Multidrug-resistant tuberculosis

Some strains of tuberculosis have become resistant to some of the standard drugs. These multidrug-resistant (MDR) strains have infected both people with HIV and HIV-negative healthcare workers. The likelihood of dying from MDR tuberculosis is high, especially for HIV-positive people, unless treatment can begin very soon after infection with appropriately tailored therapy.

Outbreaks of MDR tuberculosis have been successfully controlled in Cuba, Hong Kong and the United States,1 but cases of MDR tuberculosis are highest in areas with the fastest growing HIV epidemic, particularly the former Soviet republics, China and South Africa.2 3 It seems that the spread of MDR tuberculosis is being fuelled by a high prevalence of tuberculosis in HIV-positive patients, and also by poor adherence to anti-tuberculosis medication.4 5 Worldwide, ten per cent of new TB cases are estimated to be resistant to at least one first-line drug, but this prevalence rises to 57% in Kazakhstan.6 In China one study found that the majority of cases of MDR cases were attributable to new infection, not poor adherence to medication.7

MDR tuberculosis is no more easy to transmit than the more common form of M. tuberculosis. It can be very difficult to determine when HIV-positive people who are undergoing treatment for MDR tuberculosis cease to be infectious, because the M. tuberculosis organisms may disappear from their sputum for a short period, but reappear a short while later. This makes it very difficult to determine when a patient is truly non-infectious, so affected people may be hospitalised and isolated for many months.

MDR tuberculosis is significantly more difficult to treat and requires extra drugs such as streptomycin, kanamycin, clarithromycin (Klaricid / Klaricid XL), amikacin (Amikin), capreomycin (Capastat) or other antibiotics. These are more expensive, more toxic and less effective and require a longer course of treatment. Drug selection in patients suspected to have MDR tuberculosis should be guided by history and local drug susceptibility patterns whenever possible. Usually, initial treatment is with the four-drug regimen plus at least additional two drugs to which the patient's M. tuberculosis is thought to be susceptible. In people with culture-confirmed MDR tuberculosis, at least three drugs should be used for at least twelve months after the sputum conversion. Most experts recommend that treatment last 18 to 24 months.

Extensively drug-resistant tuberculosis (XDR-TB ) is TB resistant to isoniazid, rifampicin, all the fluoroquinolone TB drugs and at least one of the injectable drugs used to treat multi-drug resistant TB. In August 2006 South African researchers reported that an outbreak of XDR-TB at a rural hospital in Kwazulu Natal had killed over people within a month of diagnosis,8 and within weeks cases of XDR-TB were being identified all over South Africa.

XDR-TB has been identified in every region of the world, including Europe, among TB cases initially defined as multidrug-resistant.

References

  1. Frieden TR et al. Original articles: the emergence of drug-resistant tuberculosis in New York City. N Engl J Med 328: 521-526, 1993
  2. Fischl MA et al, An outbreak of tuberculosis caused by multiple-drug-resistant tubercle bacilli among patients with HIV infection. Ann Intern Med 117: 177-183, 1992
  3. Fischl MA et al. Clinical presentation and outcome of patients with HIV infection and tuberculosis caused by multiple-drug-resistant bacilli. Ann Intern Med 117: 184-190, 1992
  4. Chengeta B et al. A case-control study on tuberculosis treatment interruption-2002. First National HIV / AIDS / STI / Other Related Infectious Diseases Research Conference, Gaborone, abstract MBT11-6, 2003
  5. Ngirubiu PK et al. Anti-tuberculosis drug resistance and anonymous HIV surveillance among tuberculosis (TB) patients in Botswana, 2002. First National HIV / AIDS / STI / Other Related Infectious Diseases Research Conference, Gaborone, abstract MBT11-5, 2003
  6. Aziz MA et al. Epidemiology of antituberculosis drug resistance (the Global Project on Anti-tuberculosis Drug Resistance Surveillance): an updated analysis. The Lancet 368: 2142–2154, 2006
  7. Li X et al. Transmission of drug-resistant tuberculosis among treated patients in Shanghai, China. J Infect Dis 195: 864-869, 2007
  8. Gandhi NR et al. High prevalence and mortality from extensively-drug resistant (XDR) TB in TB/HIV coinfected patients in rural South Africa. Sixteenth International AIDS Conference, Toronto, abstract ThLB0210, 2006
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