1402
between the estimated outcome at the first time point of the intervention and that predicted by the preintervention trend, and the change in trend (slope change), defined as the difference between the preintervention slope and the intervention slope. The intervention trend was also estimated. For all other variables and rates, including those for anti-
microbials or antimicrobial groups with a high frequency of monthly zero use, average rates during the preintervention and intervention periods were compared using the Wilcoxon signed rank test. All tests of significance were 2-tailed, and a P value≤.05 was considered statistically significant.
Results Patient population and antimicrobial utilization
During the preintervention and intervention periods, 591 and 626 patients received outpatient hemodialysis at the enrolled facilities, respectively. Patient demographics and clinical characteristics were not statistically different between the 2 time periods (Table 1). Antimicrobial utilization by type, during the 28-month period, was as follows, given in doses per 100 patient months: vancomycin (12.32), cefazolin (3.30), gentamicin (2.17), cefepime (0.68), ceftazidime (0.19), ampicillin (0.15), daptomycin (0.11), and ceftriaxone (0.06).
Effect of the antimicrobial stewardship program
For all antimicrobials, there was no statistically significant change in level immediately after the intervention. The model estimated a change in slope after intervention (P=.06), resulting in a statis- tically significant decreasing trend of 6% monthly reduction in antimicrobial doses per 100 patient months (P=.02) (Table 2, Fig. 1a). The observed mean monthly rate of antimicrobial doses per 100 patient months at the beginning of the intervention was 22.6 doses, and this rate decreased to 10.5 at the end of the intervention. There were no significant changes in level or trend for vancomycin doses (Table 2, Fig. 1b). There were no statistically significant differences in the mean monthly rates for broad- spectrum cephalosporins (ie, cefepime, ceftazidime, or ceftriax- one), gentamicin, or cefazolin (Table 3).
Table 1. Patient Characteristics in the Preintervention and Intervention Periods
P Variable
Age, y, mean (± SD) Male, % Race, % White Black Other
Diabetes mellitus, %
Patients with tunneled catheters, %
Preintervention Intervention 65.7 ( ±2.3) 65.4 (±2.3) 63.6
63.5
65.1 29.2 5.7
57.3 12.6
63.9 28.2 7.9
60.2 12.8
.06 1.0
Value .56
1.0 .44 Clinical outcomes
We detected no significant changes in the mean rate of hospital admissions, all bloodstream infections (BSIs) and methicillin- resistant Staphylococcus aureus BSIs between the 2 periods (mean rate±SD during the preintervention period vs the intervention period): rate of hospital admissions per year (1.9±0.3 vs 1.8±0.4; P=.44), rate of all BSIs per 100 patient months (0.5±0.4 vs 0.5±0.3; P=.43), rate of methicillin-resistant Staphylococcus aureus BSIs per 100 patient months (0.04±0.06 vs 0.14±0.09; P=.06). The mean composite of facility-level quality measures also did not differ between the preintervention and intervention periods (mean score, 344±14 vs 357±11; P=.06).
Inappropriate antimicrobial use
During the monthly conference calls, criteria for antimicrobial administration were reviewed for each antimicrobial dose. Data for individual doses were compiled into antimicrobial courses, defined as antimicrobials administered for the treatment of an infection episode. In total, 220 antimicrobial courses were administered during the intervention period. During the calls, sufficient data to make informed recommendations were available for 145 (66%) courses. Antimicrobial adjustments were recom- mended for 30 (20.6%) of these courses. Reasons for adjustment in prescribing included (1) change from vancomycin to cefazolin for MSSA BSIs (40%), (2) antimicrobials discontinued as criteria for presumed BSIs, access-site infection or skin/soft-tissue infec- tion were not met (34%), (3) change from third- or fourth- generation cephalosporins to cefazolin for the treatment of an infection caused by a cefazolin-susceptible gram-negative patho- gen (12%), (4) discontinuation of dual antimicrobial therapy as single agent was sufficient (8%), and (5) other (6%).
Discussion
A multifaceted antimicrobial stewardship program specifically targeting the unique aspects of outpatient hemodialysis facilities was developed and implemented in 6 outpatient hemodialysis facilities over a 12-month period. The implementation of this educational and behavioral program was associated with sig- nificant reductions in antimicrobial use. During the intervention period, prescribing of all antimicrobial doses per 100 patient months decreased by 6% per month, with an initial mean of 22.6 antimicrobial doses per 100 patient months down to a mean of 10.5 antimicrobial doses per 100 patient months at the end of the intervention. We detected no significant increase in the incidence of negative clinical outcomes associated with reducing anti- microbial exposure. Mean rates of hospitalizations and BSIs were comparable between the preintervention and intervention periods. Analyses of specific antimicrobial types, including van- comycin, cefazolin, gentamicin, and broad-spectrum cephalos- porins, did not demonstrate significant decreases, which may reflect small sample sizes. A component of this antimicrobial stewardship program
included monthly reviews of the indications for all prescribed antimicrobials with the clinical managers of the enrolled facilities. Over the 12-month intervention period, these recommendations led to changes in 20.6% of antimicrobial courses. The most fre- quent recommendation was to prescribe cefazolin instead of vancomycin for an MSSA infection. Prescribing cefazolin instead of vancomycin in this setting is important for 2 reasons. First, it
Erika M.C. D’Agata et al
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