cited the constraints of single center study.…”

Fungal Infections in Newborn

“…Merkezlere göre invaziv kandidiyazis (İK) sıklığı değişken olmakla beraber Candida türleri ÇDDA bebeklerde kan akım enfeksiyonunun nedenleri içinde sıklık sırasına göre üçüncü sıradadır (9). ÇDDA bebeklerde antifungal tedavilere rağmen kandidaya bağlı mortalite %30 ve yaşayanlarda nörogelişimsel bozukluk %59-73 gibi yüksek oranlardadır (9)(10)(11)(12). Ayrıca, İK'i olan prematüre bebeklerde periventriküler lökomalazi (PVL), prematüre retinopatisi (PR) ve bronkopulmoner displazi (BPD) gelişme olasılığı daha yüksektir (11,12).…”

Invasive Candida infections in the nursery: state of the art

“…(3) ICI are severe, and ICI-related mortality is still unacceptably high (up to 30%, compared with some 77% for invasive fungal infections caused by Aspergillus spp.). (4) Contrary to other high-risk patients, in preterm neonates the risk condition for fungal and Candida infections is destined to vanish as days of stay in the NICU go by. Availability of mother's fresh milk, and ability of the neonate to tolerate it as he gets older, is critical since maternal fresh milk provides innate defenses that may be helpful to overcome the risky time-window.…”