Importance: Many of the 4.5 billion annual episodes of diarrhea are treated unnecessarily with antibiotics; prevalence of antibiotic resistance among diarrheal pathogens is increasing. Knowledge-based antibiotic stewardship interventions typically yield little change in antibiotic use. Objective: To compare antibiotic use among adult outpatients with diarrhea given bismuth subsalicylate (BSS) or placebo. Design, Setting, and Participants: This randomized clinical trial took place from April to October 2014. Participants were patients aged 15 to 65 years with acute, nonbloody diarrhea from 22 outpatient clinics in Karachi, Pakistan. Participants were interviewed about symptoms and health care utilization during the 5 days after enrollment. Group assignment was concealed from participants, field staff, and the statistician. Primary analysis occurred from August to September 2015. Interventions: Participants were randomly assigned (1:1) to receive BSS or placebo for 48 hours or less. Main Outcomes and Measures: Use of systemic antibiotics within 5 days of enrollment. Secondary outcomes included measures of duration and severity of illness. Results: Among eligible patients, 39 declined to participate, 440 enrolled, and 1 enrolled participant was lost to follow-up, for a total of 439 patients included in the analysis. Median (interquartile range) participant age was 32 (23-45) years and 187 (43%) were male. Two hundred twenty patients were randomized to BSS and 220 were randomized to placebo. Overall, 54 participants (12%) used systemic antibiotics (16% in the placebo group and 9% in the BSS group); all antibiotic use followed consultation with a physician. Use of any antibiotic was significantly lower in the BSS group (20 of 220 vs 34 of 219 patients; odds ratio [OR], 0.54; 95% CI, 0.30-0.98), as was use of fluoroquinolones (8 of 220 vs 20 of 219 patients; OR, 0.38; 95% CI, 0.16-0.88). Rates of care seeking and hospitalization were similar between groups and no difference was detected in timing of diarrhea resolution. However, those in the BSS group less commonly received intravenous rehydration (14 of 220 vs 27 of 219 patients; OR, 0.48; 95% CI, 0.25-0.95) and missed less work (median [interquartile range], 0 [0-1] vs 1 [0-1] day; P = .04) during follow-up. Conclusions and Relevance: This study found less antibiotic use among participants given BSS for acute diarrhea in a setting where antibiotics are commonly used to treat diarrhea. Encouraging health care professionals in such settings to recommend BSS as frontline treatment for adults with diarrhea, and promoting BSS for diarrhea self-management, may reduce antibiotic use and rates of antibiotic resistance globally. Trial Registration: ClinicalTrials.gov identifier: NCT02047162.

In south Asia, where diarrhea is common and antibiotics are accessible without prescription, antimicrobial resistance is an emerging and serious problem. However, beliefs and behaviors related to antimicrobial resistance are poorly understood. We explored laypersons' and health-care providers' (HCP) awareness and perceptions of antimicrobial resistance in the context of treatment of adult diarrheal disease in Karachi, Pakistan. In-depth, open-ended interviews were conducted with 40 laypersons and 45 HCPs in a lower-middle-class urban neighborhood. Interviews conducted in Urdu were audiotaped, transcribed, translated, and coded using applied thematic analysis. Slightly over half of laypersons and two-thirds of HCPs were aware that antimicrobial medication could lose effectiveness, but misperceptions were common. Laypersons and HCPs often believed that "the body becomes immune" or "bacteria attack more strongly" if medications are taken "improperly." Another prevalent theme was that causes and effects of antimicrobial resistance are limited to the individual taking the antimicrobial medication and to the specific diarrheal episode. Participants often attributed antimicrobial resistance to patient behaviors; HCP behavior was rarely discussed. Less than half of the HCPs were aware of treatment guidelines. To combat antimicrobial resistance in urban Pakistan, a health systems strategy and community-supported outreach campaigns on appropriate antimicrobial use are needed.

BACKGROUND: We assessed the association between the duration of diarrhoea and the risk of pneumonia incidence among children <5 years of age. METHODS: We analysed data from a cluster randomized controlled trial in Karachi, Pakistan, which assessed the effect of promoting hand washing with soap (antibacterial and plain) on child health. Field workers visited households with children <5 years of age weekly and asked primary caregivers if their child had diarrhoea, cough or difficulty breathing in the preceding week. We used the WHO clinical case definitions for diarrhoea and pneumonia. We used adjusted time-to-event analyses with cumulative diarrhoea prevalence over the previous 2 and 4 weeks as exposure and pneumonia as outcome. We calculated the attributable risk of pneumonia due to recent diarrhoea across the intervention groups. RESULTS: 873 households with children <5 years were visited. Children had an increased risk of pneumonia for every additional day of diarrhoea in the 2 weeks (1.06, 95% CI: 1.03-1.09) and 4 weeks (1.04, 95% CI: 1.03-1.06) prior to the week of pneumonia onset. The attributable risk of pneumonia cases due to recent exposure to diarrhoea was 6%. A lower associated pneumonia risk following diarrhoea was found in the control group: (3%) compared with soap groups (6% in antibacterial soap, 9% in plain soap). CONCLUSION: Children <5 years of age are at an increased risk of pneumonia following recent diarrhoeal illness. Public health programmes that prevent diarrhoea may also reduce the burden of respiratory illnesses.

OBJECTIVE: To evaluate handwashing behaviour 5 years after a handwashing intervention in Karachi, Pakistan. METHODS: In 2003, we randomised neighbourhoods to control, handwashing promotion, or handwashing promotion and water treatment. Intervention households were given soap +/- water treatment product and weekly handwashing education for 9 months. In 2009, we re-enrolled 461 households from the three study groups: control (160), handwashing (141), and handwashing + water treatment (160) and assessed hygiene-related outcomes, accounting for clustering. RESULTS: Intervention households were 3.4 times more likely than controls to have soap at their handwashing stations during the study visit [293/301 (97%) vs. 45/159 (28%), P < 0.0001]. While nearly all households reported handwashing after toileting, intervention households more commonly reported handwashing before cooking [relative risk (RR) 1.2 (95% confidence interval (CI) 1.0-1.4)] and before meals [RR 1.7 (95% CI, 1.3-2.1)]. Control households cited a mean of 3.87 occasions for washing hands; handwashing households, 4.74 occasions; and handwashing + water treatment households, 4.78 occasions (P < 0.0001). Households reported purchasing a mean of 0.65 (control), 0.91 (handwashing) and 1.1 (handwashing + water treatment) bars of soap/person/month (P < 0.0001). CONCLUSIONS: Five years after receiving handwashing promotion, intervention households were more likely to have soap at the household handwashing station, know key times to wash hands and report purchasing more soap than controls, suggesting habituation of improved handwashing practices in this population. Intensive handwashing promotion may be an effective strategy for habituating hygiene behaviours and improving health.

OBJECTIVE: To evaluate associations between handwashing promotion and child growth and development. DESIGN: Cluster randomized controlled trial. SETTING: Informal settlements in Karachi, Pakistan. PARTICIPANTS: A total of 461 children who were enrolled in a trial of household-level handwashing promotion in 2003 and were younger than 8 years at reassessment in 2009. INTERVENTIONS: In 2003, neighborhoods were randomized to control (n = 9), handwashing promotion (n = 9), or handwashing promotion and drinking water treatment (n = 10); intervention households received free soap and weekly handwashing promotion for 9 months. MAIN OUTCOME MEASURES: Anthropometrics and developmental quotients measured with the Battelle Developmental Inventory II at 5 to 7 years of age. RESULTS: Overall, 24.9% (95% CI, 20.0%-30.6%) and 22.1% (95% CI, 18.0%-26.8%) of children had z scores that were more than 2 SDs below the expected z scores for height and body mass index for age, respectively; anthropometrics did not differ significantly across study groups. Global developmental quotients averaged 104.4 (95% CI, 101.9-107.0) among intervention children and 98.3 (95% CI, 93.1-103.4) among control children (P = .04). Differences of similar magnitude were measured across adaptive, personal-social, communication, cognitive, and motor domains. CONCLUSIONS: Although growth was similar across groups, children randomized to the handwashing promotion during their first 30 months of age attained global developmental quotients 0.4 SDs greater than those of control children at 5 to 7 years of age. These gains are comparable to those of at-risk children enrolled in publicly funded preschools in the United States and suggest that handwashing promotion could improve child well-being and societal productivity. TRIAL REGISTRATION: clinicaltrials.gov IDENTIFIER: NCT01538953. (2012 American Medical Association. All rights reserved.)

Diarrhea burden is often estimated using cross-sectional surveys. We measured variability in diarrhea prevalence among children < 5 years of age living in squatter settlements in central Karachi, Pakistan. We pooled data from non-intervention control households from studies conducted from 2002 through 2006. The prevalence of diarrhea varied on average by 29% from one week to the next, by 37% from one month to the next, and during peak diarrhea season by 32% from one year to the next. During 24 months when the same nine neighborhoods were under surveillance, each month the prevalence of diarrhea varied by at least an order of magnitude from the lowest to the highest prevalence neighborhood, and each neighborhood recorded the highest diarrhea prevalence during at least one month. Cross-sectional surveys are unreliable measures of diarrhea prevalence.

In an earlier study in Karachi, Pakistan, households that received free soap and handwashing promotion for 9 months reported 53% less diarrhea than controls. Eighteen months after the intervention ended, these households were enrolled in a follow-up study to assess sustainability of handwashing behavior. Upon re-enrollment, mothers in households originally assigned to the intervention were 1.5 times more likely to have a place with soap and water to wash hands (79% versus 53%, P = 0.001) and when asked to wash hands were 2.2 times more likely to rub their hands together at least three times (50% versus 23%, P = 0.002) compared with controls. In the ensuing 14 months, former intervention households reported a similar proportion of person-days with diarrhea (1.59% versus 1.88%, P = 0.66) as controls. Although intervention households showed better handwashing technique after 2 years without intervention, their soap purchases and diarrhea experience was not significantly different from controls.