Plasmids Found to Confer Antibiotic Resistance Among Unrelated Bacteria at US Hospital

The results of a new study have revealed that carbapenem resistance conferred by plasmids can be transferred among unrelated bacteria in the health care setting, underscoring the need for more granular laboratory testing methods in public health institutions to investigate outbreaks of antibiotic-resistant pathogens. The study was presented at the 2018 ASM Microbe meeting in Atlanta, Georgia, on June 10, 2018.

According to the US Centers for Disease Control and Prevention (CDC), carbapenem-resistant Enterobacteriaceae (CRE) are responsible for more than 9000 health care-associated infections and 600 deaths each year in the United States, making them an urgent public health threat.

In 2017, a team of investigators, including Richard Stanton, PhD, a health scientist in the CDC’s Division of Healthcare Quality Promotion, investigated an outbreak of CRE in 18 patients at a primary care hospital in Kentucky using whole-genome sequencing as a means of identifying the carbapenemases and their potential source. The team analyzed 20 carbapenemase-producing isolates (18 Klebsiella pneumoniae, 2 Escherichia coli) and found that 9 of the isolates had 1 beta-lactamase (bla) gene variant (blaKPC-2), 8 had blaKPC-3, and 1 had blaNDM1.

Further analysis revealed that the K pneumoniae were not clonal, varying between 0 and <1100 SNPs. Indeed, they had 4 different sequence types. The E coli isolates were determined to be related. According to the study abstract, “Long-read sequencing determined that the blaKPC-2 and blaKPC-3 genes were harbored on 2 distinct plasmids, sharing only 48% homology. The blaKPC-2 gene was found on a 128kb plasmid with IncFIB and IncFII replicons that also included a blaTEM-1A gene. The plasmid harboring the blaKPC-3 gene was 164kb, with IncFIA and IncFIB replicons, as well as blaOXA-9, blaTEM-1A, and 6 additional antimicrobial resistance genes.”

Perhaps most alarming is that the investigators found that homologous sequences to 164kb were “found in K pneumoniae isolates from 4 different STs (including ST258) and both of the E coli, suggesting horizontal transfer between unrelated bacteria.

Speaking about these results in a news release, Dr. Stanton is quoted as saying, “This outbreak shows us how drug resistance genes can be shared among otherwise unrelated bacteria co-existing in a patient’s microbial community or in the environment.”

This finding may suggest that infection control and detection efforts at health care institutions may want to look for multiple strains in order to quell outbreaks. Typical outbreak response efforts focus on 1 strain of the bacteria. Because of the propensity for these bacteria to be found in the environment as well, infection control efforts should be shored up to focus on environmental areas such as sinks and drains where plasmid sharing may occur.