The oxacillinase variant, OXA-1152, in Pandoraea sputorum contributes to discrepancies in carbapenem resistance

<i>Pandoraea</i> species are emerging multidrug-resistant pathogens with inconsistent carbapenem susceptibility, being resistant to meropenem but susceptible to imipenem, which complicates treatment. Here, we identified a previously uncharacterized oxacillinase gene, <i>bla</i> _OXA-1152, in 12 <i>Pandoraea sputorum</i> strains from Wuhan, China. Deleting <i>bla</i> _OXA-1152 reduced meropenem and imipenem minimal inhibitory concentrations (MICs) by 64- and 4-fold, respectively, while reintroducing it into <i>P. sputorum</i> and <i>E. coli DH5α</i> restored resistance. Mechanistically, OXA-1152 exhibited stronger binding and hydrolysis efficiency for meropenem than imipenem. Combining avibactam with carbapenems restored susceptibility to meropenem and further reduced imipenem MICs, highlighting OXA-1152's role in resistance variation. These findings reveal the molecular basis of carbapenem resistance discrepancy in <i>Pandoraea</i> and suggest avibactam-carbapenem combinations as a promising therapeutic strategy, offering broader implications for treating multidrug-resistant infections.