Although Pakistan has a high burden of multidrug-resistant tuberculosis (MDR-TB), little is known about prevalence, management, and risk factors for adverse drug reactions (ADRs) in MDR-TB patients in Pakistan. To evaluate occurrence, management, and risk factors for ADRs in MDR-TB patients, and its impact on treatment outcomes, this observational cohort study was conducted at programmatic management unit for drug resistant TB of Lady Reading Hospital Peshawar, Pakistan. A total of 181 MDR-TB patients enrolled at the study site from January 1, 2012 to February 28, 2013 were included. Patients with drug resistant TB other than MDR-TB, transferred out patients and those who were still on treatment at the end of study duration (January 31, 2015) were excluded. Patients were followed until treatment outcomes were reported. ADRs were determined by laboratory data and/or clinical criteria. SPSS 16 was used for data analysis. A total of 131 patients (72.4%) experienced at least 1 ADR. Gastrointestinal disturbance was the most commonly observed adverse event (42%), followed by psychiatric disturbance (29.3%), arthralgia (24.3%), and ototoxicity (21%). Potentially life-threatening ADRs, such as nephrotoxicity (2.7%) and hypokalemia (2.8%) were relatively less prevalent. Owing to ADRs, treatment regimen was modified in 20 (11%) patients. On multivariate analysis, the only risk factor for ADRs was baseline body weight ≥ 40 kg (OR = 2.321, P-value = 0.013). ADRs neither led to permanent discontinuation of treatment nor adversely affected treatment outcomes. Adverse effects were prevalent in current cohort, but caused minimal modification of treatment regimen, and did not negatively impact treatment outcomes. Patient with baseline body weight ≥ 40 kg should be closely monitored.
Although Pakistan has a high burden of multidrug-resistant tuberculosis (MDR-TB), little is known about the management and treatment outcomes of MDR-TB patients in Pakistan.
At present, within the management of multidrug resistant tuberculosis (MDR-TB) much attention is being paid to the traditional microbiological and clinical indicators. Evaluation of the impact of MDR-TB treatment on patients' Health Related Quality of Life (HRQoL) has remained a neglected area.
To evaluate the predictive value of time to sputum culture conversion (SCC) in predicting cure and factors associated with time to SCC and cure in multidrug-resistant tuberculosis (MDR-TB) patients, a retrospective study was conducted at programmatic management unit of drug resistant tuberculosis (TB), Peshawar. A total of 428 pulmonary MDR-TB patients enrolled at the study site from January 1, 2012 to August 31, 2014 were followed until treatment outcome was recorded. Survival analysis using Cox proportional hazards model and multivariate binary logistic regression were, respectively, used to identify factors associated with time to SCC and cure. A P value < 0.05 was considered statistically significant. Overall, 90.9% patients achieved SCC, and 76.9% were cured. Previous use of second-line drugs (SLDs) (hazard ratio [HR] = 0.637; 95% confidence interval [CI] = 0.429-0.947), ofloxacin resistance (HR = 0.656; 95% CI = 0.522-0.825) and lung cavitation (HR = 0.744; 95% CI = 0.595-0.931) were significantly associated with time to SCC. In predicting cure, sensitivities of SCC at 2, 4, and 6 months were 64.1% (95% CI = 58.69-69.32), 93.0% (95% CI = 89.69-95.52), and 97.6% (95% CI = 95.27-98.94), respectively, whereas specificities were 67.7% (95% CI = 57.53-76.73), 51.5% (95% CI = 41.25-61.68), and 44.4% (95% CI = 34.45-54.78), respectively. Furthermore, patients' age of 41-60 (odds ratio [OR] = 0.202; 95% CI = 0.067-0.605) and > 60 years (OR = 0.051; 95% CI = 0.011-0.224), body weight > 40 kg (OR = 2.950; 95% CI = 1.462-5.952), previous SLD use (OR = 0.277; 95% CI = 0.097-0.789), lung cavitation (OR = 0.196; 95% CI = 0.103-0.371) and ofloxacin resistance (OR = 0.386; 95% CI = 0.198-0.749) were significantly associated with cure. Association of SCC with cure was substantially stronger at 6 months (OR = 32.10; 95% CI = 14.34-71.85) than at 4 months (OR = 14.13; 95% CI = 7.92-25.21). However in predicting treatment outcomes, the combined sensitivity and specificity of SCC at 4 months was comparable to SCC at 6 months. Patients with risk factors for delayed SCC were also at high risk of unsuccessful outcomes.
Various studies have reported culture conversion at two months as a predictor of successful treatment outcome in multidrug-resistant tuberculosis (MDR-TB).