Evaluation of in-vitro susceptibility of ß-lactam-resistant Gram-negative bacilli to ceftazidime-avibactam and ceftolozane-tazobactam from clinical samples of a general hospital in southern Brazil

• Published in: Revista da Sociedade Brasileira de Medicina Tropical Vol. 56
• Main Authors: Carvalho, Thaisa Noceti, Kobs, Vanessa Cristine, Hille, Daniela, Deglmann, Roseneide Campos, Melo, Luiz Henrique, França, Paulo Henrique Condeixa de
• Format: Journal Article
• Language: English
• Published: Brazil Sociedade Brasileira de Medicina Tropical - SBMT 2023; Sociedade Brasileira de Medicina Tropical (SBMT)
• Subjects: Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Antimicrobial resistance; beta-Lactamases - genetics; Brazil; Carbapenems; Ceftazidime - pharmacology; Ceftazidime-avibactam; Ceftolozane-tazobactam; Cephalosporins - pharmacology; Drug Combinations; Genetic marker; Gram-negative bacilli; Gram-Negative Bacteria - genetics; Hospitals, General; In vitro activity; Klebsiella pneumoniae; Lactams; Major; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Tazobactam - pharmacology; TROPICAL MEDICINE; Brazil; Ceftolozane-tazobactam; Gram-negative bacilli; Antimicrobial resistance; Genetic marker; Ceftazidime-avibactam; In vitro activity
• ISSN: 0037-8682; 1678-9849; 1678-9849
• DOI: 10.1590/0037-8682-0277-2022

The spread of carbapenemase- and extended-spectrum β-lactamase (ESBL)-producing gram-negative bacilli (GNB) represent a global public health threat that limits therapeutic options for hospitalized patients. This study aimed to evaluate the in-vitro susceptibility of β-lactam-resistant GNB to ceftazidime-avibactam (C/A) and ceftolozane-tazobactam (C/T), and investigate the molecular determinants of resistance.
Overall, 101 clinical isolates of Enterobacterales and Pseudomonas aeruginosa collected from a general hospital in Brazil were analyzed. Susceptibility to the antimicrobial agents was evaluated using an automated method, and the minimum inhibitory concentrations (MIC50/90) of C/A and C/T were determined using Etest®. The β-lactamase-encoding genes were investigated using polymerase chain reaction.
High susceptibility to C/A and C/T was observed among ESBL-producing Enterobacterales (100% and 97.3% for CLSI and 83.8% for BRCAST, respectively) and carbapenem-resistant P. aeruginosa (92.3% and 87.2%, respectively). Carbapenemase-producing Klebsiella pneumoniae exhibited high resistance to C/T (80%- CLSI or 100%- BRCAST) but high susceptibility to C/A (93.4%). All carbapenem-resistant K. pneumoniae isolates were susceptible to C/A, whereas only one isolate was susceptible to C/T. Both antimicrobials were inactive against metallo-β-lactamase-producing K. pneumoniae isolates. Resistance genes were concomitantly identified in 44 (44.9%) isolates, with bla CTX-M and bla SHV being the most common.
C/A and C/T were active against microorganisms with β-lactam-resistant phenotypes, except when resistance was mediated by metallo-β-lactamases. Most C/A- and C/T-resistant isolates concomitantly carried two or more β-lactamase-encoding genes (62.5% and 77.4%, respectively).