Carbapenem-resistant Enterobacterales across the UK: a nationwide study of carbapenemase testing and novel antimicrobial activity

Background Carbapenem-resistant Enterobacterales (CRE) are increasing in the UK, but the drivers of this rise and effective treatment options remain uncertain. Methods Ninety-seven acute NHS Trusts, including 192 UK hospitals, submitted data on 8,840 consecutive, non-duplicate CRE (October 2023–September 2024) and local laboratory methods. Results Predominant CRE species were Klebsiella pneumoniae (30.4%, 2,709/8,840), E. coli (29.3%, 2,592/8,840), Enterobacter cloacae complex (22.2%, 1,966/8,840). 21.8% (1,927/8,840) of CRE were collected in outpatient settings. Overall, 85.5% (7,279/8,513) of CRE underwent carbapenemase detection testing, with significant variation depending on species, specimen type and baseline antibiogram. Carbapenemases detected were OXA-48-like (22.3%, 1,967/8,840), NDM (18.6%, 1,645/8,840), KPC (9.2%, 817/8,840), IMP (2.0%, 178/8,840), VIM (0.7%, 62/8,840), multi-carbapenemase producers (4.0%, 351/8,840). 51.2% (4,526/8,840) of CRE were tested against ≥1 novel agent. In-house antimicrobial susceptibility testing availability was common for ceftazidime–avibactam (90.7%, 88/97) and cefiderocol (73.2%, 71/97), while less common for meropenem–vaborbactam (40.2%, 40/97), imipenem–relebactam (21.6%, 21/97), aztreonam–avibactam (11.3%, 11/97). OXA-48-like- (97.6%, 1,138/1,166) and KPC-producers (96.2%, 429/446) remained susceptible to ceftazidime–avibactam. KPC-producers to meropenem–vaborbactam (99.4%, 160/161) and imipenem–relebactam (98.4%, 62/63). Cefiderocol resistance was 32.4% overall and higher among NDM- (58.4%) and multi-carbapenemase-producers (50.3%). Ceftazidime–avibactam plus aztreonam synergy was performed for 17.2% (286/1,658) of aztreonam-resistant metallo-β-lactamase-producers; synergy was observed in 78.7% (225/286) of cases. Colistin resistance was 10.6% (153/1,445) among non-intrinsically resistant species. Conclusions Whilst most UK CRE are tested for carbapenemases, coverage gaps persist. The community burden of CRE is increasing. Cefiderocol resistance is concerningly high, particularly among metallo-β-lactamase-producers.