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Objective: Current scores for predicting sepsis outcomes are limited by generalizability, complexity, and electronic medical record (EMR) integration. Here, we validate a simple EMR-based score for sepsis outcomes in a large multi-centre cohort., Design: A simple electronic medical record-based predictor of illness severity in sepsis (SEPSIS) score was developed (4 additive lab-based predictors) using a population-based retrospective cohort study., Setting: Internal medicine services across four academic teaching hospitals in Toronto, Canada from April 2010-March 2015 (primary cohort) and 2015-2019 (secondary cohort)., Patients: We identified patients admitted with sepsis based upon receipt of antibiotics and positive cultures., Measurements and Main Results: The primary outcome was in-hospital mortality and secondary outcomes were ICU admission at 72 hours, and hospital length of stay (LOS). We calculated the area under the receiver operating curve (AUROC) for the SEPSIS score, qSOFA, and NEWS2. We then evaluated the SEPSIS score in a secondary cohort (2015-2019) of hospitalized patients receiving antibiotics. Our primary cohort included 1,890 patients with a median age of 72 years (IQR: 56-83). 9% died during hospitalization, 18.6% were admitted to ICU, and mean LOS was 12.7 days (SD: 21.5). In the primary and secondary (2015-2019, 4811 patients) cohorts, the AUROCs of the SEPSIS score for predicting in-hospital mortality were 0.63 and 0.64 respectively, which were similar to NEWS2 (0.62 and 0.67) and qSOFA (0.62 and 0.68). AUROCs for predicting ICU admission at 72 hours, and length of stay > 14 days, were similar between scores, in the primary and secondary cohorts. All scores had comparable calibration for predicting mortality., Conclusions: An EMR-based SEPSIS score shows a similar ability to predict important clinical outcomes compared with other validated scores (qSOFA and NEWS2). Because of the SEPSIS score's simplicity, it may prove a useful tool for clinical and research applications., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cressman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Empiric antibiotic treatment selection should provide adequate coverage for potential pathogens while minimizing unnecessary broad-spectrum antibiotic use. We sought to pilot a sepsis treatment algorithm to individualize antibiotic recommendations, and thereby improve early antibiotic de-escalation while maintaining adequacy of coverage (Early-IDEAS)., Methods: In this observational study, the Early-IDEAS decision support algorithm was derived from previous Gram- negative and Gram-positive prediction rules and models along with local guidelines, and then applied to prospectively identified consecutive adults within 24 hours of suspected sepsis. The primary outcome was the proportion of patients for whom de-escalation of the primary antibiotic regimen was recommended by the algorithm. Secondary outcomes included: (1) proportion of patients for whom escalation was recommended; (2) number of recommended de-escalation steps along a pre-specified antibiotic cascade; and (3) adequacy of therapy in patients with culture-confirmed infection., Results: We screened 578 patients, of whom 107 eligible patients were included. The Early-IDEAS treatment recommendation was informed by Gram-negative models in 76 (71%) patients, Gram-positive rules in 64 (59.8%), and local guidelines in 27 (25.2%). Antibiotic de-escalation was recommended in almost half of all patients (n = 52, 48.6%), with a median of 2 steps down the a priori antibiotic treatment cascade. No treatment change was recommended in 45 patients (42.1%), and escalation was recommended in 10 (9.3%). Among the 17 patients with positive blood cultures, both the clinician prescribed regimen and the algorithm recommendation provided adequate coverage for the isolated pathogen in 12 patients (70.6%), (p = 1). Among the 25 patients with positive relevant, non-blood cultures, both the clinician prescribed regimen and the algorithm recommendation provided adequate coverage in 20 (80%), (p = 1)., Conclusion: An individualized decision support algorithm in early sepsis could lead to substantial antibiotic de-escalation without compromising adequate antibiotic coverage., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Bucheeri et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: We aimed to estimate associations between COVID-19 incidence and mortality with neighbourhood-level immigration, race, housing, and socio-economic characteristics., Methods: We conducted a population-based study of 28,808 COVID-19 cases in the provincial reportable infectious disease surveillance systems (Public Health Case and Contact Management System) which includes all known COVID-19 infections and deaths from Ontario, Canada reported between January 23, 2020 and July 28, 2020. Residents of congregate settings, Indigenous communities living on reserves or small neighbourhoods with populations <1,000 were excluded. Comparing neighbourhoods in the 90th to the 10th percentiles of socio-demographic characteristics, we estimated the associations between 18 neighbourhood-level measures of immigration, race, housing and socio-economic characteristics and COVID-19 incidence and mortality using Poisson generalized linear mixed models., Results: Neighbourhoods with the highest proportion of immigrants (relative risk (RR): 4.0, 95%CI:3.5-4.5) and visible minority residents (RR: 3.3, 95%CI:2.9-3.7) showed the strongest association with COVID-19 incidence in adjusted models. Among individual race groups, COVID-19 incidence was highest among neighbourhoods with the high proportions of Black (RR: 2.4, 95%CI:2.2-2.6), South Asian (RR: 1.9, 95%CI:1.8-2.1), Latin American (RR: 1.8, 95%CI:1.6-2.0) and Middle Eastern (RR: 1.2, 95%CI:1.1-1.3) residents. Neighbourhoods with the highest average household size (RR: 1.9, 95%CI:1.7-2.1), proportion of multigenerational families (RR: 1.8, 95%CI:1.7-2.0) and unsuitably crowded housing (RR: 2.1, 95%CI:2.0-2.3) were associated with COVID-19 incidence. Neighbourhoods with the highest proportion of residents with less than high school education (RR: 1.6, 95%CI:1.4-1.8), low income (RR: 1.4, 95%CI:1.2-1.5) and unaffordable housing (RR: 1.6, 95%CI:1.4-1.8) were associated with COVID-19 incidence. Similar inequities were observed across neighbourhood-level sociodemographic characteristics and COVID-19 mortality., Conclusions: Neighbourhood-level inequities in COVID-19 incidence and mortality were observed in Ontario, with excess burden experienced in neighbourhoods with a higher proportion of immigrants, racialized populations, large households and low socio-economic status., Competing Interests: The authors have declared that no competing interests exist.

Objective: To describe antibiotic treatment durations that pediatric infectious diseases (ID) and critical care clinicians usually recommend for bloodstream infections in critically ill children., Design: Anonymous, online practice survey using five common pediatric-based case scenarios of bloodstream infections., Setting: Pediatric intensive care units in Canada, Australia and New Zealand., Participants: Pediatric intensivists, nurse practitioners, ID physicians and pharmacists., Main Outcome Measures: Recommended treatment durations for common infectious syndromes associated with bloodstream infections and willingness to enrol patients into a trial to study treatment duration., Results: Among 136 survey respondents, most recommended at least 10 days antibiotics for bloodstream infections associated with: pneumonia (65%), skin/soft tissue (74%), urinary tract (64%) and intra-abdominal infections (drained: 90%; undrained: 99%). For central vascular catheter-associated infections without catheter removal, over 90% clinicians recommended at least 10 days antibiotics, except for infections caused by coagulase negative staphylococci (79%). Recommendations for at least 10 days antibiotics were less common with catheter removal. In multivariable linear regression analyses, lack of source control was significantly associated with longer treatment durations (+5.2 days [95% CI: 4.4-6.1 days] for intra-abdominal infections and +4.1 days [95% CI: 3.8-4.4 days] for central vascular catheter-associated infections). Most clinicians (73-95%, depending on the source of bloodstream infection) would be willing to enrol patients into a trial of shorter versus longer antibiotic treatment duration., Conclusions: The majority of clinicians currently recommend at least 10 days of antibiotics for most scenarios of bloodstream infections in critically ill children. There is practice heterogeneity in self-reported treatment duration recommendations among clinicians. Treatment durations were similar across different infectious syndromes. Under appropriate clinical conditions, most clinicians would be willing to enrol patients into a trial of shorter versus longer treatment for common syndromes associated with bloodstream infections., Competing Interests: The authors have declared that no competing interests exist.

Older adults are at increased risk of herpes zoster (HZ) and post-herpetic neuralgia (PHN) and HZ vaccines are available to help prevent infection. The objective of our study was to provide updated data on incidence of HZ and PHN related to clinical and demographic factors in older adults to inform immunization practices. We conducted a population-based, retrospective cohort study and included all cases of HZ seen in outpatient, emergency department, and hospital settings for adults aged 65 years and over between April 1, 2002 to August 31, 2016 in Ontario, Canada. We calculated the incidence of HZ and PHN, and estimated the proportion within each subgroup that developed PHN. We also assessed incidence by neighbourhood-level income quintile before and after the availability of vaccine for private purchase. The average annual incidence of HZ in any setting was 59.0 per 10,000 older adults, with higher incidence in outpatient as opposed to hospital settings. Incidence was higher in the oldest age groups, females, and those classified as immunocompromised or frail. Relative to the pre-vaccine era, the disparities in incidence of HZ by neighbourhood-level income increased, with higher rates of HZ and PHN seen in those residing in lower income quintiles. Additional prevention efforts should be targeted toward adults who are immunocompromised, frail, and those living in lower socioeconomic quintiles. Future work should assess the impact of the zoster vaccine program with a particular focus on equity in the publicly-funded era., Competing Interests: The authors have declared that no competing interests exist.

Objective: Many jurisdictions lack comprehensive population-based antibiotic use data and rely on third party companies, most commonly IQVIA. Our objective was to validate the accuracy of the IQVIA Xponent antibiotic database in identifying high prescribing physicians compared to the reference standard of a highly accurate population-wide database of outpatient antimicrobial dispensing for patients ≥65 years., Methods: We conducted this study between 1 March 2016 and 28 February 2017 in Ontario, Canada. We evaluated the agreement and correlation between the databases using kappa statistics and Bland-Altman plots. We also assessed performance characteristics for Xponent to accurately identify high prescribing physicians with sensitivity, specificity, positive predictive value (PPV), and negative predictive value., Results: We included 9,272 physicians. The Xponent database has a specificity of 92.4% (95%CI 92.0%-92.8%) and PPV of 77.2% (95%CI 76.0%-78.4%) for correctly identifying the top 25th percentile of physicians by antibiotic volume. In the sensitivity analysis, 94% of the top 25th percentile physicians in Xponent were within the top 40th percentile in the reference database. The mean number of antibiotic prescriptions per physician were similar with a relative difference of -0.4% and 2.7% for female and male patients, respectively. The error was greater in rural areas with a relative difference of -8.4% and -5.6% per physician for female and male patients, respectively. The weighted kappa for quartile agreement was 0.68 (95%CI 0.67-0.69)., Conclusion: We validated the IQVIA Xponent antibiotic database to identify high prescribing physicians for patients ≥65 years, and identified some important limitations. Collecting accurate population-based antibiotic use data will remain vital to global antimicrobial stewardship efforts., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Accurate prediction of embolic events in infective endocarditis could inform critical clinical decisions, such as the timing of cardiac surgical intervention. However, many embolic events occur before hospital admission and echocardiography and are thus non-modifiable. We aimed to identify time-sensitive variables that predict embolic events in infective endocarditis, focusing on those that occur after diagnosis., Methods: Clinical, microbiological, and echocardiographic characteristics were collected from 116 patients with definite or probable left-sided infective endocarditis admitted to Sunnybrook Health Sciences Centre (Toronto, Canada) between October 2013 and July 2016; associations between these characteristics and embolic events were identified using simple logistic regression., Results: The mean (SD) age was 66 (17) years; 82 patients (71%) were men. The most frequent microorganisms were Staphylococcus aureus (23%) and viridans group streptococci (21%). Seventy-nine (68%) patients had left-sided vegetations, with involvement of the aortic valve in 34 (43%) patients, mitral valve in 37 (47%) patients, and both in 8 (10%) patients. The mean (SD) vegetation size was 10 (7) mm. Forty-three unique patients (37%) had 50 embolic events, with most (34/43; 79%) having a first embolic event (38/50; 76%) before or on the day of echocardiography. There were no significant predictors of the 11 patients with an embolic event after echocardiography; significant predictors of an embolic event at any time were single valve vegetation vs. no vegetation (OR, 4.75; 95% confidence interval [CI], 1.76-12.78) and, among patients with a vegetation, mitral vs. aortic valve location (OR, 4.43; 95%CI, 1.63-12.04)., Conclusions: Associations between patient and echocardiographic characteristics and embolism in patients with infective endocarditis may be time-sensitive, as few embolic events occurred after clinical and echocardiographic assessment., Competing Interests: The authors have declared that no competing interests exist.

Background: A multidisciplinary approach has been recommended for the management of patients with infective endocarditis. We evaluated the impact of multidisciplinary case conferences on morbidity, mortality, and quality of care for these patients., Methods: We conducted a quasi-experimental study of consecutive patients admitted for infective endocarditis before (2013/10/1-2015/10/12, n = 97) and after (2015/10/13-2017/11/30, n = 80) implementation of case conferences to discuss medical and surgical management. These occurred as face-to-face discussions or electronically (for non-complex patients), and included physicians from cardiac surgery, cardiology, critical care, infectious diseases and neurology. We assessed process-of-care and clinical outcomes, with the primary outcome being complications up to 90 days after hospital discharge., Results: A case conference was held for 80/80 (100%) of patients in the post-intervention group. After the intervention, more patients received inpatient cardiology assessment (81.3% [post-intervention] vs. 63.9% [pre-intervention], p = 0.01), and more patients with definite infective endocarditis underwent cardiac surgery treatment (44.6% vs. 21.7%, p = 0.007). All pre-intervention and post-intervention patients received guideline-concordant antimicrobial therapy. There was no difference in rates of complications (40.0% vs. 51.5%, p = 0.13) or mortality up to 90 days after hospital discharge (26.3% vs. 17.5%, p = 0.20). In multivariable analyses, the intervention was not associated with differences in mortality (odds ratio 1.87, 95% confidence interval 0.88-3.99) or a composite measure of complications and mortality (odds ratio 0.86, 95% confidence interval 0.46-1.58)., Conclusion: We successfully implemented a standardized multidisciplinary case conference protocol for patients with infective endocarditis. This intervention had no detectable effect on complications or mortality., Competing Interests: The authors have declared that no competing interests exist.

Contaminated surfaces serve as an important reservoir for Clostridium difficile transmission. Current strategies to detect environmental contamination of C. difficile rely heavily on culture, and often only indicate presence versus absence of spores. The goal of this study was to compare quantitative PCR (qPCR) to culture for the detection and quantification of C. difficile from inert surfaces. First, we compared the limit of detection (LOD) of a 16S rRNA gene and toxin B gene qPCR assay for detection of C. difficile in solution. Second, we compared the LODs of 16S rRNA gene qPCR versus culture for detection of C. difficile from surfaces. Solution experiments were performed by direct seeding of spores into neutralizing broth, whereas surface experiments involved seeding of spores onto plastic test surfaces, and recovery using sponge swabs. Both experiments were conducted using spores expressing short (NAP1) and long (NAP4) hair lengths. Combining data from both strains, the overall LOD for C. difficile cells in solution was 1.4 cells for 16S rRNA gene and 23.6 cells for toxin B gene qPCR (p<0.001). The overall LOD for C. difficile cells from surfaces was 17.1 cells for 16S rRNA gene qPCR and 54.5 cells for culture (p = 0.05), and was not statistically different between strains for each method (p = 0.52). Overall, the proportion of C. difficile cells recovered from surfaces was good when detected by 16S rRNA gene qPCR and culture (qPCR: 76%, culture: 67%, p = 0.36), but, 16S rRNA gene qPCR was capable of detecting lower levels of surface contamination. Future work attempting to measure the presence of C. difficile on environmental surfaces should consider using qPCR., Competing Interests: The authors have declared that no competing interests exist.

Few studies have evaluated the mortality or quantified the economic burden of community-onset Clostridium difficile infection (CDI). We estimated the attributable mortality and costs of community-onset CDI. We conducted a population-based matched cohort study. We identified incident subjects with community-onset CDI using health administrative data (emergency department visits and hospital admissions) in Ontario, Canada between January 1, 2003 and December 31, 2010. We propensity-score matched each infected subject to one uninfected subject and followed subjects in the cohort until December 31, 2011. We evaluated all-cause mortality and costs (unadjusted and adjusted for survival) from the healthcare payer perspective (2014 Canadian dollars). During our study period, we identified 7,950 infected subjects. The mean age was 63.5 years (standard deviation = 22.0), 62.7% were female, and 45.0% were very high users of the healthcare system. The relative risk for 30-day, 180-day, and 1-year mortality were 7.32 (95% confidence interval [CI], 5.94-9.02), 3.55 (95%CI, 3.17-3.97), and 2.59 (95%CI, 2.37-2.83), respectively. Mean attributable cumulative 30-day, 180-day, and 1-year costs (unadjusted for survival) were $7,434 (95%CI, $7,122-$7,762), $12,517 (95%CI, $11,687-$13,366), and $13,217 (95%CI, $12,062-$14,388). Mean attributable cumulative 1-, 2-, and 3-year costs (adjusted for survival) were $10,700 (95%CI, $9,811-$11,645), $13,312 (95%CI, $12,024-$14,682), and $15,812 (95%CI, $14,159-$17,571). Infected subjects had considerably higher risk of all-cause mortality and costs compared with uninfected subjects. This study provides insight on an understudied patient group. Our study findings will facilitate assessment of interventions to prevent community-onset CDI.

Hospital mortality rates are elevated in critically ill patients with bloodstream infections. Given that mortality may be even higher if appropriate treatment is delayed, we sought to determine the effect of inadequate initial empiric treatment on mortality in these patients. A retrospective cohort study was conducted across 13 intensive care units in Canada. We defined inadequate initial empiric treatment as not receiving at least one dose of an antimicrobial to which the causative pathogen(s) was susceptible within one day of initial blood culture. We evaluated the association between inadequate initial treatment and hospital mortality using a random effects multivariable logistic regression model. Among 1,190 patients (1,097 had bacteremia and 93 had candidemia), 476 (40%) died and 266 (22%) received inadequate initial treatment. Candidemic patients more often had inadequate initial empiric therapy (64.5% versus 18.8%), as well as longer delays to final culture results (4 vs 3 days) and appropriate therapy (2 vs 0 days). After adjustment, there was no detectable association between inadequate initial treatment and mortality among bacteremic patients (Odds Ratio (OR): 1.02, 95% Confidence Interval (CI) 0.70-1.48); however, candidemic patients receiving inadequate treatment had nearly three times the odds of death (OR: 2.89, 95% CI: 1.05-7.99). Inadequate initial empiric antimicrobial treatment was not associated with increased mortality in bacteremic patients, but was an important risk factor in the subgroup of candidemic patients. Further research is warranted to improve early diagnostic and risk prediction methods in candidemic patients.

Antibiotic therapy is the principal risk factor for Clostridium difficile infection (CDI), but little is known about how risks cumulate over the course of therapy and abate after cessation. We prospectively identified CDI cases among adults hospitalized at a tertiary hospital between June 2010 and May 2012. Poisson regression models included covariates for time since admission, age, hospitalization history, disease pressure, and intensive care unit stay. Impacts of antibiotic use through time were modeled using 4 measures: current antibiotic receipt, time since most recent receipt, time since first receipt during a hospitalization, and duration of receipt. Over the 24-month study period, we identified 127 patients with new onset nosocomial CDI (incidence rate per 10,000 patient days [IR] = 5.86). Of the 4 measures, time since most recent receipt was the strongest independent predictor of CDI incidence. Relative to patients with no prior receipt of antibiotics in the last 30 days (IR = 2.95), the incidence rate of CDI was 2.41 times higher (95% confidence interval [CI] 1.41, 4.13) during antibiotic receipt and 2.16 times higher when patients had receipt in the prior 1-5 days (CI 1.17, 4.00). The incidence rates of CDI following 1-3, 4-6 and 7-11 days of antibiotic exposure were 1.60 (CI 0.85, 3.03), 2.27 (CI 1.24, 4.16) and 2.10 (CI 1.12, 3.94) times higher compared to no prior receipt. These findings are consistent with studies showing higher risk associated with longer antibiotic use in hospitalized patients, but suggest that the duration of increased risk is shorter than previously thought.

Background: The role of public reporting in improving hospital quality of care is controversial. Reporting of hospital-acquired infection rates has been introduced in multiple health care systems, but its relationship to infection rates has been understudied. Our objective was to determine whether mandatory public reporting by hospitals is associated with a reduction in hospital rates of Clostridium difficile infection., Methods and Findings: We conducted a longitudinal, population-based cohort study in Ontario (Canada's largest province) between April 1, 2002, and March 31, 2010. We included all patients (>1 y old) admitted to 180 acute care hospitals. Using Poisson regression, we developed a model to predict hospital- and age-specific monthly rates of C. difficile disease per 10,000 patient-days prior to introduction of public reporting on September 1, 2008. We then compared observed monthly rates of C. difficile infection in the post-intervention period with rates predicted by the pre-intervention predictive model. In the pre-intervention period there were 33,634 cases of C. difficile infection during 39,221,113 hospital days, with rates increasing from 7.01 per 10,000 patient-days in 2002 to 10.79 in 2007. In the first calendar year after the introduction of public reporting, there was a decline in observed rates of C. difficile colitis in Ontario to 8.92 cases per 10,000 patient-days, which was significantly lower than the predicted rate of 12.16 (95% CI 11.35-13.04) cases per 10,000 patient-days (p<0.001). Over this period, public reporting was associated with a 26.7% (95% CI 21.4%-31.6%) reduction in C. difficile cases, or a projected 1,970 cases averted per year (95% CI 1,476-2,500). The effect was specific to C. difficile, with rates of community-acquired gastrointestinal infections and urinary tract infections unchanged. A limitation of our study is that this observational study design cannot rule out the influence of unmeasured temporal confounders., Conclusions: Public reporting of hospital C. difficile rates was associated with a substantial reduction in the population burden of this infection. Future research will be required to discern the direct mechanism by which C. difficile infection rates may have been reduced in response to public reporting. Please see later in the article for the Editors' Summary.

Background: Evidence-based priority setting is increasingly important for rationally distributing scarce health resources and for guiding future health research. We sought to quantify the contribution of a wide range of infectious diseases to the overall infectious disease burden in a high-income setting., Methodology/principal Findings: We used health-adjusted life years (HALYs), a composite measure comprising premature mortality and reduced functioning due to disease, to estimate the burden of 51 infectious diseases and associated syndromes in Ontario using 2005-2007 data. Deaths were estimated from vital statistics data and disease incidence was estimated from reportable disease, healthcare utilization, and cancer registry data, supplemented by local modeling studies and national and international epidemiologic studies. The 51 infectious agents and associated syndromes accounted for 729 lost HALYs, 44.2 deaths, and 58,987 incident cases per 100,000 population annually. The most burdensome infectious agents were: hepatitis C virus, Streptococcus pneumoniae, Escherichia coli, human papillomavirus, hepatitis B virus, human immunodeficiency virus, Staphylococcus aureus, influenza virus, Clostridium difficile, and rhinovirus. The top five, ten, and 20 pathogens accounted for 46%, 67%, and 75% of the total infectious disease burden, respectively. Marked sex-specific differences in disease burden were observed for some pathogens. The main limitations of this study were the exclusion of certain infectious diseases due to data availability issues, not considering the impact of co-infections and co-morbidity, and the inability to assess the burden of milder infections that do not result in healthcare utilization., Conclusions/significance: Infectious diseases continue to cause a substantial health burden in high-income settings such as Ontario. Most of this burden is attributable to a relatively small number of infectious agents, for which many effective interventions have been previously identified. Therefore, these findings should be used to guide public health policy, planning, and research.

Background: Bacterial resistance to antibiotics is thought to develop only in the presence of antibiotic pressure. Here we show evidence to suggest that fluoroquinolone resistance in Escherichia coli has developed in the absence of fluoroquinolone use., Methods: Over 4 years, outreach clinic attendees in one moderately remote and five very remote villages in rural Guyana were surveyed for the presence of rectal carriage of ciprofloxacin-resistant gram-negative bacilli (GNB). Drinking water was tested for the presence of resistant GNB by culture, and the presence of antibacterial agents and chloroquine by HPLC. The development of ciprofloxacin resistance in E. coli was examined after serial exposure to chloroquine. Patient and laboratory isolates of E. coli resistant to ciprofloxacin were assessed by PCR-sequencing for quinolone-resistance-determining-region (QRDR) mutations., Results: In the very remote villages, 4.8% of patients carried ciprofloxacin-resistant E. coli with QRDR mutations despite no local availability of quinolones. However, there had been extensive local use of chloroquine, with higher prevalence of resistance seen in the villages shortly after a Plasmodium vivax epidemic (p<0.01). Antibacterial agents were not found in the drinking water, but chloroquine was demonstrated to be present. Chloroquine was found to inhibit the growth of E. coli in vitro. Replica plating demonstrated that 2-step QRDR mutations could be induced in E. coli in response to chloroquine., Conclusions: In these remote communities, the heavy use of chloroquine to treat malaria likely selected for ciprofloxacin resistance in E. coli. This may be an important public health problem in malarious areas.