In vitro activity of ceftazidime/avibactam and comparators against carbapenemase-producing Enterobacterales and Pseudomonas aeruginosa isolates collected globally between 2016 and 2018.

This study reports the antimicrobial activity of ceftazidime/avibactam (CZA) and comparators against carbapenemase-producing Enterobacterales (N = 1992) and carbapenemase-producing Pseudomonas aeruginosa (N = 784) collected in Africa/Middle East, Asia/South Pacific, Europe and Latin America (2016-2018). Minimum inhibitory concentrations (MICs) and susceptibility were determined using broth microdilution methodology and EUCAST breakpoints. Carbapenemase-encoding genes were detected using multiplex PCR. No isolates of carbapenemase-producing, metallo-β-lactamase (MBL)-negative Enterobacterales from Africa/Middle East or Latin America were resistant to CZA; resistance rates in Europe and Asia/South Pacific were ≤4.5%. Colistin had the lowest resistance rate among MBL-positive isolates (6.0-11.4%). Enterobacterales isolates collected in Latin America predominantly carried a KPC carbapenemase (77.6%), whereas in Africa/Middle East OXA-48-like carbapenemases were most frequently detected (55.9%), and in Asia/South Pacific most isolates carried NDM carbapenemases (56.2%). Among all Enterobacterales carrying KPC carbapenemases, the lowest rate of resistance was to CZA (1.5%), and among isolates carrying NDM carbapenemases it was to colistin (10.8%). Among carbapenemase-producing, MBL-negative P. aeruginosa, resistance rates to CZA were 8.6% for isolates collected in Europe and 53.2% in Latin America. Isolates in each region most frequently carried VIM carbapenemases, ranging from 41.7% of isolates in Asia/South Pacific to 86.2% in Africa/Middle East. No P. aeruginosa carrying KPC or NDM carbapenemases and 1.0% of isolates carrying GES carbapenemases were resistant to colistin. Given the limited therapeutic options to treat infections caused by carbapenemase-positive Enterobacterales and P. aeruginosa, continued surveillance of CZA activity as well as agents such as colistin is crucial.

Kiratisin P ，Kazmierczak K ，Stone GG 《-》

In vitro antimicrobial susceptibility of clinical respiratory isolates to ceftazidime-avibactam and comparators (2016-2018).

Piérard D ，Stone GG 《BMC INFECTIOUS DISEASES》

In vitro activity of ceftazidime-avibactam and comparators against Gram-negative bacterial isolates collected in the Asia-Pacific region as part of the INFORM program (2015-2017).

Ko WC ，Stone GG 《Annals of Clinical Microbiology and Antimicrobials》

In Vitro Activity of Ceftazidime-Avibactam against Clinical Isolates of Enterobacteriaceae and Pseudomonas aeruginosa Collected in Asia-Pacific Countries: Results from the INFORM Global Surveillance Program, 2012 to 2015.

The in vitro activities of ceftazidime-avibactam and comparators against 9,149 isolates of Enterobacteriaceae and 2,038 isolates of Pseudomonas aeruginosa collected by 42 medical centers in nine countries in the Asia-Pacific region from 2012 to 2015 were determined as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance program. Antimicrobial susceptibility testing was conducted by Clinical and Laboratory Standards Institute (CLSI) broth microdilution, and isolate subset analysis was performed on the basis of the resistant phenotypes and β-lactamase content. Ceftazidime-avibactam demonstrated potent in vitro activity (MIC, ≤8 μg/ml) against all Enterobacteriaceae tested (99.0% susceptible) and was the most active against isolates that were metallo-β-lactamase (MBL) negative (99.8% susceptible). Against P. aeruginosa, 92.6% of all isolates and 96.1% of MBL-negative isolates were susceptible to ceftazidime-avibactam (MIC, ≤8 μg/ml). The rates of susceptibility to ceftazidime-avibactam ranged from 97.0% (Philippines) to 100% (Hong Kong, South Korea) for Enterobacteriaceae and from 83.1% (Thailand) to 100% (Hong Kong) among P. aeruginosa isolates, with lower susceptibilities being observed in countries where MBLs were more frequently encountered (Philippines, Thailand). Ceftazidime-avibactam inhibited 97.2 to 100% of Enterobacteriaceae isolates, per country, that carried serine β-lactamases, including extended-spectrum β-lactamases, AmpC cephalosporinases, and carbapenemases (KPC, GES, OXA-48-like). It also inhibited 91.3% of P. aeruginosa isolates that were carbapenem nonsusceptible in which no acquired β-lactamase was detected. Among MBL-negative Enterobacteriaceae isolates that were ceftazidime nonsusceptible, meropenem nonsusceptible, colistin resistant, and multidrug resistant, ceftazidime-avibactam inhibited 96.1, 87.7, 100, and 98.8% of isolates, respectively, and among MBL-negative P. aeruginosa isolates that were ceftazidime nonsusceptible, meropenem nonsusceptible, colistin resistant, and multidrug resistant, ceftazidime-avibactam inhibited 79.6, 83.6, 83.3, and 68.2% of isolates, respectively. Overall, clinical isolates of Enterobacteriaceae and P. aeruginosa collected in nine Asia-Pacific countries from 2012 to 2015 were highly susceptible to ceftazidime-avibactam.

Karlowsky JA ，Kazmierczak KM ，Bouchillon SK ，de Jonge BLM ，Stone GG ，Sahm DF ... -  《-》

In vitro activity of ceftazidime-avibactam against Enterobacterales and Pseudomonas aeruginosa isolates collected in Latin America as part of the ATLAS global surveillance program, 2017-2019.

The Antimicrobial Testing Leadership and Surveillance (ATLAS) global surveillance program collected clinical isolates of Enterobacterales (n = 8416) and Pseudomonas aeruginosa (n = 2521) from 41 medical centers in 10 Latin American countries from 2017 to 2019. In vitro activities of ceftazidime-avibactam and comparators were determined using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method. Overall, 98.1% of Enterobacterales and 86.9% of P. aeruginosa isolates were susceptible to ceftazidime-avibactam. When isolates were analyzed by country of origin, susceptibility to ceftazidime-avibactam for Enterobacterales ranged from 97.8% to 100% for nine of 10 countries (except Guatemala, 86.3% susceptible) and from 75.9% to 98.4% for P. aeruginosa in all 10 countries. For Enterobacterales, 100% of AmpC-positive, ESBL- and AmpC-positive, GES-type carbapenemase-positive, and OXA-48-like-positive isolates were ceftazidime-avibactam-susceptible as were 99.8%, 91.8%, and 74.7% of ESBL-positive, multidrug-resistant (MDR), and meropenem-nonsusceptible isolates. Among meropenem-nonsusceptible isolates of Enterobacterales, 24.4% (139/570) carried a metallo-β-lactamase (MBL); 83.3% of the remaining meropenem-nonsusceptible isolates carried another class of carbapenemase and 99.4% of those isolates were ceftazidime-avibactam-susceptible. Among meropenem-non-susceptible isolates of P. aeruginosa (n = 835), 25.6% carried MBLs; no acquired β-lactamase was identified in the majority of isolates (64.8%; 87.2% of those isolates were ceftazidime-avibactam-susceptible). Overall, clinical isolates of Enterobacterales collected in Latin America from 2017 to 2019 were highly susceptible to ceftazidime-avibactam, including isolates carrying ESBLs, AmpCs, and KPCs. Country-specific variation in susceptibility to ceftazidime-avibactam was more common among isolates of P. aeruginosa than Enterobacterales. The frequency of MBL-producers among Enterobacterales from Latin America was low (1.7% of all isolates; 146/8,416), but higher than reported in previous surveillance studies.

Karlowsky JA ，Kazmierczak KM ，Valente MLNF ，Luengas EL ，Baudrit M ，Quintana A ，Irani P ，Stone GG ，Sahm DF ... -  《-》