Background. The global spread of carbapenemase-producing Enterobacterales has become an epidemiological risk for healthcare systems by limiting available antimicrobial treatments. The COVID-19 pandemic worsened this scenario, prompting the emergence of extremely resistant microorganisms. Methods. Between March 2020 and September 2021, the NRL confirmed 82 clinical Enterobacterales isolates harboring a combination of bla_KPC and MBL genes. Molecular typing was analyzed by PFGE and MLST. Modified double-disk synergy (MDDS) tests were used for phenotypic studies. Results. Isolates were submitted from 28 hospitals located in seven provinces and Buenos Aires City, including 77 K. pneumoniae, 2 K. oxytoca, 2 C. freundii, and 1 E. coli. Almost half of K. pneumoniae isolates (n = 38; 49.4%), detected in 15 hospitals, belong to the CC307 clone. CC11 was the second clone, including 29 (37.7%) isolates (22, ST11 and 7, ST258) from five cities and 12 hospitals. Three isolates belonging to CC45 were also detected. The carbapenemase combinations observed were as follows: 55% bla_KPC-2 plus bla_NDM-5; 32.5% bla_KPC-2 plus bla_NDM-1; 5% bla_KPC-3 plus bla_NDM-1; 5% bla_KPC-2 plus bla_IMP-8; and 2.5% strain with bla_KPC-2 plus bla_NDM-5 plus bla_OXA-163. Aztreonam/avibactam and aztreonam/relebactam were the most active combinations (100% and 91% susceptible, respectively), followed by fosfomycin (89%) and tigecycline (84%). Conclusions. The MDDS tests using ceftazidime-avibactam/EDTA and aztreonam/boronic acid disks improved phenotypic classification as dual producers. The successful high-risk clones of K. pneumoniae, such as hyper-epidemic CC307 and CC11 clones, drove the dissemination of double carbapenemase-producing isolates during the COVID-19 pandemic.

The COVID-19 pandemic has exacerbated the global antimicrobial resistance (AMR) crisis. Consequently, it is more urgent than ever to prioritize AMR containment and support countries in improving the detection, characterization, and rapid response to emerging AMR threats. We conducted a prospective, multicenter study to assess the prevalence of carbapenemase-producing Enterobacterales in infectious processes in Argentina during the post-COVID-19 pandemic period and explore therapeutic alternatives for their treatment (RECAPT-AR study). Methods: A total of 182 hospitals participated by submitting Enterobacterales clinical isolates to the National Reference Laboratory (NRL) during the first three weeks of November 2021. Inclusion criteria were defined as an ertapenem MIC ≥ 0.5 mg/L, a zone diameter ≤ 22 mm. Carbapenemase genes and those coding for major extended-spectrum β-lactamases were molecularly characterized using multiplex PCR at the NRL. Antibiotic susceptibility testing followed international standards (CLSI and EUCAST). Results: The NRL analyzed 821 Enterobacterales isolates. Metallo-β-lactamase (MBL, 42.0%) and KPC (39.8%) accounted for 81.8% of carbapenemases, followed by OXA-163 (7.4%), a variant of OXA-48 with additional activity against extended-spectrum cephalosporins, and enzyme combinations (8.3%). These combinations included NDM plus KPC (3.4%), OXA-163 plus KPC (2.4%), and OXA-163 plus NDM (2.1%). Klebsiella pneumoniae was the main species recovered, representing 76% of the isolates. According to the carbapenemase classes or combinations, tigecycline exhibited a susceptibility range of 33–83%, fosfomycin 59–81%, colistin 27–78%, and amikacin 17–81%. Ceftazidime-avibactam (CZA) and imipenem-relebactam (IMR) showed 92% and 98% susceptibility against serine carbapenemases, respectively. Meanwhile, aztreonam-avibactam (AZA) exhibited 96–98% susceptibility against all carbapenemase classes. Conclusions: A new epidemiological landscape has emerged, characterized by the equivalent circulation of NDM and KPC. K. pneumoniae remains the primary species responsible for their dissemination. The co-production of carbapenemase combinations, particularly KPC plus NDM, was confirmed, mainly in K. pneumoniae. High activity was observed for AZA against MBLs and for CZA and IMR against KPC and OXA-163 carbapenemases.