Evaluating the potential for respiratory metagenomics to improve treatment of secondary infection and detection of nosocomial transmission on expanded COVID-19 intensive care units

Abstract

Background Clinical metagenomics (CMg) has the potential to be translated from a research tool into routine service to improve antimicrobial treatment and infection control decisions. The SARS-CoV-2 pandemic provides added impetus to realise these benefits, given the increased risk of secondary infection and nosocomial transmission of multi-drug-resistant (MDR) pathogens linked with the expansion of critical care capacity. Methods CMg using nanopore sequencing was evaluated in a proof-of-concept study on 43 respiratory samples from 34 intubated patients across seven intensive care units (ICUs) over a 9-week period during the first COVID-19 pandemic wave. Results An 8-h CMg workflow was 92% sensitive (95% CI, 75–99%) and 82% specific (95% CI, 57–96%) for bacterial identification based on culture-positive and culture-negative samples, respectively. CMg sequencing reported the presence or absence of β-lactam-resistant genes carried by Enterobacterales that would modify the initial guideline-recommended antibiotics in every case. CMg was also 100% concordant with quantitative PCR for detecting Aspergillus fumigatus from 4 positive and 39 negative samples. Molecular typing using 24-h sequencing data identified an MDR-K. pneumoniae ST307 outbreak involving 4 patients and an MDR-C. striatum outbreak involving 14 patients across three ICUs. Conclusion CMg testing provides accurate pathogen detection and antibiotic resistance prediction in a same-day laboratory workflow, with assembled genomes available the next day for genomic surveillance. The provision of this technology in a service setting could fundamentally change the multi-disciplinary team approach to managing ICU infections. The potential to improve the initial targeted treatment and rapidly detect unsuspected outbreaks of MDR-pathogens justifies further expedited clinical assessment of CMg.

Optimizing Nanopore Sequencing for Rapid Detection of Microbial Species and Antimicrobial Resistance in Patients at Risk of Surgical Site Infections

“…Comparison of NS to SC found that on average NS could identify up to 77% of cultured bacterial species and 76% of cultured fungal species, and predicted up to 81% of observed AMR phenotypes. These results are comparable to previous studies comparing NS and SC results ( 17 , 28 , 38 , 52 ), suggesting that NS could be used to guide early antimicrobial therapy following surgery. Given the speed with which NS can identify microbial species and predict AMR phenotypes, future investigations should determine whether NS can be used in replacement of bile cultures for detection and characterization of bile microbes.…”

Corynebacterium striatum—Got Worse by a Pandemic?

“…Since the COVID-19 pandemic has significantly increased the number of hospitalized and even ventilated patients and has been shown to cause immune system-disruption effects, it seemed important to investigate the impact of the pandemic on the incidence of this opportunistic bacterium. To the authors' knowledge, only one publication has examined this issue and detected a hospital outbreak involving 14 patients across three COVID-19 intensive care units [4]. For this reason, we have investigated the prevalence and resistance characteristics of this species at the Clinical Center of the University of Szeged between 2012 and 2021, with a special focus on the impact of the COVID-19 pandemic.…”

“…Of these, the role of Corynebacterium striatum (C. striatum) is special and controversial. Since this species was first described as a potentially pathogenic bacterium in the 1980s, now is increasingly regarded as an opportunistic pathogen, especially but not exclusively in immunosuppressed patients [4][5][6]. The role of C. striatum has been demonstrated in several nosocomial infections.…”

“…Since the species is a member of the normal human skin and mucous membrane flora, it is often classified as a contaminant in the respiratory tract. However, recently, an increasing number of publications have demonstrated its pathogenicity in the respiratory tract, especially in the immunosuppressed patient population [4,6,15]. The number of these patients has dramatically increased during the years of the COVID-19 pandemic [26][27][28].…”

“…The number of these patients has dramatically increased during the years of the COVID-19 pandemic [26][27][28]. In spite of this, the role of C. striatum in the light of the pandemic has only been investigated in one publication, and that also only focuses partially on this species using clinical metagenomics methods [4]. For this reason, we aimed to investigate the prevalence and resistance pattern of this species in a retrospective study between 2012 and 2021 at the Clinical Center of the University of Szeged, Hungary.…”