Abstract
Clinical metagenomics (CMg), referred to as the application of next-generation sequencing (NGS) to clinical samples, is a promising tool for the diagnosis of hospital-acquired pneumonia (HAP). Indeed, CMg allows identifying pathogens and antibiotic resistance genes (ARGs), thereby providing the information required for the optimization of the antibiotic regimen. Hence, provided that CMg would be faster than conventional culture, the probabilistic regimen used in HAP could be tailored faster, which should lead to an expected decrease of mortality and morbidity. While the inference of the antibiotic susceptibility testing from metagenomic or even genomic data is challenging, a limited number of antibiotics are used in the probabilistic regimen of HAP (namely beta-lactams, aminoglycosides, fluoroquinolones, glycopeptides and oxazolidinones). Accordingly, based on the perspective of applying CMg to the early diagnostic of HAP, we aimed at reviewing the performances of whole genomic sequencing (WGS) of the main HAP-causing bacteria (Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, Stenotrophomonas maltophilia and Staphylococcus aureus) for the prediction of susceptibility to the antibiotic families advocated in the probabilistic regimen of HAP.
Highlights
Clinical metagenomics (CMg) refers to the concept of sequencing the DNA of a clinical sample with the purpose of recovering clinical information [1]
We excluded S. pneumoniae, Haemophilus influenzae, Legionella pneumophila and Branhamella catarrhalis, which are occasionally found in hospital-acquired pneumonia (HAP) but are mostly susceptible to the probabilistic antibiotic options recommended for the HAP treatment. Provided that they would be correctly identified by CMg, no specific genotype-to-phenotype analysis shall be undertaken with regards to the antibiotics used in the probabilistic treatment of HAP
CTX-M ESBLs, which confer a low-level resistance to ceftazidime, and EUCAST advocates ceftazidime, and EUCAST advocates considering as susceptible a strain with a ceftazidime MIC ≤ 1 considering as susceptible a strain with a ceftazidime MIC ≤ 1 mg/L, whereas in next-generation sequencing (NGS) interpretation, mg/L, whereas in NGS interpretation, a strain harbouring a blaCTX-M gene shall be considered as a strain harbouring a blaCTX-M gene shall be considered as resistant to all 3GC
Summary
Clinical metagenomics (CMg) refers to the concept of sequencing the DNA of a clinical sample (without any prior culturing step) with the purpose of recovering clinical information [1]. In the context of the diagnostic of infections, CMg consists in sequencing samples in order to identify putative pathogen(s) and to predict their antibiotic susceptibility profiles. The time to antibiotic susceptibility results is usually 48 h, during which a probabilistic antibiotic regimen is given, considering or not the possibility of the presence of resistant bacteria as a causal agent of the pneumonia according to the risk factors of the patient [21]. Susceptible to the probabilistic antibiotic options recommended for the HAP treatment Provided that they would be correctly identified by CMg, no specific genotype-to-phenotype analysis shall be undertaken with regards to the antibiotics used in the probabilistic treatment of HAP
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