Global Threat of Carbapenem-Resistant Gram-Negative Bacteria

Abstract

Infections caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria (GNB), including carbapenem-resistant (CR) Enterobacterales (CRE; harboring mainly blaKPC, blaNDM, and blaOXA-48-like genes), CR- or MDR/XDR-Pseudomonas aeruginosa (production of VIM, IMP, or NDM carbapenemases combined with porin alteration), and Acinetobacter baumannii complex (producing mainly OXA-23, OXA-58-like carbapenemases), have gradually worsened and become a major challenge to public health because of limited antibiotic choice and high case-fatality rates. Diverse MDR/XDR-GNB isolates have been predominantly cultured from inpatients and hospital equipment/settings, but CRE has also been identified in community settings and long-term care facilities. Several CRE outbreaks cost hospitals and healthcare institutions huge economic burdens for disinfection and containment of their disseminations. Parenteral polymyxin B/E has been observed to have a poor pharmacokinetic profile for the treatment of CR- and XDR-GNB. It has been determined that tigecycline is suitable for the treatment of bloodstream infections owing to GNB, with a minimum inhibitory concentration of ≤ 0.5 mg/L. Ceftazidime-avibactam is a last-resort antibiotic against GNB of Ambler class A/C/D enzyme-producers and a majority of CR-P. aeruginosa isolates. Furthermore, ceftolozane-tazobactam is shown to exhibit excellent in vitro activity against CR- and XDR-P. aeruginosa isolates. Several pharmaceuticals have devoted to exploring novel antibiotics to combat these troublesome XDR-GNBs. Nevertheless, only few antibiotics are shown to be effective in vitro against CR/XDR-A. baumannii complex isolates. In this era of antibiotic pipelines, strict implementation of antibiotic stewardship is as important as in-time isolation cohorts in limiting the spread of CR/XDR-GNB and alleviating the worsening trends of resistance.

An Update of Mobile Colistin Resistance in Non-Fermentative Gram-Negative Bacilli

“…Polymyxins and carbapenems are considered last-resort antibiotics for the treatment of Gram-negative bacteria; however, owing to their misuse, the problem of antibiotic resistance is worsening, particularly in low-to middle-income countries (de Carvalho et al, 2022). A multicenter surveillance study in Taiwan found that the incidence of MDR, XDR, and CR P. aeruginosa infections in hospitalized patients increased from 25.1% to 27.5%, 7.7 to 8.4%, and 19.7% to 27.5%, respectively, between 2016 and 2018 (Jean et al, 2022). In the past decade, hospital-associated P. aeruginosa has showed high MDR/CR numbers in Europe, with prevalence rates of more than 30% (Micek et al, 2015).…”

“…In China, Acinetobacter spp. showed a high level of resistance to all carbapenems caused by plasmids carrying various carbapenemase genes (Jean et al, 2022). In a 2022 report from Europe, healthcare-associated isolates of CR-Acinetobacter spp.…”

Effect of Colistin, Fosfomycin and Meropenem/Vaborbactam on Carbapenem-Resistant Enterobacterales in Egypt: A Cross-Sectional Study

“…The increasing Carbapenem-resistant Enterobacterales (CRE) isolates are a severe threat worldwide due to the poor prognosis and limited therapeutic options. [1][2][3] The production of carbapenemases such as Klebsiella pneumoniae carbapenemase (KPC), Metallo-β-lactamases (MBLs) and oxacillinases (OXA) enzymes mainly cause carbapenem resistance. Moreover, the deficiency in the outer-membrane protein expression plays a minor role in carbapenem resistance.…”

Comments on “Impact of Antibiotic Stewardship Rounds in the Intensive Care Setting: A Prospective Cluster-Randomized Crossover Study”

“…As an infectious disease specialist struggling to propel the proper use of antibiotics, I have gone through the most recent article in your esteemed journal written by Seidelman et al [1]. In this age of antimicrobial resistance [2], promoting antimicrobial stewardship is increasingly highlighted worldwide [3]. Therefore, evaluating the clinical impacts of antibiotic stewardship rounds in intensive care units (ICU) where broad-spectrum antibiotics are prescribed is vital.…”