neonatal antimicrobial stewardship 1141


figure 2. Late-onset sepsis evaluation and prescription events per 100 NICU attending days for 13 neonatologists, from 2011 to 2016. The gray lines represent provider-specific evaluation and prescription rates and the single black line represents the mean number of evaluation and prescription events for the entire group. Each period represents 1 year.


events was observed (P<.0001), declining by an average of 2.65 evaluations per attending per year (Figure 2). In 2016, the number of evaluations reached 8.4 per 100 NICU attending days, with less variability (range, 3.8–13.9 evaluations per 100 NICU attending days).


Compliance


Compliance with clinical guidelines was noted in 1,738 of 1,760 (98.75%) treatment courses performed during the stewardship period. In 22 cases of noncompliance, most deviations were related to improper selection of initial empiric coverage (eg, vancomycin instead of ampicillin for suspected EOS).


Balancing Measures


During the stewardship period, no infants with culture-proven or clinical infection developed a recurrent infection within 7 days of discontinuation of their antibiotic course. However, 3 infants who had an initial negative EOS evaluation underwent subsequent evaluation and treatment within 72 hours of discontinuation of the initial antibiotic course, all of which were secondary to spontaneous intestinal perforation. In all 3 cases, the subsequent evaluation was negative, but prolonged courses of antibiotics were administered.


discussion


In 2015, antibiotic resistance was labeled a national public health crisis in the United States.27 With the rise of antibiotic- resistant organisms outpacing development of new anti- microbials, drug shortages compromising availability of existing therapies, and more data emerging on the adverse effects of repeated and unnecessary antibiotic exposures,6–13 the practice of antibiotic stewardship has become one of necessity. Although development of antimicrobial resistance is multifactorial, inap- propriate antibiotic prescription is a major contributing factor.6


The Centers for Disease Control and Prevention estimate that approximately 50% of antibiotic prescription is unnecessary or not optimally effective.17 Cantey et al4 observed that 72% of infants in a level III NICU received at least 1 antibiotic course, with only 5% of antibiotics prescribed for treatment of culture-proven infection. Schulman et al28 documented 40-fold variation in antibiotic use among 127 California NICUs, with utilization varying from 2.4% to 97.1% of PD. No significant correlations were observed between antibiotic use and the burden of proven infection or NEC, surgical volume, or mortality. Patel et al29 assessed adherence to the Centers for Disease Control and Prevention’s 12-step campaign in 4 NICUs and determined that 24% of antibiotic days were inappropriate. A survey distributed to neonatologists revealed that some perceived antimicrobial resistance to be more of a national than local issue, and some lacked confidence in the accurate diagnosis and treatment of certain infections.30 To breakdown some of these barriers, we created guidelines


to assist with diagnosis and treatment, and we conducted an educational program that focused on the adverse consequences of repeated antibiotic exposures. We relied on timely data collection and distribution to allowfor real-time feedback and to facilitate open dialogue. Prior to ASP implementation, there was little transparency regarding antibiotic prescription practices but, with time, clinicians began to approach ASP team members for advice. This culture change is exemplified in our high rate of guideline compliance and reduction in LOS evaluations, and our outcomes reflect 3 major programmatic accomplishments: (1) a more thoughtful approach to antimicrobial prescription, (2) less variability in practice and, (3) adherence to evidence- based practices. We observed a significant decline in LOS evaluation and prescription events with ASP implementation that did not translate into a significant overall reduction in antimicrobial utilization. In our NICU, LOS evaluations encompass 20% of all prescription events, with EOS accounting for the majority. Our data highlight the need to focus additional efforts on the approach to EOS, which necessitates improvements in existing guidelines that drive practice.24–26 In particular, more accurate identification of those who require antibiotic therapy is greatly needed. Kiser et al31 demonstrated that application of the Committee on Fetus and Newborn’s guidelines for evaluation and treatment of infants exposed to maternal chorioamnionitis24 resulted in many well-appearing infantswith sterile blood cultures being treated with prolonged antibiotic courses, subjected to invasive procedures, and hospitalized for prolonged periods. The National Institute of Child Health and Human Development recently held a workshop to re-evaluate the management of newborns with a maternal diagnosis of chorioamnionitis. The recommended changes, if implemented, could substantially reduce unnecessary antimicrobial utilization in newborns.32 In addition, researchers at Kaiser Permanente have developed a multivariable risk prediction tool for early-onset infection.33 Implementation of their model in several NICUs significantly


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