New York Times, By DONALD G. McNEIL Jr.
A dangerous new mutation that makes some bacteria resistant to almost all antibiotics has become increasingly common in India and Pakistan and is being found in patients in Britain and the United States who got medical care in those countries, according to new studies.
Experts in antibiotic resistance called the gene mutation, named NDM-1, “worrying” and “ominous,” and they said they feared it would spread globally.
But they also put it in perspective: there are numerous strains of antibiotic-resistant germs, and although they have killed many patients in hospitals and nursing homes, none have yet lived up to the “superbug” and “flesh-eating bacteria” hyperbole that greets the discovery of each new one.
“They’re all bad,” said Dr. Martin J. Blaser, chairman of medicine at New York University Langone Medical Center. “Is NDM-1 more worrisome than MRSA? It’s too early to judge.”
(MRSA, or methicillin-resistant staphylococcus aureus, is a hard-to-treat bacterium that used to cause problems only in hospitals but is now found in gyms, prisons and nurseries, and is occasionally picked up by healthy people through cuts and scrapes.)
Bacteria with the NDM-1 gene are resistant even to the antibiotics called carbapenems, used as a last resort when common antibiotics have failed. The mutation has been found in E. coli and in Klebsiella pneumoniae, a frequent culprit in respiratory and urinary infections.
“I would not like to be working at a hospital where this was introduced,” said Dr. William Schaffner, chairman of preventive medicine at Vanderbilt University. “It could take months before you got rid of it, and treating individual patients with it could be very difficult.”
A study tracking the spread of the mutation from India and Pakistan to Britain was published online on Tuesday in the journal Lancet.
In June, the Centers for Disease Control and Prevention noted the first three cases of NDM-1 resistance in this country and advised doctors to watch for it in patients who had received medical care in South Asia. The initials stand for New Delhi metallo-beta-lactamase.
“Medical tourism” to India for many surgeries — cosmetic, dental and even organ transplants — is becoming more common as experienced surgeons and first-class hospitals offer care at a fraction of Western prices. Tourists and people visiting family are also sometimes hospitalized. The Lancet researchers found dozens of samples of bacteria with the NDM-1 resistance gene in two Indian cities they surveyed, which they said “suggests a serious problem.”
Also worrying was that the gene was found on plasmids — bits of mobile DNA that can jump easily from one bacteria strain to another. And it is found in gram-negative bacteria, for which not many new antibiotics are being developed. (MRSA, by contrast, is a gram-positive bacteria, and there are more drug candidates in the works.)
Dr. Alexander J. Kallen, an expert in antibiotic resistance at the C.D.C., called it “one of a number of very serious bugs we’re tracking.”
But he noted that a decade ago, New York City hospitals were the epicenter of infections with other bacteria resistant to carbapenem antibiotics. Those bacteria, which had a different mutation, were troubling, but did not explode into a public health emergency.
Drug-resistant bacteria like those with the NDM-1 mutation are usually a bigger threat in hospitals, where many patients are on broad-spectrum antibiotics that wipe out the normal bacteria that can hold antibiotic-resistant ones in check.
Also, hospital patients generally have weaker immune systems and more wounds to infect, and are examined with more scopes and catheters that can let bacteria in.
Gram-negative Enterobacteriaceae with resistance to carbapenem conferred by New Delhi metallo-β-lactamase 1 (NDM-1) are potentially a major global health problem. We investigated the prevalence of NDM-1, in multidrug-resistant Enterobacteriaceae in India, Pakistan, and the UK.
Enterobacteriaceae isolates were studied from two major centres in India—Chennai (south India), Haryana (north India)—and those referred to the UK’s national reference laboratory. Antibiotic susceptibilities were assessed, and the presence of the carbapenem resistance gene blaNDM-1 was established by PCR. Isolates were typed by pulsed-field gel electrophoresis of XbaI-restricted genomic DNA. Plasmids were analysed by S1 nuclease digestion and PCR typing. Case data for UK patients were reviewed for evidence of travel and recent admission to hospitals in India or Pakistan.
We identified 44 isolates with NDM-1 in Chennai, 26 in Haryana, 37 in the UK, and 73 in other sites in India and Pakistan. NDM-1 was mostly found among Escherichia coli (36) and Klebsiella pneumoniae (111), which were highly resistant to all antibiotics except to tigecycline and colistin. K pneumoniae isolates from Haryana were clonal but NDM-1 producers from the UK and Chennai were clonally diverse. Most isolates carried the NDM-1 gene on plasmids: those from UK and Chennai were readily transferable whereas those from Haryana were not conjugative. Many of the UK NDM-1 positive patients had travelled to India or Pakistan within the past year, or had links with these countries.
The potential of NDM-1 to be a worldwide public health problem is great, and co-ordinated international surveillance is needed.
European Union, Wellcome Trust, and Wyeth.