Aztreonam plus ceftazidime/avibactam broth disk elution test: failure to detect Escherichia coli with PBP-3...

Metallo-β-lactamase (MBL)-producing Enterobacterales are increasing in frequency and treatment options are limited. Aztreonam/avibactam (AZA) and aztreonam (ATM) plus ceftazidime/avibactam (CZA) showed activities against these organisms. Escherichia coli with PBP3 insertions (YRIN, YRIK) showed decreased activities to AZA and have been linked with treatment failures.

We used well-characterized global collections of MBL-producing Enterobacterales (n = 86) to evaluate if MICs generated by AZA MIC Test Strips (MTS) could be used as substitute testing for ATM-CZA Broth Disk Elution (ATM-CZA BDE). We also determined if AZA (breakpoint of 4/4 µg/ml) or ATM-CZA BDE could detect E. coli with PBP-3 insertions.

The AZA MTS at ≤ 2/4µg/ml and ≥ 8/4µg/ml) showed 100% categorical agreement with ATM-CZA BDE but was less labour-intensive and more cost-effective. A strain with AZA MIC of 4/4 µg/ml tested not susceptible with ATM-CZA BDE, resulting in a very major error rate of 1/9 (11%). ATM-CZA BDE and AZA MICs (1-4 µg/ml) reported 76% (42/55) of E. coli with bla_NDMs that contained YRIK/YRIN insertions, as susceptible.

AZA MIC Test Strips can reliably predict ATM-CZA BDE results, except for strains with MICs of 4/4 µg/ml. ATM-CZA BDE failed to detect most of E. coli with PBP-3 insertions. E. coli with AZA MICs ranging from 1/4 to 4/4 µg/ml could be screened for PBP-3 insertions, and patients infected with such isolates, should be monitored for possible treatment failures with AZA or ATM-CZA.