Multidrug-resistant tuberculosis treatment failure detection depends on monitoring interval and microbiological method.

Debate persists about monitoring method (culture or smear) and interval (monthly or less frequently) during treatment for multidrug-resistant tuberculosis (MDR-TB). We analysed existing data and estimated the effect of monitoring strategies on timing of failure detection.We identified studies reporting microbiological response to MDR-TB treatment and solicited individual patient data from authors. Frailty survival models were used to estimate pooled relative risk of failure detection in the last 12 months of treatment; hazard of failure using monthly culture was the reference.Data were obtained for 5410 patients across 12 observational studies. During the last 12 months of treatment, failure detection occurred in a median of 3 months by monthly culture; failure detection was delayed by 2, 7, and 9 months relying on bimonthly culture, monthly smear and bimonthly smear, respectively. Risk (95% CI) of failure detection delay resulting from monthly smear relative to culture is 0.38 (0.34-0.42) for all patients and 0.33 (0.25-0.42) for HIV-co-infected patients.Failure detection is delayed by reducing the sensitivity and frequency of the monitoring method. Monthly monitoring of sputum cultures from patients receiving MDR-TB treatment is recommended. Expanded laboratory capacity is needed for high-quality culture, and for smear microscopy and rapid molecular tests.

Predictors of poor outcomes among patients treated for multidrug-resistant tuberculosis at DOTS-plus projects.

The Objective of this analysis was to identify predictors of death, failure, and default among MDR-TB patients treated with second-line drugs in DOTS-plus projects in Estonia, Latvia, Philippines, Russia, and Peru, 2000-2004. Risk ratios (RR) with 95% confidence intervals (CI) were calculated using multivariable regression. Of 1768 patients, treatment outcomes were: cure/completed - 1156 (65%), died - 200 (11%), default - 241 (14%), failure - 118 (7%). Independent predictors of death included: age>45 years (RR = 1.90 (95%CI 1.29-2.80), HIV infection (RR = 4.22 (2.65-6.72)), extrapulmonary disease (RR = 1.54 (1.04-2.26)), BMI<18.5 (RR = 2.71 (1.91-3.85)), previous use of fluoroquinolones (RR = 1.91 (1.31-2.78)), resistance to any thioamide (RR = 1.59 (1.14-2.22)), baseline positive smear (RR = 2.22 (1.60-3.10)), no culture conversion by 3rd month of treatment (RR = 1.69 (1.19-2.41)); failure: cavitary disease (RR = 1.73 (1.07-2.80)), resistance to any fluoroquinolone (RR = 2.73 (1.71-4.37)) and any thioamide (RR = 1.62 (1.12-2.34)), and no culture conversion by 3rd month (RR = 5.84 (3.02-11.27)); default: unemployment (RR = 1.50 (1.12-2.01)), homelessness (RR = 1.52 (1.00-2.31)), imprisonment (RR = 1.86 (1.42-2.45)), alcohol abuse (RR = 1.60 (1.18-2.16)), and baseline positive smear (RR = 1.35 (1.07-1.71)). Patients with biomedical risk factors for treatment failure or death should receive heightened medical attention. To prevent treatment default, management of patients who are unemployed, homeless, alcoholic, or have a prison history requires extra measures to insure treatment completion.