Safety and Efficacy of Nafcillin for Empiric Therapy of Late-Onset Sepsis in the NICU

Abstract

BACKGROUND AND OBJECTIVE: In 2014 at Nationwide Children’s Hospital, the Neonatal Antimicrobial Stewardship Program recommended nafcillin over vancomycin for empirical therapy of possible late-onset sepsis (LOS) in infants without a history of methicillin-resistant Staphylococcus aureus colonization or infection. We report our experience with this guideline and assess its safety. METHODS: We retrospectively reviewed all infants who received nafcillin or vancomycin for empirical treatment of possible LOS at 3 NICUs before (January 2013–May 2014) and after (January 2017–March 2019) implementation of a vancomycin reduction guideline. Safety measures included duration of blood culture positivity, recurrence of infection with the same previously identified pathogen in the 14 days after discontinuation of antibiotic therapy, and mortality. RESULTS: Among 366 infants who received a first antibiotic course for possible LOS, 84% (95 of 113) and 25% (62 of 253) received empirical therapy with vancomycin before and after the guideline implementation, respectively, representing a 70% reduction. Nafcillin use increased by 368%. Duration of blood culture positivity did not differ before and after the guidance. In 2 infants, antibiotic therapy was restarted within 14 days of discontinuation of the initial therapy for recurrence of the same infection; both had received empirical vancomycin. Overall in-hospital mortality was 10%, and there was no difference before (9%) and after (10%) implementation of the vancomycin reduction guidance (odds ratio, 0.97). CONCLUSIONS: Nafcillin can be a safe alternative to vancomycin for empirical therapy of LOS among NICU infants who do not have a history of methicillin-resistant S aureus infection or colonization.

Experience With a Vancomycin-sparing Empiric Antibiotic Guideline for Late-onset Sepsis in a Level-4 Neonatal Intensive Care Unit

“…7,9 We observed MRSA bloodstream infections at a similarly low rate [3/250 (1.2%) LOS events] as others. 7,9 However, our guideline’s MRSI risk criteria failed to predict the single MRSA bacteremia among PostG infants. Case review revealed that a nasal MRSA screening had been negative 4 days before and positive 3 days after the sepsis evaluation.…”

“…Our experience aligns well with others' and highlights the usefulness of a multiprong approach to optimally reduce unnecessary neonatal vancomycin use. [5][6][7][8] Despite noted vancomycin reduction, guideline adherence was incomplete. Beside clinical decompensation/ill appearance, suspected NEC despite absent MRSI risk factors stood out.…”

“…Our report confirms that a vancomycin-sparing LOS guideline helps reduce vancomycin usage in a level-4 NICU. [5][6][7][8] As most NICU antimicrobial use is for empirical therapy, this guideline allowed a cut of one-third of unit-wide vancomycin use in addition to the previously achieved 30% reduction for stopping vancomycin after 48 hours when no MRSI had been isolated. Our experience aligns well with others' and highlights the usefulness of a multiprong approach to optimally reduce unnecessary neonatal vancomycin use.…”

“…Our risk criteria for MRSI-supporting empiric vancomycin initiation included a central line present and hemodynamic instability in addition to previous MRSA colonization or infection while others have focused solely on latter. [5][6][7] CoNS, one of the primary organisms for central line-associated infections, represents a low-virulence pathogen and a delayed start of effective treatment with vancomycin was shown to have no adverse clinical effect. 7 In our experience, presence of central line and hemodynamic instability were noted in 47% (118/250) and 10% (26/250) of infants with suspected LOS, respectively.…”

Short-course empiric antibiotic therapy for possible early-onset sepsis in the NICU

“…The input from the NEO-ASP during the study period informed practice and was a driving force responsible for its implementation and adherence. (24) The nding of only three positive bacterial blood cultures during the study period limits the safety of the intervention. However, the majority of antibiotic use in the NICU is in situations where the cultures are sterile and therein lies the relevance to every day NICU practice.…”