Dataset Information

High mortality among patients hospitalized for drug-resistant tuberculosis with acquired second-line drug resistance and high HIV prevalence.

ABSTRACT:

Objectives

We compared mortality between HIV-positive and HIV-negative South African adults with drug-resistant tuberculosis (DR-TB) and high incidence of acquired second-line drug resistance.

Methods

We performed a retrospective review of DR-TB patients with serial second-line TB drug susceptibility tests (2008-2015) who were hospitalized at a specialized TB hospital. We used Kaplan-Meier analysis and Cox models to examine associations with mortality.

Results

Of 245 patients, the median age was 33 years, 54% were male and 40% were HIV-positive, 96% of whom had ever received antiretroviral therapy (ART). At initial drug resistance detection, 99% of patients had resistance to at least rifampicin and isoniazid, and 18% had second-line drug resistance (fluoroquinolones and/or injectable drugs). At later testing, 88% of patients had acquired additional second-line drug resistance. Patient-initiated treatment interruptions (> 2 months) occurred in 47%. Mortality was 79%. Those with HIV had a shorter time to death (p = 0.02; log-rank): median survival time from DR-TB treatment initiation was 2.44 years [95% confidence interval (CI): 2.09-3.15] versus 3.99 years (95% CI: 3.12-4.75) for HIV-negative patients. HIV-positive patients who received ART within 6 months before DR-TB treatment had a higher mortality hazard than HIV-negative patients [adjusted hazard ratio (aHR) ratio = 1.82, 95% CI: 1.21-2.74]. By contrast, HIV-positive patients who did not receive ART within 6 months before DR-TB treatment did not have a significantly higher mortality hazard than HIV-negative patients (aHR = 1.09; 95% CI: 0.72-1.65), although those on ART had lower median CD4 counts than those not on ART (157 vs. 281 cells/μL, respectively; p = 0.02).

Conclusions

A very high incidence of acquired second-line drug resistance and high overall mortality were observed, reinforcing the need to reduce the risk of acquired resistance and for more effective treatment.

SUBMITTER: Anderson K

PROVIDER: S-EPMC9588462 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

High mortality among patients hospitalized for drug-resistant tuberculosis with acquired second-line drug resistance and high HIV prevalence.

Anderson Kim K Pietersen Elize E Shepherd Bryan E BE Bian Aihua A Dheda Keertan K Warren Robin R Sterling Timothy R TR van der Heijden Yuri F YF

HIV medicine 20220524 10

<h4>Objectives</h4>We compared mortality between HIV-positive and HIV-negative South African adults with drug-resistant tuberculosis (DR-TB) and high incidence of acquired second-line drug resistance.<h4>Methods</h4>We performed a retrospective review of DR-TB patients with serial second-line TB drug susceptibility tests (2008-2015) who were hospitalized at a specialized TB hospital. We used Kaplan-Meier analysis and Cox models to examine associations with mortality.<h4>Results</h4>Of 245 patien ...[more]

PMID: 35608016

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Project description:BackgroundResistance to second-line drugs develops during treatment of multidrug-resistant (MDR) tuberculosis, but the impact on treatment outcome has not been determined.MethodsPatients with MDR tuberculosis starting second-line drug treatment were enrolled in a prospective cohort study. Sputum cultures were analyzed at a central reference laboratory. We compared subjects with successful and poor treatment outcomes in terms of (1) initial and acquired resistance to fluoroquinolones and second-line injectable drugs (SLIs) and (2) treatment regimens.ResultsOf 1244 patients with MDR tuberculosis, 973 (78.2%) had known outcomes and 232 (18.6%) were lost to follow-up. Among those with known outcomes, treatment succeeded in 85.8% with plain MDR tuberculosis, 69.7% with initial resistance to either a fluoroquinolone or an SLI, 37.5% with acquired resistance to a fluoroquinolone or SLI, 29.3% with initial and 13.0% with acquired extensively drug-resistant tuberculosis (P < .001 for trend). In contrast, among those with known outcomes, treatment success increased stepwise from 41.6% to 92.3% as the number of drugs proven effective increased from ≤1 to ≥5 (P < .001 for trend), while acquired drug resistance decreased from 12% to 16% range, depending on the drug, down to 0%-2% (P < .001 for trend). In multivariable analysis, the adjusted odds of treatment success decreased 0.62-fold (95% confidence interval, .56-.69) for each increment in drug resistance and increased 2.1-fold (1.40-3.18) for each additional effective drug, controlling for differences between programs and patients. Specific treatment, patient, and program variables were also associated with treatment outcome.ConclusionsIncreasing drug resistance was associated in a logical stepwise manner with poor treatment outcomes. Acquired resistance was worse than initial resistance to the same drugs. Increasing numbers of effective drugs, specific drugs, and specific program characteristics were associated with better outcomes and less acquired resistance.

Project description:BACKGROUND: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) have emerged in high-HIV-prevalence settings, which generally lack laboratory infrastructure for diagnosing TB drug resistance. Even where available, inherent delays with current drug-susceptibility testing (DST) methods result in clinical deterioration and ongoing transmission of MDR and XDR-TB. Identifying clinical predictors of drug resistance may aid in risk stratification for earlier treatment and infection control. METHODS: We performed a retrospective case-control study of patients with MDR (cases), XDR (cases) and drug-susceptible (controls) TB in a high-HIV-prevalence setting in South Africa to identify clinical and demographic risk factors for drug-resistant TB. Controls were selected in a 1:1:1 ratio and were not matched. We calculated odds ratios (OR) and performed multivariate logistic regression to identify independent predictors. RESULTS: We enrolled 116, 123 and 139 patients with drug-susceptible, MDR, and XDR-TB. More than 85% in all three patient groups were HIV-infected. In multivariate analysis, MDR and XDR-TB were each strongly associated with history of TB treatment failure (adjusted OR 51.7 [CI 6.6-403.7] and 51.5 [CI 6.4-414.0], respectively) and hospitalization more than 14 days (aOR 3.8 [CI 1.1-13.3] and 6.1 [CI 1.8-21.0], respectively). Prior default from TB treatment was not a risk factor for MDR or XDR-TB. HIV was a risk factor for XDR (aOR 8.2, CI 1.3-52.6), but not MDR-TB. Comparing XDR with MDR-TB patients, the only significant risk factor for XDR-TB was HIV infection (aOR 5.3, CI 1.0-27.6). DISCUSSION: In this high-HIV-prevalence and drug-resistant TB setting, a history of prolonged hospitalization and previous TB treatment failure were strong risk factors for both MDR and XDR-TB. Given high mortality observed among patients with HIV and drug-resistant TB co-infection, previously treated and hospitalized patients should be considered for empiric second-line TB therapy while awaiting confirmatory DST results in settings with a high-burden of MDR/XDR-TB.

Project description:IntroductionTo date, acquired resistance to second-line antituberculosis drugs (SLDs) during multi-drug resistant tuberculosis (MDR-TB) treatment is becoming a public health concern. Different studies have assessed the incidence of acquired resistance to SLDs. However, the findings are inconsistent and there is limited global evidence. Thus, we are going to assess the incidence and predictors of acquired resistance to SLDs during MDR-TB treatment.Methods and analysisWe designed this protocol following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Electronic databases and grey literature sources will be searched systematically for articles published up to 25 March 2023. Studies reporting the incidence and predictors of acquired resistance to SLDs in MDR-TB patients will be explored. The studies will be managed using Endnote X8 citation manager and a stepwise approach will be followed to select studies. Data will be summarised using Microsoft Excel 2016 spreadsheet. A Newcastle-Ottawa Scale quality assessment and cochrane risk-of-bias tools will be used to assess the study's quality. The authors will independently search databases, select studies, assess the study's quality and extract data. Data will be analysed using STATA V.17 software. We will estimate the pooled incidence of acquired resistance with 95% CI. In addition, the pooled effect measures (OR, HR, risk ratio) with their 95% CI will be estimated. Heterogeneity will be assessed using the I2 statistics. Publication bias will be assessed using funnel plot and Egger's test. A subgroup analysis will be conducted for the primary outcome (acquired resistance) per each study characteristics such as WHO regional category, country's TB/MDR-TB burden, data collection period and per the specific second-line anti-TB drug.Ethics and disseminationSince this study will be based on data extraction from published studies, ethical approval is not mandatory. The study will be published in peer-reviewed scientific journals and the findings will be presented at different scientific conferences.Prospero registration numberCRD42022371014.

Dataset Information

High mortality among patients hospitalized for drug-resistant tuberculosis with acquired second-line drug resistance and high HIV prevalence.

Objectives

Methods

Results

Conclusions

Publications

High mortality among patients hospitalized for drug-resistant tuberculosis with acquired second-line drug resistance and high HIV prevalence.

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