Antimicrobial resistance has been a growing concern in the health care community. But a publication by Chinese researchers in The Lancet Infectious Diseases last fall kicked things up a notch. The work found the mcr-1 gene, which confers resistance to the antibiotic colistin, in Escherichia coli isolates taken from raw meat, pigs raised as food animals and a small percentage of hospitalized patients. Most concerning, mcr-1 exists on a plasmid, meaning it could potentially spread antibiotic resistance to other bacterial species.
“When this happened, everyone started getting concerned, because if the resistance is on a plasmid and can spread, it’s going to eventually affect the use of colistin --- which is increasingly used as a last resort for multidrug-resistant infections --- as a drug to treat humans,” says Barry N. Kreiswirth, Ph.D., founding director of the Public Health Research Institute (PHRI) Tuberculosis Center at New Jersey Medical School, part of Rutgers University in Newark, N.J.
The paper prompted Kreiswirth and others to re-examine their own collections of bacterial isolates from countries worldwide to look for colistin-resistant strains harboring mcr-1, prompting numerous additional publications. Kreiswirth’s laboratory then decided to look at carbapenem-resistant bacteria from a nearby hospital in Newark. He and his colleagues pulled about 50 strains, finding one E. coli strain from a New Jersey patient with a complicated urinary tract infection that carried not only mcr-1 but also blaNDM-5, which confers resistance to broad-spectrum carbapenem antibiotics used to treat multidrug-resistant Gram-negative infections.
Around the same time this spring, Walter Reed investigators published their report of mcr-1 found in a Pennsylvania patient in Antimicrobial Agents and Chemotherapy. The Centers for Disease Control and Prevention in June then issued a health alert calling for Enterobacteriaceae isolates with a minimum inhibitory concentration (MIC) to colistin of 4 µg/ml or higher to be tested for confirmation and the presence of mcr-1. The mcr-1 isolate from Kreiswirth’s group had a colistin MIC of only 3 µg/ml, however. Kreiswirth knew it was time to publish his own findings, which appeared this week in mBio.
“Others in the U.S. had found mcr-1 positives, but the significance of this paper was this was the first example so far in our country of having the colistin resistance associated within the same strain as carbapenem resistance,” says Kreiswirth.
The strain, isolated in 2014 from a 76-year-old man who had emigrated from India a year prior to developing infection, did respond to other antimicrobial agents and was treated successfully. But Kreiswirth says the case presents a sound reminder to monitor and track multidrug-resistant organisms: “The good news is that this did not cause a major outbreak of drug-resistant infection. The bad news is that since this occurred two years ago, there are clearly other strains out there we haven’t detected yet. The carbapenem resistance and the colistin resistance genes are on separate plasmids, which means they can spread to other bacteria.”
Kreiswirth’s lab used various molecular techniques to identify and compare the different bacteria found in the man’s urine samples, finding that the E. coli strain harbored resistance to several classes of antibiotics, including aminoglycosides, beta-lactams, chloramphenicol, fluoroquinolones, rifampin, sulfonamides, and tetracycline. Additional testing found that the plasmids isolated were highly similar to ones previously reported by Kreiswirth’s group from clinical infections in China.
The lab also identified the E. coli strain as a variant of ST405, one of the main disease-causing strains of the bacteria, which has frequently been associated with community-onset urinary tract infections, says lead study author José R. Mediavilla, MBS, MPH, a research teaching specialist at PHRI.
“Most mcr-1 cases appear to be happening in E. coli, the most common cause of urinary tract infections,” Mediavilla says. “These strains are probably already in the community and could spread further, essentially building toward a situation where you’re going to have difficult if not impossible to treat urinary infections. Active surveillance efforts involving all colistin- and carbapenem-resistant organisms are imperative to determine mcr-1 prevalence and prevent further dissemination.”
-- Karen Blum