Relebactam enhances the activity of imipenem against Burkholderia cepacia complex isolates.
BACKGROUND Burkholderia cepacia complex (BCC) is a group of ≥21 related organisms, including B. cepacia, Burkholderia cenocepacia, and Burkholderia multivorans. BCC can cause opportunistic infections in people who are immunocompromised and those with comorbidities or lung conditions. BCC exhibits intrinsic and acquired resistance to antimicrobial agents; additional treatment options may improve patient outcomes. METHODS BCC isolates were collected as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART) global surveillance program from 2016-2019 and 2020-2022. Susceptibility of isolates to imipenem and imipenem/relebactam was tested in vitro, and the effects of imipenem/cilastatin/relebactam on BCC burden were evaluated in vivo. RESULTS In total, 346 and 293 BCC isolates were collected from 2016-2019 and 2020-2022, respectively, the most common were B. cepacia (2016-2019: n=145/346; 2020-2022: n=124/293) and B. cenocepacia (2016-2019: n=137/346; 2020-2022: n=119/293). In vitro, imipenem/relebactam reduced 50% and 90% minimum inhibitory concentrations for BCC isolates by 8-16-fold versus imipenem alone. In vivo, imipenem/cilastatin/relebactam initiation at 2 hours post-challenge significantly reduced BCC burden versus imipenem/cilastatin for one of five strains (-1.67 log colony-forming units [CFU]/g; P<0.01) at therapeutic imipenem doses and four of five strains at subtherapeutic imipenem doses (-1.19 to -1.93 log CFU/g; all P<0.05). CONCLUSION Imipenem/relebactam effectively inhibited the growth of BCC isolates in vitro and reduced bacterial burden of BCC isolates in vivo. There are no interpretive susceptibility criteria for imipenem/relebactam against BCC; however, these results warrant further investigation in clinical studies.