Whole genome sequencing to identify host genetic risk factors for severe outcomes of hepatitis a virus infection

Abstract Background The increasing incidence of carbapenemase-producing Enterobacteriaceae (CPE) is a global health concern, as treatment options are extremely limited. The prevalence of CPE in UK hospitals is unknown, as national screening guidelines only recommend screening in patients considered to be at high-risk of CPE. Patients in intensive care units (ICU) are at high-risk of healthcare-associated infections caused by multidrug-resistant organisms (MDRO). Methods We conducted a six-month prospective surveillance study to determine the prevalence of MDRO in a UK teaching hospital ICU. Between June and December 2016, all adult patients admitted to ICU were screened for MDRO on admission, on discharge, and weekly during their ICU stay. Surveillance samples included stool or rectal swabs, urine, sputum or tracheal aspirates, and wound swabs (if wounds were present). Isolates were characterized phenotypically before undergoing whole-genome sequencing (WGS), epidemiological, and phylogenetic analyses. Results During the first week of the study we identified stool carriage of a multidrug-resistant Klebsiella pneumoniae strain in two patients neither of whom had recognized risk factors for CPE. Both isolates were resistant to all antibiotics tested, apart from colistin, and were PCR-positive for the blaNDM-1 gene. Enhanced surveillance by the infection control team identified four additional patients in several wards who had stool carriage (n = 3) or bloodstream infection (n = 1) with a blaNDM-1K. pneumoniae isolate. Epidemiological links were identified between these six patients. Five months later, a second outbreak of multidrug-resistant K. pneumoniae was detected, involving stool carriage by four patients on two different wards. Environmental screening identified environmental contamination with multidrug-resistant K. pneumoniae on one ward. DNA sequence analysis confirmed that a novel blaNDM-1K. pneumoniaelineage (ST78) was responsible for both outbreaks in the hospital. Conclusion We identified two unsuspected blaNDM-1K. pneumoniae outbreaks in patients with no recognized risk factors for CPE. This highlights the importance of prospective surveillance for MDRO in high-risk settings, such as ICUs, and supports the use of rapid WGS to support outbreak investigations in real-time. Disclosures All authors: No reported disclosures.

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Faculty Opinions recommendation of Genome-wide analyses as part of the international FTLD-TDP whole-genome sequencing consortium reveals novel disease risk factors and increases support for immune dysfunction in FTLD.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.735063315.793568271 ◽

2019 ◽

Author(s):

Barbara Borroni

Keyword(s):

Risk Factors ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Disease Risk ◽

Immune Dysfunction ◽

Whole Genome ◽

Genome Wide ◽

Genome Sequencing Consortium

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Emergence and Within-Host Genetic Evolution of Methicillin-ResistantStaphylococcus aureusResistant to Linezolid in a Cystic Fibrosis Patient

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00720-18 ◽

2018 ◽

Vol 62 (12) ◽

Cited By ~ 7

Author(s):

Caroline Rouard ◽

Fabien Garnier ◽

Jeremy Leraut ◽

Margaux Lepainteur ◽

Lalaina Rahajamananav ◽

...

Keyword(s):

Cystic Fibrosis ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Generation Time ◽

Strong Increase ◽

Whole Genome ◽

Content Type ◽

Mrsa Infection ◽

Host Genetic ◽

Mrsa Strains

ABSTRACTMethicillin-resistantStaphylococcus aureus(MRSA) infection has increased in recent years among cystic fibrosis (CF) patients. Linezolid (LZD) is one of the antistaphylococcal antibiotics widely used in this context. Although LZD resistance is rare, it has been described as often associated with long-term treatments. Thirteen MRSA strains isolated over 5 years from one CF patient were studied for LZD resistance emergence and subjected to whole-genome sequencing (WGS). Resistance emerged after three 15-day LZD therapeutic regimens over 4 months. It was associated with the mutation of G to T at position 2576 (G2576T) in all 5rrlcopies, along with a very high MIC (>256 mg/liter) and a strong increase in the generation time. Resistant strains isolated during the ensuing LZD therapeutic regimens and until 13 months after LZD stopped harbored only 3 or 4 mutatedrrlcopies, associated with lower MICs (8 to 32 mg/liter) and low to moderate generation time increases. Despite these differences, whole-genome sequencing allowed us to determine that all isolates, including the susceptible one isolated before LZD treatment, belonged to the same lineage. In conclusion, LZD resistance can emerge rapidly in CF patients and persist without linezolid selective pressure in colonizing MRSA strains belonging to the same lineage.

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