Congresso Brasileiro de Microbiologia 2023

Congresso Brasileiro de Microbiologia 2023

Resumo: 75-2

75-2

GENOMIC ANALYSIS AND ANTIMICROBIAL ACTIVITY OF Β-LACTAM/Β-LACTAMASE INHIBITORS AND OTHER AGENTS AGAINST KPC-PRODUCING KLEBSIELLA PNEUMONIAE CLINICAL ISOLATES FROM BRAZILIAN HOSPITALS

Autores:

Carlos Camargo (IAL SP - Instituto Adolfo Lutz) ; Amanda Yaeko Yamada (IAL SP - Instituto Adolfo Lutz, FMUSP - Faculdade de Medicina USP) ; Andreia Rodrigues Souza (IAL SP - Instituto Adolfo Lutz) ; Marcos Paulo Vieira Cunha (IAL SP - Instituto Adolfo Lutz) ; Monique Ribeiro Casas (IAL SP - Instituto Adolfo Lutz) ; Maristela Pinheiro Freire (FMUSP - Faculdade de Medicina USP) ; Pasqual Barretti (FMB - Faculdade de Medicina UNESP)

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 (CAZ-AVI), 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%). Genomic analysis of the plasmids carrying the blaKPC-33 or blaKPC-44 (CAZ-AVI resistant isolates) showed that they were of IncFIIK, IncX3/IncU, and IncN types. Although high in vitro susceptibility rates were detected for meropenem-vaborbactam and cefiderocol, only ceftazidime-avibactam is currently available in Brazil. In fact, detection of CAZ-AVI resistance was not associated with a specific clone or plasmid, indicating that genomic adaptations in KPC-2-producing K. pneumoniae can occur in favorable conditions. 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.

Palavras-chave:

Ceftazidime-avibactam, Illumina, KPC-33, KPC-44, whole genome sequencing

Agência de fomento:

FAPESP (2020/06157-2; 2018/21193-5; 2018/21192-9; 2017/50333-7); CNPq (402158/2021-0; 302543/2021-0); Pfizer/Wyeth.