Prediction of antimicrobial resistance in Klebsiella pneumoniae using genomic and metagenomic next-generation sequencing data.
J Antimicrob Chemother
; 79(10): 2509-2517, 2024 Oct 01.
Article
en En
| MEDLINE
| ID: mdl-39028665
ABSTRACT
OBJECTIVES:
Klebsiella pneumoniae is a significant pathogen with increasing resistance and high mortality rates. Conventional antibiotic susceptibility testing methods are time-consuming. Next-generation sequencing has shown promise for predicting antimicrobial resistance (AMR). This study aims to develop prediction models using whole-genome sequencing data and assess their feasibility with metagenomic next-generation sequencing data from clinical samples.METHODS:
On the basis of 4170 K. pneumoniae genomes, the main genetic characteristics associated with AMR were identified using a LASSO regression model. Consequently, the prediction model was established, validated and optimized using clinical isolate read simulation sequences. To evaluate the efficacy of the model, clinical specimens were collected.RESULTS:
Four predictive models for amikacin, ciprofloxacin, levofloxacin, and piperacillin/tazobactam, initially had positive predictive values (PPVs) of 92%, 98%, 99%, 94%, respectively, when they were originally constructed. When applied to clinical specimens, their PPVs were 96%, 96%, 95%, and 100%, respectively. Meanwhile, there were negative predictive values (NPVs) of 100% for ciprofloxacin and levofloxacin, and 'not applicable' (NA) for amikacin and piperacillin/tazobactam. Our method achieved antibacterial phenotype classification accuracy rates of 95.92% for amikacin, 96.15% for ciprofloxacin, 95.31% for levofloxacin and 100% for piperacillin/tazobactam. The sequence-based prediction antibiotic susceptibility testing (AST) reported results in an average time of 19.5 h, compared with the 67.9 h needed for culture-based AST, resulting in a significant reduction of 48.4 h.CONCLUSIONS:
These preliminary results demonstrated that the performance of prediction model for a clinically significant antimicrobial-species pair was comparable to that of phenotypic methods, thereby encouraging the expansion of sequence-based susceptibility prediction and its clinical validation and application.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Infecciones por Klebsiella
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Pruebas de Sensibilidad Microbiana
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Metagenómica
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Secuenciación de Nucleótidos de Alto Rendimiento
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Klebsiella pneumoniae
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Antibacterianos
Límite:
Humans
Idioma:
En
Revista:
J Antimicrob Chemother
Año:
2024
Tipo del documento:
Article
País de afiliación:
China