Table 2.

Comprehensive Summary of Results.

Reference	Study design and study period	Study aim	Patients and setting	Country	AMS team	Intervention target	Intervention and comparator (who provided, how, where, when and how much)	Intervention subcategory (EPOC taxonomy)	Intervention function (education, persuasion, restriction, environmental restructuring, enablement)	Outcomes	Bias assessment
Pavese et al 26	Controlled before-after study Preintervention: February 2005 Postintervention: June 2005	To assess the effectiveness of an education session aimed to reduce inappropriate antibiotic use for patients with positive urine culture results	Adult inpatients with positive urine culture results Control group: Preintervention (N = 57), Postintervention (N = 80) Intervention group: Preintervention (N = 58), Postintervention (N = 57) One university affiliated tertiary teaching hospital	France	Yes (hospital’s multidisciplinary antimicrobial stewardship team)	Physicians	Educational session for physicians conducted by an infectious diseases physician (1-hour didactic session followed by group discussion, review and presentation of guidelines, and comment on 1-page report on inappropriate antibiotic use for UTIs) compared to dissemination of guideline and 1-page report on inappropriate antibiotic use for UTIs.	Educational meetings	Education (educational meetings)	Preintervention vs postintervention • Inappropriate antibiotic therapy  ◼ I: 65.5% vs 29.8%  ◼ C: 45.6% vs 43.8%  ◼ P = .007 (for first-order interaction between study group and period)	Serious
Linares et al 27	Quasi-experimental controlled study Convenience sample of urine samples collected 2-3 days per week (duration NR)	To determine whether a standardized memorandum added to the electronic medical record could result in a decrease in mean antimicrobial days for ASB, asymptomatic candiduria, and culture-negative pyuria	Inpatients with a urine culture or urinalysis that could trigger antimicrobial use for possible UTI (urine cultures with any growth and urinalyses with a report of pyuria, leukocyte esterase, or a nitrate) Control group (N = 30) Intervention group (N = 24) A tertiary Veterans Affairs teaching hospital	USA	NR	Prescribers	Educational memorandum reminding physicians of evidence-based guidelines against treating ASB and culture-negative pyuria was placed in charts of patients receiving systemic antimicrobials (this was done within 48 hours of urinalysis or urine culture collection if any of the following criteria were met: no documented UTI-related symptoms, presence of < 105 CFU/mL of a single pathogen on urine culture, or no pyuria) compared to usual care.	Reminders	Enablement (circumstantial reminders)	Intervention vs control • Mean number of antimicrobial-days for ASB  ◼ 2.2 +/- 3.06 vs 6.3 +/− 4.2 (absolute mean reduction = 4.1 days; relative reduction = 65%; unpaired t-test: P < .001)	Serious
Leis et al 28	Controlled before-after study January/June 2013 baseline period February/July 2013 intervention period	To evaluate impact of modified reporting for positive urine cultures	Noncatheterized inpatients compared to catheterized patients (control group) on medical and surgical units Control group: Preintervention (N = 28) Postintervention (N = 49) Intervention group: Preintervention (N = 37) Postintervention (N = 37) One acute care teaching hospital	Canada	NR	Clinicians	Positive urine cultures were not automatically released to the unit, instead the lab released a standard statement and recommended if clinicians strongly suspected a UTI to call the microbiology laboratory. Results were only released if any clinician providing care to the patient called the lab Culture results for catheterized patients (control) were released automatically	The use of information and communication technology	Restriction (selective reporting of laboratory cultures)	Baseline vs post-intervention—rate of ASB treatment • I: 48% vs 12%, P = .002 • C: 42% vs 41% • Control rate of ASB treatment remained significantly above Intervention group ( P = .01) No clinical signs of UTI or sepsis in the intervention arm 72 hours after urine specimen collection	Serious
Irfan et al 29	Controlled before-after study (time series data) January 30, 2012—April 17, 2012, baseline period January 30th—April 30th, 2012, intervention period	To identify risk factors for unnecessary treatment and to assess the impact of an educational intervention focused on these risk factors on treatment of ABU	Hospitalized patients with positive urine cultures on general internal medicine teaching units. Two academic, tertiary acute care centers Baseline N = 160 patients total with ASB Intervention period - Control group (N = 29) - Intervention group (N = 24 patients)	Canada	If the senior author was not available, another infectious diseases physician delivered the session.	Prescribers	Initial education on ASB at Medical Grand Rounds for all residents and staff physicians in general internal medicine. As well, 15-minute educational sessions were offered as part of rounds on the clinical teaching units every 4 weeks for residents. The educational sessions included: an algorithm on management of UTI that emphasized nontreatment for ASB, and verbal feedback on baseline findings and recently encountered patients that were inappropriately managed. Comparator: control site and preintervention at the study site.	Educational meetings, educational materials, and audit and feedback	Education (educational meetings, dissemination of educational materials), Enablement (audit and feedback)	Intervention vs control site: • Inappropriate antibiotic use in ASB patients  ◼ Baseline: intervention 8/19 (42%) vs control 10/15 (67%) (OR 0.4, 95% CI 0.1-1.5; P = .15)  ◼ Postintervention: intervention 2/24 (8%) vs control 14/29 (48%) (OR 0.1, 0.02-0.5; P < .001) • Positive urine cultures ordered unnecessarily: intervention 24/93 (25.8%) vs control 29/62 (46.7%) (OR 0.4, 0.2-0.8; P = .007) Preintervention vs postintervention: • Odds of inappropriate treatment with antibiotics compared to baseline  ◼ Intervention OR 0.1 (95% CI, 0.02-0.7; P < .01)  ◼ Control OR 0.5 (95% CI, 0.1-1.7; P = .25)	Serious
Trautner et al 30	Controlled before-after study July 2010 to June 2013	To evaluate the effectiveness and sustainability of an intervention to reduce urine culture ordering and antimicrobial prescribing for catheter-associated ASB compared with standard quality improvement methods	Patients with urinary catheters on acute medicine wards and long-term care units (total 289 754 bed-days). Intervention targeted the health care professionals who order urine cultures and prescribe antimicrobials. Two tertiary Veterans Affairs teaching hospitals: the intervention site and comparison site	USA	Health care providers who participated in the Kicking-CAUTI project, previously and included three infectious diseases physicians	Prescribers treating patients with ASB or CAUTI (medical residents, staff physicians, nurses, physician assistants)	Email distribution of guidelines, algorithm pocket card distribution, and internal medicine grand rounds. Internal medicine team-based audit and feedback, in-service workshops with long-term care personnel, and Kicking CAUTI surveys. CAUTI working group established by a champion physician. Comparator: standard quality improvement methods (email distribution of guidelines, algorithm pocket card distribution, internal medicine grand rounds, and didactic overview of guidelines).	Educational materials, reminders, and audit and feedback	Education (dissemination of educational materials), environmental restructuring (reminders; pocket-size summaries), Enablement (audit and feedback)	Baseline vs intervention vs maintenance • Total number of urine cultures ordered and reported by the microbiology lab per 1000 bed-days  ◼ I: 41.2 vs 23.3 (P < .001) vs 12.0 (P < .001)  ◼ C: 49.3 vs 54.4 vs 46.6 (NS) • Urine cultures ordered per month over time between the two sites  ◼ Decreased (P < .001) • Incidence rates of overtreatment of ASB per 1000 bed-days  ◼ I: 1.6 vs 0.6 (P < .001) vs 0.4 (P < .001)  ◼ C: 0.6 vs 0.6 vs 0.5 (NS) • Rate of CAUTI undertreatment  ◼ Similar in all 3 periods at both sites.	No Information
O’Brien et al 201531	ITS January 1, 2006, to December 31, 2012	To evaluate the impact of stewardship initiated antimicrobial restriction on empirical use of ciprofloxacin on the nonsusceptibility of E. coli urinary isolates to ciprofloxacin	Hospitalized patients with positive urine cultures containing E. coli isolates. N = 3714 urine cultures during the study period A tertiary and quaternary academic medical center	USA	Yes and an on call infectious disease physician were available.	Prescribers treating patients with positive urine cultures containing E. coli	Formulary restriction on empirical use of ciprofloxacin (if the intended use of ciprofloxacin did not meet the indications listed on the restriction the prescriber was advised to consult with the antimicrobial stewardship team or on call ID physician for approval of the agent). Comparator: no formulary restrictions.	Local consensus process	Restriction (formulary restriction)	Preintervention vs postintervention • Ciprofloxacin use (DDD/1000 patient-days)  ◼ 141.1 vs 39.8 (P = NR) Over the entire 7-year period • E. coli urinary isolates nonsusceptible to ciprofloxacin  ◼ increased from 20.7% to 32.8% (P = .025) • After the introduction of ciprofloxacin restriction E. coli urinary isolates nonsusceptible to ciprofloxacin  ◼ decreased from 41.5% to 32.8% (P = NR)	Serious
Keller et al 32	ITS Baseline: September 2014 to June 2015 Post-intervention: September 2015 to June 2016	To design a multifaceted intervention to reduce unnecessary urinalysis and urine culture orders and treatment of ASB and investigate its impact	Hospitalized adult patients 18 years of age or older (Sample size NR) Large tertiary medical center	USA	NR	Department of medicine clinicians, institution wide health care providers	Multifaceted intervention (provider education and passive electronic clinical decision support) compared to usual care. Materials were disseminated through hospital-wide computer workstation screensavers and a 1-page e-mailed newsletter. CDS tool included simple informational messages recommending against urine testing without symptoms and against treating ASB; these messages accompanied electronic health record, orders for urinalysis, UC, and antibiotics commonly used within the institution to treat UTI. The information was displayed automatically when orders for these tests and antibiotics were selected.	Educational materials, reminders	Education Enablement (decision support through computerized systems or through circumstantial reminders)	Preintervention vs postintervention percentage of monthly admissions • Total urinalysis  ◼ 70.5% vs 60.3% (P = .24) • Total urine cultures  ◼ 18.2% to 11.8% (P < .001) • Urinalysis followed by antibiotic within 1-24 hours  ◼ 4.4 to 3.9% (P = .021) • Urine culture results followed by antibiotic within 24 hours  ◼ 1.7% to 1.5% (P = .036)	No information
Jenkins et al 33	Before and after study (secondary analysis of main outcomes using ITS analysis) Baseline: January 1, 2014 to December 31, 2014 Postintervention: July 1, 2015 to December 31, 2015	To assess effects of the collaborative on prespecified performance metrics	Adults 18 years of age or older with UTIs* admitted to hospital (N = 1530 baseline, N = 2530 postintervention) 26 teaching and nonteaching tertiary and community hospitals that were part of the Colorado Hospital Association	USA	Team lead at each hospital was identified and asked to organize a multidisciplinary team to carry out the intervention; the team lead was either an infectious diseases (ID) physician or pharmacist, when possible. Half of teams included an ID physician or pharmacist. 11 hospitals with established antibiotic stewardship program (ASP) 15 hospitals Considering an ASP or ASP in development	NR	Implementation of evidence-based guidelines for diagnosis and treatment of UTIs among adult inpatients. Hospitals were provided with guidance to promote uptake of guidelines using strategies feasible and appropriate at each site, for example, through education, prospective audit and feedback, or incorporation of recommendations into order sets. Colorado Hospital Association provided a number of services to support teams throughout the intervention period. This included quarterly performance reports, monthly webinars with pertinent antibiotic stewardship educational content, twice-monthly coaching newsletters, optional site visits, access to local and national antibiotic stewardship experts, and 3 in-person educational meetings.	Clinical practice guidelines, local consensus processes (guideline implementation), educational materials, educational meetings	Education (educational meetings, dissemination of educational materials)	Baseline vs intervention periods • Significant decrease trend of fluoroquinolone use  ◼ Decreased (P = .03) • Trends for proportion of cases meeting IDSA criteria for symptomatic UTI  ◼ NS (P = .10) • Duration of therapy  ◼ NS (P = .99)	Serious
Hecker et al 34	Quasi-experimental, ITS analysis January 1, 2008 through 2016	To determine the impact of stewardship interventions on UTI syndromes and fluoroquinolone use	Inpatients with a positive urine cultures (Sample size NR) Academic urban level 1 trauma center	USA	Yes (a formal antimicrobial stewardship program was implemented)	Prescribers treating patients with ASB or UTIs	Grand rounds and prescriber education, electronic medical record modifications (displaying previous urine cultures and links to ASB, uncomplicated UTI, and complicated UTI guidelines), and audit and feedback interventions were implemented in areas that had frequent nonadherence to guidelines. Grand rounds and small group educational sessions were provided. Educational sessions included data collected from the baseline evaluation as well as information on diagnosis and treatment of UTI, ASB, and appropriate use of urinary catheters.	Local consensus process, reminders, educational meetings, and audit and feedback	Education (educational meetings), environmental restructuring (EHR modifications including displaying previous urine cultures and links to ASB, uncomplicated UTI, and complicated UTI guidelines) Enablement (audit and feedback)	Over the 2-year intervention period • Inpatient fluoroquinolone use  ◼ Rate ratio = .91 (adjusted P < .01)  ◼ Change in slope of quarterly DDD/1000 patient days = −21.3 (adjusted P < .01)	Serious
Yoon et al 35	Controlled before-after study Baseline period: January 1, 2016—May 31, 2016 Intervention period: June 1, 2016 to August 31, 2016	To test the hypothesis that the introduction of the SCRIPT app would increase prescriber adherence to guidelines	Adult patients (>18 years) with UTI who had been admitted for ≥4 hours Control group: One Tertiary care teaching hospital; 1 teaching community hospital, and 1 non-teaching community hospital Preintervention (N = 422) Postintervention (N = 407) Intervention group: Tertiary care hospital Preintervention (N = 209) Postintervention (N = 211)	New Zealand	Yes	Prescribers	Development and implementation of a mobile phone app (SCRIPT) which provided the ACH antibiotic guidelines in a user-friendly, decision-making process format compared to usual care. The existing ACH antibiotic guidelines were directly mapped into decision trees that branched out to the eventual antibiotic treatment recommendations.	Local consensus processes (guideline implementation)	Enablement (decision support through computerized systems)	Baseline vs intervention • Guideline adherence  ◼ I : 47% vs 50% (P = .49)  ◼ C (Site 1): 45% vs 40% (P = .28)  ◼ C (Site 2/3): 24% vs 29% (P = .25)	Serious
Spoorenberg et al 38	Randomized trial Baseline period: February to November 2009 Intervention Implementation: April 15 to October 15 2010 Post-intervention: From 6 months after the intervention was implemented	To assess the effectiveness, measured as the before-and-after intervention performance on quality indicators, of 2 improvement strategies	Adults (≥ 16 years) who were referred to the hospital (inpatient/outpatient clinic) and diagnosed by an internist or urologist with a complicated UTI (including catheter-associated UTIs) as main diagnosis and treated as such. Baseline (N = 1964) Group 1 (N = 963) Group 2 (N = 1064) Internal Medicine and Urology departments of 19 teaching and nonteaching hospitals	The Netherlands	No	Prescribers	Group 1: Multi-faceted strategy (MFS) consisting of 3 phases: Phase I: feedback report (plenary meeting and MFS feedback report 1) Phase II: Standardized improvement activities initiated by the QUANTI trial team (standardized LOC meeting; kick-off meeting; improvement plan; Feedback report 2) Phase III: Optional and additional improvement activities (extra LOC meeting[s]; pocket (reminder) card; reminders; additional improvement actions) Group 2: Competitive feedback strategy (CFS): providing individual feedback to professionals by nonanonymously ranking the various departments. Competitive feedback reports contained, for each QI, a list of all 38 departments’ performance scores, in which the names of the MFS departments were blinded but the others were visible.	Educational sessions, reminders ("Critical-care pathway"-reminder pocket cards; reminder phone calls), and audit and feedback	Education (educational meetings), environmental restructuring (reminders) Enablement (audit and feedback)	Preintervention vs postintervention • Perform a urine culture (T1-T0)  ◼ MFS: +7.4% (P = .01)  ◼ CFS: +6.6% (P = .008) • Prescribe according to national guideline (T1-T0)  ◼ MFS: +1.4% (P = .83)  ◼ CFS: +3.2% (P = .32) • Switch from IV to oral therapy within 72 hours (T1-T0)  ◼ MFS: −2.9% (P = .47)  ◼ CFS: +4.5% (P = .48) • Tailor antibiotic treatment based on culture result (T1-T0)  ◼ MFS: +3.8% (P = .46)  ◼ CFS: +6.8% (P = .03) • Treatment duration should be at least 10 days (T1-T0)  ◼ MFS: −0.1% (P = .78)  ◼ CFS: −0.1% (P = .97) • Treat UTI in men according to national guideline (T1-T0)  ◼ MFS: +3.1% (P = .23)  ◼ CFS: +5.1% (P = .047) • Total QI set performance (mean of all patients [T1-T0])  ◼ MFS: +3.3% (P = .043)  ◼ CFS: +3.9% (P = .010)	Some concerns
Daley et al 36	Randomized, parallel, superiority trial January 3, 2017 to March 27, 2017	To compare two different methods of reporting positive urine cultures under the hypothesis that modified reporting of positive urine cultures among inpatients would reduce treatment of ASB without increasing untreated UTI, pyelonephritis, bacteraemia, or death	Inpatients aged 18 or older, with positive urine cultures (N = 55 urine cultures in the standard arm and N = 55 urine cultures in the intervention arm). Two tertiary care academic hospitals	Canada	NR	Prescribers	Modified report of positive urine cultures that informed the physician that significant bacterial growth was detected and unless requested, bacterial identification and susceptibility information was not provided compared to standard report (control) which included bacterial count, identification, and antibiotic susceptibility information along with drug dosages and cost.	The use of information and communication technology	Restriction (selective reporting of laboratory cultures)	Intervention vs comparator • Proportion of appropriate antibiotic prescribed  ◼ 80.0% vs 52.7% (ITT analysis, P = .002) • Bacteremia rate (cases)  ◼ 1 vs 2 • Untreated UTI  ◼ 2/20 vs 2/14 (P = .37) • Death(s)  ◼ 2 vs 1 • Cost savings (mean ± SD)  ◼ $19.84 ± $64.88 vs $35.78 ± $109.77 (P = .37)	Some concerns
Ridgway et al 37	Randomized controlled trial July 1, 2015, to June 30, 2018	To investigate the impact of WISCA utilization during active antimicrobial stewardship surveillance	RCT with crossover design Adult patients (N = 1803 patients with UTIs enrolled in the study) diagnosed with UTI during an inpatient hospitalization at four community and tertiary teaching hospitals	USA	Yes	Primary providers	WISCA (an electronic clinical decision support tool for inpatient antimicrobial stewardship) was utilized by the ASP physician to determine the most appropriate antibiotic regimen for patients with ABI or UTI. Intervention group: audit and feedback performed by the ASP physician to the primary provider via page or phone call and via written documentation in the electronic health record. Control group: the ASP physician recorded the recommended antibiotic in the study database but did not communicate the recommendation to the patient’s provider.	Reminders, educational outreach through review of individual patients and recommendations for change	Education (educational outreach through review of individual patients with recommendation for change) Enablement (decision support; educational outreach by review and recommend change)	Intervention vs comparator • Mean LOS (days [SD])  ◼ 4.50 (4.39) vs 4.54 (4.42) (P = .6899)  ◼ Subgroup: multivariable linear regression model coefficient estimate for UTI = .144 (P = .4809) • 30-day mortality  ◼ 5.49% vs 5.37% (P = .8730)  ◼ Subgroup: multivariable linear regression model adjusted OR for UTI = 1.494 (P = .1284)	High

Quality of care: Appropriateness of antimicrobial use, guideline adherence. Patient outcomes: Mortality, resolution of infection (including resolution of symptoms, if applicable), complications of infection, recurrence of infection, bacteremia. Utilization of services: Length of hospital stay, admission to intensive care units, re-admission rates. Adverse effects or harms: Medication associated adverse effects, antimicrobial resistance, colonization with multidrug resistant strains, C. difficile infection. Resource use: Cost, human resources, time, microbiologic testing, antimicrobial use metrics.

Abbreviations: ASB, asymptomatic bacteriuria; ASP, Antimicrobial stewardship physician; B, baseline; C, control; I, intervention; M, maintenance; FU, follow-up; CAUTI, catheter-associated urinary tract infection; CDI, C. difficile infection; CDS, computer decision support; CFU, colony-forming units; DDD, defined daily doses; IDSA, Infectious Diseases Society of America; IRR, incidence rate ratios; ITS, interrupted time series; ITT, intention-to-treat; LOS, length of stay; QI, quality indicator; RCT, randomized controlled trial; RR, rate ratio; UTI, urinary tract infection; WISCA, weighted incidence syndromic combination antibiogram; NR, not reported.

^*Results of the intervention for patients with skin and soft tissue infections reported separately and not included in this review.