Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients.

Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB

Multidrug-Resistant Tuberculosis Treatment Failure Detection Depends on Monitoring Interval and Microbiological Method Multidrug-resistant tuberculosis treatment failure detection depends on monitoring interval and microbiological method behalf of the Col

Citation Multidrug-resistant tuberculosis treatment failure detection depends on monitoring interval and microbiological method. ABSTRACT 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. @ERSpublications Monthly culture monitoring is crucial to earlier detection of treatment failure in MDR-TB patient

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

Effect of previous treatment on association of number of likely effective drugs with treatment success—during different phases of treatment.

<p>Likely effective, drugs to which isolate susceptible in laboratory testing. <i>n</i>, number of patients in subgroup of interest. aOR, adjustment described in footnotes for <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001300#pmed-1001300-t003" target="_blank">Table 3</a>. Success, defined as cure or treatment completion; see Methods for definitions. Initial intensive phase, period when injectable given. Continuation phase, period when no injectable given. Only 18 studies provided information regarding drug susceptibility testing and the number of drugs in the initial phase, while only 15 of these described the number of drugs in the continuation phase. Bold, estimates are significantly different from the reference group.</p

'Iter Lapponicum'

<p>Crude treatment success versus failure or relapse or death by study with exact 95% CI, as well as number of subjects with success and number of subjects treated. Fixed and der Simonian and Laird random effects pooled estimates are given (purple dots). Two studies that used only first-line TB drugs are indicated by a red square.</p

Study selection.

<p>Study selection.</p

Association of treatment success with duration (adjusted odds and upper bound of CI shown).

<p>(A) Duration of initial intensive phase in all patients (reference group 1.0–2.5 mo). (B) Duration of initial intensive phase—restricted to patients not previously treated with second-line drugs (reference group 1.0–2.5 mo). (C) Total duration of therapy in all patients (reference group is 6.0–12.5 mo). Patients receiving therapy for less than 6 or more than 36 mo excluded from analysis. Note: For duration of 24.6–27.5 mo the upper limit of the CI was 30.2. This is truncated at 21. (D) Total duration of therapy—analysis restricted to patients not previously treated with second-line drugs (reference group is 6.0–12.5 mo. Patients receiving therapy for less than 6 or more than 36 mo excluded from analysis). Note: For duration of 24.6–27.5 mo, the upper limit of the CI was 56.5. This is truncated at 21.</p