Time and personnel requirements for antimicrobial stewardship in small hospitals in a rural area in Germany

Journal of Infection and Public Health 13 (2020) 1946–1950

Contents lists available at ScienceDirect

Journal of Infection and Public Health journal homepage: http://www.elsevier.com/locate/jiph

Original Article

Time and personnel requirements for antimicrobial stewardship in small hospitals in a rural area in Germany Irit Nachtigall a,b , Sascha Tafelski b , Edwin Heucke c , Oliver Witzke d , Annedore Staack e , Sabine Recknagel-Friese f , Christine Geffers g , Marzia Bonsignore h,∗ a

Department for Hygiene, Helios Kliniken Ost and Bad Saarow, Pieskower Str. 33, 15526 Bad Saarow, Germany Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Klinik für Anästhesiologie mit Schwerpunkt Operative Intensivmedizin, Campus Charité Mitte, Charitéplatz 1, 10115 Berlin, Germany c Helios Cluster Saxony-Anhalt, Helios Bördeklinik, Kreiskrankenhaus 4, 39387 Oschersleben, Germany d Universitätsmedizin Essen, Department of Infectious Diseases, West German Centre of Infectious Diseases, University Duisburg-Essen, Hufelandstraße 55, 45147 Essen, Germany e Helios Klinik Jerichower Land, August-Bebel-Str. 55a, 39288 Burg, Germany f Helios Klinikum Erfurt, Nordhäuser Str. 74, 99089 Erfurt, Germany g Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institut für Hygiene und Umweltmedizin, Hindenburgdamm 27, 12203 Berlin, Germany h Zentrum für Hygiene, Evangelische Kliniken Gelsenkirchen, Munckelstr. 27, 45879 Gelsenkirchen, Germany b

a r t i c l e

i n f o

Article history: Received 17 June 2020 Received in revised form 2 September 2020 Accepted 5 October 2020 Keywords: Antibiotic stewardship Antimicrobial stewardship programm Clostridioides difficile

a b s t r a c t Background: In order to control their anti-infectives consumption, hospitals are required to provide multidisciplinary teams comprising among others an infectiologist, a microbiologist and a pharmacist. Small hospitals though often do not dispose of the defaulted personnel. This study illustrates a solution for an antimicrobial stewardship program (ASP) in small community hospitals in a rural area in Germany. Methods: Four hospitals of ca. 200 beds each, jointly hired an antimicrobial stewardship expert to start a common ASP. This expert did rounds on every ward once a week, mostly as chard reviews with the physician in charge. Outside the rounds, he could be consulted by mail. Working time and number of visited patients were documented. Anti-infectives consumption, incidence of Clostridioides difficile infections (CDI) and mortality rates were retrieved from routinely collected data. The intervention period (01/2018–12/2018) was compared to the preintervention period (01/2017–12/2017). Results: 3321 patients were visited in the intervention period. In average, 20 patients were seen per day and 20 min were needed per patient/ chard. About 65% of the expert’s working time was needed for rounds, 15% for driving between the hospitals. The anti-infectives consumption of the 4 hospitals in the preintervention period amounted to 50 defined daily doses per 100 occupied bed days. The total consumption was reduced by 10% and of quinolones by 36%. The incidence of hospital-acquired CDI receded from 0.14 to 0.07 cases per 100 patient days (−50%, p = 0.001). The overall in-hospital mortality did not change. Conclusions: A single expert was able to implement a successfull ASP in 4 hospitals. While multidisciplinary antimicrobial stewardship teams are ideal for tertiary care hospitals, small hospitals need a more practical solution. This survey shows that one expert can be sufficient for several small hospitals even with the distances in a rural setting. © 2020 The Authors. Published by Elsevier Ltd on behalf of King Saud Bin Abdulaziz University for Health Sciences. This is an open access article under the CC BY-NC-ND license (http://creativecommons. org/licenses/by-nc-nd/4.0/).

Introduction

∗ Corresponding author. E-mail addresses: [email protected] (I. Nachtigall), [email protected] (M. Bonsignore).

The main element in the fight against the world-wide increase in antimicrobial resistances is the limitation of the (over-) use of anti-infectives. The need to intervene in the threatening development has reached the agenda of politics, and pressure is increased

https://doi.org/10.1016/j.jiph.2020.10.001 1876-0341/© 2020 The Authors. Published by Elsevier Ltd on behalf of King Saud Bin Abdulaziz University for Health Sciences. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

I. Nachtigall et al.

on health care providers to develop antimicrobial stewardship programs (ASPs). These programs usually contain a bundle of measures aiming to improve the quality of anti-infectives prescription practice regarding indication, substance, dosage and duration. Several publications have shown that ASPs can reduce the consumption of antibiotics [1–5] and consequently antibiotic resistance and the incidence of Clostridioides-difficile-infections (CDI). In the USA, since September 2019 hospitals are required to develop and implement antimicrobial stewardship programs in order to receive payments from the Centers for Medicare and Medicaid Services (CMS) [6]. In Germany, the law for infection control (Infektionsschutzgesetz) of 2011 commits hospitals to analyse and confront their consumption of anti-infectives and to follow the guidelines of the Commission for Anti-infectives, Resistence und Therapy (Commission ART). The German-Austrian practice guideline for use of anti-infectives in hospitals recommends creating multidisciplinary committees in hospitals in charge of ASPs [7].These teams should include a clinician with expertise in infectiology (ideally an infectious disease specialist), a hospital pharmacist, a microbiologist (ideally a clinical microbiologist) and an infection control physician. Core tasks of antimicrobial stewardship teams are the analysis of anti-infectives consumption, the development of facility-specific clinical practices guidelines, in-house teaching and prospective audit and feed-back. The estimated personnel requirement for antimicrobial stewardship is one full-time equivalent (FTE) per 500 acute care beds [7]. About 80% of the hospitals in Germany though, have a size of 400 acute care beds or less [8]. Arithmetically, they would need less than one FTE. With an already limited time quota needed to be shared between several team members, a multidisciplinary committee becomes difficult to build. Furthermore, most small community hospitals don‘t provide infectious diseases specialists; microbiology and pharmacy are often outsourced. The majority of studies on antimicrobial stewardship that led to national and international guidelines have been performed in large, academic hospitals and tertiary facilities. The lack of resources and personnel in smaller hospitals limits the application of the guidelines. Therefore, more applicable solutions need to be developed for this section of the healthcare system. The objective of this study was to assess a possible approach for implementing an antimicrobial stewardship program in small community hospitals in a rural area.

Methods We conducted a retrospective analysis of an antimicrobial stewardship program in small hospitals. Four hospitals of approx. 200 acute care beds each (in total 789 beds) started a common antimicrobial stewardship program. This included the hospitals of Burg, Köthen, Neindorf/Oschersleben and Zerbst. The hospitals are part of the Helios Group, a private health care provider comprising 86 hospitals in Germany. The 4 hospitals lay in a rural area in the eastern part of Germany, within a radius of 70 km. They provide what in the German hospital rating system is regarded as basic care, including internal medicine, geriatrics, surgery, gynaecology and obstetrics, paediatrics, urology, otolaryngology (ENT) and include 46 beds of intensive care (Table 1). Since 2010, the German Association of Infectiology has been offering specialization courses in antimicrobial stewardship addressing physicians and pharmacists. The courses of a total duration of 160 h conclude with the title “antimicrobial stewardship expert”. Aim of this education initiative is to create a wide-spread basic knowledge in Germany to promote ASPs. In 2017, the ASP project was planned, and an antimicrobial stewardship expert was hired. In November and December 2017, a “dry run” of the planned routine visits was conducted to examine the

Journal of Infection and Public Health 13 (2020) 1946–1950

feasibility. The dry run followed the masterplan that was developed by the team of the hospital in Köthen: • • • • • • • •

08:30–09:00 Trauma surgery 09:00–09:30 Orthopedics 09:30–10:30 Cardiology 10:30–11:00 Gynecology Break 11:30–12:30 General and Vascular Surgery 12:30–13:30 Gastroenterology 13:30–15:30 Intensive Care Medicine

After a planning and trial phase, the project started on January 01, 2018. From Mondays to Thursdays, the expert visited daily one of the hospitals and did rounds on all wards. Every patient receiving anti-infectives or with any question related to infectious diseases was discussed. The rounds were absolved mostly as chard review with one of the physicians in charge, independently from the habitual ward round. In more complicate or unclear cases, the patients were visited at their beds. To review the therapies, microbiological findings and laboratory parameters were evaluated as well as the medical history and the secondary diagnoses. Outside the rounds, the expert could be consulted by mail. These were answered after the visiting hours or in breaks. No telephone number was introduced, so the visiting hours were not disturbed. Each visiting day was followed by the postprocessing of the ward rounds and the finalisation of the documentation done on the ward. Additionally, the expert did in-house teachings. Fridays were dedicated to the work on facility-specific clinical practices guidelines, to gaining resistance analyses from the different laboratories that serve the hospitals, to preparing lectures and to documentation. At the beginning of the program, the expert introduced “antibiotic stickers”. These stickers had to be placed in the paper chards on day 1 and day 3 of the antibiotic therapy. On the sticker on day 1, the focus, the antibiotic, the way of application (intravenous or oral) and the start had to be documented; on day 3 the microbiological findings, and if needed an adjustment of the therapy. Both stickers had to be signed by the prescribing doctor. In the pre-intervention period, the only existing guideline in the hospitals on anti-infectives was one on perioperative antibiotic prophylaxis. The Helios group has an antimicrobial stewardship task force, that includes antimicrobial stewardship experts, infectiologists, microbiologists and pharmacists. They develop stringent group-wide guidelines for therapy and prophylaxis and provide anti-infectives consumption analyses. With beginning of the program, the expert adapted these guidelines to each facility and published them in the separate intranets. For special questions and complicated infectiological cases he could contact members of the task force. No changes in infection control and prevention were applied during the study period. Before the project started, no restrictions for anti-infectives prescriptions were applied.

Anti-infectives consumption and microbiological data Antiiinfectives use data is monitored continuously for each hospital of the Helios Group, expressed in defined daily doses (DDD) per 100 occupied bed-days (OBD) and includes antibacterial, antifungal, antimycobacterial and antiviral drugs. The consumption is monitored for single substances as well as for substance classes according to the WHO ATC group classification. In each of these hospitals, infection control nurses document all infections with C. difficile as well as their origin (hospital versus community acquired) with a specially programmed, intranet-based database (iNOK). 1947

I. Nachtigall et al.

Journal of Infection and Public Health 13 (2020) 1946–1950

Table 1 Structural data of the hospitals included in the study. Hospital

Number of beds

Cases in 2017

Cases in 2018

Fatalities 2017/rate

Fatalities 2018/rate

Departments

Burg

231

11,636

12,174

239/0.021

270/ 0.022

Köthen

214

11,104

11,534

245/0.022

230/0.020

Neindorf

184

9888

9996

273/0.028

255/0.026

Zerbst

160

9040

8608

129/0.014

120/0.014

Internal medicine, geriatrics, surgery, gynecology and obstetrics, pediatrics, ENT Internal medicine, surgery, urology, gynecology and obstetrics Internal medicine, geriatrics, surgery, urology Internal medicine, surgery, ENT

Total

789

41,668

42,312

886/0.021

875/0.021

Outcomes The primary outcome was defined as time needed per patient and number of visits that were possible in the working hours of the expert. Secondary outcome parameters were defined as differences in anti-infectives consumption expressed as DDD/100 OBD, the incidence of nosocomial infections with C. difficile and death of any cause. The preintervention period for anti-infectives consumption, C. difficile-infections and mortality was defined from January to December 2017, the intervention period from January to December 2018.

Table 2 Working time of the antimicrobial stewardship expert. Action

Time per week (appr.)

Rounds Consultations per mail Teaching, facility-specific guidelines Driving Total

26 h; 20 min per patient 4h 5h 7h 42 h

Statistics Data on anti-infectives consumption, nosocomial infections with C. difficile and on mortality of the four hospitals were aggregated. Exploratory analysis of data was based on descriptive statistics. Frequencies of numbers and mean as the measures of central tendency were used according to scale level. Statistical significance was analysed by paired t-tests with corresponding confidence intervals of observed differences or by non-parametric Wilcoxon signed-rank test in case of deviations from normal distribution of data. All analyses were performed with SPSS 25.0 with two-sided alpha level of <5% and two-sided. The study is a retrospective observational study with non-confirmatory design and was approved by the responsible ethics committee.

Results In the year of the intervention, the expert discussed in total 3321 patients with a current anti-infective therapy or with a problem related to infectious diseases; these were about 8% of all in-patients in the 4 hospitals in 2018. In average, 20 patients were visited each day and 20 min were needed per patient. 12% of the anti-infective therapies needed correction; the most common intervention was the ending of an anti-infective therapy (8% of all visits), followed by the recommendation of change or deescalation (4%). About 65% of the expert’s working time was needed for rounds, about 15% for driving between the hospitals (Table 2). The average anti-infectives consumption of the 4 hospitals before start of the ASP amounted to 50 DDD/ 100 OBD. All hospitals reduced their consumption in the first year of the program, on average by 10% (Table 2, p = 0.023. The consumption of quinolones was reduced by 36% (p = 0.19), of 3rd-generation-cephalosporins by 20% (p = 0.52), of carbapenems by 20% (p = 0.595), while penicillins increased by 32% (p = 0.006) (Fig. 1).

Fig. 1. Development of antibiotic consumption by substance class (WHO ATC group classification). (DDD = defined daily doses, OBD = occupied bed-days, ASP = Antimicrobial stewardship program).

In the same period, the incidence of hospital-acquired CDI receded from 0,14 to 0,07 cases per 100 patients (−50%, p = 0,001), while the incidence of community acquired CID did not decrease significantly (p = 0,51). The death rate and the total number of in-patients did not change significantly between the pre-ASP and the ASP period (Table 3). Discussion Effects The antimicrobial stewardship program achieved a significant reduction in the overall use of anti-infectives, with a specific reduction in the consumption of quinolones, 3rd-generationcephalosporins and carbapenems, although not all reductions reached significance level. The effectiveness of ASPs has been described in many studies. Excessive prescriptions of cephalosporins, quinolones, clindamycin and carbapenems have been associated with increased rates of MRSA, extended spectrum beta-lactamases and CDI [9–11]. 1948

I. Nachtigall et al.

Journal of Infection and Public Health 13 (2020) 1946–1950

Table 3 Summary of results.

Patient No. Total anti-infectives consumption (DDD/ 100 OBD) 3-Generation-Cephalosporines (DDD/100 OBD) Quinolones (DDD/100 OBD) Carbapenems (DDD/100 OBD Penicillins (DDD/ 100 OBD) Community acquired CDI (cases/100 patients) Hospital acquired CDI (cases/100 patients) In-hospital mortality (deaths/100 patients)

2017

2018

Change

P-value

CI 95-intervals

41,668 49.94 4.12 7.02 2.19 13.5 0.17 0.14 2.13

42,312 44.87 3.27 4.48 1.99 17.81 0.13 0.07 2.06

+1.6% −10% −21% −36% −9% +32% −24% −50% −3%

0.513 0.023 0.581 0.068 0.595 0.006 0.51 0.001 0.825

−853.96 to 531.96 1.31–8.83 −2.99 to 4.77 −2.35 to 7.44 −0.88 to 1.29 −6.21 to −2.40 −0.11 to 0.18 0.05–0.08 −33.54 to 39.04

DDD = defined daily doses; OBD = occupied bed-days; CDI = Clostridioides-difficile-infections.

Depending on the initial situation and the interventions chosen, reductions in the antibiotic consumption by 10–30% [2,12,5,3] have been reported with a concomitant decrease in antibiotic resistance [2,13,14] and CDI [15,13,16,17]. The antimicrobial stewardship program in this study achieved a shift in prescriptions from cephalosporins, quinoles and carbapenems to penicillins, the antibiotic class with the least risk of collateral damage. This was associated with a significant reduction of the incidence of hospital acquired CDI. The results of this program are consistent with findings in studies conducted in large academic hospitals. Personnel The time required for the ASP in 4 hospitals with a total of 789 beds was 42 h per week (full-time position). The Austrian-German antimicorbial stewardship guideline estimate the time required for ASPs at one full-time equivalent (FTE) per 500 beds [7]. This is founded on several studies that have successfully implemented programs with an average personnel quota of this size [18,19,13]. However, the guidelines refer to some studies that achieved better results with higher staffing levels [20,21] and to the fact that there are several recommendations for more personnel. The European health authority ECDC specifies 1–3 FTEs per 500 beds [22], France recommends 3.3 FTEs per 500 beds [23] and USA 1.4 FTEs per 500 beds [24]. The one FTE recommended in the Austrian-German guideline is therefore regarded as a minimum requirement. The time contingent of the expert in the present study was approx. 0.76 FTE per 500 beds and therefore below the recommendations. The fact that his working time was still enough to achieve the described results might be explained in part with a lower complexity of patients in small hospitals compared to those in highly specialised institutions. Furthermore, this could indicate that weekly ward rounds are a time efficient strategy for antimicrobial stewardship; and last, the support provided by the superordinate antimicrobial stewardship task force will have facilitated the success of a single person. In Germany, the increasing economic pressure on hospitals leads to a growing trend of single facilities joining healthcare systems and networks. This creates the opportunity to share resources that might not be accessible otherwise and, like in our study, makes at least part of the expertise required for ASPs possible.

tals found significant decreases in antibiotics consumptions only when multiple measures were combined [25]. In direct comparison, post-prescription reviews and feedback have been found to be more effective than pre-prescription authorization [26]. In our study, the focus was on the weekly chard visit on every ward. It included all patients with a question related to infectious diseases and included therefore more patients than a pure post-prescription review would do. The visits accounted for 65% of the total working time. The most common corrective intervention was ending the therapies, which led to a noticeable decrease in overall antiinfectives consumption. The stronger effect though was the change in the substances chosen, with a decrease in the use of substances more prone to induce antibiotic resistance and CDI and an increase in penicillins. Since the expert rarely documented advising a substance change, this shift cannot be only due to the visits. In part, these findings could be a result of a Hawthorne effect [27]: it is possible that the physicians modified their anti-infectives practices because they knew that their therapy would be questioned. To another part this could be the result of education and training in the use of guidelines, achieving a behavioural change. As described elsewhere, especially in smaller hospitals methods that convince the staff and enable them to decide by themselves are more effective in the long run than methods that focus on restrictions [28–30].

Limitations This study is an uncontrolled before and after study. A better design would have been to add a suitable control group out of the other hospitals in the Helios Group. To demonstrate the impact of the antimicrobial stewardship program, we focussed on the reduction of anti-infectives use density and the shift in the substances. Other indicators of prescribing quality like the duration of therapy, shifts from intravenous to oral, or the adequate microbial diagnostics were not measured. The implemented interventions were very site-specific; it is hardly possible to draw general lessons from the results.

Strategy

Conclusion

In general, the core elements of antimicrobial stewardship programs are facility-specific clinical practices guidelines, prescription restrictions, education and prospective audit & feed-back. An antimicrobial stewardship audit means the evaluation of the prescribed anti-infectives with regard to indication, substance, dose and duration at the patient level; the results are usually discussed directly with the prescribing doctors. The ideal weighting of the single core elements of ASPs in limited working time is not yet clear. A cluster-randomized intervention in small hospi-

This survey examines the time and personnel that was needed for a successful antimicrobial stewardship program in four small community hospitals in a rural area. It shows data from a section of the health care system which provides care for a great share of patients, but is underrepresented in research, since most studies are carried out in large, academic hospitals. Taking into account the specific study characteristics and the consequent limitations, the results could be helpful for similar hospitals planning a new antimicrobial stewardship program. 1949

I. Nachtigall et al.

Journal of Infection and Public Health 13 (2020) 1946–1950

Authors’ contributions All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Irit Nachtigall and Marzia Bonsignore. Statistical analysis was performed by Sascha Tafelski. The first draft of the manuscript was written by Irit Nachtigall and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

[10] [11]

[12]

[13]

Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

[14]

[15]

Competing interests O.W. has received research grants for clinical studies, speaker’s fees, honoraria and travel expenses from Amgen,Astellas,Bristol-Myers Squibb,Chiesi,Hexal,JanssenCilag,MSD,Novartis,Roche,Pfizer, andSanofi. O.W. is supported by an unrestricted grant of the Rudolf-Ackermann-Stiftung(Stiftung für Klinische Infektiologie). I.N., S.T., E.H., A.S., S.R-F., C.G. and M.B. have no conflicts of interest.

[16]

[17]

[18]

Ethical approval [19]

The study is a retrospective observational study with nonconfirmatory design and was approved by the ethics committee of the Ärztekammer Berlin.

[20]

References

[21]

[1] Karanika S, Paudel S, Grigoras C, Kalbasi A, Mylonakis E. Systematic review and meta-analysis of clinical and economic outcomes from the implementation of hospital-based antimicrobial stewardship programs. Antimicrob Agents Chemother 2016;60(8):4840–52. [2] Bonsignore M, Balamitsa E, Nobis C, Tafelski S, Geffers C, Nachtigall I. Antibiotic stewardship an einem Krankenhaus der Grund-und Regelversorgung. Anaesthesist 2018;67(1):47–55. [3] Vaughn VM, Gandhi T, Conlon A, Chopra V, Malani AN, Flanders SA. The association of antibiotic stewardship with fluoroquinolone prescribing in Michigan hospitals: a multi-hospital cohort study. Clin Infect Dis 2019;69(8):1269–77. [4] Schröder S, Klein M-K, Heising B, Lemmen SW. Sustainable implementation of antibiotic stewardship on a surgical intensive care unit evaluated over a 10-year period. Infection 2019:1–8. [5] Kaki R, Elligsen M, Walker S, Simor A, Palmay L, Daneman N. Impact of antimicrobial stewardship in critical care: a systematic review. J Antimicrob Chemother 2011;66(6):1223–30. [6] Centers for Medicare & Medicaid Services (CMS). Medicare and Medicaid Programs; Regulatory Provisions To Promote Program Efficiency, Transparency, and Burden Reduction; Fire Safety Requirements for Certain Dialysis Facilities; Hospital and Critical Access Hospital (CAH) Changes To Promote Innovation, Flexibility, and Improvement in Patient Care. www.federalregister.gov/ documents/2019-20736. [Accessed 30 September 2019]. [7] Fachgesellschaften AdWM. S3-Leitlinie 092/001–Strategien zur Sicherung rationaler Antibiotika-Anwendung im Krankenhaus; 2018. [8] Statistisches Bundesamt. Gesundheit, Grunddaten der Krankenhäuser, Fachserie 12 Reihe 6.1.1; 2017 https://www.destatis. de/DE/Publikationen/Thematisch/Gesundheit/Krankenhaeuser/ GrunddatenKrankenhaeuser2120611177004.pdf? blob=publicationFile. [9] Hamprecht A, Rohde A, Behnke M, Feihl S, Gastmeier P, Gebhardt F, et al. Colonization with third-generation cephalosporin-resistant Enterobacteriaceae

[22]

[23]

[24]

[25]

[26]

[27]

[28]

[29]

[30]

1950

on hospital admission: prevalence and risk factors. J Antimicrob Chemother 2016;71(10):2957–63. Gastmeier P. Antibiotic Stewardship und Hygiene–2 Seiten einer Medaille. Anästhesiolo Intensivmed Notfallmed Schmerzther 2017;52(04):248–59. Tacconelli E, De Angelis G, Cataldo MA, Pozzi E, Cauda R. Does antibiotic exposure increase the risk of methicillin-resistant Staphylococcus aureus (MRSA) isolation? A systematic review and meta-analysis. J Antimicrob Chemother 2008;61(1):26–38. Scholze K, Wenke M, Schierholz R, Groß U, Bader O, Zimmermann O, et al. The reduction in antibiotic use in hospitals: a retrospective single-center study on microbiological characteristics and mortality. Dtsch Ärztebl Int 2015;112(42):714. Carling P, Fung T, Killion A, Terrin N, Barza M. Favorable impact of a multidisciplinary antibiotic management program conducted during 7 years. Infect Control Hosp Epidemiol 2003;24(9):699–706. Saizy-Callaert S, Causse R, Furhman C, Le Paih M, Thébault A, Chouaıd C. Impact of a multidisciplinary approach to the control of antibiotic prescription in a general hospital. J Hosp Infect 2003;53(3):177–82. Dancer S, Kirkpatrick P, Corcoran D, Christison F, Farmer D, Robertson C. Approaching zero: temporal effects of a restrictive antibiotic policy on hospital-acquired Clostridium difficile, extended-spectrum ␤-lactamaseproducing coliforms and meticillin-resistant Staphylococcus aureus. Int J Antimicrob Agents 2013;41(2):137–42. Sarma J, Marshall B, Cleeve V, Tate D, Oswald T, Woolfrey S. Effects of fluoroquinolone restriction (from 2007 to 2012) on Clostridium difficile infections: interrupted time-series analysis. J Hosp Infect 2015;91(1):74–80. Talpaert MJ, Gopal Rao G, Cooper BS, Wade P. Impact of guidelines and enhanced antibiotic stewardship on reducing broad-spectrum antibiotic usage and its effect on incidence of Clostridium difficile infection. J Antimicrob Chemother 2011;66(9):2168–74. Gums JG, Yancey Jr RW, Hamilton CA, Kubilis PS. A randomized, prospective study measuring outcomes after antibiotic therapy intervention by a multidisciplinary consult team. Pharmacother: J Hum Pharmacol Drug Ther 1999;19(12):1369–77. Standiford HC, Chan S, Tripoli M, Weekes E, Forrest GN. Antimicrobial stewardship at a large tertiary care academic medical center: cost analysis before, during, and after a 7-year program. Infect Control Hosp Epidemiol 2012;33(4):338–45. Doernberg SB, Abbo LM, Burdette SD, Fishman NO, Goodman EL, Kravitz GR, et al. Essential resources and strategies for antibiotic stewardship programs in the acute care setting. Clin Infect Dis 2018;67(8):1168–74. Ibrahim NH, Maruan K, Khairy HAM, Hong YH, Dali AF, Neoh CF. Economic evaluations on antimicrobial stewardship programme: a systematic review. J Pharm Pharm Sci 2017;20:397–406. European Centre for Disease Prevention and Control. Proposals for EU guidelines on the prudent use of antimicrobials in humans. Stockholm: ECDC; 2017 [Accessed 1 January 2020]. Le Coz P, Carlet J, Roblot F, Pulcini C. Human resources needed to perform antimicrobial stewardship teams’ activities in French hospitals. Med Mal Infect 2016;46(4):200–6. Centers for Medicare & Medicaid Services (CMS). Medicare and medicaid programs; hospital and critical access hospital (CAH) changes to promote innovation, flexibility, and improvement in patient care; 2016 https://www. federalregister.gov/documents/2016/06/16/2016-13925/medicare-andmedicaid-programs-hospital-and-critical-access-hospital-cah-changes-topromote. Stenehjem E, Hersh AL, Buckel WR, Jones P, Sheng X, Evans RS, et al. Impact of implementing antibiotic stewardship programs in 15 small hospitals: a clusterrandomized intervention. Clin Infect Dis 2018;67(4):525–32. Tamma PD, Avdic E, Keenan JF, Zhao Y, Anand G, Cooper J, et al. What is the more effective antibiotic stewardship intervention: preprescription authorization or postprescription review with feedback? Clin Infect Dis 2017;64(5):537–43. Yanes AF, McElroy LM, Abecassis ZA, Holl J, Woods D, Ladner DP. Observation for assessment of clinician performance: a narrative review. BMJ Qual Saf 2016;25(1):46–55. Goff DA, Reeve W, Naumovski S, Epson E, Zenilman J, Kaye KS, et al. Approaches to modifying the behavior of clinicians who are noncompliant with antimicrobial stewardship program guidelines. Rev Infect Dis 2016;63(4):532–8. Anderson DJ, Watson S, Moehring RW, Komarow L, Finnemeyer M, Arias RM, et al. Feasibility of core antimicrobial stewardship interventions in community hospitals. JAMA Netw Open 2019;2(8), e199369-e. Davey P, Brown E, Charani E, Fenelon L, Gould IM, Holmes A, et al. Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database Syst Rev 2013;(4).