Activity of Dimercaptosuccinic Acid in Combination with Carbapenems Against Carbapenem-Resistant .

Carbapenenemase producers, particularly the metallo-β-lactamase (MBL) types in , have emerged as an urgent threat in health care settings. MBLs require zinc at their catalytic site and can be inhibited by dimercaptosuccinic acid (DMSA), a metal chelator known for the treatment of lead and mercury intoxication. Isogenic strains of wild-type and OprD-deleted PA14, were constructed, producing the MBLs VIM-2, NDM-1, SPM-1, IMP-1, and AIM-1, or the non-MBL carbapenemases, GES-5 and KPC-2. In addition, 59 previously characterized clinical isolates of producing different ß-lactamases (including carbapenemases), and with known outer-membrane porin OprD status, were utilized. Minimal inhibitory concentrations values of imipenem and meropenem, and DMSA combinations were determined, and time-kill assays were performed with PA14 expressing VIM-2. Results indicated a significant additive effect of DMSA (most effective at 3 mM) and carbapenems in recombinant and clinical strains of expressing MBLs, in particular against VIM producers, which are the most prevalent carbapenemases in . This effect was best evidenced with meropenem and in strains without OprD modification. DMSA shows promising efficacy, particularly in combination therapy with meropenem, for treating infections caused by MBL-producing .