In Vitro Susceptibility to Ceftazidime/Avibactam and Comparators in Clinical Isolates of Enterobacterales from Five Latin American Countries

Abstract

Background: High rates of resistance to third-generation cephalosporins and carbapenems in Enterobacterales have been reported in Latin America. Ceftazidime/avibactam (CZA) is the combination of a third-generation cephalosporin and a non-β-lactam β-lactamase inhibitor, which has shown activity against isolates producing class A, C and D β-lactamases. Herein, we evaluated the activity of CZA and comparators against clinical isolates of Enterobacterales in Latin America. Methods: The activity of CZA and comparators was evaluated against clinical isolates of Enterobacterales from Argentina, Brazil, Chile, Colombia and Mexico that were collected between January 2016 and October 2017. One specific phenotypic subset was evaluated. A carbapenem non-susceptible (CNS) phenotype was defined as any isolate displaying a minimum inhibitory concentration (MIC) ≥1 mg/L for ertapenem. Results: CZA was active against 95.8% of all isolates and 77.5% of CNS isolates. Fosfomycin (FOS) and tigecycline (TGC) were the second most active antibiotics with 93.4% of Enterobacterales being susceptible. Conclusions: The results of this study underline the potential therapeutic role of CZA in Latin America.

In Vitro Susceptibility to Ceftazidime-Avibactam and Comparator Antimicrobial Agents of Carbapenem-Resistant Enterobacterales Isolates

“…Polymyxins and tigecycline are often used as a first-line treatment for CRE infections, owing to their susceptibility profiles against CRE. Overall, our studied isolates possessed low polymyxin B and tigecycline MICs (83.6% of studied isolates have polymyxin B MIC of ≤2 mg/L; overall tigecycline MIC 90 : 2 mg/L), similar to internationally published data [ 38 , 39 ]. However, expert recommendations have opined the avoidance of polymyxin use due to increased nephrotoxicity [ 6 ].…”

Molecular Mechanisms of Resistance to Ceftazidime/Avibactam in Clinical Isolates of Enterobacterales and Pseudomonas aeruginosa in Latin American Hospitals

“…Previously, our group determined the rates of susceptibility to CZA and other relevant antibiotics of clinical Enterobacterales isolates collected prior to the introduction of this antibiotic into the clinical practice in Latin America. The resistance rate found in that study was 4.2% ( 23 ). Herein, we reassess the phenotypic resistance to CZA of the 94 CZA-resistant Enterobacterales strains identified in that previous study; describe the phenotypic resistance rates to CZA of 492 P. aeruginosa clinical isolates collected between 2016 and 2017; and explore the molecular mechanisms leading to CZA resistance in these clinical isolates using whole-genome sequencing (WGS).…”

“…In a previous study, we evaluated the in vitro activity of CZA against a set of 2,252 clinical isolates of Enterobacterales in Latin America, finding that 4.2% were resistant ( 23 ). However, combined phenotypic tests performed in this study confirmed the CZA-resistant phenotype of only 18/94 isolates.…”

In Vitro Activity of “Old” and “New” Antimicrobials against the Klebsiella pneumoniae Complex

“…However, in this study, the value for KPCpositive strains was slightly lower, around 64%, although the number of strains analyzed was smaller. A further study from Latin America [23] reported varying susceptibility of K. pneumoniae strains to fosfomycin, ranging from 90.9% for strains isolated in Chile to 100% for strains isolated in Mexico, with a total of 601 K. pneumoniae isolates included. For carbapenem-non-susceptible K. pneumoniae strains (183), the susceptibility values were 71.4% and 100%, respectively.…”