16 July 2008

Please route to the Dept. of Unintended Consequences.

Via the open-access Journal PLoS One, an unnerving report of Canadian researchers finding fluoroquinolone resistance in E. coli in a group who are vanishingly unlikely to have ever taken a quinolone: indigenous Indians in isolated villages in the Guyanese rainforest.

For most people the most familiar quinolone is likely to be ciprofloxacin (Cipro), a very valuable antibiotic in the arsenal because it works against a broad array of Gram-positive and Gram-negative organisms and is off-patent and therefore relatively inexpensive. (Cipro became a household word in the US during the anthrax attacks — it is given prophylactically on suspicion of exposure to inhalational anthrax — and was recently given a "black box" warning by the FDA because of an association with tendon ruptures.)

Quinolone resistance has certainly been recorded: In 2003, a team found 4.0 percent of E. coli in US intensive care units were resistant to cipro. The Canadians — 20 volunteer medical personnel from Ontario — found 5.4 percent among the Guyanese. That's in a setting where there is no selective antibiotic pressure, because no one is taking antibiotics.

Aha: But they are taking malaria prophylaxis, including the extremely common and cheap antimalarial chloroquine. The team theorizes that chloroquine is sufficiently chemically similar to the quinolones to provoke the development of resistance. If correct, this is very bad news: Malaria is a major killer especially of children, so no one is about to stop prescribing a cheap, effective antimalarial in a highly malarious area. In fact, the WHO and other agencies are preparing a new antimalarial program called ACT (for "artemisin combination therapy"; artemisin is a botanical) that includes a drug family called quinolines that are chemically similar to chloroquine.

Controlling malaria is an important public health goal, but so is controlling antibiotic resistance, especially resistance to effective drugs that poor countries can afford. As one of the authors, Michael Silverman of Oshawa, Ont. warned as the study was releasing:"Chloroquine use for malaria may make the fluoroquinolones less effective for many common tropical diseases such as typhoid fever, diarrheal illnesses, and possibly also tuberculosis and pneumonia in the developing world."

The cite is: Davidson RJ, Davis I, Willey BM, Rizg K, Bolotin S, et al. (2008) Antimalarial Therapy Selection for Quinolone Resistance among Escherichia coli in the Absence of Quinolone Exposure, in Tropical South America. PLoS ONE 3(7): e2727. doi:10.1371/journal.pone.0002727

1 comment:

Dr. Susan Biali said...

Thank you for this excellent post on an important (and scary) subject. For a Canadian M.D. who routinely and confidently prescribes cipro to her patients, the thought that resistance may be emerging in this surprising fashion is very frightening indeed. Keep up the great work!
Susan Biali, M.D. Vancouver, Canada