1138 infection control & hospital epidemiology october 2017, vol. 38, no. 10


undergoes at least 1 major surgical procedure during their stay, and those necessitating any procedure other than major cardiothoracic surgery recover in the NICU. All neonates admitted to our NICU and prescribed antimicrobials from January 1, 2011, to June 30, 2016, were eligible for inclusion. The Yale University Human Investigation Committee approved this investigation.


Program Design and Implementation The design process for this ASP began in July 2012. At that time, the only component of an ASP that existed at our institution was formulary restriction for select antimicrobials. A multi- disciplinary team was formed consisting of a neonatologist, a neonatal-perinatal medicine fellow (who led the initiative), a pediatric infectious diseases physician, a pediatric clinical pharmacist, a NICU registered nurse, and an infection control practitioner. Core members completed educational training modules on principles of antimicrobial stewardship.22 Partici- pation was voluntary, and no funding was directly applied to the design, implementation, or maintenance of the program. A review of medical literature was undertaken to develop


clinical guidelines for common neonatal infections to curtail provider-to-provider variability in prescription. Recommenda- tions focused on evaluation and treatment and included standard durations of treatment for “clinical sepsis” (ie, culture-negative sepsis) and postoperative antibiotic prophylaxis. NICU-specific antibiograms were compiled and included. A draft of the guide- lines was distributed to staff for feedback and, once finalized, published on our hospital-based intranet to facilitate access. A unit-wide educational effort was launched in early 2013.


Sessions were held that (1) outlined the principles and strategies of antibiotic stewardship, (2) introduced clinical guidelines, (3) reviewed baseline data, and (4) described outcome measures. The program was officially launched on May 1, 2013, as the first ASP at YNHCH. To facilitate implementation and reinforce key concepts, a


pediatric clinical pharmacist attended patient care rounds. A daily report from the electronic medical record was generated and distributed to ASP team members that included all prescribed antimicrobials and their rationales, and all cultures and their results. Reports were reviewed daily to allow for timely prescriber audit and feedback. Recommendations were then made to the clinical care team that included interpretation of positive cultures, opportunities to narrow broad-spectrum antimicrobial coverage, suggested duration of therapy, and discontinuation of antimicrobials in the setting of negative cultures and resolution of clinical signs of infection. The ASP teammet quarterly to review data, discuss feedback,


address programmatic issues, and make modifications. A monthly summary was distributed to all staff detailing the number of evaluations for suspected infection, antibiotic utilization, positive cultures, and compliance with guidelines. An educational topic was selected based on any guideline deviations or consistent themes.


Study Design and Outcomes


We conducted a quasi-experimental study with interrupted time series aimed at determining the impact of an ASP on antimicrobial utilization in the YNHCH NICU. The preintervention period was defined as January 1, 2011, through June 30, 2012, and the stewardship period was July 1, 2012, through June 30, 2016. Our primary outcomemeasure was days of therapy (DOT) per 1,000 patient days (PD), compiled monthly. Data were collected from the Pediatric Health Infor- mation System, which includes comprehensive data from some of the largest children’s hospitals with the most demanding standards of pediatric service in North America. The aggregate sumof antimicrobial use in ourNICUincluded any antibacterial or antifungal administered intravenously, intramuscularly, or orally and excluded antivirals, topical, ophthalmic, and nebulized antimicrobials. Data were collected separately for ampicillin, gentamicin/tobramycin, vancomycin, cefotaxime, and clindamycin, which constituted 92% of antimicrobials prescribed in our NICU. Notably, tobramycin was substituted for gentamicin from April through November 2011 due to a shortage. Gentamicin and tobramycin data were therefore combined. Standard empiric antibiotic regimens in our NICU include (1) ampicillin and gentamicin for suspected early-onset sepsis (EOS; laboratory confirmed blood or cerebrospinal fluid culture at ≤72 hours of life), (2) vancomycin and gentamicin for suspected late-onset sepsis (LOS; >72 hours of life), and (3) ampicillin and gentamicin (with clindamycin added for ≥ stage IIA23) for NEC. Our standard practice is to discontinue empiric therapy after 48 hours in the setting of negative cultures and resolution of clinical signs of infection. As a secondary outcome, we assessed the number of


attending-specific LOS evaluation and antimicrobial prescrip- tion events per 100 days of NICU service (ie, the decision to obtain cultures and initiate antimicrobials for each neonatologist pertimespenton-servicein theNICU).Eventswerecompared annually for 13 attending neonatologists who remained on faculty for at least 5 years of the study period. The decision to perform an LOS evaluation is made primarily by the neonatol- ogist based on clinical assessment and judgment regarding the likelihood of infection. Alternatively, the decision to initiate evaluation and treatment for EOS has traditionally been based on application ofmanagement guidelines and algorithms created by national organizations and expert panels.24–26 We surmised that educational efforts conducted as part of our ASP (ie, the emphasis on weighing the perceived risk of infection vs that of unnecessary antibiotic exposure) would more directly influence the decision-making scenario surrounding a LOS evaluation. As balancing measures, each infection was reviewed in detail


for timeliness of recognition. We also assessed whether infants with clinical or culture-proven infections had recurrence of infection within 7 days of discontinuation of their treatment course, and whether infants with a negative evaluation had antibiotics restarted within 72 hours of discontinuation of their initial course.


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