Medical tourism, family travel and international migration have combined to import a potent new form of antibiotic resistance halfway around the planet—and the physician-researchers who have tracked its rapid spread say it is already on the verge of becoming untreatable.
News of the new resistance factor has been percolating in smaller medical reports for a few months, including the weekly bulletin of the US Centers for Disease Control and Prevention (which I covered on my blog in June). But Wednesday's announcement, published "ahead of print" on the website of the journal Lancet Infectious Disease, signals a higher level of concern.
Effectively, it sounds an international alarm bell.
The resistance factor, known as New Delhi metallo-beta-lactamase, or NDM-1, has already has been found in India and Pakistan, Sweden, the Netherlands, Australia, Canada and the US. It is appearing in very common bacteria, such as the gut bacterium E. coli, a common cause of urinary tract infections, and in other bacteria that cause illnesses such as pneumonia.
All of the bacteria in which NDM-1 has been found have been what are called Gram-negative bacteria. That's a significant concern—because while new drugs to treat increasingly resistant Gram-positive bacteria such as MRSA are in short supply throughout medicine, drugs for the class known as Gram-negative have been even slower to come to market.
"NDM-1, found in India and Pakistan, Sweden, the Netherlands, Australia, Canada and the US, is appearing in bacteria that cause urinary tract infections and pneumonia."
For several years, authorities, such as the Infectious Diseases Society of America, have been warning that the lack of new drugs for Gram-negatives is a true crisis that warrants creating new incentives for pharmaceutical companies to invest in antibiotic development.
The bacteria reported on in Wednesday's study—a survey that covered India, Pakistan and the United Kingdom—were resistant to multiple classes of drugs: beta-lactams, fluoroquinolones, aminoglycosides and, most troublingly, carbapenems, which are generally considered the drug class of last resort for Gram-negatives. It has responded to only a few antibiotics, including one called colistin that the medical profession shelved decades ago because it is considered toxic to the kidneys.
Explanation of the Dangers
The real threat revealed in Wednesday's news, though, is not the pattern of resistance—medicine does occasionally see very highly resistant organisms—but that the facts that it is widespread and also the manner in which it is spread.
The first indication of NDM-1 was picked up in 2008, in a 59-year-old Swedish resident who was of South Asian origin and hospitalized in India while visiting. When he was hospitalized again after his return to Sweden, physicians discovered that he had a urinary tract infection with a never-seen resistance mechanism.
Last year, the UK's Health Protection Agency put out a national alert about NDM-1, warning that the novel mechanism had gone from never-seen in 2007 to four occurrences in 2008 to 18 in the first half of 2009. The agency underlined that the bug was being transported via the long-standing two-way population movement between England and South Asia, augmented by elective medical tourism: Two of the UK patients had gone to India for cosmetic surgery. In June, the CDC said it had found the same resistance pattern in three patients in three US states, all of whom had undergone recent medical care in South Asia.
The paper published Wednesday, by the researchers who treated that first Swedish case, constitutes a survey for the prevalence of NDM-1 in India, Pakistan and the UK, and its results are very troubling. The authors found it throughout South Asia—at medical centers in north and south India and at sites in India and Pakistan—and in 37 patients in the UK who had family or business ties to South Asia or had gone there for medical care.
Three Important Details Behind the Science
Several points in the report—addressing both the microbiology of NDM-1 and the economic conditions that may have fostered its spread—bear close scrutiny because they are so unnerving.
First: it is happening in India, which not only harbors major manufacturers of generics, but also has very high rates of antibiotic use. Some Indian researchers have been warning for years in the country's medical journals that the subcontinent is on the verge of a home-brewed crisis of drug resistance (Indian Journal of Bioscience, Indian Journal of Medical Microbiology, Indian Journal of Medical Ethics).
Second: it's linked to medical care and especially to medical tourism, which has become a booming international industry, not only for elective options such as cosmetic surgery, but because it offers an inexpensive way to perform major procedures sometimes a long way from the patient's home. A studycovered last January by The Independent in London recommended shipping UK patients to India for care, suggesting it could save the beleaguered health service more than $200 million.
Third: is the fact that this resistance pattern is spreading via a plasmid—a snippet of DNA, not on a chromosome, that reproduces on its own and can move freely between organisms.
Resistance that is spread via plasmid can move with incredible speed; its emergence is not dependent on a bacterium's exposure to a drug, or on a mother bacterium passing the resistance pattern down to daughter cells. The researchers' results prove that NDM-1 has spread widely, because they found it not only in hospital patients, but also outside in the community, causing common illnesses such as urinary tract infections.
That testifies not only to NDM-1's wide distribution, but also to how difficult it might be to conduct surveillance for its presence—or, put another way, how easily it could evade detection while it continues to spread. It is not likely that physicians are going to culture every UTI that comes their way, either in the resource-poor developing world or in the overstressed conditions of Western medicine.
That's a critical point because, given the drought of new drugs for Gram-negatives, surveillance may be the best or even only bet for controlling or at least slowing NDM-1's further spread. It's the urgent recommendation of the author of a companion Lancet ID editoriral, also published Wednesday on the journal's website:
“The spread of these multiresistant bacteria merits very close monitoring and worldwide, internationally funded, multicentre surveillance studies, especially in countries that actively promote medical tourism. Patients who have had medical procedures in India should be actively screened for multiresistant bacteria before they receive medical care in their home country. The consequences will be serious if family doctors have to treat infections caused by these multi-resistant bacteria on a daily basis.”
Maryn McKenna is a journalist and author of SUPERBUG: The Fatal Menace of MRSA, who blogs for Superbugtheblog.com.