The effect of antibiotic use on survival of patients with resected pancreatic ductal adenocarcinoma.

e15773 Background: Recent studies showed that gut microbial dysbiosis can affect carcinogenesis and tumor responses to therapies. Antibiotics, key pharmacologic agents that modulate microbiota diversity and bacterial strains, can lead to dysbiosis. Recent studies have postulated a tumor promoting effect for some pancreatic ductal adenocarcinoma (PDAC)-associated gut bacteria. However, the effects of antibiotic use on PDAC patients outcome is yet to be discovered. Methods: We examined a total of 342 patients who were diagnosed with PDAC between 2003-2015 and underwent primary tumor resection. Antibiotic exposure was defined as the use of antibiotics for ≥7 days between diagnosis and surgery. We collected data on patient demographics, presurgical antibiotic use, duration, type and reason, disease and therapy characteristics, and prognostic parameters. We analyzed and compared the objective responses, progression free survival (PFS) and overall survival (OS). Results: From a total 342 patients with resected PDAC, 147 patients (43%) used antibiotics for ≥7 days duration during the presurgical period. The most frequently used antibiotics were quinolones (80.4%), beta-lactams (38.2%), nitroimidazoles (23%), glycopeptides (15.3%), tetracyclines (8.6%), and macrolides (6.7%). The median OS for patients with antibiotic use was 1007 vs. 940 days for those without antibiotic use (p = 0.57). The median PFS was 374 for patients with antibiotic use and 313 days for those without antibiotic use (p = 0.51). The effect of individual antibiotics was examined and statistical analysis was done for possible confounding factors including disease stage, treatment type, and the reason for antibiotic use. Tetracyclines use was found to be significantly associated with worse survival on resected PDAC patients and was not affected by confounding factors such as skin infections. The median OS of patients who had tetracycline for ≥7 days was 687 vs. 1004 days for those not exposed to this antibiotic (HR 1.836; p = 0.015). Although not statistically significant, PFS was shorter with tetracycline use. Conclusions: We conducted the first retrospective, single-center cohort study on resected PDAC patients examining the potential influence of antibiotic use on survival. Tetracycline use in resectable PDAC patients is associated with clinically significant decreased PFS and statistically significant worse OS. Further multicenter studies with larger population would be necessary to confirm these findings that could help clinical practice for infectious treatment in PDAC patients.