Association of Antibiotic Receipt With Survival Among Patients With Metastatic Pancreatic Ductal Adenocarcinoma Receiving Chemotherapy.

Importance: The prognosis for patients with metastatic pancreatic ductal adenocarcinoma (PDAC) is dismal, due in part to chemoresistance. Bacteria-mediated mechanisms of chemoresistance suggest a potential role for antibiotics in modulating response to chemotherapy. Objective: To evaluate whether use of peritreatment antibiotics is associated with survival among patients with metastatic PDAC treated with first-line gemcitabine or fluorouracil chemotherapy. Design, Setting, and Participants: Using the population-based Surveillance, Epidemiology, and End Results-Medicare linked database, this retrospective cohort study analyzed data for patients diagnosed with PDAC between January 1, 2007, and December 31, 2017. Data analysis was conducted between September 1, 2021, and January 15, 2023. The population-based sample included 3850 patients with primary metastatic PDAC treated with first-line gemcitabine or fluorouracil chemotherapy. Patients who received antibiotics were matched based on propensity scores to patients who did not receive antibiotics. Exposures: Receipt of 5 or more days of oral antibiotics or 1 injectable antibiotic in the month before or after beginning first-line chemotherapy. Main Outcomes and Measures: Overall survival and cancer-specific survival. The end of follow-up was December 31, 2019, for overall survival and December 31, 2018, for cancer-specific survival. Results: Of the 3850 patients treated with first-line gemcitabine (3150 [81.8%]) or fluorouracil (700 [18.2%]), 2178 (56.6%) received antibiotics. The mean (SD) age at diagnosis was 74.2 (5.8) years and patients were predominantly women (2102 [54.6%]), White (3396 [88.2%]), and from metropolitan areas (3393 [88.1%]) in the northeastern or western US (2952 [76.7%]). In total, 1672 propensity-matched pairs were analyzed. Antibiotic receipt was associated with an 11% improvement in overall survival (hazard ratio [HR], 0.89; 95% CI, 0.83-0.96; P = .003) and a 16% improvement in cancer-specific survival (HR, 0.84; 95% CI, 0.77-0.92; P < .001) among patients treated with gemcitabine. In contrast, there was no association between antibiotic receipt and overall survival (HR, 1.08; 95% CI, 0.90-1.29; P = .41) or cancer-specific survival (HR, 1.12; 95% CI, 0.90-1.36; P = .29) among patients treated with fluorouracil. In a subgroup of gemcitabine-treated patients who received antibiotics, nonpenicillin ß-lactams were associated with an 11% survival benefit (HR, 0.89; 95% CI, 0.81-0.97; P = .01). Conclusions and Relevance: In this cohort study, receipt of perichemotherapy antibiotics was associated with improved survival among patients treated with gemcitabine, but not fluorouracil, suggesting that antibiotics may modulate bacteria-mediated gemcitabine resistance and have the potential to improve PDAC outcomes.

A gastric resident drug delivery system for prolonged gram-level dosing of tuberculosis treatment.

Multigram drug depot systems for extended drug release could transform our capacity to effectively treat patients across a myriad of diseases. For example, tuberculosis (TB) requires multimonth courses of daily multigram doses for treatment. To address the challenge of prolonged dosing for regimens requiring multigram drug dosing, we developed a gastric resident system delivered through the nasogastric route that was capable of safely encapsulating and releasing grams of antibiotics over a period of weeks. Initial preclinical safety and drug release were demonstrated in a swine model with a panel of TB antibiotics. We anticipate multiple applications in the field of infectious diseases, as well as for other indications where multigram depots could impart meaningful benefits to patients, helping maximize adherence to their medication.