Treatment strategies will need to be changed because of drug resistance

BMJ 1996; 313 doi: https://doi.org/10.1136/bmj.313.7048.45b (Published 06 July 1996) Cite this as: BMJ 1996;313:45
  1. Jon S Friedland,
  2. Gio Simoes
  1. Senior lecturer MSc student Department of Infectious Diseases and Bacteriology, Royal Postgraduate Medical School Hammersmith Hospital, London W12 0NN

    EDITOR,—Dale I Morse notes that the emergence of multidrug resistant Mycobacterium tuberculosis has been one of the spurs to supervised chemotherapy.1 Other aspects of treatment protocols are equally important in controlling the emergence of drug resistance. Currently, the British National Formulary recommends that standard treatment for tuberculosis should be with three drugs (isoniazid, rifampicin, and pyrazinamide). Indications for adding a fourth drug include previous default from treatment and immigration from areas of the world with a high prevalence of drug resistance. The upsurge in tuberculosis in Britain, however, is mainly due to increasing poverty, not immigration.2 Resistance to one or two drugs is not thought to be an important problem in Britain despite experience in other developed countries.3

    In this infectious diseases unit we reviewed the sensitivities of 360 sequential positive cultures of M tuberculosis to first line antituberculous treatments (isoniazid, rifampicin, pyrazinamide, ethambutol, and streptomycin). Infected patients had presented between 1990 and 1994 to either this postgraduate teaching hospital or a nearby district general hospital. Less than 10% were known to be HIV seropositive. Forty nine isolates were resistant to at least one antituberculous drug. Seventeen were resistant to isoniazid, three to rifampicin, two to ethambutol, 19 to streptomycin, and six to both isoniazid and streptomycin. Two patients had tuberculosis that was resistant to at least three drugs, of whom one repeatedly defaulted from the clinic while the other was a Nigerian with his first presentation of pulmonary tuberculosis. The pattern of drug resistance was similar to that in a previous study, but the incidence has more than doubled since that study.4

    Mycobacteria were detectable on sputum examination in 159 patients. Thus within the local urban community there is great potential for transmission of M tuberculosis that is resistant to one drug. In addition, patients may well receive what is effectively two-drug treatment on diagnosis, which will accelerate the emergence of drug resistance. Since multidrug resistance is the result of the sequential acquisition of resistance to single drugs,5 treatment strategies must be altered as resistance to single drugs becomes more common and not when multidrug resistance is established. If our findings are confirmed elsewhere, British policies for treating tuberculosis will need to be revised soon. Fourdrug empirical treatment of tuberculosis should then become normal practice, pending definitive results from drug sensitivity tests of the organism being treated.


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