I’ve written before about antibiotic resistance in the developing world. Because these poor communities don’t have access to many antibiotics, one wouldn’t expect high frequencies of resistance to antibiotics. Resistance to ciprofloxacin (‘Cipro’) is all the more shocking because these communities don’t have access to this relatively expensive drug*. Not only is ciprofloxacin resistance observed, but, in these communities, it occurs at higher frequencies than in intensive care units in developed countries.
So what’s a possible culprit?
Sadly, a recent paper in PLoS ONE suggests that treatment of malaria with chloroquine leads to ciprofloxacin resistance. Chloroquine inhibits proteins (polymerases) that make DNA; mutations in these genes confer resistance against chloroquine–and ciprofloxacin. While chloroquine is effective against malaria (and cheap), it is only weakly effective against bacteria. Also, chloroquine stays in the body for days (which, again, is good for treatment malaria which has a resistant phase in its life cycle). This is a perfect situation for the evolution of resistance: a continuous, low-dose exposure.
The authors found that patients treated with chloroquine acquired ciprofloxacin resistant E. coli. These resistant E. coli had mutations in the expected genes. When the authors selected for resistance to chloroquine in E. coli in the lab, they found… ciprofloxacin resistance.
Keep in mind that ciprofloxacin resistance, in severely ill patients, increases the chance of death four-fold. These strains aren’t difficult to treat per se, but ciprofloxacin therapy, which is often used to treat severe infections (particularly in developing countries), will fail. Meanwhile, the patient is getting sicker, sometimes irreversibly so.
This is why we need new classes of antimalarials that kill malaria in novel ways.
*Ciprofloxacin, by developed world standards, is quite cheap, which should give you some idea just how destitute these communities are.
Cited articles: 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
Lautenbach E, Metlay JP, Bilker WB, Edelstein PH, Fishman NO. 2005. Association between Fluoroquinolone Resistance and Mortality in Escherichia coli and Klebsiella pneumoniae Infections: The Role of Inadequate Empirical Antimicrobial Therapy. Clinical Infectious Diseases 41:923-929.