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Antifungal Treatment and Outcome in Very Low Birth Weight Infants: A Population-based Observational Study of the
Ingmar Fortmann1, Annika Hartz1, Pia Paul1
1From the Department of Pediatrics, University of Lübeck, Germany.
Background:
The diagnostic proof of fungal infection in preterm infants is difficult. Antifungal treatment (AFT) is often initiated empirically when infants with suspected infection do not improve despite broad-spectrum antibiotic therapy. It was the aim of our study to determine the rate of exposure to empirical AFT in a large cohort of very low birth weight infants (VLBWI) of the German Neonatal Network and to address associated risks and outcomes.
Methods:
The epidemiologic database consisted of n = 13,343 VLBWI born in 54 German Neonatal Network centers between 2009 and 2015. AFT was defined as number of neonates who got any dose of at least one of the following antifungal drugs: fluconazole, amphotericin B, voriconazole and caspofungin (denominator: number of infants enrolled in German Neonatal Network) for treatment (not prophylaxis) of (suspected) fungal infection. Univariate and logistic regression analyses were used to identify risk factors for exposure to AFT and associated short-term morbidities and long-term outcomes at 5-year follow-up.
Results:
In our cohort, 724 out of 13,343 (5.4%) VLBWI were exposed to empiric AFT and had a mean gestational age of 25.7 (±2.1) weeks. Forty-four out of 13,343 (0.3%) had proven bloodstream infection with Candida spp. The main risk factors for exposure to AFT were gestational age, postnatal steroid treatment, need for abdominal surgery and use of carbapenems. Notably, AFT was associated with adverse outcomes such as bronchopulmonary dysplasia [adjusted odds ratio (OR): 1.9; 95% confidence interval (CI): 1.6-2.3; P < 0.001) and retinopathy of prematurity requiring intervention (adjusted OR: 1.69; 95% CI: 1.3-2.3; P <0.001) but not mortality. In the subgroup of infants available for 5-year follow-up (n = 895), exposure to AFT was associated with a risk for cerebral palsy (adjusted OR: 2.79; 95% CI: 1.11-7.04; P = 0.04) and intelligence quotient < 85 (adjusted OR: 2.07; 95% CI: 1.01-4.28; P = 0.049).
Conclusions:
A significant proportion of VLBWI is exposed to AFT, specifically those born <26 weeks. Exposed infants were found to have a higher risk for adverse outcomes, which may reflect their significant vulnerability in general. Given the observational design of our study, it remains unclear whether potential side effects of empirical or target AFT itself contribute to adverse outcome. Future studies need to include risk-based strategies and stewardship programs to restrict the use of antifungal management in VLBWI.
Insights
Empirical antifungal treatment (AFT) in very low birth weight infants (VLBWI) is common, especially for those born before 26 weeks. AFT is linked to increased risks of adverse outcomes, including cerebral palsy and lower IQ scores.
Area of Science:
- Neonatal Medicine
- Infectious Diseases
- Pediatric Pharmacology
Background:
- Diagnosing fungal infections in preterm infants is challenging.
- Empirical antifungal treatment (AFT) is often initiated for suspected infections in preterm infants not responding to antibiotics.
- This study investigated AFT exposure rates, risks, and outcomes in very low birth weight infants (VLBWI).
Purpose of the Study:
- Determine the rate of empirical AFT exposure in a large cohort of VLBWI.
- Identify risk factors associated with AFT exposure.
- Analyze the short-term and long-term outcomes linked to AFT in VLBWI.
Main Methods:
- Utilized a database of 13,343 VLBWI from the German Neonatal Network (2009-2015).
- Defined AFT as any dose of fluconazole, amphotericin B, voriconazole, or caspofungin for treatment.
- Employed univariate and logistic regression analyses to assess risk factors and outcomes.
Main Results:
- 5.4% of VLBWI (724/13,343) received empirical AFT, with a mean gestational age of 25.7 weeks.
- Risk factors for AFT included lower gestational age, postnatal steroids, abdominal surgery, and carbapenem use.
- AFT exposure was associated with bronchopulmonary dysplasia, retinopathy of prematurity, cerebral palsy, and lower IQ scores, but not mortality.
Conclusions:
- A significant proportion of VLBWI, particularly those born before 26 weeks, are exposed to AFT.
- AFT is associated with increased risks of adverse neurodevelopmental and respiratory outcomes.
- Further research is needed on risk-based strategies and stewardship programs to optimize antifungal use in VLBWI.
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