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

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 infection and gut-colonisation with 3GCR-GN and VRE among patients admitted to an Australian ICU. 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 (6% vs 2% E. coli, 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: 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.