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

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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

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 13, n. 1, p. 9-pg., 2023-09-05.

Resumo

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. (AU)

• Processo FAPESP: 18/21192-9 - EMU concedido no processo 2017/50333-7: MALDI-TOF
• Beneficiário: Carlos Henrique Camargo
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 17/50333-7 - Plano de desenvolvimento institucional em pesquisa do Instituto Adolfo Lutz (PDIp)
• Beneficiário: Carlos Henrique Camargo
• Modalidade de apoio: Auxílio à Pesquisa - Programa Modernização de Institutos Estaduais de Pesquisa
• Processo FAPESP: 20/06157-2 - Epidemiologia genômica de enterobactérias produtoras da carbapenemase NDM em isolados clínicos brasileiros
• Beneficiário: Carlos Henrique Camargo
• Modalidade de apoio: Auxílio à Pesquisa - Regular