Genomic analysis and antimicrobial activity of β-lactam/β-lactamase inhibitors and other agents against KPC-producing Klebsiella pneumoniae clinical isolates from Brazilian hospitals

• Published in: Scientific reports 2023-09, Vol.13 (1), p.14603-14603, Article 14603
• Main Authors: Camargo, Carlos Henrique, Yamada, Amanda Yaeko, de Souza, Andreia Rodrigues, Cunha, Marcos Paulo Vieira, Ferraro, Pedro Smith Pereira, Sacchi, Claudio Tavares, dos Santos, Marlon Benedito, Campos, Karoline Rodrigues, Tiba-Casas, Monique Ribeiro, Freire, Maristela Pinheiro, Barretti, Pasqual
• Format: Article
• Language: English
• Subjects: 631/326/107; 631/326/1762; Antimicrobial activity; Antimicrobial agents; beta-Lactamase Inhibitors; Brazil; Carbapenems; Cefiderocol; Ceftazidime; Clinical isolates; Colistin; Drug resistance; Drugs; Genomic analysis; Genomics; Hospitals; Humanities and Social Sciences; Klebsiella pneumoniae; Lactams; Meropenem; multidisciplinary; Multidrug resistance; Phenotypes; Polymyxin B; Science; Science (multidisciplinary); Virulence; Whole genome sequencing; β Lactamase; β-Lactam antibiotics
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-41903-x

Carbapenem-resistant Klebsiella pneumoniae (CRKP) are highly disseminated worldwide, and isolates co-resistant to other antimicrobial agents pose a threat to effective antimicrobial therapy. Therefore, evaluation of novel antimicrobial drugs is needed to identify potential treatments with better outcomes. We evaluated the in vitro activity of novel antimicrobial drugs/combinations against 97 KPC-producing Klebsiella pneumoniae isolates recovered from different hospitals in Brazil during 2021–2022. Clonality, resistance and virulence genes were detected by whole-genome sequencing. The majority of the isolates (54.6%) were classified as extensively drug resistant or multidrug resistant (44.3%); one isolate showed a pandrug resistance phenotype. The most active antimicrobial agents were meropenem-vaborbactam, cefiderocol, and ceftazidime-avibactam, with sensitivities higher than 90%; resistance to ceftazidime-avibactam was associated with KPC-33 or KPC-44 variants. Colistin and polymyxin B were active against 58.6% of the isolates. The 97 isolates were distributed into 17 different sequence types, with a predominance of ST11 (37.4%). Although high in vitro susceptibility rates were detected for meropenem-vaborbactam and cefiderocol, only ceftazidime-avibactam is currently available in Brazil. Our findings showed limited susceptibility to antimicrobial drugs employed for infection treatment of carbapenem-resistant K. pneumoniae , underscoring the urgent need for stringent policies for antimicrobial stewardship to preserve the activity of such drugs.