India Reports Completely Drug-Resistant TB

By Maryn McKenna | January 9, 2012  

Well, this is a bad way to start the year.

Over the past 48 hours, news has broken in India of the existence of at least 12 patients infected with tuberculosis that has become resistant to all the drugs used against the disease. Physicians in Mumbai are calling the strain TDR, for Totally Drug-Resistant. In other words, it is untreatable as far as they know.

News of some of the cases was published Dec. 21 in an ahead-of-print letter to the journal Clinical Infectious Diseases, which just about everyone missed, including me. (But not, thankfully, the hyper-alertglobal-health blogger Crawford Kilian, to whom I hat-tip.) That letter describes the discovery and treatment of four cases of TDR-TB since last October. On Saturday, the Times of India disclosed that there are actually 12 known cases just in one hospital, the P. D. Hinduja National Hospital and Medical Research Centre; in the article, Hinduja’s Dr. Amita Athawale admits, “The cases we clinically isolate are just the tip of the iceberg.” And as a followup, the Hindustan Times reported yesterday that most hospitals in the city — by extension, most Indian cities — don’t have the facilities to identify the TDR strain, making it more likely that unrecognized cases can go on to infect others.

 Why this is bad news: TB is already one of the world’s worst killers, up there with malaria and HIV/AIDS, accounting for 9.4 million cases and 1.7 million deaths in 2009, according to the WHO. At the best of times, TB treatment is difficult, requiring at least 6 months of pill combinations that have unpleasant side effects and must be taken long after the patient begins to feel well.

Because of the mismatch between treatment and symptoms, people often don’t take their full course of drugs — and from that (and some other factors I’ll talk about in a minute) we get multi-drug resistant and extensively drug-resistant, MDR and XDR, TB. MDR is resistant to the first-choice drugs, requiring that patients instead be treated with a larger cocktail of “second-line” agents, which are less effective, have more side effects, and take much longer to effect a cure, sometimes 2 years or more. XDR is resistant to the three first-line drugs and several of the nine or so drugs usually recognized as being second choice.

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More MRSA Found In U.S. Retail Meat (Turkey, Too)

By Maryn McKenna

There are two new studies out that confirm, once again, that drug-resistant staph or MRSA — normally thought of as a problem in hospitals and out in everyday life, in schoolkids, sports teams, jails and gyms — is showing up in animals and in the meat those animals become.

The strain of staph that shows up in farm animals, known as “livestock-associated” MRSA or MRSA ST398, first emerged in pigs in the Netherlands, and has been widely identified in retail meat in Europe. (You can find a long archive of posts on ST398 here, and more here.) But that same strain has been difficult to identify in the United States. That may be due in part to the U.S. having a uniquely massive epidemic of community-associated MRSA, far larger than in any other country, which likely both obscures any animal epidemic from detection, and possibly also fills the ecological niche that livestock-associated staph might otherwise occupy. But, it must be said, there’s also remarkably little political will to look for livestock-associated MRSA (though the U.S. Department of Agriculture has now funded a study).

Nevertheless, individual investigators keep trying, and when they look for the pathogen, they find it, such as in these studies from May and this one from April. Now, two other teams have as well.

First, and most important because of the group’s past research: In a pilot study, Blake Hanson and colleagues from the lab of Tara Smith at University of Iowa tested 165 samples of turkey, pork, chicken and beef bought at 22 food stores across the state of Iowa. They found staph on 27 samples and MRSA on two, both pork (1.2 percent); one of the two was a subtype (spa type t034) that falls under ST398. (The other was a spa type usually associated with human MRSA infections, t008.)

This finding is important because Smith and team are the people who first identified livestock-associated MRSA ST398 in pigs and farmworkers in the U.S. They’re also the recipients of that USDA grant funding the search for more of it. They probably know ST398 better than any other U.S. team looking at the strain — and unlike the other research groups, they are embedded in pig country.

They found something else interesting in this research. One of the hallmarks of ST398 has been that — unlike human-associated MRSA strains — it is resistant to tetracycline. That’s an important signal.  While human MRSA is multi-drug resistant, it is usually still susceptible to tetracycline, because tetracycline is not used in human MRSA infections and thus the bug has no exposure that encourages it to evolve resistance. However, tetracycline is very commonly given to animals raised for meat in confined conditions, which is presumably where ST398 worked up or picked up its tetracycline-resistance gene.

In this paper, all of the staph found in pork and turkey was tetracycline-resistant even when it was not MRSA (which, definitionally, is resistant to methicillin or its close analog oxacillin). Six of the seven staph-containing turkey samples were t034, and one was t337, which is associated with another MRSA strain that has emerged in pigs in China. “This suggests that turkeys, in addition to pigs, are a possible reservoir for both the ST398 and ST9 strains in the United States,” the authors say.

Tetracycline resistance is also an important signal in the second new paper, from researchers at the University of Maryland and the U.S. Food and Drug Administration. They tested 694 samples of ground beef, ground pork and ground turkey bought in the Washington, D.C., area. Twenty-nine percent were staph; 17 percent each of the pork and turkey harbored MRSA. Here are the resistance profiles —

When tested for susceptibility to 22 antimicrobials, 69 percent of the S. aureus isolates were resistant to tetracycline, 26 percent to penicillin, 17 percent to ampicillin, 13 percent to methicillin, 8 percent to erythromycin, 4.5 percent to clindamycin, 1.5 percent to gentamicin, and 0.5% to chloramphenicol, oxacillin, cefoxitin, or quinupristin-dalfopristin

— once again, a lot of tetracycline resistance in staph, in meat from animals that would have received tetracycline as they grew. (The paper doesn’t sort the isolates by MLST or spa type, and thus doesn’t say whether any of the isolates were ST398.)

Given how consistently resistant staph, MRSA, and ST398 are showing up in U.S. food products, you’d think we’d want to track down exactly where and how often these resistant strains are emerging. Unfortunately, no. A Government Accountability Report that was released in September to almost no notice scolds the federal health and food agencies for doing very little — despite an earlier GAO push in 2004 for them to do better. The report says:

Since GAO’s 2004 report, FDA began collecting data from drug companies on antibiotics sold for use in food animals, but the data do not show what species antibiotics are used in or the purpose of their use, such as for treating disease or improving animals’ growth rates. Also, although USDA agencies continue to collect use data through existing surveys of producers, data from these surveys provide only a snapshot of antibiotic use practices. In addition, agencies’ data on resistance are not representative of food animals and retail meat across the nation and, in some cases, because of a change in sampling method, have become less representative…. Without detailed use data and representative resistance data, agencies cannot examine trends and understand the relationship between use and resistance.

Clearly, agriculture isn’t going to offer this data on its own. And as the report makes clear, the U.S. government (unlike those of Canada, the Netherlands or Denmark) isn’t pushing. Until it does, the search for MRSA and other resistant organisms in meat is likely to to proceed via papers like these two: incremental, local and subject to the initiative of individual investigators — but not able to tell the general public as much as they deserve to know about risks in their food.