BACKGROUND: The role of changes in gut microflora on upper gastrointestinal (UGI) perforations is not known. We conducted a retrospective case-control study to examine the relationship between antibiotic exposure-a proxy for microbiome modulation-and UGI perforations in a national sample. METHODS: We queried a 5% random sample of Medicare (2009-2013) to identify patients > /= 65 years old hospitalized with UGI (stomach or small intestine) perforations using International Classification of Diseases diagnosis codes. Cases with UGI perforations were matched with 4 controls, each based on age and sex. Exposure to outpatient antibiotics (0-30, 31-60, 61-90 days) prior to case patients' index hospitalization admission data was determined with Part D claims. Univariate and multivariable regression analyses were performed to evaluate the effect of antibiotic exposure on UGI perforation. RESULTS: Overall, 504 cases and 2016 matched controls were identified. Compared to controls, more cases had antibiotic exposure 0-30 days (19% vs. 3%, p < 0.001) and 31-60 days (5% vs. 2%, p < 0.001) prior to admission. In adjusted analyses, antibiotic exposure 0-30 days prior to admission was associated with 6.8 increased odds of an UGI perforation (95% CI 4.8, 9.8); 31-60 days was associated with 1.9 increased odds (95% CI 1.1, 3.3); and 61-90 days was associated with 3.7 increased odds (95% CI 2.0, 6.9). CONCLUSIONS: Recent outpatient antibiotic use, in particular in the preceding 30 days, is associated with UGI perforation among Medicare beneficiaries. Exposure to antibiotics, one of the most modifiable determinants of the microbiome, should be minimized in the outpatient setting.

Objective: More than 266 million courses of antibiotics are dispensed to outpatients annually in the US, with the rising elderly population consuming a substantial number of antibiotics. At least 30% of these antibiotics prescribed are unnecessary. Alterations in gut microbiome are known to cause stomach and small intestine (SSI) perforations. However, the impact of antibiotic exposure outcomes of SSI perforations among the elderly has not been studied. We examined the relationship between antibiotic exposure, as a proxy for microbiome modulation, and SSI perforation outcomes in a nationwide sample of elderly patients. Methods: A 5% random sample of Medicare beneficiaries (2009-2011) was queried to identify patients with SSI perforations. Previous outpatient antibiotic exposure (0-30, 31-60, 61-90 days prior to admission) was assessed. Clinical characteristics were compared between no previous antibiotic exposure (NPA) and previous antibiotic exposure (PA) patients. Primary outcome was in-hospital mortality. Secondary outcomes included length of stay and 30-day readmission. Univariate and multivariable regression analyses were performed. Results: Overall, 401 patients ≥ 65 years had SSI perforations (68.3% with NPA and 31.7 % with PA). Mean age (± SD) was 80 years (± 8). Overall in-hospital mortality was 13%. There was a significant difference in the rates of mortality (12% in NPA vs. 18 % in 0-30 days PA, 17% 31-60 days PA, and 8% 61-90 days PA, P= 0.002). After adjustment of other factors, a trend toward increased in-hospital mortality was observed among patients in 0-30 days PA (odds ratio [OR] 2.0, 95% confidence interval [CI] (0.9, 4.7) and was significantly associated with ICU admission (OR 4.3, 95% CI (1.8, 10.2). Conclusion: Recent antibiotic use increases illness severity and may increase mortality among elderly patients with SSI perforations. Exposure to antibiotics, one of the most modifiable determinants of microbiota, should be minimized in the outpatient setting.