In this before-after study, we evaluated the impact of an ID specialist-led daily postprescription carbapenem intervention with weekly feedback for long-term carbapenem users. Our intervention was effective in reducing carbapenem consumption without causing a change in in-hospital mortality or an increase in the consumption of alternate broad-spectrum antimicrobials. We found that the number of courses of carbapenem, but not the duration of carbapenem use, decreased, indicating a possible beneficial effect of our intervention on improving prescribing behavior.
The present study has three important findings. First, it is noteworthy that our study demonstrates the positive effect of our ASP even in a resource-limited setting. There is limited information on in-hospital ASP in Asia, and resources and settings are diverse among each country and hospital [9, 13, 14]. In Japan, the resources were generally insufficient to meet the demands for implementing an ideal ASP [15], and therefore there is a necessity in developing ID-trained pharmacists and ID specialists [9]. Although PPRF is a well-established intervention, there are few resource-rich Japanese hospitals implementing early PPRF against overall antimicrobial use for 48–72 hours. Therefore, we must make a practical plan to implement the stewardship according to available institutional resources: e.g., focusing on broad-spectrum antimicrobials and/or longer duration of use, and providing once-weekly intervention [16–19]. In our hospital, the number of ID physicians was particularly insufficient; there were no ID fellows, and one (part time) and two (full time and part time) ID specialists worked in the baseline and intervention periods, respectively. As a result, only an FTE of 0.16 was devoted to the additional stewardship activity by an ID specialist; however, it is noteworthy that our strategy had a positive effect on reducing carbapenem consumption. Hence, we highlight the positive impact of our ASP strategy, which may be a reasonable and acceptable alternative, particularly in resource-limited settings.
Second, our study indicates that a predominant factor in the decrease of carbapenem consumption might be in behavior change among prescribers. In our study, ESBL-producing Enterobacteriaceae strains were more frequently identified in the intervention period than in the baseline period, a trend similar to that seen in national and local surveillance data in Japan [11]. Therefore, it is meaningful that carbapenem consumption decreased in the intervention period, despite being one of the first-line agents for ESBL-producing Enterobacteriaceae. Interestingly, although we did not provide alternate empirical antimicrobial choices or restrict carbapenem prescription, empirical carbapenem use decreased, which suggests that our intervention was indirectly or comprehensively relevant to changing prescribing behavior. Prescription trends of all available intravenous antimicrobials at our facility showed that the monthly trend in piperacillin-tazobactam consumption increased only temporarily before decreasing, but the change in level was not significant after the initiation of the intervention. There was no compensatory increase in the other antipseudomonal agents including fourth-generation cephalosporins, fluoroquinolones, and aminoglycosides (Table S1). Further, carbapenem-sparing agents such as ceftazidime-avibactam and ceftolozane-tazobactam were not available in our hospital during the study period. As a result, the comprehensive evaluation enables us to know that our intervention might promote optimal use of antimicrobials—that is, reduce unnecessary empirical carbapenem use and using narrow-spectrum antimicrobials such as first- and third-generation cephalosporins—without a change in in-hospital mortality. Thus, we emphasize that not only a reduction in carbapenem consumption but also the positive impact of ASPs on optimizing the use of antimicrobials; the concepts supported by several previous reports [19, 20].
Third, our study suggests that, in addition to intervention made by the ID specialist, several factors comprehensively affected the reduction in carbapenem consumption and optimal use of antimicrobials. We only provided direct intervention for 96 (7.7%) of 1,241 courses of carbapenem, and the duration of carbapenem use was not influenced by this. Similar to our weekly feedback, weekly e-mail-based notification alone failed to show a positive impact on reducing carbapenem consumption in a previous study [19]. However, by adding the weekly feedback to the daily intervention on carbapenem use for ≥ 14 days, synergistic positive effects and a competitive mindset among departments may occur. Further, a hospital president approved our intervention and announced the importance of the intervention and information on antimicrobial resistance to all medical staff at the facility before the initiation of our intervention. The credit and education might yield a further positive influence on growing awareness problems on antimicrobials and changing prescribing behavior. Moreover, leadership of ID consultation services changed from hospitalists to the ID specialist since April 2017 (four month before the initiation of our intervention). We conducted several in-hospital notifications to increase the use of ID consultation services. The campaign and daily ID consultation service without ASP activities might achieve a positive impact on optimal use of antimicrobials. We believe that, in addition to daily intervention, the weekly feedback, president’s credit, education of medical staff, and campaigns of using ID consultation services all comprehensively and synergistically contributed to a reduction in carbapenem consumption and optimal use of antimicrobials. Hence, we believe that taking action is important without giving up ASP activities in resource-limited settings.
This study has several limitations. First, this is a single-center study in Japan, and thus, it is uncertain whether our hospital-based ASP strategy can be applicable worldwide. Schweitzer et al described that only 48% and 23% of studies evaluating antimicrobial stewardship interventions reported clinical and microbiological outcomes, respectively [21]. However, we evaluated these outcomes, and it is noteworthy that our ASP strategy led to a decrease in carbapenem consumption with prescribing behavior change in a resource-limited setting. Second, we could not investigate the length of hospital stay among patients with infectious diseases and infectious disease-related total medical cost reduction. However, we would like to emphasize the impact on cost reduction that our ASP accomplished on overall intravenous antimicrobial-related saving of $255,352 in addition to annual estimated carbapenem-related savings ($83,745) on the basis of the annual purchasing cost. Third, there is evidence that the implementation of hospital-based ASP had a positive influence on microbiological outcomes [13, 22, 23]; however, our study did not show the positive microbiological impact on the hospital-acquired multidrug-resistant pathogens and infections. This may be because of the insufficient number of events and short observation period. Further, several studies showed a synergistic effect of hand-hygiene improvement combined with ASP on microbiological outcomes in the hospital [14, 24]. Thus, we should promote the implementation of hospital-based ASP with hand-hygiene intervention as well as a local-regional ASP to improve microbiological outcomes, and continue further outcome evaluation.
This before-after study showed the positive impact of an ID specialist-led ASP on reductions in carbapenem consumption and antimicrobial-related cost without adversely affecting the increase of broad-spectrum antimicrobial consumption and in-hospital mortality. We believe that an important path to success in hospital-based ASP is investigating institutional/local issues of antimicrobial prescription and making a practical plan according to available institutional resources. In particular, the favorable and reliable relationship between prescribers and the AST is vital in bringing about high compliance and prescribing behavior change among prescribers, which can finally lead to optimal use of antimicrobials. Even in resource-limited settings, we advocate that taking any action is warranted even if it is not PPA and early PPRF.