Abstract and Introduction
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.
Coagulase-negative staphylococci (CoNS) are the most common cause of late-onset bloodstream infections (BSI) in hospitalized infants, accounting for 48% of infections. CoNS BSI has been shown to increase the incidence of intraventricular hemorrhage, retinopathy of prematurity, bronchopulmonary dysplasia, cerebral palsy and neurodevelopmental impairment. These long-term complications are associated with increased hospital length of stay and increased costs.
To avoid these complications, infants with suspected infection often receive empirical antibiotic therapy while awaiting culture results. Agents used for empirical antibiotic therapy vary by institution, postnatal age and clinical symptoms but frequently include vancomycin due to the high risk of CoNS infection.
Vancomycin is used for treatment of infections caused by CoNS and other gram-positive organisms, which are frequently resistant to beta-lactam antibiotics. However, use of empirical vancomycin is associated with increased incidence of infections caused by resistant organisms such as vancomycin-resistant Enterococcus and highly resistant enteric gram-negative bacteria. Moreover, the impact of empirical vancomycin therapy on the outcome of infants with CoNS infections is unknown.
In the current study, we used a large, nationally representative database to evaluate whether empirical vancomycin therapy improves outcomes for infants with CoNS BSI.