Antibiotics were less commonly administered to patients who were given bismuth subsalicylate to treat acute diarrhea in a setting in which antibiotics are commonly used,  according to data published in JAMA Network Open.

In a randomized clinical trial, participants aged 15 to 65 years with acute non-bloody diarrhea from 22 outpatient clinics in Karachi, Pakistan were randomly assigned in a 1:1 ratio to receive either bismuth subsalicylate or placebo for <48 hours. Patients were also interviewed regarding their symptoms and healthcare utilization during the 5 days post-enrollment.

A total of 440 patients were enrolled in and completed the study; 1 patient was lost to follow up, resulting in 220 patients receiving bismuth subsalicylate and the remaining 219 placebo. During the 5-day follow-up, 12% of all participants used systemic antibiotics: 16% of the placebo group and 9% of the bismuth subsalicylate group. With regard to patients who consulted a physician, 71% received antibiotics; no patient who consulted a pharmacist received antibiotics. Overall, patients commonly subjectively assessed their illnesses as not requiring antimicrobial treatment.

The use of any antibiotic was significantly lower in the bismuth subsalicylate group (odds ratio [OR] 0.54; 95%CI, 0.30-0.98) as was the use of fluoroquinolones (OR 0.38; 95% CI, 0.16-0.88). There was no difference in time to diarrhea resolution and the rates of care-seeking and hospitalization were similar in both groups. Researchers highlighted the fact that patients in the bismuth subsalicylate group missed work less frequently (median, 0 day vs 1 day; P = .04) and less commonly received intravenous rehydration (OR, 0.48; 95%CI, 0.25-0.95).

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Investigators noted that by offering alternative medication they redirected patients in both groups away from antibiotics, which likely reduced use in both groups. Also, the rates of use were lower than anticipated and investigators believe that, “we likely would have observed a larger relative reduction in antibiotic use had we not controlled antibiotic use at enrollment in the placebo group.” However, the drivers of this relative reduction were unclear. Other limitations included the fact that additional treatments used in the placebo group may have masked differences in illness course between the groups. Further, investigators may have underestimated the effect of bismuth subsalicylate on antibiotic use because only participants who had not used antibiotics at the time of presentation and patients who consented to the study were included. Antibiotic use at enrollment or during the study may also have been misclassified.

The data demonstrated, “lower odds of antibiotic use following [bismuth subsalicylate] for acute diarrhea in a setting where antibiotic use for diarrhea is typically high.” Researchers cautioned that interventions to reduce inappropriate antibiotic use are likely to vary by illness and setting. According to this data, investigators believe that, “encouraging health care professionals and pharmacists in settings with high diarrhea incidence to recommend [bismuth subsalicylate] as frontline treatment for adults with diarrhea, and promoting [bismuth subsalicylate] for diarrhea self-management, may reduce antibiotic use and rates of antibiotic resistance globally.”

Reference

Bowen A, Agboatwalla M, Pitz A, Salahuddin S, Brum J, Plikaytis B. Effect of bismuth subsalicylate vs placebo on use of antibiotics among adult outpatients with diarrhea in Pakistan: A randomized clinical trial. JAMA Netw Open. 2019;2:e199441.