TB with resistance to second-line drugs increasing, a 'serious and emerging public health threat' warn doctors

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Tuberculosis (TB) with resistance to second-line drugs is becoming increasingly prevalent around the world, according to data from the World Health Organization and the US Centers for Disease Control released on World TB Day (24th March) and published in the March 24th edition of Morbidity and Mortality Weekly Report. Individuals who have TB with resistance to second-line drugs have a significantly increased risk of death compared to patients with resistance to first-line drugs, and the investigators express concern about the emergence “untreatable” strains of TB.

During the 1990s, TB with resistance to isoniazid and rifampin - two drug used in first-line anti-TB therapy – emerged as a major health problem across the world. This is usually called multidrug-resistant TB (MDR-TB) and when it occurs, it requires the use of second line drugs that are less effective, more toxic and costlier.

In 2000, monitoring was introduced of the worldwide prevalence of TB with resistance to second line drugs and the appropriate use of measures to prevent the emergence of resistance.


second-line treatment

The second preferred therapy for a particular condition, used after first-line treatment fails or if a person cannot tolerate first-line drugs.

multidrug-resistant tuberculosis (MDR-TB)

A specific form of drug-resistant TB, due to bacilli resistant to at least isoniazid and rifampicin, the two most powerful anti-TB drugs. MDR-TB usually occurs when treatment is interrupted, thus allowing organisms in which mutations for drug resistance have occurred to proliferate.

first-line therapy

The regimen used when starting treatment for the first time.



directly observed therapy (DOT)

When a health care professional watches as a person takes each dose of a medication, to verify that all doses are taken as prescribed.

WHO and the US CDC surveyed an international network of 25 TB reference laboratories on six continents. A total of 17,690 TB isolates obtained between 2000 and 2004 were included in the investigators analysis. They established that, overall, 20% of isolates showed evidence of multidrug-resistant TB, and 2% had resistance to second line TB drugs.

In addition, population-based data on the drug susceptibility of TB isolates were obtained for the US between 1993 – 2004, Latvia between 2000- 2004, and South Korea for 2004.

Just under 170,000 isolates from the US were eligible for inclusion in the investigators’ analysis. Of these, 2,700 (2%) were multidrug-resistant, and of these 74 (4%) exhibited resistance to second-line drugs. There was a non-significant increase in the incidence of TB with resistance to second-line drugs (3.9% before 1996 vs. 4.5% in 2004, p = 0.11), but the investigators noted that patients with resistance to second-line drugs were 64% more likely to die of TB than individuals who only had resistance to first-line TB therapy.

Results from Latvia showed that of the 605 patients with multidrug-resistant TB between 2000 – 2002, 115 (19%) had resistance to second-line treatment. This increased from 15% in 2000 to 21% in 2002 (non significant, p = 0.11). Individuals with resistance to second-line TB therapy were 54% more likely to die of TB than patients who only had resistance to first-line drugs.

Of the multidrug-resistant isolates obtained from South Korea, 15% had resistance to second-line TB therapy.

TB with resistance to second-line treatment options was also identified in other regions of the world, particularly Eastern Europe and Western Asia (14%).

“The findings of this report indicate that extensively drug resistant TB has a wide geographical distribution,” write the investigators, adding “it is associated with worse treatment outcomes than multidrug-resistant TB. A growing number and proportion of extensive drug-resistant TB cases could seriously hamper TB control globally.”

The investigators call for international population-based surveillance of TB with resistance to second-line therapy.

Control of TB with extensive resistance will “rely on quality assured and internationally recommended treatment regimens administered under strict supervision” as part of the Directly Observed Therapy Short course Plus (DOTS-Plus) programme, conclude the investigators. They warn that “the existence of extensive drug-resistance TB [is] a serious and emerging public health threat.”


Wright A et al. Emergence of Mycobacterium tuberculosis with extensive resistance to second-line drugs – worldwide, 2000 – 2004. MMWR 55(11): 301.