The importance of monitoring a new antibiotic: ceftazidime/avibactam usage and resistance experience from England, 2016 to 2020

Background: Ceftazidime/avibactam, launched in the United Kingdom (UK) in March 2017, is an antibiotic against multidrug-resistant Gram-negative pathogens. It was selected for the government's subscription model pilot, for incentivising new antibiotic development, which began in December 2020. Aim: Ahead of the pilot, we assessed ceftazidime/avibactam testing, resistance (2016−2020) and usage (2017−2020) levels in England, as baselines for future surveillance. Methods: From routine surveillance samples, we retrieved reported ceftazidime/avibactam resistance categorisation. From reference laboratory samples, we reviewed minimum inhibitory concentration (MICs) and molecular data. Among surveillance samples, per cent resistance was estimated. Referred samples' MICs, by carbapenemase gene presence, were investigated. Ceftazidime/avibactam hospital use was measured in defined daily doses (DDDs). Results: Overall, 6.3% (4,200/66,914; 95% confidence interval (95%CI):6.1-6.4%) of surveillance-reported ceftazidime/avibactam-tested Gram-negative bacteria were resistant. Percentage resistance per bacterial species varied over time, somewhat stabilising as testing was established, with between April 2019 and March 2020, 1.3% Escherichia coli (288/22,736; 95%CI:1.1−1.4%), 12.6% Pseudomonas aeruginosa (690/5,495; 95%CI:11.7−13.5%) and 6.1% of Klebsiella pneumoniae (314/5,179; 95%CI:5.4−6.7%) being resistant. For 8,437 referred Enterobacterales, MIC determination found 11.5% (968/8,437; 95%CI:10.8-12.2%) resistant. Among resistant isolates, 89.3% (864/968; 95%CI:87.1-91.1%) had metallo-β-lactamase (MBL) genes. Of 908 MBL-negative isolates, producing≥1 non-metallo-carbapenemase(s), 2.1% (19/908; 95%CI:1.3-3.2%) were resistant. Since March 2017, 69.5% (105/151) of English National Health Service Trusts used ceftazidime/avibactam.Monthly usage progressed from 21 to 744 DDDs in March 2020. Conclusion: For appropriate treatment, carbapenemase gene detection and variant identification in ceftazidime/avibactam surveillance matters. Detecting emerging resistant pathogens and preventing spread within healthcare settings requires vigilance.