In vitro susceptibility of carbapenem resistant Enterobacterales to meropenem-vaborbactam and ceftazidime-avibactam at a single academic medical centre

Abstract

Background

Carbapenem-resistant Enterobacterales (CRE) are considered an urgent threat. Ceftazidime-avibactam and meropenem-vaborbactam contain β-lactamase inhibitors active against CRE isolates including those that produce Klebsiella pneumoniae carbapenemases (KPC).

Methods

Retrospective chart review of CRE isolates from 1 January 2016 to 1 November 2018. Collected data includes a descriptive overview of measured MIC values, resistance mechanism via a polymerase chain reaction test (Xpert Carba-R, Cepheid, Sunnyvale CA), as well as clinical outcomes.

Results

Of 106 isolates reviewed, 86 isolates met the inclusion criteria from 85 individual subjects. The breakpoint:MIC ratio for ceftazidime-avibactam overall was 4, while for meropenem-vaborbactam this ratio was 32 (p < 0.0001). For KPC isolates, ceftazidime-avibactam MIC₅₀/MIC₉₀ in 2016, 2017, and 2018 were 2/4 mg/L (n = 32), 2/4 mg/L (n = 17), and 2/8 mg/L (n = 30), respectively. The meropenem-vaborbactam MIC₅₀/MIC₉₀, for KPC isolates in 2016, 2017, and 2018 were 0.06/0.125 mg/L (n = 32), 0.06/0.1 mg/L (n = 17), and 0.06/0.5 mg/L (n = 30), respectively. Microbiologic cure was 75% (n = 16) in ceftazidime-avibactam subjects and 58.3% (n = 12) in subjects treated with alternative agents (p = 0.43). The 14- and 30-day mortality was numerically higher in subjects treated with alternate agents when compared ceftazidime-avibactam 2/9 (22.2%) vs 3/17 (17.6%) (p = 1.00) and 4/9 (44.4%) vs 4/17 (28.6%) (p = 0.38), respectively. For ceftazidime-avibactam, 30-day mortality in 2016, 2017, and 2018 was 0/5 (0%), 0/2 (0%), and 4/10 (40%).

Conclusion

Selective pressure from the use of ceftazidime-avibactam at our institution may be decreasing its utility as a first-line agent for CRE infections. Meropenem-vaborbactam maintained low MIC values and may be a promising treatment option for CRE.

Keywords:

• Meropenem-vaborbactam
• ceftazidime-avibactam
• antibiotic susceptibility
• minimum inhibitory concentration

Acknowledgements

This study was completed internally, with internal statistical assistance.

We thank the Microbiology Laboratory for their tireless efforts in assisting with this project. A portion of this data was presented via poster presentation at the 2019 American Society for Microbiology (ASM) Microbe meeting.

Ethics approval

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Disclosure statement

No potential conflict of interest was reported by the author(s).

Code availability

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Additional information

Funding

The authors did not receive support from any organisation for the submitted work.