Screening for Metallo-Beta-Lactamases Using Non-Carbapenem Agents: Effective Detection of MBL-Producing Enterobacterales and Differentiation of Carbapenem-Resistant Enterobacterales

Abstract

Metallo-beta-lactamases (MBLs) are enzymes that break down carbapenem antibiotics, leading to carbapenem-resistant organisms. Carbapenemase-resistant Enterobacterales (CRE) is one of them. Outbreaks of CRE infection can occur in healthcare facilities and lead to increased deaths, illness, and medical costs. This study was conducted to detect MBLs using non-carbapenem agents and exclude MBLs among CRE isolates. A total of 3776 non-duplicate sequential Enterobacterales isolates from a single facility were screened between January 2019 and December 2022 using non-carbapenem agents, ceftazidime and cefoperazone/sulbactam. Positive 153 isolates (4.0%) were further tested using carbapenemase-confirmation tests and verified through polymerase chain reaction (PCR) testing. Fifteen imipenemase (IMP)-type MBL-producing Enterobacterales (0.4%) including one susceptible to carbapenems were identified. Moreover, 160 isolates (4.2%) meeting the criteria for CRE were directly subjected to PCR testing. All fourteen CRE isolates with MBLs identified through PCR testing were found to be the same strains screened using ceftazidime and cefoperazone/sulbactam. Screening using ceftazidime and cefoperazone/sulbactam can effectively detect MBL-producing Enterobacterales strains. This screening method showed comparable results to screening with meropenem, potentially serving as a supplementary approach and contributing to differentiating between MBL- and non-MBL-producing CRE strains. Our findings support these screening methods, particularly in regions where IMP-type MBLs are prevalent.

Epidemiological Characteristics of Carbapenem-Resistant Enterobacterales in Japan: A Nationwide Analysis of Data from a Clinical Laboratory Center (2016–2022)

“…According to nationwide surveys in Japan, the frequency of infections caused by carbapenem-resistant K. aerogenes and E. cloacae is the highest, unlike the global trend [15]. This finding is consistent with those of other domestic studies [28,29]. The CRE percentages obtained in this study were 0.28% (313/110,371) for K. aerogenes and 0.47% (869/184,221) for E. cloacae.…”

“…In particular, K. aerogenes is mostly non-CP, and its resistance to carbapenems is greatly influenced by the use of antibiotics [31]. Consequently, it is more likely to be detected in relatively large-scale acute-care hospitals [28,29]. Non-CP K. aerogenes isolates were characterized by resistance to imipenem and susceptibility to meropenem in a previous study [29].…”

“…Consequently, it is more likely to be detected in relatively large-scale acute-care hospitals [28,29]. Non-CP K. aerogenes isolates were characterized by resistance to imipenem and susceptibility to meropenem in a previous study [29]. Resistance mechanisms involve the overproduction of AmpC βlactamase, the action of efflux pumps, and the downregulation of porins [32][33][34][35].…”

“…Resistance mechanisms involve the overproduction of AmpC βlactamase, the action of efflux pumps, and the downregulation of porins [32][33][34][35]. Similarly, E. cloacae produces AmpC β-lactamase, but unlike K. aerogenes, E. cloacae is considered a representative CP species in Japan [28,29].…”