Journal Article

Genomic surveillance of antimicrobial resistant bacterial colonisation and infection in intensive care patients

Abbott, Iain J., Spelman, Denis W., Hawkey, Jane, Garlick, Jill S., Wick, Ryan R., Gorrie, Claire L., Judd, Louise M., Pilcher, David V., Holt, Kathryn E., Wyres, Kelly L., McGloughlin, Steve A., Watson, Kerrie M., Jenney, Adam W. J., Macesic, Nenad, Mirčeta, Mirianne, Pratt, Nigel F.

2021

Overview

Background Third-generation cephalosporin-resistant Gram-negatives (3GCR-GN) and vancomycin-resistant enterococci (VRE) are common causes of multi-drug resistant healthcare-associated infections, for which gut colonisation is considered a prerequisite. However, there remains a key knowledge gap about colonisation and infection dynamics in high-risk settings such as the intensive care unit (ICU), thus hampering infection prevention efforts. Methods We performed a three-month prospective genomic survey of infecting and gut-colonising 3GCR-GN and VRE among patients admitted to an Australian ICU. Bacteria were isolated from rectal swabs ( n  = 287 and n  = 103 patients ≤2 and > 2 days from admission, respectively) and diagnostic clinical specimens between Dec 2013 and March 2014. Isolates were subjected to Illumina whole-genome sequencing ( n  = 127 3GCR-GN, n  = 41 VRE). Multi-locus sequence types (STs) and antimicrobial resistance determinants were identified from de novo assemblies. Twenty-three isolates were selected for sequencing on the Oxford Nanopore MinION device to generate completed reference genomes (one for each ST isolated from ≥2 patients). Single nucleotide variants (SNVs) were identified by read mapping and variant calling against these references. Results Among 287 patients screened on admission, 17.4 and 8.4% were colonised by 3GCR-GN and VRE, respectively. Escherichia coli was the most common species ( n  = 36 episodes, 58.1%) and the most common cause of 3GCR-GN infection. Only two VRE infections were identified. The rate of infection among patients colonised with E. coli was low, but higher than those who were not colonised on admission ( n  = 2/33, 6% vs n  = 4/254, 2%, respectively, p  = 0.3). While few patients were colonised with 3GCR- Klebsiella pneumoniae or Pseudomonas aeruginosa on admission ( n  = 4), all such patients developed infections with the colonising strain. Genomic analyses revealed 10 putative nosocomial transmission clusters (≤20 SNVs for 3GCR-GN, ≤3 SNVs for VRE): four VRE, six 3GCR-GN , with epidemiologically linked clusters accounting for 21 and 6% of episodes, respectively (OR 4.3, p  = 0.02). Conclusions 3GCR- E. coli and VRE were the most common gut colonisers. E. coli was the most common cause of 3GCR-GN infection, but other 3GCR-GN species showed greater risk for infection in colonised patients. Larger studies are warranted to elucidate the relative risks of different colonisers and guide the use of screening in ICU infection control.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Age / Anti-Bacterial Agents - pharmacology / Antibiotic resistance / Antibiotics / Antimicrobial agents / Antimicrobial resistance / Antimicrobial resistance (AMR) / Australia - epidemiology / Cephalosporin Resistance - genetics / Cephalosporins / Clusters / Colonisation / Colonization / Critically ill / Cross infection / Cross Infection - epidemiology / Cross Infection - microbiology / Cross Infection - prevention & control / Disease control / Disease transmission / Drug resistance / Drug resistance in microorganisms / Drug Resistance, Multiple, Bacterial - genetics / E coli / Epidemiology / Escherichia coli - genetics / Escherichia coli - isolation & purification / Escherichia coli - pathogenicity / Ethics / Gastrointestinal Tract - microbiology / Gene mapping / Gene sequencing / Genetic aspects / Genomes / Genomic analysis / Genomic surveillance / Genomics / Gram-negative bacterial infections / Hospitals / Humans / Infection Control - methods / Infection Control - standards / Infectious Diseases / Intensive care / Intensive Care Units - standards / Intensive Care Units - statistics & numerical data / Internal Medicine / Klebsiella / Medical Microbiology / Medicine / Medicine & Public Health / Multidrug resistance / Nosocomial infection / Nosocomial infections / Nucleotide sequence / Nucleotides / Organisms / Parasitology / Patients / Prospective Studies / Pseudomonas aeruginosa / Risk assessment / Risk factors / Staphylococcus infections / Statistics / Strain analysis / Transmission / Tropical Medicine / Vancomycin / Vancomycin-Resistant Enterococci - genetics / Vancomycin-Resistant Enterococci - isolation & purification / Whole genome sequencing