Impact of GeneXpert MTB/RIF® on treatment initiation and outcomes of RIF-resistant and RIF-susceptible TB patients in Vladimir TB dispensary, Russia

Abstract

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.

Xpert MTB/RIF Use Is Associated With Earlier Treatment Initiation and Culture Conversion Among Patients With Sputum Smear-Negative Multidrug-Resistant Tuberculosis

“…The majority of patients from these meta-analyses and included studies had drug-susceptible TB, and there is much more limited data on the impact of the Xpert assay among patients with drug-resistant TB—a population that stands to benefit more from rapid diagnosis. Similar to our results, studies in Russia and South Africa found nonsignificant trends towards improved treatment outcomes with the use of Xpert assay [ 17 , 25 ]. In contrast, a large study of 952 MDR-TB patients in Kazakhstan found that the use of the Xpert versus culture-based methods was associated with a much higher rate of favorable outcomes (74 vs 49%, P < .0001) [ 26 ].…”

“…Our finding of a substantially decreased time to second-line treatment of 13 versus 56 days with the use of the Xpert highlights the large therapeutic impact of rapid molecular tests on initiation of appropriate treatment, particularly for RR-TB, and is line with other studies. Studies from additional high-burden MDR-TB countries in the region, including Latvia and Russia, have also demonstrated a similar reduction in time to second-line treatment initiation of approximately 1 month among MDR-TB patients with the use of the Xpert compared with culture and phenotypic DST [ 16 , 17 ]. Studies in South Africa also found a decreased time to MDR-TB treatment initiation with use of Xpert, including a reduction of 25 days with Xpert use compared with an algorithm utilizing the MTBDR plus line probe assay in an urban setting [ 18 ].…”

The Role of GeneXpert MTB/RIF in Reducing Treatment Delay Among Multidrug Resistance Tuberculosis Patients: A Propensity Score Matched Analysis

“…This finding was supported by previous studies conducted in Ethiopia, South Africa, and Russia. 3 , 6 , 7 , 20 …”

“…Another study from Russia showed that the availability of the GeneXpert test for the initial diagnosis of drug-resistant tuberculosis had significantly reduced the time to initiation of second-line drugs. 6 In addition, the GeneXpert test showed greater sensitivity compared to sputum smear microscopy and it has also a shorter laboratory processing time than other tests. 7 , 8 The expansion of ambulatory MDR-TB treatment centers, conditional amendment of treatment guidelines, and introduction of short regimen are some of the interventions used to reduce treatment delay and related problems.…”

FAST tuberculosis transmission control strategy speeds the start of tuberculosis treatment at a general hospital in Lima, Peru

“…Xpert testing was also likely a prime factor in decreasing the overall time to TB treatment initiation, as has been demonstrated in other settings. 35 The use of Xpert testing as part of the FAST strategy additionally led to the identification of 18 patients (24%) with RR/MDR-TB in the prospective cohort relative to only 4 (5.3%) with MDR-TB in the historical cohort. There was no reported secular increase in the prevalence of MDR-TB between these contiguous study periods.…”