Activity of β-Lactam Antibiotics against Metallo-β-Lactamase-Producing Enterobacterales in Animal Infection Models: a Current State of Affairs

Metallo-beta-lactamases (MBLs) result in resistance to nearly all beta-lactam antimicrobial agents, as determined by currently employed susceptibility testing methods. However, recently reported data demonstrate that variable and supraphysiologic zinc concentrations in conventional susceptibility testing media compared with physiologic (bioactive) zinc concentrations may be mediating discordant in vitro-in vivo MBL resistance. While treatment outcomes in patients appear suggestive of this discordance, these limited data are confounded by comorbidities and combination therapy. To that end, the goal of this review is to evaluate the extent of beta-lactam activity against MBL-harboring Enterobacterales in published animal infection model studies and provide contemporary considerations to facilitate the optimization of current antimicrobials and development of novel therapeutics.

Automated summary

Metallo-beta-lactamases (MBLs) lead to resistance to almost all beta-lactam antimicrobial agents, with varying zinc concentrations in testing media possibly mediating discrepancies in MBL resistance. Treatment outcomes are influenced by comorbidities and combination therapy.