Extensively drug-resistant tuberculosis worsens treatment outcomes for HIV-negative patients too

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HIV-negative patients with extensively drug-resistant tuberculosis (XDR-TB) were more than four times more likely to fail treatment than HIV-negative patients with non-XDR-TB, according to the findings of a prospective Korean study published in the November 15th issue of Clinical Infectious Diseases. The presence of extensive drug resistance (XDR) was an independent poor prognostic factor in HIV-negative patients with multidrug-resistant TB (MDR-TB).

Nevertheless, treatment was successful in around half of HIV-negative patients.

MDR-TB, characterised by resistance to isoniazid and rifampicin, is an escalating serious public health problem worldwide. It requires longer treatment, more frequent hospitalisation, higher cost of treatment, and results in a higher mortality. The incidence of MDR-TB varies from 3% to 14 % of all new TB cases.

Glossary

extensively drug-resistant TB (XDR-TB)

A form of drug-resistant tuberculosis in which bacteria are resistant to isoniazid and rifampicin, the two most powerful anti-TB drugs, plus any fluoroquinolone and at least one injectable second-line drug. 

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.

treatment failure

Inability of a medical therapy to achieve the desired results. 

isoniazid

An antibiotic that works by stopping the growth of bacteria. It is used with other medications to treat active tuberculosis (TB) infections, and on its own to prevent active TB in people who may be infected with the bacteria without showing any symptoms (latent TB). 

epidemiology

The study of the causes of a disease, its distribution within a population, and measures for control and prevention. Epidemiology focuses on groups rather than individuals.

The public health problem of MDR-TB has been exacerbated by the emergence of MDR-TB isolates which are resistant to isoniazid, rifampicin, any flouroquinolone, and injectable second-line drugs. This is called extensively drug resistant tuberculosis (XDR-TB) and has been reported so far in 37 countries and a recent survey puts the prevalence of XDR-TB up to 10-19 % of all MDR-TB cases in certain countries.

Important insights about the epidemiology of XDR-TB in HIV-positive patients have recently emerged. However, the epidemiology of XDR-TB and treatment outcomes in HIV-negative patients remains unknown. Studies of XDR-TB in HIV-negative patients are urgently needed to guide policy on the management of XDR-TB in such patients.

A team of Korean investigators addressed this issue by investigating the impact of XDR on treatment outcomes in HIV-negative patients with MDR-TB. The study took place between January 1996 and December 2005 at Seoul National University Hospital in Seoul, Republic of Korea.

Individuals had confirmed MDR-TB and were receiving treatment according to the institution treatment guidelines. Laboratory and radiographic results obtained at the time of MDR-TB diagnosis were reviewed and analyzed.

MDR-TB was defined as TB caused by bacilli resistant to isoniazid and rifampicin. XDR-TB was TB caused by bacilli showing resistance to both isoniazid and rifampicin, any fluoroquinolone, and at least one of the three injectable anti-TB drugs, capreomycin, kanamycin, and amikacin.

Treatment was considered successful if the patient completed treatment and was cured. A patient was considered ‘cured’ if treatment was completed and five culture-negative results were observed during the final twelve months of treatment. Treatment was considered ‘completed’ if the patient completed treatment but did not meet the definition of cured or failed treatment because of lack of bacteriological results

Treatment failure occurred if the patient treatment was a ‘failure’ or a ‘relapse’. A relapse was recorded if the cured patient or the patient who had completed treatment resumed treatment over six months after completion of the first treatment due to the emergence of MDR-TB. Failure was defined as two or more out of five cultures being recorded positive in the final twelve months or anyone of the final three cultures being positive.

Statistical models were used to assess the impact of XDR-TB on treatment outcomes. Out of a total of 211 non–HIV–infected patients with MDR-TB included in the final analysis, 43 patients (20.4%) had XDR-TB. The demographic characteristic of XDR-TB and non-XDR-TB patients were similar. However, XDR-TB patients had a greater incidence of bilateral cavities at the time of diagnosis of MDR-TB.

Treatment failure occurred in 19 patients (44.2%) with XDR-TB, and in 27.4% with non–XDR-TB (P = 0.057). XDR-TB increased the risk for treatment failure more than 4-fold (adjusted odds ratio [OR], 4.46; 95% confidence interval [CI], 1.35–14.74). Underlying co-morbidity increased the risk more than 2-fold (adjusted OR, 2.62; 95% CI, 1.00–6.87).

In addition to XDR-TB and co-morbidity, albumin level was another independent risk factor for treatment failure. A higher level of albumin was inversely associated with treatment failure (adjusted OR, 0.87; 95% CI, 0.77–0.97).

The findings of this study provide useful insights about the epidemiology and treatment outcomes of XDR-TB and MDR-TB in HIV-negative patients. Interestingly, treatment was successful in at least 50 % of XDR-TB patients. Similar studies must be conducted under different epidemiological settings in order to obtain a more complete picture of XDR-TB in HIV-negative patients. This will facilitate the development of treatment guidelines in these patients.

References

Hye-Ryoun K et al. Impact of extensive drug resistance on treatment outcomes in non–HIV-infected patients with multidrug-resistant tuberculosis. Clinical Infectious Diseases 45: 1290-1295, 2007.