Efficacy and In Vitro Activity of Novel Antibiotics for Infections With Carbapenem-Resistant Gram-Negative Pathogens

Abstract

Infections by Gram-negative multi-drug resistant (MDR) bacterial species are difficult to treat using available antibiotics. Overuse of carbapenems has contributed to widespread resistance to these antibiotics; as a result, carbapenem-resistant Enterobacterales (CRE), A. baumannii (CRAB), and P. aeruginosa (CRPA) have become common causes of healthcare-associated infections. Carbapenems, tigecycline, and colistin are the last resource antibiotics currently used; however, multiple reports of resistance to these antimicrobial agents have been documented worldwide. Recently, new antibiotics have been evaluated against Gram-negatives, including plazomicin (a new aminoglycoside) to treat CRE infection, eravacycline (a novel tetracycline) with in vitro activity against CRAB, and cefiderocol (a synthetic conjugate) for the treatment of nosocomial pneumonia by carbapenem-non-susceptible Gram-negative isolates. Furthermore, combinations of known β-lactams with recently developed β-lactam inhibitors, such as ceftazidime-avibactam, ceftolozane-tazobactam, ceftazidime-tazobactam, and meropenem-vaborbactam, has been suggested for the treatment of infections by extended-spectrum β-lactamases, carbapenemases, and AmpC producer bacteria. Nonetheless, they are not active against all carbapenemases, and there are reports of resistance to these combinations in clinical isolates.This review summarizes and discusses the in vitro and clinical evidence of the recently approved antibiotics, β-lactam inhibitors, and those in advanced phases of development for treating MDR infections caused by Gram-negative multi-drug resistant (MDR) bacterial species.

Role of the multi-drug efflux systems on the baseline susceptibility to ceftazidime/avibactam and ceftolozane/tazobactam in clinical isolates of non-carbapenemase-producing carbapenem-resistant Pseudomonas aeruginosa

“…However, further analysis may be performed to evaluate this hypothesis in more detail, and the role of other RND efflux systems should not be discarded. Another contribution of this study is that Non-CP-CRPA isolates presented high levels of susceptibility to CZA and C/T, consistent with previously published studies in which both combined treatments are suggested to be effective against CRPA (Grupper et al, 2017;Shortridge et al, 2018;Wi et al, 2018;Sader et al, 2020;Lomovskaya et al, 2021;Rivas et al, 2021;Cruz-Lopez et al, 2022). Interestingly, our results showed that CZA and C/T activity decrease considerably as strains exhibited a wider multi-drug resistance profile, especially in XDR and DTR strains.…”

Metabolomics Method in Understanding and Sensitizing Carbapenem-Resistant Acinetobacter baumannii to Meropenem

“…Moreover, resistance to β-lactamase inhibitors is reported in CRAB and extensively drug-resistant (XDR) A. baumannii. , Hence, there is an urgent need to explore new methods for treating CRAB infections. The present study uses the recently developed reprogramming metabolomics approach to explore a method for potentiating Meropenem to kill CRAB.…”

Evaluation of the BD Phoenix CPO Detect Panel for Detection and Classification of Carbapenemase Producing Enterobacterales

“…Most of such novel agents exhibited in vitro activity against various β-lactamases of Ambler class A, class B, and class D; however, ceftazidime-avibactam, ceftolozane-tazobactam, and meropenem-vaborbactam were found to be inactive against MBL [40]. Flora Cruz-López et al described ceftazidime-avibactam as active against class A, class C, and some class D β-lactamases [41]. Avibactam combined with ceftazidime has been reported to restore its activity against CRE isolates carrying KPC and OXA-48 carbapenemases [42], but it is not active against MBL producing strains [43].…”