Third-generation cephalosporin-resistant Gram-negative organisms (3GCR-GN) and vancomycin-resistant enterococci (VRE) are the most common drug-resistant bacteria colonized in the gut among patients in the intensive care unit (ICU), according to results of a prospective study published in BMC Infectious Diseases. Although Escherichia coli was the most common cause of Gram-negative infection, other species posed a greater risk for infection in patients colonized with Gram-negative organisms.

Investigators conducted a 3-month prospective genomic surveillance study of infecting and gut-colonizing 3GCR-GN and VRE among adult patients admitted to the ICU. Study inclusion was limited to adult patients who were likely to be in the ICU for at least 2 days.

The investigators collected baseline rectal screening swabs and diagnostic isolates from a total of 287 patients within 2 days of initial ICU admission and then every 5 to 7 days thereafter of their ICU stay. The median age was 57 (interquartile range, 44-71) years, 64.5% were men, and most (76%) patients had recently been hospitalized prior to admission to the ICU.


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After determining which rectal swabs contained gut-colonizing 3GCR-GN and VRE, the investigators used whole genome sequencing to identify bacterial species, multi-locus sequence types, and species-specific antimicrobial-resistant genes. They used chromosomal single-nucleotide variants (SNV) to determine probable strain transmission events.

There were 50 patients with baseline screening swabs colonized by 3GCR-GN (n=56 isolates, 17.4%) and 24 patients with swabs colonized by VRE (n=24 isolates, 8.4%). In female patients only, a significant association was noted between age and VRE colonization, with a median age of 73.5 years in VRE carriers vs 55.5 years in non-VRE carriers (P =.04).

Between day 3 and week 12 of ICU admission, the investigators collected 138 rectal swabs from 103 patients, of which 18.1% (n=25) were positive for more than 1 3GCR-GN, and 10.9% (n=15) were positive for VRE. Of 61 patients negative for 3GCR-GN at baseline, 15 (24.6%) developed positive cultures, and of the 75 patients negative for VRE at baseline, 13 (17.3%) developed positive cultures.

The most common colonizers among a total of 33 3GCR-GN respiratory, wound, and bloodstream infection episodes were E coli (30.3%) and Klebsiella pneumoniae (18.2%). Among 62 3GCR-GN infections, E coli was the most common gut colonizer (58%). However, in patients who were gut-colonized at baseline screening, infection rates for K pneumoniae and P aeruginosa, rather than E coli,were significantly increased compared with those who were not gut-colonized at baseline.

Most of the 3GCR-GN colonization and infection isolates were predicted to be multidrug resistant, and multidrug resistance was common among E coli (n=44 episodes, 96%), K pneumoniae (n=9 episodes, 90%), and Serratia marcescens (n=3 episodes, 100%). Extended-spectrum β-lactamase (ESBL) genes identified via whole-genome sequencing were seen in 20 representative 3GCR-GN colonization isolates (32.3%) and 12 representative 3GCR-GN infection isolates (36.4%), consisting mostly of multidrug-resistant K pneumonia- and E coli-carrying genes.

Of 35 VRE isolates representing distinct episodes, 91% carried the vanB vancomycin resistance operon, 9% carried the vanA operon that confers resistance to both vancomycin and teicoplanin, and 91% had genes that were predicted to be multidrug resistant.

A diverse collection of bacterial strains was reported, with 62 identified among 3GCR-GN swabs and 24 different strains of E coli alone. Most 3GCR-GN sequence types were unique to a single patient; however, 10 (42%) E coli and 5 (63%) VRE strains were found in multiple patients.

The investigators defined probable 3GCR-GN strain transmission events using a threshold of at least 20 SNVs, and they identified 6 transmission clusters involving 2 to 3 patients each. With 1 exception, all patients had either overlapping ICU stays or less than 14 days between their respective ICU stays. The investigators estimated 6 (6.3%) 3GCR-GN episodes resulted from recent nosocomial transmission.

Using a threshold of at least 3 SNVs for VRE transmission events, the investigators identified 4 transmission clusters involving 2 to 7 patients each. They conservatively estimated that 8 (28.6%) VRE episodes resulted from recent nosocomial transmission. The estimated transmission burden for VRE was significantly increased compared with 3GCR-GN (odds ratio, 4.3; 95% CI, 1.2-16.6; P =.02).

Study limitations included the investigators’ inability to follow all patients beyond the 3-month study period, underpowering due to the study’s short duration, and the small sample size.

The investigators noted that transmission events occurred even though patients were subjected to infection prevention and control (IPC) contact precautions during their hospitalization and thus called for “targeted approaches to IPC aimed at limiting the [multidrug resistant] disease burden.”

Reference

Wyres KL, Hawkey J, Mirčeta M, et al. Genomic surveillance of antimicrobial resistant bacterial colonisation and infection in intensive care patients. BMC Infect Dis. 2021;21(1):683. doi:10.1186/s12879-021-06386-z