MDR and XDR Tuberculosis Literature: Commentary by Dr. John G. Bartlett -- April 2007

John G. Bartlett, MD


Medscape Infectious Diseases 

Gandhi NR, Moll A, Sturm AW, et al. Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. Lancet 2006;368:1575-1580. The purpose of this study was to assess the prevalence and consequences of multidrug-resistant tuberculosis (MDRTB) and extensively drug-resistant tuberculosis (XDRTB) in KwaZulu Natal, South Africa.

Methods: The authors increased surveillance for MDRTB with sputum cultures and drug susceptibility testing in patients with suspected TB. The analysis included genotyping of resistant strains and susceptibility testing for first- and second-line drugs.

Results: Sputum cultures for TB were done on 1539 patients; results showed 542 (35%) were positive; 221 (40%) were MDRTB and 53 (24%) of the MDRTB were XDRTB. These results are summarized in the Table.

Analysis of the 53 cases involving XDRTB showed only approximately 50% had received therapy for tuberculosis, 2/3 had been hospitalized within the previous 2 years, and all 44 who had HIV serology were positive. Of particular note was the observation that 52 of the 53 died and the median time to death among these patients from the time of the positive culture result was 16 days.

Genotyping indicated 39 of 46 strains were in the KZN family.

Conclusion: The authors conclude that this study shows the presence and potential serious consequences of XDRTB in resource-limited areas with high rates of HIV, and they emphasize the need for 'urgent local and international intervention.'

Comment: This is an extremely disturbing report that was presented by Dr. Gandhi at the 2006 International AIDS Conference in Toronto; in this report he finished by warning that this strain of TB could undo all of the achievements to date in the international effort to treat and control the HIV epidemic in the developing world. KwaZulu Natal is a rural province in South Africa in which about 80% of patients with active TB have HIV co-infection; mortality rates in those with co-infection are reported as high as 40% per year despite treatment for TB. The authors of the present study note that the rate of MDRTB was only 1.7% when surveyed in 2000-2002, but had increased to 9% in 2003-2006. XDRTB is defined as MDR (resistance to IMH and rifampin) plus resistance to at least 3 of the 6 second-line drugs. In the United States, these account for about 4% of the MDR strains and up to 15% to 19% in reports from Korea and Latvia.[1] This susceptibility pattern renders these strains virtually untreatable.[2] The authors of the report summarized above emphasize 4 needs:

  • There needs to be better surveillance to determine the full extent of MDR and XDR tuberculosis in the areas with high prevalence rates of HIV;

  • Treatment programs need to be strengthened to improve the rates of treatment including access to second-line drugs;

  • Infection control practices, especially those within healthcare settings, need to be enhanced with inclusion of protection of healthcare workers; and

  • There needs to be simpler and more aggressive testing to detect TB and drug resistance in resource-limited areas.

In a more recent editorial comment, Raviglione and Smith[3] call attention to the unique features of this epidemic that emphasize the important points noted previously. This includes the fact that most of the patients in KwaZulu-Natal province had never been treated, most had been hospitalized suggesting nosocomial acquisition, and all who were tested had HIV infection. XDRTB has been reported in at least 17 countries. Their conclusion is that the 'global threat of XDRTB has great significance for the public health field' and 'its very existence is a reflection of weakness in tuberculosis management.'


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