Safety and Efficacy of Anti-Fungal agents in Cholangiocarcinoma Patients: A Multi-Center Retrospective Case-Controlled Study

BackgroundComorbid conditions in cancer patients arising from coinfections are one of the main risks of mortality. Recurrent infections are well-known for reducing quality of life in cancer patients. Long-term efficacy of anti-fungal and anti-bacterial agents for drug repositioning is of great importance. In this longitudinal study long term risk and benefits of anti-fungal plus anti-bacterial agents are compared to anti-bacterial agents. MethodsIn this multi-center study, patients (n = 3048) diagnosed with cholangiocarcinoma from 1st January 2010 to 1st January 2021 at Severance hospital were analyzed. All patients (n = 983) received standard therapy were included, post propensity score matching (n = 153) patients were included in arm-A treated with anti-bacterial plus anti-fungal agents and (n = 153) in arm-B treated with anti-bacterial agents. Using cox-proportional hazard model, and random forest analyses, efficacy of antimicrobials prescribed during cancer treatment. Post-chemotherapy and post-diagnosis survival in infected were compared among groups. Lastly post infection end-stage leukopenia and leukocytosis events 30 days prior to death were compared. ResultsIn this study total (n = 306) cholangiocarcinoma patients were included post propensity score matching. There is no significant difference in mean days survived post-cancer diagnosis 712 days (95% CI 605 - 818) arm-A and 615 days (95% CI 536 - 693) survived by arm-B with (p-value 0.15). During chemotherapy antibiotic treated arm-A patients survived mean 896 days (95% CI 568 - 1223) compared to arm-B 622 days (95% CI 501 - 742) with p-value 0.05. Significant statistical difference in end-stage mortality caused by chemotherapy induced co-infection and leukopenia were found higher in arm-A (14%) compared to arm-B (3%) with (p-value 0.05). Post exposure to anti-fungals hazard ratio of fluconazole (n = 113) users compared to non-users (n = 40) of arm-A patients were 1.391 (0.994 - 1.949) with p-value 0.07. Hazard ratio of arm-A fluconazole user Vs arm-B teicoplanin treated patients were 1.027 (0.763 - 1.384) with p-value 0.8. ConclusionPatients co-treated with anti-bacterial and anti-fungal agents during chemotherapy survived significantly longer compared to patients treated with anti-bacterial agents alone. Co-treated patients experienced more leukopenia than patients treated with anti-bacterial drugs 8 days prior to death. Mortalities post fluconazole or teicoplanin exposure suggested end-stage fungal or bacterial infections were fatal.