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

Rapid Molecular Detection of Rifampicin Resistance Facilitates Early Diagnosis and Treatment of Multi-Drug Resistant Tuberculosis: Case Control Study

Multi-drug resistant tuberculosis (MDR-TB) is a major public health concern since diagnosis is often delayed, increasing the risk of spread to the community and health care workers. Treatment is prolonged, and the total cost of treating a single case is high. Diagnosis has traditionally relied upon clinical suspicion, based on risk factors and culture with sensitivity testing, a process that can take weeks or months. Rapid diagnostic molecular techniques have the potential to shorten the time to commencing appropriate therapy, but have not been put to the test under field conditions.This retrospective case-control study aimed to identify risk factors for MDR-TB, and analyse the impact of testing for rifampicin resistance using RNA polymerase B (rpoB) mutations as a surrogate for MDR-TB. Forty two MDR-TB cases and 84 fully sensitive TB controls were matched by date of diagnosis; and factors including demographics, clinical presentation, microbiology findings, management and outcome were analysed using their medical records. Conventionally recognised risk factors for MDR-TB were absent in almost half (43%) of the cases, and 15% of cases were asymptomatic. A significant number of MDR-TB cases were identified in new entrants to the country. Using rpoB mutation testing, the time to diagnosis of MDR-TB was dramatically shortened by a median of 6 weeks, allowing patients to be commenced on appropriate therapy a median of 51days earlier than those diagnosed by conventional culture and sensitivity testing.MDR-TB is frequently an unexpected finding, may be asymptomatic, and is particularly prevalent among TB infected new entrants to the country. Molecular resistance testing of all acid fast bacilli positive specimens has the potential to rapidly identify MDR-TB patients and commence them on appropriate therapy significantly earlier than by conventional methods

Comparison of MDR-TB cases diagnosed by <i>rpoB</i> mutation versus culture alone.

<p>IQR = interquartile range.</p><p>AE = adverse event.</p

Comparison of methods of diagnosis in MDR-TB cases and controls.

*<p>Median (inter-quartile range (IQR)).</p><p>AFB = acid fast bacilli, GW = gastric washing, BAL = bronchoalveolar lavage.</p><p>FNA = fine needle aspiration of a lymph node/TB mass.</p><p>NA = Not applicable.</p

Comparison of outcomes for MDR-TB cases and controls.

*<p>Median (interquartile (IQR) range).</p><p>C of O = country of origin.</p><p>NA = not applicable.</p

Comparison of risk factors amongst MDR-TB cases and controls.

*<p>Odds ratio given for a 10 year increase in age.</p><p>NA = Not applicable.</p><p>NS = Not significant.</p><p>SEA = Southeast Asia.</p><p>ISC = Indian subcontinent (India, Pakistan and Sri Lanka).</p

Flow chart illustrating the 22 year case-control patients selected for the study.

<p>Flow chart illustrating the 22 year case-control patients selected for the study.</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

Clinical characteristics and treatment received of patients included in the analysis.

<p>Percentages are of all 9,153 patients. Extensive disease defined as AFB-smear positive, or cavities on chest x-ray if no information about AFB-smear. Prior TB therapy: defined as treatment with any, or second-line TB drugs for 1 mo or more. Later generation quinolones included levofloxacin, moxifloxacin, gatifloxacin, and sparfloxacin. Cycloserine included terizidone—a dimer of D-cycloserine given in some centers. Drugs analysed as group 5 included: amoxicillin-clavulanate, macrolides (azithromycin, roxithromycin, clarithromycin), clofazimine, thiacetazone, imipenem, linezolid, high dose INH, and thioridazine. Relapse ascertained in only 2,261 patients (14 cohorts).</p><p>SD, standard deviation.</p