Opioid exposure as a potential risk factor for vancomycin-resistant enterococci colonization in the absence of antimicrobial exposure.

BACKGROUND: Antimicrobial exposure leads to an increased risk of colonization and spread of vancomycin-resistant enterococci. Studies have also implicated exposure to nonantimicrobial medications as a potential risk factor for an increased risk of colonization with these pathogens. METHODS: A matched case-control study was performed to determine specific nonantimicrobial medications associated with vancomycin-resistant enterococci rectal colonization. Cases and controls were defined as persons who were not exposed to antimicrobials in the preceding 12 months and in whom vancomycin-resistant enterococci rectal colonization was and was not detected at hospital admission, respectively. Matching was performed by the date of admission. Data were extracted from electronic medical records and included patient demographics, clinical data, and exposure to non-antimicrobial medications in the preceding 90 days. RESULTS: Vancomycin-resistant enterococci colonization was identified among 2,919 (4.8%) patients during their first admission among 59,986 admissions. Among these patients, 27 cases were identified and were matched to 63 controls. Exposure to opioids was the only independent risk factor associated with colonization (adjusted odds ratio 3.8 [95% confidence interval 1.4-10.8], P-value = .01). CONCLUSIONS: Opioid exposure may increase the risk of vancomycin-resistant enterococci colonization. Preventing the acquisition of these pathogens may require infection-prevention efforts targeting persons exposed to opioids.

High Burden of Intestinal Colonization With Antimicrobial-Resistant Bacteria in Chile: An Antibiotic Resistance in Communities and Hospitals (ARCH) Study.

BACKGROUND: Antimicrobial resistance is a global threat, heavily impacting low- and middle-income countries. This study estimated antimicrobial-resistant gram-negative bacteria (GNB) fecal colonization prevalence in hospitalized and community-dwelling adults in Chile before the coronavirus disease 2019 pandemic. METHODS: From December 2018 to May 2019, we enrolled hospitalized adults in 4 public hospitals and community dwellers from central Chile, who provided fecal specimens and epidemiological information. Samples were plated onto MacConkey agar with ciprofloxacin or ceftazidime added. All recovered morphotypes were identified and characterized according to the following phenotypes: fluoroquinolone-resistant (FQR), extended-spectrum cephalosporin-resistant (ESCR), carbapenem-resistant (CR), or multidrug-resistant (MDR; as per Centers for Disease Control and Prevention criteria) GNB. Categories were not mutually exclusive. RESULTS: A total of 775 hospitalized adults and 357 community dwellers were enrolled. Among hospitalized subjects, the prevalence of colonization with FQR, ESCR, CR, or MDR-GNB was 46.4% (95% confidence interval [CI], 42.9-50.0), 41.2% (95% CI, 37.7-44.6), 14.5% (95% CI, 12.0-16.9), and 26.3% (95% CI, 23.2-29.4). In the community, the prevalence of FQR, ESCR, CR, and MDR-GNB colonization was 39.5% (95% CI, 34.4-44.6), 28.9% (95% CI, 24.2-33.6), 5.6% (95% CI, 3.2-8.0), and 4.8% (95% CI, 2.6-7.0), respectively. CONCLUSIONS: A high burden of antimicrobial-resistant GNB colonization was observed in this sample of hospitalized and community-dwelling adults, suggesting that the community is a relevant source of antibiotic resistance. Efforts are needed to understand the relatedness between resistant strains circulating in the community and hospitals.

Prevalence and trends of Clostridioides difficile infection among persons requiring maintenance hemodialysis: A systematic review and meta-analysis.

OBJECTIVE: Clostridioides difficile infection (CDI) is among the most common cause of healthcare-associated infections. Persons requiring maintenance hemodialysis (MHD) are at increased risk of CDI and associated mortality compared to persons not requiring MHD. Given the clinical impact of CDI among persons requiring MHD, we aimed to quantify the burden of CDI and trends over time in this patient population. STUDY DESIGN: A systematic review and meta-analysis of studies reporting rates of CDI among persons requiring MHD in MEDLINE, Embase, Web of Science Core Collection, CINAHL, and Cochrane Central Register of Controlled Trials were performed. Searches were conducted on May 17, 2021, and March 4, 2022. RESULTS: In total, 2,408 titles and abstracts were identified; 240 underwent full text review. Among them, 15 studies provided data on rates of CDI among persons requiring MHD, and 8 of these also provided rates among persons not requiring MHD. The pooled prevalence of CDI among persons requiring MHD was 19.14%, compared to 5.16% among persons not requiring MHD (odds ratio [OR], 4.35; 95% confidence interval [CI], 2.07-9.16; P = .47). The linear increase in CDI over time was significant, increasing an average of 31.97% annually between 1993 and 2017 (OR, 1.32; 95% CI, 1.1-1.58; P < .01). The linear annual increase was similar among persons requiring and not requiring MHD (OR, 1.28; 95% CI, 1.13-1.45; P = .11). CONCLUSIONS: Persons requiring MHD have a 4-fold higher risk of CDI compared to persons not requiring MHD, and rates of CDI are increasing over time in both groups.

Provider adherence to training components from the Trial to Reduce Antimicrobial use In Nursing home residents with Alzheimer's disease and other Dementias (TRAIN-AD) intervention.

Background: The Trial to Reduce Antimicrobial use In Nursing home residents with Alzheimer's disease and other Dementias (TRAIN-AD) was a cluster randomized clinical trial evaluating a multicomponent program to improve infection management among residents with advanced dementia. This report examines facility and provider characteristics associated with greater adherence to training components of the TRAIN-AD intervention. Methods: Logistic regression was used to identify facility and provider characteristics associated with: 1. Training seminar attendance, 2. Online course completion, and 3. Overall adherence, defined as participation in neither seminar nor course, either seminar or course, or both seminar and course. Results: Among 380 participating providers (nurses, N = 298; prescribing providers, N = 82) almost all (93%) participated in at least one training activity. Being a nurse was associated with higher likelihood of any seminar attendance (adjusted odds ratio (AOR) 5.37; 95% confidence interval (CI), 2.80-10.90). Providers who were in facilities when implementation begun (AOR, 3.01; 95% CI, 1.34-6.78) and in facilities with better quality ratings (AOR, 2.70; 95% CI, 1.59-4.57) were more likely to complete the online course. Prevalent participation (AOR, 2.01; 95% CI, 1.02-3.96) and higher facility quality (AOR, 2.44; 95% CI, 1.27-4.66) were also significantly associated with greater adherence to either seminar or online course. Conclusion: TRAIN-AD demonstrates feasibility in achieving high participation among nursing home providers in intervention training activities. Findings also suggest opportunities to maximize adherence, such as enhancing training efforts in lower quality facilities and targeting of providers who join the facility after implementation start-up.

The Trial to Reduce Antimicrobial Use in Nursing Home Residents With Alzheimer Disease and Other Dementias (TRAIN-AD): A Cluster Randomized Clinical Trial.

Importance: Antimicrobials are extensively prescribed to nursing home residents with advanced dementia, often without evidence of infection or consideration of the goals of care. Objective: To test the effectiveness of a multicomponent intervention to improve the management of suspected urinary tract infections (UTIs) and lower respiratory infections (LRIs) for nursing home residents with advanced dementia. Design, Setting, and Participants: A cluster randomized clinical trial of 28 Boston-area nursing homes (14 per arm) and 426 residents with advanced dementia (intervention arm, 199 residents; control arm, 227 residents) was conducted from August 1, 2017, to April 30, 2020. Interventions: The intervention content integrated best practices from infectious diseases and palliative care for management of suspected UTIs and LRIs in residents with advanced dementia. Components targeting nursing home practitioners (physicians, physician assistants, nurse practitioners, and nurses) included an in-person seminar, an online course, management algorithms (posters, pocket cards), communication tips (pocket cards), and feedback reports on prescribing of antimicrobials. The residents' health care proxies received a booklet about infections in advanced dementia. Nursing homes in the control arm continued routine care. Main Outcomes and Measures: The primary outcome was antimicrobial treatment courses for suspected UTIs or LRIs per person-year. Outcomes were measured for as many as 12 months. Secondary outcomes were antimicrobial courses for suspected UTIs and LRIs when minimal criteria for treatment were absent per person-year and burdensome procedures used to manage these episodes (bladder catherization, chest radiography, venous blood sampling, or hospital transfer) per person-year. Results: The intervention arm had 199 residents (mean [SD] age, 87.7 [8.0] years; 163 [81.9%] women; 36 [18.1%] men), of which 163 (81.9%) were White and 27 (13.6%) were Black. The control arm had 227 residents (mean [SD] age, 85.3 [8.6] years; 190 [83.7%] women; 37 [16.3%] men), of which 200 (88.1%) were White and 22 (9.7%) were Black. There was a 33% (nonsignificant) reduction in antimicrobial treatment courses for suspected UTIs or LRIs per person-year in the intervention vs control arm (adjusted marginal rate difference, -0.27 [95% CI, -0.71 to 0.17]). This reduction was primarily attributable to reduced antimicrobial use for LRIs. The following secondary outcomes did not differ significantly between arms: antimicrobials initiated when minimal criteria were absent, bladder catheterizations, venous blood sampling, and hospital transfers. Chest radiography use was significantly lower in the intervention arm (adjusted marginal rate difference, -0.56 [95% CI, -1.10 to -0.03]). In-person or online training was completed by 88% of the targeted nursing home practitioners. Conclusions and Relevance: This cluster randomized clinical trial found that despite high adherence to the training, a multicomponent intervention promoting goal-directed care for suspected UTIs and LRIs did not significantly reduce antimicrobial use among nursing home residents with advanced dementia. Trial Registration: ClinicalTrials.gov Identifier: NCT03244917.

Suggestions for the prevention of Clostridioides difficile spread within outpatient hemodialysis facilities.

Clostridioides difficile infections (CDIs) cause substantial morbidity and mortality. Patients on maintenance hemodialysis are 2 to 2.5 times more likely to develop CDI, with mortality rates 2-fold higher than the general population. Hospitalizations due to CDI among the maintenance hemodialysis population are high, and the frequency of antibiotic exposures and hospitalizations may contribute to CDI risk. In this report, a panel of experts in clinical nephrology, infectious diseases, and infection prevention provide guidance, based on expert opinion and published literature, aimed at preventing the spread of CDI in outpatient hemodialysis facilities.

Factors Associated With Antimicrobial Use in Nursing Home Residents With Advanced Dementia.

OBJECTIVES: Widespread antimicrobial misuse among nursing home (NH) residents with advanced dementia raises concerns regarding the emergence of multidrug-resistant organisms and avoidable treatment burden in this vulnerable population. The objective of this report was to identify facility and resident level characteristics associated with receipt of antimicrobials in this population. DESIGN: Cross-sectional analysis of baseline data from the Trial to Reduce Antimicrobial use in Nursing home residents with Alzheimer's disease and other Dementias (TRAIN-AD). SETTING AND PARTICIPANTS: Twenty-eight Boston area NHs, 430 long stay NH residents with advanced dementia. MEASURES: The outcome was the proportion of residents who received any antimicrobials during the 2 months prior to the start of TRAIN-AD determined by chart review. Multivariable logistic regression was used to identify resident and facility characteristics associated with this outcome. RESULTS: A total of 13.7% of NH residents with advanced dementia received antimicrobials in the 2 months prior to the start of TRAIN-AD. Residents in facilities with the following characteristics were significantly more likely to receive antimicrobials: having a full time nurse practitioner/physician assistant on staff [adjusted odds ratio (aOR) 3.02; 95% confidence interval (CI), 1.54, 5.94], fewer existing infectious disease practices (eg, antimicrobial stewardship programs, established algorithms for infection management) (aOR, 2.35; 95% CI 1.14, 4.84), and having fewer residents with severely cognitively impaired residents (aOR 1.96; 95% CI 1.12, 3.40). No resident characteristics were independently associated with receipt of antimicrobials. CONCLUSIONS AND IMPLICATIONS: Facility-level characteristics are associated with the receipt of antimicrobials among residents with advanced dementia. Implementation of more intense infectious disease practices and targeting the prescribing practices of nurse practitioners/physician assistants may be critical targets for interventions aimed at reducing antimicrobial use in this population.

Opportunities to Improve Antibiotic Prescribing in Outpatient Hemodialysis Facilities: A Report From the American Society of Nephrology and Centers for Disease Control and Prevention Antibiotic Stewardship White Paper Writing Group.

Antibiotic use is necessary in the outpatient hemodialysis setting because patients receiving hemodialysis are at increased risk for infections and sepsis. However, inappropriate antibiotic use can lead to adverse drug events, including adverse drug reactions and infections with Clostridioides difficile and antibiotic-resistant bacteria. Optimizing antibiotic use can decrease adverse events and improve infection cure rates and patient outcomes. The American Society of Nephrology and the US Centers for Disease Control and Prevention created the Antibiotic Stewardship in Hemodialysis White Paper Writing Group, comprising experts in antibiotic stewardship, infectious diseases, nephrology, and public health, to highlight strategies that can improve antibiotic prescribing for patients receiving maintenance hemodialysis. Based on existing evidence and the unique patient and clinical setting characteristics, the following strategies for improving antibiotic use are reviewed: expanding infection and sepsis prevention activities, standardizing blood culture collection processes, treating methicillin-susceptible Staphylococcus aureus infections with ß-lactams, optimizing communication between nurses and prescribing providers, and improving data sharing across transitions of care. Collaboration among the Centers for Disease Control and Prevention; American Society of Nephrology; other professional societies such as infectious diseases, hospital medicine, and vascular surgery societies; and dialysis provider organizations can improve antibiotic use and the quality of care for patients receiving maintenance hemodialysis.

Efficacy and safety of sofosbuvir in the treatment of hep C among patients on hemodialysis: a systematic review and meta-analysis.

Hepatitis C virus (HCV) infection among maintenance hemodialysis patients is implicated in increased morbidity and mortality compared to uninfected patients. Sofosbuvir (SOF)-based regimens may not be optimal among patients requiring hemodialysis. Several studies, however, provide evidence that use of SOF among HCV-positive patients with renal impairment, is effective and safe. We searched Pubmed and Embase to identify studies reporting the efficacy and safety of SOF-based regimens for the treatment of HCV-positive patients on maintenance hemodialysis and performed a random effects meta-analysis. The overall pooled estimate of the efficacy of SOF-based therapy was 95% (95% CI 91-98%). The efficacy of the SOF-based regimen was 92% (95% CI 80-99%), 98% (95% CI 96-100%), and 100% (95% CI 95-100%) for the following doses: 400 mg on alternate days, 400 mg daily, and 200 mg daily, respectively. The most frequent adverse event was fatigue with a pooled prevalence of 16% (95% CI 5-29%), followed by anemia 15% (95% CI 3-31%), and nausea or vomiting 14% (95% CI 4-27%). Anemia was more prevalent in treatment regimens containing ribavirin (46%, 95% CI 33-59%) compared to ribavirin-free regimens (3%, 95% CI 0-9%). This study suggests that SOF-based regimens in the treatment of HCV infection among hemodialysis patients are both effective and safe.

Covariate-constrained randomization for cluster randomized trials in the long-term care setting: Application to the TRAIN-AD trial.

Little has been reported on strategies to ensure key covariate balance in cluster randomized trials in the nursing home setting. Facilities vary widely on key characteristics, small numbers may be randomized, and staggered enrollment is often necessary. A covariate-constrained algorithm was used to randomize facilities in the Trial to Reduce Antimicrobial use In Nursing home residents with Alzheimer's Disease and other Dementias (TRAIN-AD), an ongoing trial in Boston-area facilities (14 facilities/arm). Publicly available 2015 LTCfocus.org data were leveraged to inform the distribution of key facility-level covariates. The algorithm was applied in waves (2-8 facilities/wave) June 2017-March 2019. To examine the algorithm's general performance, simulations calculated an imbalance score (minimum 0) for similar trial designs. The algorithm provided good balance for profit status (Arm 1, 7 facilities; Arm 2, 6 facilities). Arm 2 was allocated more nursing homes with the number of severely cognitive impaired residents above the median (Arm 1, 7 facilities; Arm 2, 10 facilities), resulting in an imbalance in total number of residents enrolled (Arm 1, 196 residents; Arm 2, 228 residents). Facilities with number of black residents above the median were balanced (7 facilities/arm), while the numbers of black residents enrolled differed slightly between arms (Arm 1, 26 residents (13%); Arm 2, 22 residents (10%)). Simulations showed the median imbalance for TRAIN-AD's original randomization scheme (score = 3), was similar to the observed imbalance (score = 4). Covariate-constrained randomization flexibly accommodates logistical complexities of cluster trials in the nursing home setting, where LTCfocus.org is a valuable source of baseline data. TRIAL REGISTRATION NUMBER AND TRIAL REGISTER: ClinicalTrials.gov Identifier: NCT03244917.

Antimicrobial Resistance Gene Prevalence in a Population of Patients with Advanced Dementia Is Related to Specific Pathobionts.

Long-term care facilities are significant reservoirs of antimicrobial-resistant organisms, and patients with advanced dementia are particularly vulnerable to multidrug-resistant organism (MDRO) acquisition and antimicrobial overuse. In this study, we longitudinally examined a group of patients with advanced dementia using metagenomic sequencing. We found significant inter- and intra-subject heterogeneity in microbiota composition, suggesting temporal instability. We also observed a link between the antimicrobial resistance gene density in a sample and the relative abundances of several pathobionts, particularly Escherichia coli, Proteus mirabilis, and Enterococcus faecalis, and used this relationship to predict resistance gene density in samples from additional subjects. Furthermore, we used metagenomic assembly to demonstrate that these pathobionts had higher resistance gene content than many gut commensals. Given the frequency and abundances at which these pathobionts were found in this population and the underlying vulnerability to MDRO of patients with advanced dementia, attention to microbial blooms of these species may be warranted.

Advancing Antimicrobial Stewardship in Outpatient Dialysis Centers Using the Positive Deviance Process.

Antimicrobial resistance is a major growing problem fueled by inappropriate use of antimicrobials. Patients requiring maintenance hemodialysis are at especially high risk for infections caused by antimicrobial-resistant bacteria. The Centers for Disease Control and Prevention has recommended development and implementation of antimicrobial stewardship programs to combat the spread of resistant pathogens. This article describes in detail a multifaceted antimicrobial stewardship intervention that featured staff education and a behavioral change process, Positive Deviance, and its implementation in six outpatient hemodialysis units. Results of the intervention demonstrated a 6% month-to-month reduction in antimicrobial doses/100 patient months over the course of the 12 months intervention, with a decrease in mean antimicrobial doses from 22.6/100 to 10.5/100 patient months from the beginning to the end of the intervention period. These results demonstrate the effectiveness of this multifaceted intervention in engaging staff and improving antimicrobial prescribing patterns.

The trial to reduce antimicrobial use in nursing home residents with Alzheimer's disease and other dementias: study protocol for a cluster randomized controlled trial.

BACKGROUND: Infections are common in nursing home (NH) residents with advanced dementia but are often managed inappropriately. Antimicrobials are extensively prescribed, but frequently with insufficient evidence to support a bacterial infection, promoting the emergence of multidrug-resistant organisms. Moreover, the benefits of antimicrobials remain unclear in these seriously ill residents for whom comfort is often the goal of care. Prior NH infection management interventions evaluated in randomized clinical trials (RCTs) did not consider patient preferences and lack evidence to support their effectiveness in 'real-world' practice. METHODS: This report presents the rationale and methodology of TRAIN-AD (Trial to reduce antimicrobial use in nursing home residents with Alzheimer's disease and other dementias), a parallel group, cluster RCT evaluating a multicomponent intervention to improve infection management for suspected urinary tract infections (UTIs) and lower respiratory tract infections (LRIs) among NH residents with advanced dementia. TRAIN-AD is being conducted in 28 facilities in the Boston, USA, area randomized in waves using minimization to achieve a balance on key characteristics (N = 14 facilities/arm). The involvement of the facilities includes a 3-month start-up period and a 24-month implementation/data collection phase. Residents are enrolled during the first 12 months of the 24-month implementation period and followed for up to 12 months. Individual consent is waived, thus almost all eligible residents are enrolled (target sample size, N = 410). The intervention integrates infectious disease and palliative care principles and includes provider training delivered through multiple modalities (in-person seminar, online course, management algorithms, and prescribing feedback) and an information booklet for families. Control facilities employ usual care. The primary outcome, abstracted from the residents' charts, is the number of antimicrobial courses prescribed for UTIs and LRIs per person-year alive. DISCUSSION: TRAIN-AD is the first cluster RCT testing a multicomponent intervention to improve infection management in NH residents with advanced dementia. Its findings will provide an evidence base to support the benefit of a program addressing the critical clinical and public health problem of antimicrobial misuse in these seriously ill residents. Moreover, its hybrid efficacy-effectiveness design will inform the future conduct of cluster RCTs evaluating nonpharmacological interventions in the complex NH setting in a way that is both internally valid and adaptable to the 'real-world'. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03244917 . Registered on 10 August 2017.

Fecal Microbiome Characteristics and the Resistome Associated With Acquisition of Multidrug-Resistant Organisms Among Elderly Subjects.

Infections caused by multidrug-resistant organisms (MDRO) lead to considerable morbidity and mortality. The elderly population residing in nursing homes are a major reservoir of MDRO. Our objective was to characterize the fecal microbiome of 82 elderly subjects from 23 nursing homes and compare their resistome to that of healthy young persons. Comparisons of microbiome composition and the resistome between subjects who acquired MDRO or not were analyzed to characterize specific microbiome disruption indices (MDI) associated with MDRO acquisition. An approach based on both 16S rRNA amplicon and whole metagenome shotgun (WMS) sequencing data was used. The microbiome of the study cohort was substantially perturbed, with Bacteroides, Firmicutes, and Proteobacteria predominating. Compared to healthy persons, the cohort of elderly persons had an increased number, abundance, and diversity of antimicrobial resistance genes. High proportions of study subjects harbored genes for multidrug-efflux pumps (96%) and linezolid resistance (52%). Among the 302 antimicrobial resistance gene families identified in any subject, 60% were exclusively detected within the study cohort, including Class D beta-lactamase genes. Subjects who acquired MDRO or not had significant differences in bacterial taxa; Odoribacter laneus, and Akkermansia muciniphila were significantly greater among subjects who did not acquire MDRO whereas Blautia hydrogenotrophica predominated among subjects who acquired MDRO. These findings suggest that specific MDI may identify persons at high risk of acquiring MDRO.

Acquisition of antimicrobial-resistant bacteria in the absence of antimicrobial exposure: A systematic review and meta-analysis.

OBJECTIVE: The main risk factor for acquisition of antimicrobial-resistant bacteria (ARB) is antimicrobial exposure, although acquisition can occur in their absence. The aim of this study was to quantify the proportion of patients who acquire ARB without antimicrobial exposure. STUDY DESIGN: We searched Medline, Embase, and the Cochrane library for publications between January 1, 2000, and July 24, 2017, to identify studies of ARB acquisition in endemic settings. Studies required collection of serial surveillance cultures with acquisition defined as a negative baseline culture and a subsequent positive culture for an ARB, including either multidrug-resistant gram-negative bacteria or antimicrobial-resistant enterococci. Intervention studies were excluded. For each study, the proportion of patients who acquired an ARB but were not exposed to antimicrobials during the study period was quantified. RESULTS: A total of 4,233 citations were identified; 147 underwent full-text review. Of these, 10 studies met inclusion criteria; 7 studies were considered to be at low risk of bias; and 6 studies were conducted in the intensive care unit (ICU) setting. The overall summary estimate for the proportion of patients who were not exposed to antimicrobials among those who acquired an ARB was 16.6% (95% CI, 7.8%-31.8%; P < .001), ranging from 0% to 57.1%. We observed no heterogeneity in the ICU studies but high heterogeneity among the non-ICU studies. CONCLUSION: In most included studies, a subset of patients acquired an ARB but were not exposed to antimicrobials. Future studies need to address transmission dynamics of ARB acquisition in the absence of antimicrobials.

The human microbiota and infection prevention.

The human microbiome participates in numerous aspects of human physiology and disease states. Recently, studies have begun to explore the role of the microbiome in colonization, infection and transmission of pathogens. This review provides a summary of the methodological principles used in microbiome studies and the published evidence of the impact of microbiome dysbiosis in infection prevention.

The positive effects of an antimicrobial stewardship program targeting outpatient hemodialysis facilities.

BACKGROUND: Antimicrobial stewardship programs are effective in optimizing antimicrobial prescribing patterns and decreasing the negative outcomes of antimicrobial exposure, including the emergence of multidrug-resistant organisms. In dialysis facilities, 30%-35% of antimicrobials are either not indicated or the type of antimicrobial is not optimal. Although antimicrobial stewardship programs are now implemented nationwide in hospital settings, programs specific to the maintenance dialysis facilities have not been developed. OBJECTIVE: To quantify the effect of an antimicrobial stewardship program in reducing antimicrobial prescribing.Study design and settingAn interrupted time-series study in 6 outpatient hemodialysis facilities was conducted in which mean monthly antimicrobial doses per 100 patient months during the 12 months prior to the program were compared to those in the 12-month intervention period. RESULTS: Implementation of the antimicrobial stewardship program was associated with a 6% monthly reduction in antimicrobial doses per 100 patient months during the intervention period (P=.02). The initial mean of 22.6 antimicrobial doses per 100 patient months decreased to a mean of 10.5 antimicrobial doses per 100 patient months at the end of the intervention. There were no significant changes in antimicrobial use by type, including vancomycin. Antimicrobial adjustments were recommended for 30 of 145 antimicrobial courses (20.6%) for which there were sufficient clinical data. The most frequent reasons for adjustment included de-escalation from vancomycin to cefazolin for methicillin-susceptible Staphylococcus aureus infections and discontinuation of antimicrobials when criteria for presumed infection were not met. CONCLUSIONS: Within 6 hemodialysis facilities, implementation of an antimicrobial stewardship was associated with a decline in antimicrobial prescribing with no negative effects.