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

Abstract

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 1997–2012 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 vs. 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 Of the 4364 infants with CoNS BSI, 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.

Heart rate characteristic index monitoring for bloodstream infection in an NICU: a 3-year experience

“…7 The mortality rate in the control group was threefold higher than the rates found in a recent study of 4364 infants with CoNS BSI. 19 Thus, it is possible that the benefit of a reduction in CoNS-mediated sepsis mortality associated with HRC monitoring may not translate to NICUs with typical CoNS mortality rates. Our data did not allow calculation of accurate predictive indices by episode of HRC elevation in our cohort.…”

Pentoxifylline Treatment of Very Low Birth Weight Neonates with Nosocomial Sepsis

“…22 A similar study found that among neonates with LOS due to CoNS, vancomycin started on day 1 of therapy did not decrease the 30-day mortality rate compared with delayed vancomycin therapy started after blood culture results, although it did decrease the median duration of bacteremia by a day. 23 In our study, the most frequently isolated microorganism was CoNS, with the other isolated microorganisms being S. hominis, P. aeruginosa, and C. parapsilosis. Important pentoxifylline-associated adverse events are unusual.…”

Appropriate Use of Vancomycin in NICU Despite Free-for-All Policy

“…7 The results of the SCOUT (Surveillance and Correction of Unnecessary Antibiotic Therapy) study determined culture-negative sepsis to be a large reason for the inappropriate continuation of antibiotic therapy, often 7 days or longer. 8 Another study by Ericson and colleagues 9 in 2015 strongly argued toward a new emphasis on the appropriate discontinuation of antibiotics in the NICU because of an increased risk of adverse effects as well as a lack of benefit for empiric vancomycin versus delayed start of vancomycin for the treatment of CONS bloodstream infections. The study showed an effective use of a restricted antibiotic policy to help prevent the inappropriate continuation of such drugs as vancomycin in the setting of late-onset sepsis in the NICU.…”