It is estimated that antimicrobial resistance (AMR) is responsible for nearly 5 million human deaths worldwide each year and will reach 10 million by 2050. Carbapenem-resistant Acinetobacter baumannii (CRAB) infections represent the fourth-leading cause of death attributable to antimicrobial resistance globally, but a standardized therapy is still lacking. Among the antibiotics under consideration, Sulbactam/durlobactam seems to be the best candidate to replace current back-bone agents. Cefiderocol could play a pivotal role within combination therapy regimens. Due to toxicity and the pharmacokinetics/pharmacodynamics (PK/PD) limitations, colistin (or polymyxin B) should be used as an alternative agent (when no other options are available). Tigecycline (or minocycline) and fosfomycin could represent suitable partners for both NBLs. Randomized clinical trials (RCTs) are needed to better evaluate the role of NBLs in CRAB infection treatment and to compare the efficacy of tigecycline and fosfomycin as partner antibiotics. Synergism should be tested between NBLs and \"old\" drugs (rifampicin and trimethoprim/sulfamethoxazole). Huge efforts should be made to accelerate pre-clinical and clinical studies on safer polymyxin candidates with improved lung activity, as well as on the iv rifabutin formulation. In this narrative review, we focused the antibiotic treatment of CRAB infections in view of newly developed β-lactam agents (NBLs).

Gram-negative bacteria have been one of the most studied classes in the field of microbiology, especially in the context of globally alarming antimicrobial resistance levels to these pathogens over the course of the past decades. With high numbers of these microorganisms being described as multidrug-resistant (MDR), or even extended-drug-resistant (XDR) bacteria, specialists in the field have been struggling to keep up with higher prevalence of difficult-to-treat infections caused by such superbugs. The FDA approval of novel antimicrobials, such as cefiderocol (FDC), ceftolozane/tazobactam (C/T), ceftazidime/avibactam (CZA), imipenem/relebactam (IMR), sulbactam/durlobactam (SUL-DUR) and phase 3 clinical trials\' results of aztreonam/avibactam (ATM-AVI) has proven that, while all these substances provide encouraging efficacy rates, antibiotic resistance keeps up with the pace of drug development. Microorganisms have developed more extensive mechanisms of resistance in order to target the threat posed by these novel antimicrobials, thus equiring researchers to be on a constant lookout for other potential drug candidates and molecule development. However, these strategies require a proper understanding of bacterial resistance mechanisms to gain a comprehensive outlook on the issue. The present review aims to highlight these six antibiotic agents, which have brought hope to clinicians during the past decade, discussing general properties of these substances, as well as mechanisms and patterns of resistance, while also providing a short overview on further directions in the field.
UNASSIGNED: https://www.crd.york.ac.uk/prospero/#searchadvanced, Identifier CRD42024505832.

Infections caused by carbapenem-resistant Acinetobacter baumannii (CRAB) have limited therapeutic options. Sulbactam-durlobactam is a combination of two βlactamase inhibitors with activity against CRAB under phase 3 clinical investigation. We performed a systematic review on in vitro studies reporting A. baumannii resistances against sulbactam/durlobactam. We considered \"resistant\" species to be those with MIC ≥ 8 mg/L. Ten studies were included in the review (9754 tested isolates). Overall, 2.3% of A. baumannii were resistant to sulbactam/durlobactam, and this percentage rose to 3.4% among CRAB subgroups and to 3.7% among colistin-resistant strains. Resistance was 100% among metallo β-lactamase-producing strains. Overall, in 12.5% of cases, sulbactam/durlobactam resistance was associated with the production of NDM-1, in 31.7% of cases with the substitutions in the PBP3 determinants, and in the remaining cases the resistance mechanism was unknown. In conclusion, A. baumannii resistance towards sulbactam/durlobactam is limited, except for MBL-producing strains.

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