Mono vs. combo regimens with novel beta-lactam/beta-lactamase inhibitor combinations for the treatment of infections due to carbapenemase-producing Enterobacterales : insights from the literature

AbstractCeftazidime –avibactam (CZA), meropenem–vaborbactam (MVB) and imipenem–relebactam (I–R) are combinations of old ß-lactams with novel non-ß-lactam ß-lactamase inhibitors (BLBLIs) able to inhibit some carbapenemases, such as the KPC-type, thus are becoming the standard for difficult-to-treat carbapenem ase-producingEnterobacterales (CPE); a practical question is whether these novel BLBLIs should be used as monotherapy or as part of a combination regimen with other antibiotics, and if so, with which ones, to reduce the emergence of resistant strains and to optimize their efficacy. In this short review, we assessed clinical outcomes in patients with CPE-infections treated with the novel BLBLIs as mono- or combo-regimens, and laboratory studies on the synergistic effects with other antimicrobials. Available evidence on combination therapy is scarce and mainly limited to retrospective studies involving 630 patients treated with CZA: aminoglycosides were used in 39.6% of 336 patients  treated with combo-regimens, followed by polymyxin B/colistin (24.4%), tigecycline (24.1%), carbapenems (13.4%) and fosfomycin (5.4%). Aminoglycosides could be useful in case of bloodstream and severe urinary infections. Pneumonia is a risk factor for CZA-resistance emergence: fosfomycin, due to f avorable lung pharmacokinetics/pharmacodynamics, could represent an interesting partner; fosfomycin could be added also for osteomyelitis. Tigecycline could be preferred for intrabdominal...
Source: Infection - Category: Infectious Diseases Source Type: research