For gram-negative bacteria, resistance is facile

ecoliblackandwhite.jpgA family of bacteria that includes the microbes often behind dangerous food poisoning could soon prove to be an even bigger threat to public health.

Gram-negative bacteria, which Christian Torres highlighted in Nature Medicine’s June issue, are well-suited to develop antibiotic resistance. Their thick cell wall confounds drugs that can easily penetrate their gram-positive cousins. And now, in India, members of the gram-negative Enterobacteriaceae family, which includes Escherichia coli and Salmonella, have been found to carry a gene called NDM-1 that confers resistance to almost every type of antibiotic on the market— including carbapenems, which have long been held as a last resort.

“One year ago, pan-resistant Enterobacteriaceae was unheard of,” says Tim Walsh, one of the authors of the paper documenting the find, which was published in Lancet Infectious Diseases.


This rapid rise of resistance over the past few years could be due in part to Enterobacteria’s promiscuity. Walsh says the plasmids (pieces of circular DNA that allow bacteria to exchange genetic information) found in their Indian specimens were “highly promiscuous” and carried multiple resistance genes in addition to NDM-1. One isolate had taken up as many as 10 different resistance-conferring plasmids. Some scientists think that gram-negative bacteria may have a way of transferring plasmids that’s more efficient than the way gram-positive bacteria do it, but Walsh hastens to add that this is still not well understood.

To combat the specter of a future pan-resistant superbug, Walsh says that there needs to be a large-scale, publicly funded surveillance program for antibiotic resistance. Given the global economy and the frequency of world travel, it’s unreasonable to expect that what happens in India will stay in India. Medical tourism, is a special concern; the paper documents how NDM-1 positive bacteria were isolated from patients in the UK and Sweden who had gone to India for elective surgical procedures. 3 cases of NDM-1 were reported to the US Centers for Disease Control in the first half of 2010; all were Americans that had traveled to India recently for medical care. Hospitals and nursing facilities were the favored breeding ground for MRSA, which spread from patient to patient via close quarters, medical equipment, and even doctors and nurses.

Walsh and his coauthors write that it is “disturbing, in context, to read calls in the popular press for UK patients to opt for corrective surgery in India with the aim of saving the NHS money. As our data show, such a proposal might ultimately cost… substantially more than the short-term saving”.

Lancet Infectious Diseases has another paper related to drug resistance, but in a slightly larger creature— the parasitic flatworms that cause schistosomiasis. Schistosomiasis is currently treated using the drug praziquantel, but some studies have found instances that the worms may be developing resistance. The study compared the effectiveness of an alternative drug strategy using artemisinin-based combination therapies (ACT), which are normally used to treat malaria.

The results, however, were disappointing: of the 212 Kenyan children enrolled in the drug trial, only 14% of the patients receiving ACT were cured within four weeks, as opposed to 65% of those who received praziquantel. Charles Oboyo, who conducted the Kenyan trial, thinks that changing the dosing of ACT or combining artemisinins with other drugs could provide better results.

But other experts are skeptical that finding alternative treatments is even necessary at this juncture. “There is fear that large scale use of praziquantel might result in the development of drug resistance, but it has never really been shown in clinical data,” says Jurg Utzinger, a professor at the Tropical and Public Health Institute in Basel, Switzerland. He supports reserving ACT for combating the malaria parasite, while at the same time keeping an eye out for any associated benefits against the worm menace.

Image of E.coli via Wikimedia Commons

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