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Published on: July 1, 2020
Antifungal therapy and outcomes in infants with invasive Candida infections
Simon B Ascher1, P Brian Smith, Kevin Watt
1Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.
Insights
Amphotericin B lipid products were associated with higher mortality in infants with invasive candidiasis compared to amphotericin B deoxycholate or fluconazole. Further research is needed to understand these outcomes in neonatal intensive care units.
Area of Science:
- Neonatal Medicine
- Infectious Diseases
- Pharmacology
Background:
- Invasive candidiasis poses a significant threat to neonates in intensive care units.
- Limited comparative data exists for current treatment guidelines.
Purpose of the Study:
- To compare the outcomes of different antifungal therapies in infants with invasive candidiasis.
- To identify potential differences in mortality and therapeutic failure based on treatment regimen.
Main Methods:
- Retrospective analysis of infants (≤120 days) with positive Candida cultures in US NICUs (1997-2003).
- Comparison of mortality and therapeutic failure (prolonged infection, retreatment, or death) across four antifungal strategies: amphotericin B deoxycholate, fluconazole, amphotericin B lipid products, and combination therapy.
- Logistic regression analysis controlling for key infant and infection characteristics.
Main Results:
- Overall mortality was 19% (138/730 infants).
- Amphotericin B lipid products were linked to significantly higher mortality compared to amphotericin B deoxycholate (OR 1.96) and fluconazole (OR 2.39).
Conclusions:
- Infants receiving amphotericin B lipid products experienced increased mortality versus those treated with amphotericin B deoxycholate or fluconazole.
- Potential reasons include poor kidney penetration, incorrect dosing in preterm infants, or unmeasured differences in illness severity.
Background:
Invasive candidiasis is a leading cause of mortality and morbidity in neonatal intensive care units. Treatment recommendations are limited by a lack of comparative outcomes data.
Methods:
We identified all infants ≤ 120 days of age with positive blood, urine, or cerebrospinal fluid cultures for Candida species who received amphotericin B deoxycholate, fluconazole, amphotericin B lipid products, or combination therapy admitted to one of 192 neonatal intensive care units in the United States between 1997 and 2003. Primary outcome measures included overall mortality and therapeutic failure (combined outcome of duration of infection >7 days, need for additional antifungal therapy, or death before discharge). We compared outcomes by antifungal therapy using logistic regression, controlling for gestational age, day of life at start of antifungal therapy, delay in therapy, and site of infection.
Results:
Overall, 138 of 730 (19%) infants died. On multivariable logistic regression, we observed higher overall mortality for infants receiving amphotericin B lipid products compared with infants receiving amphotericin B deoxycholate (odds ratio 1.96 [95% confidence intervals: 1.16, 3.33]; P = 0.01) or fluconazole (odds ratio 2.39 [1.18, 4.83]; P = 0.02).
Conclusions:
Infants treated with amphotericin B lipid products had higher mortality than infants treated with either amphotericin B deoxycholate or fluconazole. This finding may be related to inadequate penetration of amphotericin B lipid products into the kidneys, inappropriate dosing in premature infants, or unknown differences in acuity of illness in infants treated with amphotericin B lipid products.
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