Disrupting the microbiome, disrupting immunity: Antibiotic exposure and survival outcomes with immune checkpoint inhibitors—A systematic review.

e23430 Background: The gut microbiome plays a critical role in shaping antitumor immunity and response to immune checkpoint inhibitors (ICIs). Antibiotic exposure may disrupt microbial diversity, potentially impairing immunotherapy efficacy. However, the consistency and magnitude of this association across solid tumors remain unclear. Methods: We conducted a systematic review of PubMed to identify studies evaluating the association between antibiotic exposure and clinical outcomes in adult patients with solid tumors treated with ICIs. The search was limited to human studies published in English within the last 10 years using the following MeSH-based strategy: (antibiotics OR antimicrobial OR antibacterial) AND (immune checkpoint inhibitors OR ICI) AND (cancer OR neoplasms OR tumors) AND (treatment outcome OR survival). Of 576 records identified, 175 studies were screened in detail after application of filters and removal of duplicates. Eligible studies reported survival outcomes stratified by antibiotic exposure occurring before or during immunotherapy. Results: A total of 25 studies comprising approximately 73,567 patients with solid tumors treated with ICIs were included. Antibiotic exposure within 30–60 days before or during ICI therapy was associated with inferior overall survival (OS) in the majority of studies. 22 of 25 studies demonstrated worse OS among antibiotic-exposed patients 2 studies showed no significant association 1 study in hepatocellular carcinoma (HCC) demonstrated a variable association dependent on hepatitis infection status Across all solid tumors except HCC, antibiotic exposure was consistently associated with worse OS, with reported hazard ratios ranging from 1.08 to 2.55, and one study reporting a markedly elevated risk (HR 7.4). A large melanoma cohort did not demonstrate a significant association, representing a notable exception. Several studies suggested that outcomes varied by antibiotic class, with fluoroquinolones associated with worse survival compared with other antibiotic classes in select analyses, indicating potential class-specific effects rather than a uniform antibiotic risk. Conclusions: Antibiotic exposure surrounding immune checkpoint inhibitor initiation is associated with worse overall survival across most solid tumors, with notable exceptions in melanoma and hepatitis-dependent HCC. These findings emphasize the importance of antibiotic stewardship in patients receiving immunotherapy. When clinically appropriate, clinicians should consider delaying ICI initiation for a short duration following recent antibiotic exposure (30–60 days) and avoid unnecessary concomitant antibiotic therapy, balancing infection severity against oncologic risk. Further prospective studies are needed to define class-specific antibiotic effects.