September 24, 2012 (San Francisco, California) — Researchers have reported the first cases of companion animals in the United States harboring Escherichia coli–containing New Delhi Metallo-carbapenemase (NDM).
In the past decade, community-acquired E coli isolates have gained the ability to produce extended-spectrum beta-lactamases capable of hydrolyzing almost all beta-lactam antibiotics except carbapenems, Rajesh Nayak, PhD, reported here at the 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy. Dr. Nayak is a research scientist at the US Food and Drug Administration's National Center for Toxicological Research of the in Jefferson, Arkansas, and adjunct professor at the University of Arkansas in Fayetteville and West Virginia University in Morgantown.
The carbapenems are the last of the beta-lactam antibiotics with near universal activity against Gram-negative organisms and are crucial for the treatment of serious nosocomial infections, but now they are threatened.
Dr. Nayak told Medscape Medical News that this finding might have clinical significance for humans because pets and people live in close proximity. There is a potential for "these bacteria with the resistance genes [to] be transferred from companion animals to humans," he said.
NDM-1 is a zinc-dependent beta-lactamase encoded by the bla NDM gene. It hydrolyzes all penicillins, cephalosporins, and carbapenems. It was discovered in 2008 in Sweden in an isolate from an Indian patient who had been hospitalized in New Delhi. The genes can be carried on plasmids of different types and sizes and can be transferred among various bacterial species.
Reports in the literature have demonstrated multidrug resistance in E coli isolates from dogs and cats. In one report, 18% of isolates showed resistance to all 7 drugs in several antibiotic classes tested. Beta-lactamase genes carried on plasmids in E coli increased the minimum inhibitory concentration of extended-spectrum cephalosporins at least 16-fold.
To characterize carbapenem resistance in clinical isolates of E coli from dogs and cats, Dr. Nayak and colleagues tested samples from veterinary laboratories across the United States for susceptibility to antimicrobial agents. For the 100 isolates that exhibited reduced susceptibility to ceftazidime, cefotaxime, or meropenem, they used polymerase chain reaction to amplify and look for 10 carbapenemase genes, including bla NDM. They sequenced the plasmids from all NDM-positive samples.
The investigators found the bla NDM gene on 4 different plasmids in 6 of the E coli isolates; they did not detect any of 9 other genes coding for carbapenemases. These NDM-producing isolates had minimum inhibitory concentrations of meropenem ranging from 0.5 to 16 μg/mL. They were also resistant to beta-lactam antibiotics, including those used in combination with clavulanic acid. Two of the isolates were resistant to doxycycline, enrofloxacin, or gentamicin, and 1 was resistant to trimethoprim/sulfamethoxazole.
In a test of the ability to transfer resistance, 1 of the 6 isolates carrying the bla NDM gene successfully conjugated with an E coli recipient strain and transferred the gene, resulting in resistance to meropenem and several cephalosporins in the recipient strain.
Dr. Nayak said that NDM-producing Enterobacteriaceae are an important public-health concern. Their appearance in companion animals might limit the ability of veterinarians to treat E coli infections in these animals, which means that "there's a chance that this [form of resistance] could be transferred to humans," he said.
Potential for Spread Worrying
Jesús Rodríguez-Baño, MD, PhD, professor and head of infectious diseases at the Hospital Universitario Virgen Macarena and the University of Seville in Spain, who was not involved in the study, said the potential for NDM spread from pets to people is quite worrying because "these isolates are resistant to most antimicrobials that we have and because this type of microorganism resistance seems to be able to disseminate within different species of Enterobacteriaceae very easily.... So they probably have the ability to spread very easily into different kinds of bacteria."
However, he cautioned that it is too soon to know whether this is of clinical relevance to humans.
Dr. Rodríguez-Baño mentioned studies showing that companion animals share many microorganisms with the people they live with; however, there are no good data indicating how important these organisms are, he told Medscape Medical News.
More needs to be done to establish whether such transfers can occur and, if so, what the relevant reservoirs are so that they can be avoided. "I think it may be quite difficult because contact with animals is frequent," he predicted.
Dr. Nayak and Dr. Rodríguez-Baño have disclosed no relevant financial relationships.
52nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC): Abstract C2-1219. Presented September 11, 2012.
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