WHO Guidelines for Drug-Resistant Tuberculosis Updated

Nancy A. Melville

August 05, 2011

August 5, 2011 — New guidelines from the World Health Organization (WHO) on the management of drug-resistant tuberculosis (TB) offer the latest approaches for better control of the disease that claims millions of lives each year.

The guidelines, published online August 4 in the European Respiratory Journal, update recommendations from previous guidelines published in 2008 and are intended to help inform practitioners, particularly those in lower-income settings, of the very latest and most cost-effective standards of care for achieving optimal patient outcomes.

"The updated WHO program guidelines on [multidrug-resistant]-TB are an essential resource for healthcare professionals with a responsibility for TB patient care," stated Mario Raviglione, MD, director of the WHO Stop TB Department in a press release.

"WHO has produced this latest version to reflect important developments in TB, developments that will have a beneficial impact on clinical and operational outcomes."

The guidelines reflect the recommendations of a multidisciplinary panel of TB practitioners, public health professionals, representatives of professional societies, national TB control program staff, guideline methodologists, and other professionals.

Although there are no radical changes from the 2008 guidelines, the new guidelines include some important adjustments and provide the most updated information on issues such as diagnosis, treatment, and monitoring.

The guidelines feature 11 key recommendations for caregivers, including the following:

  • Wider use of rapid drug susceptibility testing for isoniazid and rifampicin or rifampicin alone over conventional testing upon patient diagnosis with TB and before treatment initiation to allow for earlier identification of patients with drug-resistant TB. The approach is considered the most cost-effective, and administration of appropriate treatment as quickly as possible is recommended to avoid unnecessary deaths.

  • Monitoring patients with sputum smear microscopy and culture, rather than sputum smear microscopy alone, for multidrug-resistant TB (MDR-TB) to detect failure as early as possible during treatment. Users are advised to be aware of differences in the quality of the culture performance because a false-positive result could lead to an unnecessary continuation or modification of treatment and increased risk for toxicity.

  • The use of fluoroquinolones and ethionamide, with later-generation fluoroquinolone, rather than earlier-generation forms of the drug recommended for patients with MDR-TB.

  • A focus on cost-effective ambulatory models of care that treat patients outside of the hospital rather than hospitalizing them. In addition to reducing the risk for re-infection, the ambulatory care model reduces travel and social isolation for patients.

  • For patients with MDR-TB, the minimum duration of treatment has been extended by 2 months from previous guidelines to reflect research showing improved treatment success with the longer duration. Intensive treatment should therefore last at least 8 months, and for those who have not been treated with second-line drugs for TB in the past, treatment should extend to 20 months. The duration may be adjusted for some patients according to their clinical and bacteriologic response.

  • Early use of antiretroviral agents for HIV-infected patients with TB who are receiving second-line drug regimens, irrespective of CD4 cell-count, as early as possible (within the first 8 weeks) after initiation of anti-TB treatment.

Tuberculosis claimed as many as 1.7 million lives in 2009, not including those who died from the disease while affected by AIDS. An estimated 3% of new TB cases around the world are MDR-TB — major shortcomings in healthcare systems have led to increasing resistances to anti-TB drugs.

Evidence is said to be particularly lacking in pediatric MDR-TB, the best drug regimens for treatment with isoniazid resistance, extremely drug-resistant TB or non-MDR-TB polydrug resistance, and therapy for symptomatic relief from adverse reactions linked to second-line anti-TB drugs.

The guidelines therefore place a heavy emphasis on the need for more research, while striving to help improve understanding of critical issues, such as duration, composition, and management of treatment, particularly for patients with MDR-TB.

"The new evidence-based WHO guidelines are a milestone clinicians and public health specialists were waiting anxiously to guide their interventions," said Professor G.B. Migliori, head of the Respiratory Infections Assembly at the European Respiratory Society.

"They resulted from an unprecedented collaboration among the top global experts and national program managers who accepted to share data to inform the guidelines."

Funding for the meetings and reviews involved in the updating of the guidelines came entirely from the US Agency for International Development (USAID). Four authors had performed work for Otsuka Pharmaceutical Co Ltd. and abstained from discussions relating to the recommendations on drug regimens.

Eur Respir J. Published online August 4, 2011.