Purpose <p><i>Burkholderia cepacia complex</i> (BCC) showed increased resistance to recommended therapeutic agents, including levofloxacin, ceftazidime, meropenem and trimethoprim/sulfamethoxazole (TMP/SMX). BCC genospecies have different antibiogram patterns, so genospecies dynamics may affect overall susceptibility rates. This study analyzed the clinical epidemiology of BCC bloodstream infections (BSIs), assessed in vitro susceptibility of novel antibiotics, and explored prognostic factors for outcomes of BCC BSIs</p> Methods <p>We performed molecular identification to species level and antimicrobial susceptibility test to 12 antibiotics by the CLSI broth microdilution method. The 14-day mortality was used to evaluate the outcomes of BCC BSIs. Multivariate logistic regression was used for outcome analysis</p> Results <p>From January 2021 to December 2023, the study included 122 BCC isolates and 100 adult patients with evaluable clinical outcome. Among 122 isolates, we identified 97 isolates of <i>B. cenocepacia</i>, 14 of <i>B. contaminans</i> and 11 of non-<i>cenocepacia</i> and non-<i>contaminans Burkholderia</i> by <i>recA</i> or <i>hisA</i> analysis. Cefiderocol and ceftazidime/avibactam both showed potent activity across different genospecies. Aztreonam/avibactam and ceftolozane/tazobactam showed similar and even lower activity compared to ceftazidime and meropenem. Source control was associated with better survival (adjust odds ratio, 0.02; 95% CI 0.003-0.12). Neither regimens of antibiotic therapy nor genospecies was associated with 14-day survival</p> Conclusions <p>The study highlighted the survival benefit of source control, instead of therapeutic regimens. Further, in vitro potency of cefiderocol and ceftazidime/avibactam may have a potential role to improve outcomes among patients with BCC BSIs</p>