Multidrug-Resistant Tuberculosis Treatment Outcomes in Karakalpakstan, Uzbekistan: Treatment Complexity and XDR-TB among Treatment Failures

BACKGROUND: A pilot programme to treat multidrug-resistant TB (MDR-TB) was implemented in Karakalpakstan, Uzbekistan in 2003. This region has particularly high levels of MDR-TB, with 13% and 40% among new and previously treated cases, respectively. METHODOLOGY: This study describes the treatment process and outcomes for the first cohort of patients enrolled in the programme, between October 2003 and January 2005. Confirmed MDR-TB cases were treated with an individualised, second-line drug regimen based on drug susceptibility test results, while suspected MDR-TB cases were treated with a standardised regimen pending susceptibility results. PRINCIPAL FINDINGS: Of 108 MDR-TB patients, 87 were started on treatment during the study period. Of these, 33 (38%) were infected with strains resistant to at least one second-line drug at baseline, but none had initial ofloxacin resistance. Treatment was successful for 54 (62%) patients, with 13 (15%) dying during treatment, 12 (14%) defaulting and 8 (8%) failing treatment. Poor clinical condition and baseline second-line resistance contributed to treatment failure or death. Treatment regimens were changed in 71 (82%) patients due to severe adverse events or drug resistance. Adverse events were most commonly attributed to cycloserine, ethionamide and p-aminosalicylic acid. Extensively drug resistant TB (XDR-TB) was found among 4 of the 6 patients who failed treatment and were still alive in November 2006. CONCLUSIONS: While acceptable treatment success was achieved, the complexity of treatment and the development of XDR-TB among treatment failures are important issues to be addressed when considering scaling up MDR-TB treatment

Drug resistance among 87 MDR-TB patients started on treatment.

<p>Drug resistance among 87 MDR-TB patients started on treatment.</p

Univariate analysis of factors potentially contributing to the outcomes of death and failure (combined) and default.

*<p><i>p</i><0.05. P values compare treatment success to death or failure, and to default, respectively.</p

Reasons for permanently stopping individual drugs during MDR-TB treatment

<p>Abbreviations: E = ethambutol, Z = pyrazinamide, S = streptomycin, Km = kanamycin, Cm = capreomycin, Ofx = ofloxacin, Eto = ethionamide, Cs = cycloserine, PAS = <i>p</i>-aminosalicylic acid, Amx/Clv = amoxicillin/clavulanate, Clz = clofazamine</p

Patient recruitment and outcomes from MDR-TB treatment October 2003 to January 2005.

<p>Patient recruitment and outcomes from MDR-TB treatment October 2003 to January 2005.</p

Description of 87 MDR-TB patients started on treatment

*<p>Defined as one or more of the following: inability to walk unaided, high resting respiratory rate (above 30/min) or BMI <16.0.</p