Isolates of E. coli, Klebsiella pneumoniae, and several other enterobacteria species expressing the NDM-1 multidrug resistance factor were found in 37 people in Britain, 17 of whom had been in India or Pakistan in the past year, according to Timothy R. Walsh, PhD, of Cardiff University in Wales, and colleagues.
Fourteen of the British patients had been hospitalized while they were in India or Pakistan, including at least several who had gone there for cosmetic surgery or transplant procedures, the researchers reported online in Lancet Infectious Diseases.
They also confirmed that enterobacteria carrying NDM-1 were easily found in patients hospitalized in two Indian cities more than 1,000 miles apart, suggesting these superbugs -- which resisted all antibiotics tested except for tigecycline and colistin -- are widely distributed in the region.
NDM-1 is a beta-lactamase enzyme that inactivates a range of common antibiotics. Walsh and colleagues found that the gene for it was often carried on plasmids in the bacterial nuclei, which could be easily acquired by other pathogens.
"It is disturbing, in context, to read calls in the popular press for U.K. patients to opt for corrective surgery in India with the aim of saving the NHS [National Health Service] money," they wrote, adding that the costs of treating highly resistant infections would eventually overwhelm any short-term savings.
Walsh and colleagues also noted that "medical tourism" to south Asia is also popular with Europeans and Americans. Consequently, they warned, the NDM-1 resistance factor "will likely spread worldwide."
In late June, the CDC reported that NDM-1 had been found in the U.S. for the first time, with three isolates identified in three separate state laboratories and in three different species.
"The potential for wider international spread of producers and for NDM-1-encoding plasmids to become endemic worldwide, are clear and frightening," Walsh and colleagues wrote.
They had analyzed clinical isolates of enterobacteria including E. coli, K. pneumoniae, Enterobacter cloacae, two Proteus species, and others for the presence of NDM-1.
Of 3,521 isolates from the southern Indian city of Chennai, 4% were found to carry NDM-1. Nearly a quarter of 198 isolates collected in Haryana, in the country's north, expressed NDM-1.
Most of the isolates positive for NDM-1 came from patients with urinary tract infections, bacteremia, or pneumonia.
Walsh and colleagues also tested isolates from other locations in India and Pakistan, eventually finding 73 with NDM-1.
These were in addition to the 37 isolates with NDM-1 identified in the U.K.'s national laboratory from samples sent by facilities across the country, including Scotland and Northern Ireland. The first of these was discovered in 2008.
Of the 180 isolates found in the study, 111 were K. pneumoniae and 36 were E. coli.
The researchers determined that the isolates found in Haryana were genetically identical, and the NDM-1 gene was not easily transferred to other species. Those collected elsewhere, on the other hand, were clonally diverse and the gene was carried on plasmids that could readily move among different enterobacter species.
Laboratory testing indicated that the NDM-1 isolates were resistant to all beta-lactam antibiotics, fluoroquinolones, and aminoglycosides, with the exception of two that were killed with gentamicin.
However, all but 39 were sensitive to minocycline, and only 19 were resistant to tigecycline and three to colistin. On the other hand, one K. pneumoniae isolate was resistant to both tigecycline and colistin.
The appearance of NDM-1 may "potentially herald the end of treatment with beta-lactams, fluoroquinolones, and aminoglycosides," which collectively form the backbone of therapy for Gram-negative infections, Walsh and colleagues warned.
The authors noted that in contrast to the previous decade "clinical microbiologists increasingly agree that multidrugresistant Gram-negative bacteria pose the greatest risk to public health."
In an accompanying editorial, Johann D.D. Pitout, MD, of the University of Calgary, said the appearance of NDM-1 in multiple locations "merits very close monitoring and worldwide, internationally funded, multicenter surveillance studies, especially in countries that promote medical tourism."
He also recommended that individuals having "medical procedures in India should be actively screened for multiresistant bacteria before they received medical care in their home country."
The study was funded by the EU, the Wellcome Trust, and Wyeth.
The lead author reported receiving a travel grant from Wyeth and another author reported holding or managing shares in AstraZeneca, Merck, Pfizer, Dechra, GlaxoSmithKline, and Eco Animal Health. Other authors and the editorialist declared they had no financial conflicts of interest.
Zalman S. Agus, MD Emeritus Professor
University of Pennsylvania School of Medicine and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
The Lancet Infectious DiseasesSource Reference: Kumarasamy K, et al "Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study" Lancet Inf Diseases 2010; DOI: 10.1016/S1473-3099(10)70143-2.
The Lancet Infectious DiseasesSource Reference: Pitout J, "The latest threat in the war on antimicrobial resistance" Lancet Inf Diseases 2010; DOI: 10.1016/S1473-3099(10)70143-2.