neonatal antimicrobial stewardship 1139 Statistical Analysis
Descriptive and outcome data from the entire NICU popula- tion admitted during the study period were compared between the preintervention and stewardship periods. Univariate comparisons were made via Pearson χ2 test for dichotomous data and Student t test for continuous data. Interrupted time-series analysis was used to estimate change
in antimicrobial use after ASP implementation, controlling for preintervention trends and other autocorrelations. SAS proce- dure PROC AUTOREG was used to examine change in level and/or trend of antimicrobial utilization following the inter- vention. A change in level is defined by an increase or decrease in the outcome after the intervention, which measures the abrupt intervention effect.A change in trend is defined by an increase or decrease in the slope of the period after the intervention as compared with the period preceding the intervention. This represents a gradual change in the value of the outcome post- intervention. The trend of LOS evaluations per 100 days on servicewas evaluated using linear mixed-effectsmodel,with time entered as fixed effects. A 2-sided P value<.05 was considered statistically significant. All analyses were performed with SAS software, version 9.4 (SAS Institute, Cary, NC).
results
No statistically significant difference in birth weight, gestational age, sex, the burden of laboratory-confirmed infection, or NEC was noted in the populations admitted to the NICU during the preimplementation and stewardship periods (Table 1).
Antibiotic Utilization
Mean monthly antibiotic utilization rates were 270.4 DOT per 1,000 PD in the preintervention period and 258.8 in the stewardship period, representing a 4.3% decrease from baseline. By comparison, mean monthly antibiotic utilization rates from peer NICUs in the Pediatric Health Information System were 526.8 DOT per 1,000 PD over the pre-intervention period and 416.6 during the stewardship period. Mean monthly ampicillin utilization in our NICU decreased during the stewardship phase by 12.8% from the preintervention
rate (118.6 vs 103.4 DOT per 1,000 PD). Mean monthly vanco- mycin utilization decreased by 35.5% from the preintervention rate (32.1 vs 20.7 DOT per 1,000 PD), and mean monthly cefo- taxime utilization decreased by 40.2% from the preintervention rate (19.4 v. 11.6DOT per 1,000 PD). Mean monthly gentamicin/ tobramycin usage increased by 19.4% from the preintervention period (68.7 vs 82.0 DOT per 1,000 PD), and mean monthly clindamycin utilization increased by 20.8% from the pre- intervention period (15.9 vs 19.2 DOT per 1,000 PD).
Interrupted Time Series Analysis
No significant month-to-month changes in overall DOT per 1,000 PD were observed before ASP implementation (P for baseline trend=.861). Following the start of stewardship period, overall DOT per 1,000 PD decreased by 14.7. This decrease was not statistically significant (P=.669). No significant month-to-month change in trend was noted during the stew- ardshipperiod(P for trend change=.838) (Figure 1a). Use of ampicillin decreased significantly by 22.5 DOT per
1,000 PD following initiation of our ASP (P=.037) (Figure 1b). No significant month-to-month change during the pre-intervention period (P for baseline trend=.235) or trend change during the stewardship period was observed (P for trend change=.217). Gentamicin/tobramycin use declined by 0.36 DOT per 1,000 PD with ASP implementation (P=.984) with no significant month-to-month changes noted pre-implementation (P for baseline trend=.314) or subsequently (P for trend change=.313) (Figure 1c). Vancomycin utilization appeared to decline before the inter-
vention, but the trend was not statistically significant (P for baseline trend=.189). At the start of the stewardship period, vancomycin use decreased by 1.1 DOT per 1,000 PD (P=.844), with no significant change in month-to-month trend noted after the intervention (P for trend change=.390) (Figure 1d). Cefotaxime use declined in the preintervention period (P for baseline trend=.061), and decreased by 0.79 days per 1,000PDat thestartofthestewardship phase(P=.889). We observed a marginally significant change in the month-to-month trend during the stewardship compared to the preintervention period (P for trend change=.065) (Figure 1e).
table 1. Comparison of Infants Admitted to the Yale-New Haven Children’s Hospital Neonatal Intensive Care Unit in the Preimplementation and Stewardship Periods
Variable Birth weight, g±SD
Any culture-proven bloodstream and/or cerebrospinal fluid infection Necrotizing enterocolitis
Gestational age, wks±SD Extremely low birth weight Male
NOTE. SD, standard deviation. aUnless otherwise noted.
Preimplementation (N=1,204), No. (%)a
2,571.3±1,013.7 35.4±4.7 118 (9.8) 674 (56) 31 (2.6) 24 (2)
Stewardship
(N=3,347), No. (%)a 2,586.6±1,006.9
35.5±4.5 282 (8.4)
1,887 (56.4) 68 (2)
72 (2.2)
P Value .652
.509 .148 .806 .252 .740
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