stewardship in the nicu 1145


period, although none exhibited a statistically significant decline. Ampicillin utilization did, however, decrease sig- nificantly (−22.5 DOT per 1,000 PD; P=.037). Yet, no cor- responding decrease in the incidence of early onset sepsis (EOS) or NEC was observed during the stewardship period; ampicillin was included in the empiric treatment regimen for these 2 indications at the study site. Although the data are not provided, the authors attribute the decreased use of ampicillin to the decreased duration of therapy for EOS and NEC as well as decreased use for urinary tract and postsurgical prophylaxis. These findings suggest that the treatment guidelines for discontinuing antibiotics were effective. The findings of Bizzarro et al7 evoke another question: Can


ampicillin (and by extension, gentamicin, which is often the additional agent used for empiric treatment of EOS) utilization be decreased even further by refining the criteria that prompt initiation and continuation of antibiotics for EOS? Determin- ing best practices to identify those infants at highest risk for EOS (ie, infants born in the setting of maternal chorio- amnionitis) has been challenging given the absence of sensitive and specific biomarkers to predict infection for this population. Currently, there are guidelines for EOS evalua- tions and initiation of antibiotic therapy.9 However, there is much concern in the neonatology community that strict adherence to these guidelines will result in otherwise well- appearing infants with sterile blood cultures but with other lab abnormalities (eg, elevated C-reactive protein or immature to total neutrophil ratio) being unnecessarily treated for ≥7 days for EOS.10 Given the growing evidence that the use of even ampicillin and gentamicin may adversely impact a neonate’s future health,6 a more accurate way to identify infants truly at risk for EOS is urgently needed. Other findings described by Bizzarro et al7 include the


remains: How is the study’s primary finding explained when implementation of an ASP would be expected to have resulted in significant declines in overall antibiotic utilization? We highlight some factors that may have been at play. First, the study NICU started off with a low rate of antibiotic utilization (270.4 DOT per 1, 000 PD) compared to peer NICUs (mean, 526.8 DOT per 1,000 PD), based on data from the Pediatric Health Information System. Prior to rolling out their ASP, the study site already utilized a restricted formulary. They had also


reduction in late-onset sepsis (LOS) evaluations by an average of 2.65 evaluations per NICU attending physician per year as well as the decrease in the physician-to-physician variability in conducting LOS evaluations during the stewardship period. These declines likely represent the confluence of multiple factors beyond the 2 core AS strategies including the use of clinical guidelines, feedback to individual practitioners regarding guideline compliance, and an ongoing concerted educational effort. Granted, the decline in LOS evaluations did not impact overall antibiotic utilization, but the fact that LOS prescriptions only accounted for ~20% of antibiotic use at the study site explains, in part, the lack of an overall effect. While these secondary outcomes are of value, the question


successfully implemented an initiative to decrease central line- associated bloodstream infections.11 These factors likely con- tributed to the low preintervention antibiotic utilization rate that left less room for improvement during the stewardship period. And, as noted previously, their stewardship inter- vention could not fully address one of the major drivers of antibiotic use: treatment of suspected EOS. Finally, the optimal outcome metric(s) for antimicrobial stewardship in the NICU is unknown. Although the authors used one of the most commonly employed metrics of DOT per 1,000 PD for their primary outcome measure, they recognized that the lack of an evidence-based metric that best correlates with the success or failure of an antimicrobial stewardship initiative could be a limitation. In conclusion, optimizing antibiotic use in the NICU is challenging given the vulnerability of neonates to infection but necessary given the adverse effects of antibiotic misuse. Bizzarro et al7 demonstrate that the implementation of a NICU-specific ASP is feasible, and their findings support the need for a multipronged approach to stewardship that includes the use of clinical guidelines, educational efforts, and audit and feedback of both adherence to guidelines and antibiotic use. Their work provides a blueprint that can guide future NICU-specific ASP efforts and can be modified to meet the needs of other NICUs. Still, ongoing work is needed as impactful stewardship interventions should not only target antibiotic prescribing, but also address the diagnostic uncer- tainties that drive antibiotic initiation and continuation; better tools to more accurately identify those neonates who truly need treatment for culture-negative EOS are particularly needed.


acknowledgments


Financial support: No financial support was provided relevant to this article. Potential conflicts of interests: All authors report no conflicts of interest


relevant to this article. Address correspondence to Lisa Saiman, MD, MPH, Columbia University


Medical Center, Department of Pediatrics, 622 W. 168th St, PH4-470, New York, NY 10032 (Ls5@cumc.columbia.edu).


references


1. Penicillin’s finder assays its future. New York Times 1945 June 26; p. 21.


2. Barlam TF, Cosgrove SE, Abbo LM, et al. Implementing an antibiotic stewardship program: guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis 2016;62:e51–e77.


3. Get smart for healthcare. Centers for Disease Control and Pre- vention website. https://www.cdc.gov/longtermcare/prevention/ antibiotic-stewardship.html. Updated February 28, 2017. Accessed July 9, 2017.


4. Kaufman D, Fairchild KD. Clinical microbiology of bacterial and fungal sepsis in very-low-birth-weight infants. Clin Microbiol Rev 2004;17:638–680.


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84  |  Page 85  |  Page 86  |  Page 87  |  Page 88  |  Page 89  |  Page 90  |  Page 91  |  Page 92  |  Page 93  |  Page 94  |  Page 95  |  Page 96  |  Page 97  |  Page 98  |  Page 99  |  Page 100  |  Page 101  |  Page 102  |  Page 103  |  Page 104  |  Page 105  |  Page 106  |  Page 107  |  Page 108  |  Page 109  |  Page 110  |  Page 111  |  Page 112  |  Page 113  |  Page 114  |  Page 115  |  Page 116  |  Page 117  |  Page 118  |  Page 119  |  Page 120  |  Page 121  |  Page 122  |  Page 123  |  Page 124  |  Page 125  |  Page 126  |  Page 127  |  Page 128  |  Page 129  |  Page 130  |  Page 131  |  Page 132  |  Page 133  |  Page 134  |  Page 135  |  Page 136  |  Page 137  |  Page 138  |  Page 139  |  Page 140  |  Page 141  |  Page 142  |  Page 143  |  Page 144