Evaluation of the MTS™ aztreonam-avibactam strip (Liofilchem) on New Delhi metallo-β-lactamase-producing Enterobacterales.

The combination of ceftazidime-avibactam (CAZ-AVI) and aztreonam (ATM) is used to treat MBL-producing Enterobacterales-related infections. The new combination aztreonam-avibactam (AZA) is currently in development. We compared results obtained with the new MIC test strip (MTS) AZA (Liofilchem) with broth microdilution method (BMD) on 41 MBL-producing Enterobacterales from 41 clinical samples. The MTS AZA was also compared to combination testing method using CAZ-AVI and ATM strips. Compared to BMD, categorical agreement (CA) was 100%. Compared with combination testing method, CA was 97.6%. The MTS AZA can be used to determine MICs levels of AZA or CAZ-AVI/ATM combinations.

Emilie CM ，Alice CM ，Marine G ，Farfour E ，Pourbaix A ，Dortet L ，Lucie L ，Marc V ... -  《-》

Comparison of testing methods assessing the in vitro efficacy of the combination of aztreonam with avibactam on multidrug-resistant Gram-negative bacilli.

Aztreonam-avibactam (ATM-AVI) combination shows promising effectiveness on most carbapenemase-producing Gram-negatives, yet standardized antibiotic susceptibility testing (AST) methods for evaluating the combination in clinical laboratories is lacking. We aimed to evaluate different ATM-AVI AST approaches. 96 characterized carbapenem-resistant clinical isolates belonging to 9 Enterobacterales (EB; n = 80) and P. aeruginosa (PA; n = 16) species, including 90 carbapenemase producers and 72 strains resistant to both CAZ-AVI and ATM, were tested. Paper disk elution (DE; Bio-Rad) and E-test gradient strips stacking (SS; bioMérieux) were performed for the ATM + CAZ-AVI combination. MIC Test Strip (MTS; Liofilchem) was evaluated for ATM-AVI MIC determination. Results were interpreted applying ATM clinical breakpoints of the EUCAST guidelines and compared to the broth microdilution method (Sensititre, Thermofisher). According to broth microdilution method, 93% of EB and 69% of PA were tested susceptible to ATM-AVI. The synergistic effect of ATM-AVI was of 95% for EB, but of only 17% for PA. The MTS method yielded higher categorical and essential agreement (CA/EA) rates for both EB (89%/91%) and PA (94%/94%) compared to SS, where the rates were 87%/83% for EB and 81%/81% for PA. MTS and SS yielded 2 and 3 major discrepancies, respectively, while 3 very major discrepancies each were observed for both methods. Concerning the DE method, CA reached 91% for EB and 81% for PA, but high number of very major discrepancies were observed for EB (n = 6; 8%) and for PA (n = 3; 19%). The ATM-AVI association displayed excellent in vitro activity against highly resistant clinical Enterobacterales strains. MTS method offers accurate ATM-AVI AST results, while the SS method might serve as better alternative then DE method in assessing the efficacy of ATM + CAZ-AVI combination. However, further investigation is needed to confirm the methods' ability to detect ATM-AVI resistance.

Deckers C ，Bélik F ，Denis O ，Bogaerts P ，Montesinos I ，Berhin C ，Bouchahrouf W ，Hoebeke M ，Evrard S ，Gilliard N ，Okur M ，Huang TD ... -  《Annals of Clinical Microbiology and Antimicrobials》

A practical laboratory method to determine ceftazidime-avibactam-aztreonam synergy in patients with New Delhi metallo-beta-lactamase (NDM)-producing Enterobacterales infection.

In response to infection with New Delhi metallo-beta-lactamase (NDM)-producing Enterobacterales, combination antimicrobial therapy with ceftazidime/avibactam (CAZ/AVI) plus aztreonam (ATM) has been explored. This study evaluated a practical laboratory method of testing for clinically significant synergy between CAZ/AVI+ATM in NDM-producing Enterobacterales. Minimum inhibitory concentrations (MICs) of clinical NDM-producing isolates were determined for ATM alone and CAZ/AVI+ATM using broth dilution. Restoration of the ATM breakpoint after the addition of CAZ/AVI was explored. A CAZ/AVI Etest/ATM disc method was compared with broth dilution. Of 43 isolates, 33 (77%) were ATM resistant (median [range] MIC = 56 [16-512] mg/L). Addition of CAZ/AVI restored the ATM breakpoint (MIC <4 mg/L) in 29 of 33 resistant isolates (89%). Overall, the Etest/disc method correlated with the findings from broth dilution in 35 of 43 cases (81%). Etest/disc sensitivity was 77% and specificity 85%. Positive predictive value was 92% and negative predictive value 61%. CAZ/AVI+ATM demonstrated significant synergy in most ATM-resistant NDM-producing Enterobacterales. The Etest/disc method is a quick, reproducible, and reliable method of testing for clinically relevant synergy in the microbiology laboratory.

Rawson TM ，Brzeska-Trafny I ，Maxfield R ，Almeida M ，Gilchrist M ，Gonzalo X ，Moore LS ，Donaldson H ，Davies F ... -  《-》

Assessment of broth disk elution method for aztreonam in combination with ceftazidime/avibactam against Enterobacterales isolates.

Song P ，Xu J ，Jiang L ，Zhang Q ，Liu C ... -  《Microbiology Spectrum》

Evaluation of Dilution Susceptibility Testing Methods for Aztreonam in Combination with Avibactam against Enterobacterales.

Kelley CJ ，Kennedy-Mendez A ，Walser ON ，Thwaites MT ，Arhin FF ，Pillar CM ，Hufnagel DA ... -  《Microbiology Spectrum》