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

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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 National Health Service Trusts, including 192 UK hospitals, submitted data on 8840 consecutive, non-duplicate CRE (October 2023 to September 2024) and local laboratory methods. RESULTS: Predominant CRE species were Klebsiella pneumoniae (30.6%, 2709/8840), Escherichia coli (29.3%, 2592/8840), Enterobacter cloacae complex (22.2%, 1966/8840). Overall, 21.8% (1927/8840) of CRE were collected in outpatient settings. Overall, 85.5% (7279/8513) 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%, 1967/8840), NDM (18.6%, 1645/8840), KPC (9.2%, 817/8840), IMP (2.0%, 178/8840), VIM (0.7%, 62/8840), multi-carbapenemase producers (4.0%, 351/8840). Overall, 51.2% (4526/8840) 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 (41.2%, 40/97), imipenem-relebactam (21.6%, 21/97), aztreonam-avibactam (11.3%, 11/97). OXA-48-like- (97.6%, 1138/1166) 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% (286/1658) of aztreonam-resistant metallo-β-lactamase-producers; synergy was observed in 78.7% (225/286) of cases. Colistin resistance was 10.6% (153/1445) 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.

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