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Treatment of Invasive Candidiasis

  2012-2013 Nelson's Pediatric Antimicrobial Therapy
  • Empirical antifungal therapy in certain high-risk oncology patients with persistent febrile neutropenia has been standard of care since the publication of a pivotal study in 1982. Recently, Greenberg et al have extrapolated this to infants in the intensive care nursery, using well-documented neonatal risk factors for developing invasive candidiasis to justify empirical antifungal prophylaxis. They performed a cohort study of infants (birth weight < 1000 g) infected with Candida and analyzed empiric antifungal therapy on the day before or on the day the first positive culture for Candida was drawn. The incidence of death or neurodevelopmental impairment was lower in infants who received empiric antifungal therapy (19 of 38; 50%) compared with those who had not (55 of 86; 64%; OR, 0.27; 95% CI, 0.08-0.86). This study will need to be validated in a randomized controlled trial, but it helps us extrapolate a successful algorithm from oncology to neonatology.

    BOTTOM LINE: Consider empiric antifungal therapy for low birth weight infants in the NICU who are known to be at high risk for developing invasive candidiasis.
  • Treatment of invasive candidiasis received further attention in a recent analysis performed by Andes and colleagues at the Mycoses Study Group. The authors used a patient-level quantitative review of randomized trials for the treatment of invasive candidiasis (albeit largely in adult patients) to assess the impact of host-, organism-, and treatment-related factors on mortality and clinical cure. Data from 1915 patients were obtained from 7 trials. Overall mortality among patients in the entire data set was 31.4%, with the rate of treatment success at 67.4%. Most relevant to pediatric medicine, the authors identified infection with Candida tropicalis (OR, 1.64; 95% CI, 1.11-2.39; P = .01) as a predictor of mortality. Conversely, removal of a central venous catheter (OR, 0.50; 95% CI, .35-.72; P = .0001) or treatment with an echinocandin antifungal (OR, 0.65; 95% CI, .45-.94; P = .02) was associated with decreased mortality. Similar findings were observed for the clinical success end point.

    BOTTOM LINE: Although the current Infectious Diseases Society of America guidelines suggest an echinocandin for treatment of more severe or neutropenic invasive candidiasis, Andes’ analysis begins the conversation that perhaps we should be using an echinocandin antifungal for all cases of invasive candidiasis. Additionally, although removal of a central venous catheter could not be conclusively shown to reduce mortality due to limitations of the dataset, most experts agree that catheter removal is a critical step in managing invasive candidiasis.     
Bill Steinbach, Contributing Editor
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