Elsevier

The Lancet

Volume 372, Issue 9647, 18–24 October 2008, Pages 1403-1409
The Lancet

Articles
Treatment of extensively drug-resistant tuberculosis in Tomsk, Russia: a retrospective cohort study

https://doi.org/10.1016/S0140-6736(08)61204-0Get rights and content

Summary

Background

Mycobacterium tuberculosis strains that cause untreatable drug-resistant disease are a threat worldwide. We describe the treatment, management, and outcomes of patients with extensively drug-resistant tuberculosis in Tomsk, Russia.

Methods

We undertook a retrospective cohort study of 608 patients with multidrug resistant tuberculosis who had treatment in civilian or prison services, between Sept 10, 2000, and Nov 1, 2004, according to the treatment strategy recommended by WHO. Clinical characteristics, management practices, and treatment outcomes of patients with extensively drug-resistant (XDR) tuberculosis and non-extensively drug-resistant (non-XDR) tuberculosis are described. The main outcome was the frequency of poor and favourable outcomes at the end of treatment.

Findings

Of 608 patients with multidrug resistant tuberculosis, 29 (4·8%) patients had baseline XDR tuberculosis. Treatment failure was more common in patients with XDR tuberculosis than in those with non-XDR tuberculosis (31% vs 8·5%, p=0·0008). 48·3% of patients with XDR tuberculosis and 66·7% of patients with non-XDR tuberculosis had treatment cure or completion (p=0·04). The frequency and management of adverse events did not differ between patients with XDR and non-XDR tuberculosis.

Interpretation

The chronic features of tuberculosis in these patients suggest that extensively drug-resistant tuberculosis may be acquired through previous treatments that include second-line drugs. Aggressive management of this infectious disease is feasible and can prevent high mortality rates and further transmission of drug-resistant strains of Mycobacterium tuberculosis.

Funding

Bill & Melinda Gates Foundation, Eli Lilly Foundation, The Open Society Institute, Frank Hatch Fellowships in Global Health Equity at the Brigham & Women's Hospital, Infectious Disease Society of America, the Heiser Foundation, the United States National Institutes of Health, and the John D and Catherine T MacArthur Foundation.

Introduction

Every year an estimated 490 000 new cases of multidrug resistant (MDR) tuberculosis arise worldwide, with a prevalence that is thought to be three times greater than this number.1, 2 MDR tuberculosis—caused by strains of Mycobacterium tuberculosis that are resistant to isoniazid and rifampin, the backbone of first-line treatment against tuberculosis—is more difficult and costly to treat than non-drug-resistant tuberculosis.3, 4 However, extensively drug-resistant (XDR) tuberculosis is an even greater threat to control of the disease. XDR tuberculosis is a subgroup of MDR tuberculosis, which is also resistant to the most effective second-line drugs against tuberculosis: any second-line aminoglycoside or capreomycin, and any fluoroquinolone.5, 6 Although the worldwide burden of XDR tuberculosis is unknown, 7% of isolates of MDR tuberculosis referred to supranational reference laboratories from 2000 to 2004 were XDR cases.1

Scarce therapeutic options and high mortality rates associated with XDR tuberculosis are a concern. A report of an outbreak of XDR tuberculosis in 53 HIV-positive patients in the province of KwaZulu Natal in the Republic of South Africa, during which 52 patients died after about 16 days from diagnosis of tuberculosis, has been a warning for the global tuberculosis community of the dangers of allowing drug resistance to flourish unchecked.7 Other reports from non-HIV-infected patients have reinforced the alarm.8, 9, 10, 11, 12, 13

Although XDR tuberculosis is referred to by some as being untreatable, aggressive clinical and programmatic management can greatly improve the outcome of the disease, which provides hope to the many infected patients. The aim of this study is to describe the clinical characteristics, management, and outcomes of patients treated for MDR and XDR tuberculosis in Tomsk, Russia.

Section snippets

Study setting

Tomsk Oblast is located in western Siberia, Russia, and has about 1·1 million inhabitants, roughly half of whom live in remote rural villages. Between 1998 and 2002, rates of MDR tuberculosis in Tomsk rose from 6·5% to 13·7% for newly detected cases, and from 26·7% to 43·6% for previously treated cases. During this time, Tomsk had implemented DOTS (directly observed treatment, short-course), the treatment strategy of WHO for non-drug-resistant tuberculosis, consisting of short-course

Results

Of the 636 patients who had treatment against MDR tuberculosis in the study period, 608 had documented baseline MDR tuberculosis and 28 were treated for presumed MDR tuberculosis on the basis of treatment or contact history, or MDR tuberculosis diagnosed before moving to Tomsk. These 28 patients are excluded from the analysis. 29 patients (4·8%) met the definition of XDR tuberculosis before starting treatment for MDR tuberculosis. The proportion of patients with XDR tuberculosis did not vary by

Discussion

We have shown that, although treatment outcomes were worse in patients with XDR tuberculosis than those in patients with MDR tuberculosis who were infected with strains that were susceptible to fluoroquinolones and at least one of the parenteral drugs, 48% of patients with XDR tuberculosis—often termed untreatable in press reports—responded favourably to treatment. Although our results for treatment outcomes were similar to those reported elsewhere,13, 26 one major difference was that the

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