Julie Autmizguine1,2,3, Sylvia Tan4, Michael Cohen-Wolkowiez5, C Michael Cotten3, Nathan Wiederhold6, Ronald N Goldberg7, Ira Adams-Chapman7, Barbara J Stoll7,8, P Brian Smith5, Daniel K Benjamin5. 1. From the Department of Pharmacology and Physiology, Université de Montréal, Montréal, Canada. 2. Department of Pediatrics, Université de Montréal, Montréal, Canada. 3. Department of Pediatrics, Duke University, Durham, NC. 4. Statistics and Epidemiology Unit, RTI International, Research Triangle Park, NC. 5. Duke Clinical Research Institute, Durham, NC. 6. University of Texas Health Science Center at San Antonio, San Antonio, TX. 7. Department of Pediatrics, Emory University, Atlanta, GA. 8. Department of Pediatrics, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX.
Abstract
BACKGROUND: Invasive candidiasis is an important cause of sepsis in extremely low birth weight infants (ELBW, < 1000 g), is often fatal, and frequently results in neurodevelopmental impairment (NDI) among survivors. We sought to assess the antifungal minimum inhibitory concentration (MIC) distribution for Candida in ELBW infants and evaluate the association between antifungal resistance and death or NDI. METHODS: This was a secondary analysis of a National Institute of Child Health and Human Development Neonatal Research Network study. MIC values were determined for fluconazole, amphotericin B and micafungin. NDI was assessed at 18-22 months adjusted age using the Bayley Scales of Infant Development. An infant was defined as having a resistant Candida isolate if ≥ 1 positive cultures from normally sterile sites (blood, cerebrospinal fluid, or urine) were resistant to ≥ 1 antifungal agent. In addition to resistance status, we categorized fungal isolates according to MIC values (low and high). The association between death/NDI and MIC level was determined using logistic regression, controlling for gestational age and Bayley Scales of Infant Development (II or III). RESULTS: Among 137 ELBW infants with IC, MICs were determined for 308 isolates from 110 (80%) infants. Three Candida isolates from 3 infants were resistant to fluconazole. None were resistant to amphotericin B or micafungin. No significant difference in death, NDI, or death/NDI between groups with low and high MICs was observed. CONCLUSIONS: Antifungal resistance was rare among infecting Candida isolates, and MIC level was not associated with increased risk of death or NDI in this cohort of ELBW infants.
BACKGROUND:Invasive candidiasis is an important cause of sepsis in extremely low birth weight infants (ELBW, < 1000 g), is often fatal, and frequently results in neurodevelopmental impairment (NDI) among survivors. We sought to assess the antifungal minimum inhibitory concentration (MIC) distribution for Candida in ELBW infants and evaluate the association between antifungal resistance and death or NDI. METHODS: This was a secondary analysis of a National Institute of Child Health and Human Development Neonatal Research Network study. MIC values were determined for fluconazole, amphotericin B and micafungin. NDI was assessed at 18-22 months adjusted age using the Bayley Scales of Infant Development. An infant was defined as having a resistant Candida isolate if ≥ 1 positive cultures from normally sterile sites (blood, cerebrospinal fluid, or urine) were resistant to ≥ 1 antifungal agent. In addition to resistance status, we categorized fungal isolates according to MIC values (low and high). The association between death/NDI and MIC level was determined using logistic regression, controlling for gestational age and Bayley Scales of Infant Development (II or III). RESULTS: Among 137 ELBW infants with IC, MICs were determined for 308 isolates from 110 (80%) infants. Three Candida isolates from 3 infants were resistant to fluconazole. None were resistant to amphotericin B or micafungin. No significant difference in death, NDI, or death/NDI between groups with low and high MICs was observed. CONCLUSIONS: Antifungal resistance was rare among infecting Candida isolates, and MIC level was not associated with increased risk of death or NDI in this cohort of ELBW infants.
Authors: James L Wynn; Sylvia Tan; Marie G Gantz; Abhik Das; Ronald N Goldberg; Ira Adams-Chapman; Barbara J Stoll; Seetha Shankaran; Michele C Walsh; Kathy J Auten; Nancy A Miller; Pablo J Sánchez; Rosemary D Higgins; C Michael Cotten; P Brian Smith; Daniel K Benjamin Journal: Clin Infect Dis Date: 2011-12-05 Impact factor: 9.079
Authors: Daniel K Benjamin; Barbara J Stoll; Marie G Gantz; Michele C Walsh; Pablo J Sánchez; Abhik Das; Seetha Shankaran; Rosemary D Higgins; Kathy J Auten; Nancy A Miller; Thomas J Walsh; Abbot R Laptook; Waldemar A Carlo; Kathleen A Kennedy; Neil N Finer; Shahnaz Duara; Kurt Schibler; Rachel L Chapman; Krisa P Van Meurs; Ivan D Frantz; Dale L Phelps; Brenda B Poindexter; Edward F Bell; T Michael O'Shea; Kristi L Watterberg; Ronald N Goldberg Journal: Pediatrics Date: 2010-09-27 Impact factor: 7.124
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Authors: Kelly C Wade; Daniel K Benjamin; David A Kaufman; Robert M Ward; Phillip B Smith; Bhuvana Jayaraman; Peter C Adamson; Marc R Gastonguay; Jeffrey S Barrett Journal: Pediatr Infect Dis J Date: 2009-08 Impact factor: 2.129
Authors: Christopher C Blyth; Sharon C A Chen; Monica A Slavin; Carol Serena; Quoc Nguyen; Deborah Marriott; David Ellis; Wieland Meyer; Tania C Sorrell Journal: Pediatrics Date: 2009-05 Impact factor: 7.124
Authors: Daniel K Benjamin; Mark L Hudak; Shahnaz Duara; David A Randolph; Margarita Bidegain; Gratias T Mundakel; Girija Natarajan; David J Burchfield; Robert D White; Karen E Shattuck; Natalie Neu; Catherine M Bendel; M Roger Kim; Neil N Finer; Dan L Stewart; Antonio C Arrieta; Kelly C Wade; David A Kaufman; Paolo Manzoni; Kristi O Prather; Daniela Testoni; Katherine Y Berezny; P Brian Smith Journal: JAMA Date: 2014-05-07 Impact factor: 157.335
Authors: Jacqueline G Gerhart; Kevin M Watt; Andrea Edginton; Kelly C Wade; Sara N Salerno; Daniel K Benjamin; P Brian Smith; Christoph P Hornik; Michael Cohen-Wolkowiez; Shahnaz Duara; Ashley Ross; Karen Shattuck; Dan L Stewart; Natalie Neu; Daniel Gonzalez Journal: CPT Pharmacometrics Syst Pharmacol Date: 2019-05-22