Will tuberculosis become resistant to all antibiotics?

The discovery of high prevalences of antibiotic resistance in some pathogen s, in some parts of the world, has provoked fears of a widespread loss of d rug efficacy. Here, we use a mathematical model to investigate the evolutio n of resistance to four major anti-tuberculosis drugs (isoniazid, rifampici n, ethambutol and streptomycin) in 47 sites around the world. The model pro vides a new method of estimating the relative risk of treatment failure for patients carrying drug-resistant strains and the proportion of patients wh o develop resistance after failing treatment. Using estimates of these two quantities together with other published data, we reconstructed the epidemi c spread of isoniazid resistance over the past 50 years. The predicted medi an prevalence of resistance among new cases today was 7.0% (range 0.9-64.3% ), close to the 6.3% (range 0-28.1%) observed. Predicted and observed preva lences of resistance to isoniazid plus rifampicin (multidrug-resistant or M DR-TB) after 30 years of combined drug use were also similar, 0.9% (0.1-5.9 %) and 1.0% (range 0-14.1%), respectively. With current data, and under pre vailing treatment: practices, it appears that MDR-TB will remain a localize d problem, rather than becoming a global obstacle to tuberculosis control. To substantiate this result, further measurements are needed of the relativ e fitness of drug-resistant strains.