Comparing the Diagnostic Performance of QuantiFERON-TB Gold Plus to Other Tests of Latent Tuberculosis Infection: A Systematic Review and Meta-analysis.

BACKGROUND: We conducted a review to compare the sensitivity, specificity, reproducibility, and predictive ability of QuantiFERON-TB Gold Plus (QFT-Plus) with that of QuantiFERON-TB Gold In-Tube (QFT-GIT; QIAGEN, Hilden, Germany) and other latent tuberculosis infection (LTBI) tests. METHODS: We searched MEDLINE, Embase, Web of Science, and the Cochrane Database of Systematic Reviews from January 2013 through May 2020. We included studies comparing QFT-Plus with at least one other LTBI test. We estimated sensitivity from studies of patients with active tuberculosis, and specificity from studies of healthy individuals with low risk of LTBI. Three independent reviewers evaluated eligibility, extracted data, and assessed risk of bias. RESULTS: Compared with QFT-GIT, the sensitivity of QFT-Plus in patients with active TB was 1.3% higher (95% confidence interval [CI], -0.3% to 2.9%); in 2 studies of patients with very low probability of LTBI, the specificity was 0.9% lower (95% CI, -2.4% to 0.6%). These differences were not statistically significant. The agreement between QFT-Plus and QFT-GIT was high, with a pooled Cohen's kappa statistic of 0.83 (95% CI, 0.79 to 0.88). The reproducibility of QFT-GIT and QFT-Plus was similarly poor. All participants in the studies to estimate sensitivity were aged ≥15 years, and only 6 were people living with human immunodeficiency virus. We found no studies to assess predictive ability. CONCLUSIONS: QFT-Plus has diagnostic performance that is very similar to that of QFT-GIT. Further studies are needed to assess the sensitivity of QFT-Plus in immunocompromised patients and younger children before concluding if this new version offers advantages.

Treatment correlates of successful outcomes in pulmonary multidrug-resistant tuberculosis: an individual patient data meta-analysis.

BACKGROUND: Treatment outcomes for multidrug-resistant tuberculosis remain poor. We aimed to estimate the association of treatment success and death with the use of individual drugs, and the optimal number and duration of treatment with those drugs in patients with multidrug-resistant tuberculosis. METHODS: In this individual patient data meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library to identify potentially eligible observational and experimental studies published between Jan 1, 2009, and April 30, 2016. We also searched reference lists from all systematic reviews of treatment of multidrug-resistant tuberculosis published since 2009. To be eligible, studies had to report original results, with end of treatment outcomes (treatment completion [success], failure, or relapse) in cohorts of at least 25 adults (aged >18 years). We used anonymised individual patient data from eligible studies, provided by study investigators, regarding clinical characteristics, treatment, and outcomes. Using propensity score-matched generalised mixed effects logistic, or linear regression, we calculated adjusted odds ratios and adjusted risk differences for success or death during treatment, for specific drugs currently used to treat multidrug-resistant tuberculosis, as well as the number of drugs used and treatment duration. FINDINGS: Of 12 030 patients from 25 countries in 50 studies, 7346 (61%) had treatment success, 1017 (8%) had failure or relapse, and 1729 (14%) died. Compared with failure or relapse, treatment success was positively associated with the use of linezolid (adjusted risk difference 0·15, 95% CI 0·11 to 0·18), levofloxacin (0·15, 0·13 to 0·18), carbapenems (0·14, 0·06 to 0·21), moxifloxacin (0·11, 0·08 to 0·14), bedaquiline (0·10, 0·05 to 0·14), and clofazimine (0·06, 0·01 to 0·10). There was a significant association between reduced mortality and use of linezolid (-0·20, -0·23 to -0·16), levofloxacin (-0·06, -0·09 to -0·04), moxifloxacin (-0·07, -0·10 to -0·04), or bedaquiline (-0·14, -0·19 to -0·10). Compared with regimens without any injectable drug, amikacin provided modest benefits, but kanamycin and capreomycin were associated with worse outcomes. The remaining drugs were associated with slight or no improvements in outcomes. Treatment outcomes were significantly worse for most drugs if they were used despite in-vitro resistance. The optimal number of effective drugs seemed to be five in the initial phase, and four in the continuation phase. In these adjusted analyses, heterogeneity, based on a simulated I2 method, was high for approximately half the estimates for specific drugs, although relatively low for number of drugs and durations analyses. INTERPRETATION: Although inferences are limited by the observational nature of these data, treatment outcomes were significantly better with use of linezolid, later generation fluoroquinolones, bedaquiline, clofazimine, and carbapenems for treatment of multidrug-resistant tuberculosis. These findings emphasise the need for trials to ascertain the optimal combination and duration of these drugs for treatment of this condition. FUNDING: American Thoracic Society, Canadian Institutes of Health Research, US Centers for Disease Control and Prevention, European Respiratory Society, Infectious Diseases Society of America.

Treatment outcomes of patients with multidrug-resistant and extensively drug-resistant tuberculosis according to drug susceptibility testing to first- and second-line drugs: an individual patient data meta-analysis.

BACKGROUND: Individualized treatment for multidrug-resistant (MDR) tuberculosis and extensively drug-resistant (XDR) tuberculosis depends upon reliable and valid drug susceptibility testing (DST) for pyrazinamide, ethambutol, and second-line tuberculosis drugs. However, the reliability of these tests is uncertain, due to unresolved methodological issues. We estimated the association of DST results for pyrazinamide, ethambutol, and second-line drugs with treatment outcomes in patients with MDR tuberculosis and XDR tuberculosis. METHODS: We conducted an analysis of individual patient data assembled from 31 previously published cohort studies of patients with MDR and XDR tuberculosis. We used data on patients' clinical characteristics including DST results, treatment received, outcomes, and laboratory methods in each center. RESULTS: DST methods and treatment regimens used in different centers varied considerably. Among 8955 analyzed patients, in vitro susceptibility to individual drugs was consistently and significantly associated with higher odds of treatment success (compared with resistance to the drug), if that drug was used in the treatment regimen. Various adjusted and sensitivity analyses suggest that this was not explained by confounding. The adjusted odds of treatment success for ethambutol, pyrazinamide, and the group 4 drugs ranged from 1.7 to 2.3, whereas for second-line injectables and fluoroquinolones, odds ranged from 2.4 to 4.6. CONCLUSIONS: DST for ethambutol, pyrazinamide, and second-line tuberculosis drugs appears to provide clinically useful information to guide selection of treatment regimens for MDR and XDR tuberculosis.