In Vitro Activity of Aztreonam-Avibactam against Enterobacteriaceae and Pseudomonas aeruginosa Isolated by Clinical Laboratories in 40 Countries from 2012 to 2015.

ABSTRACT: The combination of the monobactam aztreonam and the non-?-lactam ?-lactamase inhibitor avibactam is currently in clinical development for the treatment of serious infections caused by metallo-?-lactamase (MBL)-producing Enterobacteriaceae, a difficult-to-treat subtype of carbapenem-resistant Enterobacteriaceae for which therapeutic options are currently very limited. The present study tested clinically significant isolates of Enterobacteriaceae (n = 51,352) and Pseudomonas aeruginosa (n = 11,842) collected from hospitalized patients in 208 medical center laboratories from 40 countries from 2012 to 2015 for in vitro susceptibility to aztreonam-avibactam, aztreonam, and comparator antimicrobial agents using a standard broth microdilution methodology. Avibactam was tested at a fixed concentration of 4 ?g/ml in combination with 2-fold dilutions of aztreonam. The MIC₉₀s of aztreonam-avibactam and aztreonam were 0.12 and 64 ?g/ml, respectively, for all Enterobacteriaceae isolates; >99.9% of all isolates and 99.8% of meropenem-nonsusceptible isolates (n = 1,498) were inhibited by aztreonam-avibactam at a concentration of ?8 ?g/ml. PCR and DNA sequencing identified 267 Enterobacteriaceae isolates positive for MBL genes (NDM, VIM, IMP); all Enterobacteriaceae carrying MBLs demonstrated aztreonam-avibactam MICs of ?8 ?g/ml and a MIC₉₀ of 1 ?g/ml. Against all P. aeruginosa isolates tested, the MIC₉₀ of both aztreonam-avibactam and aztreonam was 32 ?g/ml; against MBL-positive P. aeruginosa isolates (n = 452), MIC₉₀ values for aztreonam-avibactam and aztreonam were 32 and 64 ?g/ml, respectively. The current study demonstrated that aztreonam-avibactam possesses potent in vitro activity against a recent, sizeable global collection of Enterobacteriaceae clinical isolates, including isolates that were meropenem nonsusceptible, and against MBL-positive isolates of Enterobacteriaceae, for which there are few treatment options.

SUBMITTER: Karlowsky JA 

PROVIDER: S-EPMC5571336 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature