Whole genome sequencing reveals hidden transmission of carbapenemase-producing Enterobacterales

Abstract

Carbapenemase-producing Enterobacterales (CPE) infection control practices are based on the paradigm that detected carriers in the hospital transmit to other patients who stay in the same ward. The role of plasmid-mediated transmission at population level remains largely unknown. In this retrospective cohort study over 4.7 years involving all multi-disciplinary public hospitals in Singapore, we analysed 779 patients who acquired CPE (1215 CPE isolates) detected by clinical or surveillance cultures. 42.0% met putative clonal transmission criteria, 44.8% met putative plasmid-mediated transmission criteria and 13.2% were unlinked. Only putative clonal transmissions associated with direct ward contact decreased in the second half of the study. Both putative clonal and plasmid-mediated transmission associated with indirect (no temporal overlap in patients' admission period) ward and hospital contact did not decrease during the study period. Indirect ward and hospital contact were identified as independent risk factors associated with clonal transmission. In conclusion, undetected CPE reservoirs continue to evade hospital infection prevention measures. New measures are needed to address plasmid-mediated transmission, which accounted for 50% of CPE dissemination.

Fig. 1. Disposition of isolates analysed in the study.

From September 2010 to April 2015, 1312 carbapenemase-producing Enterobacterales isolates were obtained from the National Public Health Laboratory, of which 1215 isolates had species and carbapenemase gene(s) concordant between genomic and laboratory phenotypic methods as well as metadata available. Isolates from patients who had more than one isolate carrying the same carbapenemase gene were removed (N = 314). A total of 901 index isolates formed the dataset for establishing putative clonal or plasmid-mediated transmission in terms of source-acquisition case pairs, from which 779 acquisition patients were defined.

Fig. 2. Incidence of carbapenemase-producing Enterobacterales patients from 2010 to 2015.

The data is presented as (a) total incidence of patients resulting from putative clonal or plasmid-mediated transmission, or neither, b Incidence of patients among surveillance cultures only, c Incidence of patients among clinical cultures only, d Incidence of patients resulting from putative clonal transmission stratified by hospital or ward contact, e Incidence of patients resulting from putative plasmid-mediated transmission stratified by hospital or ward contact. Incidence is defined as the number of new patient pairs per 10,000 patient-days. Surveillance culture rate is defined as the number of surveillance cultures per 10,000 patient-days. Ward contact was further classified as direct or indirect, and in the absence of any form of ward contact, direct or indirect hospital contact. Time trends are presented as six-period (month) moving averages. Lines represent the incidence point estimate and the shaded areas represent the 95% CI of the estimate.

Fig. 3. Staggered adoption of infection-prevention measures at participating study sites over study period (September 2010 to April 2015).

The coloured-bars represent the time period of adoption of the various measures with calendar years denoted on the x-axis. Specific measures are listed on the y-axis. The bars are colour-coded to differentiate the various participating hospitals.