BACKGROUND: The main advantage of GeneXpert MTB/RIF® (Xpert) molecular diagnostic technology is the rapid detection of M.tuberculosis DNA and mutations associated with rifampicin (RIF) resistance for timely initiation of appropriate treatment and, consequently, preventing further transmission of the disease. We assessed time to treatment initiation and treatment outcomes of RIF-resistant and RIF-susceptible TB patients diagnosed and treated in Vladimir TB Dispensary, Russia in 2012, before and after implementation of GeneXpert MTB/RIF® diagnostic technology. METHODS: All adult patients suspected of having TB during February-December 2012 underwent a clinical examination, chest x-ray, microscopy, culture, and phenotypic drug susceptibility testing (DST). Starting August 2012 Xpert diagnostic technology became available in the facility. We used logistic regression to compare treatment outcomes in pre-Xpert and post-Xpert periods. Kaplan-Meier curves and log-rank test were used to compare the time to treatment initiation between the groups. RESULTS: Of 402 patients screened for TB during February-December 2012, 338 were diagnosed with TB (280 RIF-susceptible, 58 RIF-resistant). RIF-resistant patients in the post-Xpert group started treatment with second-line drugs (SLD) earlier than those in pre-Xpert group (median 11 vs. 37 days, Log-rank p = 0.02). The hazard ratio for time to SLD treatment initiation was significantly higher in post-Xpert group (HR:2.06; 95%CI:1.09,3.89) compared to pre-Xpert group. Among the 53/58 RIF-resistant TB patients with available treatment outcome, 28 (53%) had successful outcomes (cured/completed treatment) including 15/26 (58%) in post-Xpert group versus 13/27 (48%) in pre-Xpert group. The observed difference, however, was not statistically significant (OR:0.69; 95%CI:0.23,2.06). Among RIF-susceptible TB cases time to treatment initiation was not significantly different between the groups (2 vs. 3 days, Log-rank p = 0.73). Of 252/280 RIF-susceptible TB cases with treatment outcome, 199 (79%) cases had successful outcome including 94/114 (82%) in post-Xpert group versus 105/138 (76%) in pre-Xpert group (OR:0.68; 95%CI:0.36,1.26). CONCLUSION: We observed that availability of Xpert for initial diagnosis significantly reduced the time to SLD treatment for RIF-resistant patients in the Vladimir TB Dispensary. Although implementation of rapid diagnostics did not improve treatment outcomes, early diagnosis of MDR-TB is important for selection of appropriate treatment regimen and prevention of transmission of drug-resistant strains of TB.

We studied the epidemiology of drug-resistant tuberculosis (TB) in Vladimir Region, Russia, in 2012. Most cases of multidrug-resistant TB (MDR TB) were caused by transmission of drug-resistant strains, and >33% were in patients referred for testing after mass radiographic screening. Early diagnosis of drug resistance is essential for preventing transmission of MDR TB.

SETTING: Drug resistance is an increasing threat to tuberculosis (TB) control worldwide. The World Health Organization advises monitoring for drug resistance, with either ongoing surveillance or periodic surveys. METHODS: The antituberculosis drug resistance survey was conducted in Lesotho in 2008-2009. Basic demographic and TB history information was collected from individuals with positive sputum smear results at 17 diagnostic facilities. Additional sputum sample was sent to the national TB reference laboratory for culture and drug susceptibility testing. RESULTS: Among 3441 eligible smear-positive persons, 1121 (32.6%) were not requested to submit sputum for culture. Among 2320 persons submitted sputum, 1164 (50.2%) were not asked for clinical information or did not have valid sputum samples for testing. In addition, 445/2320 (19.2%) were excluded from analysis because of other laboratory or data management reasons. Among 984/3441 (28.6%) persons who had data available for analysis, MDR-TB was present in 24/773 (3.1%) of new and 25/195 (12.8%) of retreatment TB cases. Logistical, operational and data management challenges affected survey results. CONCLUSION: MDR-TB is prevalent in Lesotho, but limitations reduced the reliability of our findings. Multiple lessons learned during this survey can be applied to improve the next drug resistance survey in Lesotho and other resource constrained countries may learn how to avoid these bottlenecks.

BACKGROUND: Resistance to second-line anti-tuberculosis drugs (SLD) severely compromises treatment options of drug-resistant tuberculosis (TB). We assessed the association between acquisition of resistance (AR) to second-line injectable drugs (SLI) or fluoroquinolones (FQ) and mortality among TB cases confirmed by positive culture results with available initial and final drug susceptibility test (DST) results. METHODS: We analyzed data from U.S. National TB Surveillance System, 1993-2008. Acquired resistance was defined as drug susceptibility at initial DST but resistance to the same drug at final DST. We compared survival with Kaplan-Meier curves and analyzed the association between AR and mortality using a univariate extended Cox proportional hazards model adjusted for age. RESULTS: Of 2,329 cases with both initial and final DST to SLI, 49 (2.1%) acquired resistance; 13/49 (26.5%) had treatment terminated by death versus 222 (10.0%) of those without AR to SLI (P<0.001). Of 1,187 cases with both initial and final DST to FQ, 32 (2.8%) acquired resistance; 12/32 (37.5%) had treatment terminated by death versus 121 (10.9%) of those without AR to FQ (P=0.001). Controlling for age, mortality was significantly greater among cases with AR to SLD than among cases without AR (adjusted hazard ratio (aHR)[SLI], 2.8; 95% confidence interval (CI),1.4-5.4; aHR[FQ], 1.9; 95% CI,1.0-3.5). MDR TB at treatment initiation, positive HIV status, and extrapulmonary disease were also significantly associated with mortality. CONCLUSION: Mortality was significantly greater among TB cases with AR to SLD. Providers should consider AR to SLD early in treatment, monitor DST results, and avoid premature deaths.

BACKGROUND: Standardised tuberculosis (TB) treatment through directly observed therapy (DOT) is available in South Africa, but the level of adherence to standardised TB treatment and its impact on treatment outcomes is unknown. OBJECTIVES: To describe adherence to standardised TB treatment and provision of DOT, and analyse its impact on treatment outcome. METHODS: We utilised data collected for an evaluation of the South African national TB surveillance system. A treatment regimen was considered appropriate if based on national treatment guidelines. Multivariate log-binomial regression was used to evaluate the association between treatment regimens, including DOT provision, and treatment outcome. RESULTS: Of 1 339 TB cases in the parent evaluation, 598 (44.7%) were excluded from analysis owing to missing outcome or treatment information. The majority (697, 94.1%) of the remaining 741 patients received an appropriate TB regimen. Almost all patients (717, 96.8%) received DOT, 443 (59.8%) throughout the treatment course and 274 (37.0%) during the intensive (256, 34.6%) or continuation (18, 2.4%) phase. Independent predictors of poor outcome were partial DOT (adjusted risk ratio (aRR) 3.1, 95% confidence interval (CI) 2.2 - 4.3) and previous treatment default (aRR 2.3, 95% CI 1.1 - 4.8). CONCLUSION: Patients who received incomplete DOT or had a history of defaulting from TB treatment had an increased risk of poor outcomes.

The purpose of this study was to assess the performance of Cepheid(R) Xpert MTB/RIF(R) ("Xpert") and TB-Biochip(R) MDR ("TB-Biochip"). Sputum specimens from adults with presumptive tuberculosis (TB) were homogenized and split for: (1) direct Xpert and microscopy, and (2) concentration for Xpert, microscopy, culture [Lowenstein-Jensen (LJ) solid media and Mycobacteria Growth Indicator Tube(R) (MGIT)], indirect drug susceptibility testing (DST) using the absolute concentration method and MGIT, and TB-Biochip. In total, 109 of 238 (45.8 %) specimens were culture-positive for Mycobacterium tuberculosis complex (MTBC), and, of these, 67 isolates were rifampicin resistant (RIF-R) by phenotypic DST and 64/67 (95.5 %) were isoniazid resistant (INH-R). Compared to culture of the same specimen, a single direct Xpert was more sensitive for detecting MTBC [95.3 %, 95 % confidence interval (CI), 90.0-98.3 %] than direct (59.6 %, 95 % CI, 50.2-68.5 %) or concentrated smear (85.3 %, 95 % CI, 77.7-91.1 %) or LJ culture (80.8 %, 95 % CI, 72.4-87.5 %); the specificity was 86.0 % (95 % CI, 78.9-91.3 %). Compared with MGIT DST, Xpert correctly identified 98.2 % (95 % CI, 91.5-99.9 %) of RIF-R and 95.5 % (95 % CI, 85.8-99.2 %) of RIF-susceptible (RIF-S) specimens. In a subset of 104 specimens, the sensitivity of TB-Biochip for MTBC detection compared to culture was 97.3 % (95 % CI, 91.0-99.5 %); the specificity was 78.1 % (95 % CI, 61.5-89.9 %). TB-Biochip correctly identified 100 % (95 % CI, 94.2-100 %) of RIF-R, 94.7 % (95 % CI, 76.7-99.7 %) of RIF-S, 98.2 % (95 % CI, 91.4-99.9 %) of INH-R, and 78.6 % (95 % CI, 52.1-94.2 %) of INH-S specimens compared to MGIT DST. Xpert and Biochip were similar in accuracy for detecting MTBC and RIF resistance compared to conventional culture methods.

BACKGROUND: Acquired resistance to second-line drugs (SLD) is a problem in treating patients with drug-resistant tuberculosis (TB) worldwide. The objectives of this study were to identify risk factors for acquired resistance (AR) to injectable SLD and fluoroquinolones in the US National TB Surveillance System, 1993-2008. METHODS: We selected cases with initial and final drug susceptibility test (DST) results reported. We defined AR as resistance at the final DST but susceptibility to the same drug at the initial DST. We analyzed AR using 2-way frequency tables and multivariable logistic regression. RESULTS: Baseline prevalence of multidrug-resistant (MDR) and extensively drug-resistant (XDR)TB was 12.6% (1864/14,770) and 0.38% (56/14,770), respectively. Of 2,274 individuals without initial resistance to injectable SLD, 49 (2.2%) acquired resistance. Of 1,141 initially susceptible to fluoroquinolones, 32 (2.8%) acquired resistance. AR to injectable SLD was associated with age group 25-44 years (adjusted Odds Ratio [aOR], 2.7; 95% confidence interval [CI], 1.2-6.3), positive HIV status (aOR, 2.5; 95% CI, 1.3-4.7), MDR at treatment initiation (aOR, 5.5; 95% CI, 2.9-10.5), and treatment with any SLD (aOR, 2.4; 95% CI,1.2-4.7). AR to fluoroquinolones was associated with MDR TB at treatment initiation (aOR, 6.5; 95% CI, 2.9-14.6). CONCLUSION: Among patients with initial and final DST reported, risk factors for AR to injectable SLD included age, positive HIV status, MDR TB and initial treatment with any SLD, while the only predictor for AR to fluoroquinolones was MDR TB at treatment initiation. Providers should consider monitoring SLD DST for MDR TB patients in the indicated subgroups.