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No Survival Benefit With Empirical Vancomycin Therapy for Coagulase-negative Staphylococcal Bloodstream Infections in Infants

Ericson, Jessica E. MD*†; Thaden, Joshua MD, PhD; Cross, Heather R. DPhil; Clark, Reese H. MD§; Fowler, Vance G. Jr. MD, MHS†‡; Benjamin, Daniel K. Jr. MD, PhD*†; Cohen-Wolkowiez, Michael MD, PhD*†; Hornik, Christoph P. MD, MPH*†; Smith, P. Brian MD, MPH, MHS*†for the Antibacterial Resistance Leadership Group

The Pediatric Infectious Disease Journal: April 2015 - Volume 34 - Issue 4 - p 371–375
doi: 10.1097/INF.0000000000000573
Antimicrobial Report

Background: Coagulase-negative Staphylococcus (CoNS) is the most common cause of bloodstream infections (BSI) in hospitalized infants. CoNS BSI is most reliably treated with vancomycin; however, concerns about side effects and promoting resistance often delay empirical vancomycin therapy until culture results become available.

Methods: All infants with CoNS BSI discharged from 348 neonatal intensive care units managed by the Pediatrix Medical Group from 1997 to 2012 were identified. Empirical vancomycin therapy was defined as vancomycin exposure on the day of the first positive blood culture. Delayed vancomycin therapy was defined as vancomycin exposure 1–3 days after the first positive blood culture. We used multivariable logistic regression with random effects for site to evaluate the association between the use of empirical vancomycin therapy versus delayed vancomycin therapy and 30-day mortality, controlling for gestational age, small-for-gestational age status, postnatal age on the day of the first positive culture, oxygen requirement, ventilator support and inotropic support on the day the first positive culture was obtained.

Results: A total of 4364 infants with CoNS BSI were identified; 2848 (65%) were treated with empirical vancomycin. The median postnatal age at first positive culture was 14 days (interquartile range: 9, 21). Unadjusted 30-day mortality was similar for infants treated with empirical vancomycin and infants treated with delayed vancomycin therapy [166/2848 (6%) vs. 69/1516 (4%); P = 0.08]. There was no significant difference in 30-day mortality on multivariable analysis [odds ratio: 1.14 (0.84, 1.56)]. The median duration of bacteremia was 1 day longer for infants with delayed vancomycin therapy [4 days (interquartile range: 2, 6) vs. 3 days (2, 5); P < 0.0001].

Conclusions: The median duration of bacteremia was 1 day longer in infants with CoNS BSI who received delayed vancomycin therapy. Despite this finding, empirical vancomycin therapy for CoNS BSI was not associated with improved mortality.

From the *Department of Pediatrics, Duke University; Duke Clinical Research Institute, Duke University; Department of Medicine, Duke University, Durham, NC; and §Pediatrix-Obstetrix Center for Research and Education, Sunrise, FL.

Accepted for publication September 14, 2014.

This research was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number UM1AI104681. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

E. E. Ericson receives support from the National Institute of Child Health and Human Development of the National Institutes of Health under award number 5T32HD060558. D. K. Benjamin receives support from the United States government for his work in pediatric and neonatal clinical pharmacology (1R01HD057956-05, 1K24HD058735-05, UL1TR001117, and NICHD contract HHSN275201000003I) and the nonprofit organization Thrasher Research Fund for his work in neonatal candidiasis (http://www.thrasherresearch.org); he also receives research support from industry for neonatal and pediatric drug development (http://www.dcri.duke.edu/research/coi.jsp). V. G. Fowler receives salary support for research from the National Institutes of Health (K24AI093969, 2R01AI068804, and NO1AI90023); he also served as chair of V710 Scientific Advisory Committee (Merck), has received grant support from Cerexa, Pfizer, Advanced Liquid Logic, MedImmune, and Cubist (grant pending), has been a paid consultant for Merck, Astellas, Affinium, Theravance, Bayer, Cubist, Cerexa, Durata, Pfizer, NovaDigm, Novartis, Medicines Company, Biosynexus, MedImmune, and Inimex, and has received honoraria from Merck, Astellas, Cubist, Pfizer, Theravance, and Novartis. C. P. Hornik receives salary support for research from the National Center for Advancing Translational Sciences of the National Institutes of Health (UL1TR001117). M. Cohen-Wolkowiez receives support for research from the National Center for Advancing Translational Sciences (UL1TR001117), the Food and Drug Administration (1U01FD004858- 01), the Biomedical Advanced Research and Development Authority (BARDA) (HHSO100201300009C), the nonprofit organization Thrasher Research Fund (http://www.thrasherresearch.org), and from industry for drug development in adults and children (http://www.dcri.duke.edu/research/coi.jsp). P. B. Smith receives salary support for research from the National Institutes of Health and the National Center for Advancing Translational Sciences of the NIH (HHSN267200700051C, HHSN275201000003I, and UL1TR001117); he also receives research support from industry for neonatal and pediatric drug development (http://www.dcri.duke.edu/research/coi.jsp).

Address for correspondence: P. Brian Smith, MD, MHS, MPH, Duke University Medical Center, Duke Clinical Research Institute, 2400 Pratt St, Durham, NC 27705. E-mail: brian.smith@duke.edu.

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