Determinants of drug-resistant tuberculosis in Hunan province, China: a case-control study.

BACKGROUND: Drug-resistant tuberculosis (DR-TB) is a major public health threat in Hunan Province, with an increasing clinical burden in recent years. This study aimed to identify socio-demographic and clinical factors associated with DR-TB in Hunan province, China. METHODS: A case-control study was conducted in Hunan province. Cases were all DR-TB patients who were confirmed by culture and Drug susceptibility testing (DST) and enrolled at the DR-TB treatment center of Hunan Chest Hospital from 2013 to 2018. Controls were all Drug Susceptible TB (DS-TB) patients confirmed by DST and enrolled at the same hospital during the same period. A multivariable logistic regression model was fitted to identify factors significantly associated with DR-TB. RESULTS: A total of 17,808 patients (15,534 DS-TB controls and 2274 DR-TB cases) were included in the study, with a mean age of 42.5 years (standard deviation (SD) ± 17.5 years) for cases and 46.1 years (SD ± 19.1 years) for controls. Age 15-64 years (Adjusted odds ratio (AOR = 1.5, 95% CI; 1.4, 1.8)), ethnic minorities (AOR = 1.5; 95% CI; 1.4, 1.8), and a history of previous TB treatment (AOR) = 1.84; 95% CI: 1.57, 2.15) was significantly associated with DR-TB. Being resident in a province outside Hunan was also a significant risk factor (AOR = 1.67; 1.27, 2.21) for DR-TB. CONCLUSION AND RECOMMENDATIONS: To prevent the occurrence of DR-TB in Hunan Province, interventions should be targeted at high-risk demographic groups such as ethnic minorities, individuals of productive age, and residents living outside the province. Interventions must also be targeted to previously treated cases, suggesting the appropriateness of diagnosis, treatment, and follow-up. Understanding the risk factors at the province level helps design strategies for controlling DR-TB due to variations by socioeconomic differences, quality of health care, and healthcare access.

Low serum vitamin D in North Indian multi-drug resistant pulmonary tuberculosis patients: the role of diet and sunlight.

Background: Tuberculosis (TB) and malnutrition are major global health problems, with multidrug-resistant (MDR) TB complicating international efforts. The role of vitamin D in susceptibility to and as an adjunctive treatment for TB is being studied extensively, although no study has included MDR-TB patients in context to dietary profile with vitamin D levels and sunlight exposure.Objective: This study aimed to estimate vitamin D serum levels and examine their association with dietary intake of vitamin D and sun exposure in patients with MDR-TB.Methods: North Indian participants were enrolled in three groups: MDR-TB, drug-susceptible pulmonary TB (DS-PTB), and healthy controls. All consenting participants underwent the estimation of macro- and micronutrient intake and sunlight exposure using structured questionnaires. Serum biochemistry, including 25-hydroxyvitamin D and calcium levels, was measured, and the correlation between variables was determined.Results: 747 participants were enrolled. Significant differences among the three groups were found in mean serum 25-hydroxyvitamin D levels, body mass index, macronutrient intake, dietary vitamin D and calcium content, and sun exposure index (SEI). All except sun exposure (SEI was highest in DS-PTB patients) were found to follow the trend: MDR-TB < DS-PTB < healthy controls. The mean serum vitamin D levels of all groups were deficient and correlated positively with dietary intake and SEI.Conclusion: In this study's we found significant association of serum vitamin D concentrations, dietary intake and sunlight exposure in MDR-TB, DS-PTB patients and healthy controls. Dietary intake may be more important than sun exposure in determining serum levels. However, the significance of this finding is uncertain. Further studies are required to confirm the association, direction, and potential for vitamin D supplementation to treat or prevent MDR-TB infection.

Drug-Resistant Tuberculosis and COVID-19: A Scoping Review on a New Threat to Antimicrobial Resistance.

OBJECTIVE: To assess the impact of COVID-19 on the morbidity and mortality associated with drug-resistant tuberculosis (DR-TB). METHODS: A comprehensive review of articles published in international databases since December 2019 was conducted. The findings are presented in a narrative format, supplemented with tables, diagrams, and a map created using ArcGIS software. RESULTS: Thirty-five studies were selected, highlighting the significant consequences of COVID-19 on TB and DR-TB treatment progress. Four main thematic areas were identified: Clinical and epidemiological aspects of the interaction between COVID-19 and DR-TB; Management of physical resources and the team; Challenges and circumstances; Perspectives and possibilities. CONCLUSIONS: This study revealed that the COVID-19 pandemic significantly negatively impacted the control of long-standing diseases like TB, particularly in the context of morbidity and mortality related to DR-TB.

Therapeutic Failure and Acquired Bedaquiline and Delamanid Resistance in Treatment of Drug-Resistant TB.

New classes of antitubercular drugs, diarylquinolines and nitroimidazoles, have been associated with improved outcomes in the treatment of drug-resistant tuberculosis, but that success is threatened by emerging drug resistance. We report a case of bedaquiline and delamanid resistance in a 55-year-old woman in South Africa with extensively drug-resistant tuberculosis and known HIV.

Tuberculosis and malnutrition: The European perspective.

Tuberculosis (TB) is a leading infectious cause of death worldwide, despite ongoing efforts to limit its incidence and mortality. Although the European Region has made gains in TB incidence and mortality, it now contends with increasing numbers of multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB). Malnutrition is a major contributor to the burden of TB and may also be directly caused or enhanced by the onset of TB. The presence of malnutrition may worsen TB and MDR/RR-TB related treatment outcomes and contribute to growing TB drug-resistance. Preventing and treating all forms of malnutrition is an important tool to limit the spread of TB worldwide and improve TB outcomes and treatment efficacy. We carried out a scoping review of the existing evidence that addresses malnutrition in the context of TB. Our review found malnutrition increased the risk of developing TB in high-burden settings and increased the likelihood of developing unfavorable treatment outcomes, including treatment failure, loss to follow-up, and death. The potential impact of nutritional care and improved nutritional status on patient prognosis was more difficult to evaluate due to heterogeneity of patient populations, treatment protocols, and treatment durations and goals. High-quality trials that consider malnutrition as a major risk factor and relevant treatment target when designing effective strategies to limit TB spread and mortality are needed to inform evidence-based practice. In TB patients, we suggest that widespread and regular nutritional screening, assessment, and counselling, has the potential to increase effectiveness of TB management strategies and improve patient quality of life, overall outcomes, and survival.

The socio-demographic, clinical characteristics and outcomes of tuberculosis among HIV infected adults in Lithuania: A thirteen-year analysis.

BACKGROUND: Tuberculosis (TB) is a public health problem in Lithuania, among the 18 high-priority TB countries in the European region, and the most common AIDS-indicative disease with the highest proportion in the EU/EEA since 2015. The study aimed to identify socio-demographic, clinical characteristics and their relationship with TB outcomes in TB-HIV co-infected patients in Lithuania. METHODS: A retrospective chart review analysed the characteristics of TB-HIV co-infected adults registered in State Information System of Tuberculosis over 2008-2020. The factors associated with drug-resistant TB and unsuccessful treatment outcome were identified by multivariable logistic regression. RESULTS: The study included 345 cases in 311 patients (239 new, 106 previously treated cases), median age 40 years (IQR 35-45), 80.7% male. 67.8% patients knew their HIV-positive status before TB diagnosis, median time to TB diagnosis was 8 years (IQR 4-12). 83.6% were unemployed, 50.5%-anytime intravenous drug users (IDU), 34.9% abused alcohol. Drug-resistant TB rates in new and previously treated TB cases were 38.1% and 61.3%, respectively. In multivariable analysis, higher risk of drug-resistant TB was associated with imprisonment in new (aOR 3.35; 95%CI 1.17-9.57) and previously treated (aOR 6.63; 95%CI 1.09-40.35) cases. In 52.3% of new TB cases and in 42.5% previously treated TB cases the treatment outcomes were unsuccessful. In multivariable analysis of new TB cases, current imprisonment (aOR 2.77; 95%CI 1.29-5.91) and drug-resistant TB (aOR 2.18; 95%CI 1.11-4.28) were associated with unsuccessful treatment outcome. In multivariable analysis of previously treated TB cases, female gender (aOR 11.93; 95%CI 1.86-76.69), alcohol abuse (aOR 3.17; 95%CI 1.05-9.58), drug-resistant TB (aOR 4.83; 95%CI 1.53-15.28) were associated with unsuccessful treatment outcome. CONCLUSIONS: In the TB-HIV-infected adult cohort in Lithuania, unemployment, imprisonment, IDU, alcohol abuse, known to be risk factors for TB, were very frequent. Drug resistance was an undeniable risk factor for unsuccessful treatment outcome and imprisonment was associated with drug resistant TB.

The differences in drug resistance between drug-resistant tuberculosis patients with and without diabetes mellitus in northeast China: a retrospective study.

BACKGROUND: Diabetes mellitus (DM) and drug-resistant tuberculosis (DR-TB) are serious global public health problems. This study aimed to explore the differences in drug resistance between DR-TB patients with and without DM. Risk factors for developing multidrug-resistant tuberculosis (MDR-TB) were also investigated among DR-TB patients. METHODS: The patient's basic demographic,　clinical characteristics, and drug susceptibility testing (DST) data were collected from the Chinese Disease Control Information System. Descriptive statistics were used to estimate the frequency and proportion of included variables. Categorical variables were compared using the Chi-square test or Fisher's exact test. Chi-square tests for trends were used to determine changes and trends in MDR-TB and pre-extensively drug-resistantTB (pre-XDR-TB) patterns over time. Univariate and multivariate logistic regression analysis was used to explore the risk factors of MDR-TB. RESULTS: Compared with DR-TB patients with DM, DR-TB patients without DM had significantly higher rates of mono-resistant streptomycin (SM) and any resistance to kanamycin (KM), but significantly lower rates of any resistance to protionamide (PTO) and mono-resistance to levofloxacin (LFX), and pre-XDR-TB (P<0.05). The proportion of resistance to other anti-TB drugs was not statistically different between the DR-TB with and without DM. Among DR-TB patients without and with DM, the proportion of patients with MDR-TB and pre-XDR-TB patterns showed a significant downward trend from 2016 to 2021 (P<0.05). Among DR-TB patients without DM, male, previously treated DR-TB cases, and immigration were risk factors for MDR-TB (P<0.05). In DR-TB patients with DM, a negative sputum smear is a risk factor for MDR-TB (P<0.05). CONCLUSION: There was no statistical difference in resistance patterns between DR-TB with and without DM, except in arbitrary resistance to PTO and KM, mono-resistant SM and LFX, and pre-XDR-TB. Great progress has been made in the prevention and control of MDR-TB and pre-XDR-TB. However, DR-TB patients with and without DM differ in their risk factors for developing MDR-TB.

Decentralized, Integrated Treatment of RR/MDR-TB and HIV Using a Bedaquiline-Based, Short-Course Regimen Is Effective and Associated With Improved HIV Disease Control.

BACKGROUND: In decentralized sites, with fewer resources and a high prevalence of advanced HIV, the effectiveness of the new short-course, bedaquiline-based regimen for rifampicin-resistant and multidrug-resistant tuberculosis (RR/MDR-TB) is not well-described. SETTING: Adults with pulmonary RR/MDR-TB initiating the short-course regimen in KwaZulu-Natal, South Africa were prospectively enrolled at a decentralized program that integrated person-centered TB care. METHODS: In addition to standard of care monitoring, study visits occurred at enrollment and months 1, 2, 4, 6, and 9. Favorable RR/MDR-TB outcome was defined as cure or treatment completion without loss to follow-up, death, or failure by treatment. In patients with HIV, we assessed antiretroviral therapy (ART) uptake, virologic and immunologic outcomes. RESULTS: Among 57 patients, HIV was present in 73.7% (95% CI: 60.3-84.5), with a median CD4 count of 170 cells/mm 3 (intraquartile range 49-314). A favorable RR/MDR-TB outcome was achieved in 78.9% (CI: 67.1-87.9). Three deaths occurred, all in the setting of baseline advanced HIV and elevated viral load. Overall, 21.1% (95% CI: 12.1-32.9) experienced a severe or life-threatening adverse event, the most common of which was anemia. Among patients with HIV, enrollment resulted in increased ART uptake by 24% (95% CI: 12.1%-39.4%), a significant improvement from baseline ( P = 0.004); virologic suppression during concomitant treatment was observed in 71.4% (n = 30, 95% CI: 55.4-84.3). CONCLUSION: Decentralized, person-centered care for RR/MDR-TB in patients with HIV using the short-course, bedaquiline-based regimen is effective and safe. In patients with HIV, enrollment led to improved ART use and reassuring virologic outcomes.

Early culture conversion is a poor marker of treatment outcome among people with HIV and drug-resistant TB.

OBJECTIVE: Our objective was to determine associations between early (≤2 months) culture conversion (ECC) among people with HIV and drug-resistant tuberculosis (DRTB) in Uganda. METHODS: This was a countrywide retrospective cohort of people with bacteriologically confirmed DRTB and a positive baseline culture at 16 centres in Uganda between 2013 and 2019. Data were abstracted from treatment files and unit DRTB registers. Monthly sputum cultures were performed using the Lowenstein-Jensen solid medium. RESULTS: We included 664 people with DRTB and a positive baseline culture, of whom 353 (53.4%) also had HIV. Among those living with HIV, 225 (63.7%) were male and 331 (94.3%) were on antiretroviral therapy. The median month of culture conversion was 2 (interquartile range [IQR] 1-3). ECC was observed among 226 people living with HIV (64.0%; 95% confidence interval [CI] 58.9-68.9). A DRTB treatment regimen of six or more drugs was associated with ECC among people living with HIV (adjusted odds ratio [aOR]  3.82; 95% CI 1.06-13.82; p = 0.041). Cure and overall treatment success was observed among 232 (65.7%) and 269 (76.2%) people living with HIV, respectively. However, ECC was not associated with cure (crude odds ratio [OR]  0.97; 95% CI 0.61-1.54; p = 0.901), death (OR 1.12; 95% CI 0.61-2.29; p = 0.610), or overall treatment success (OR 1.29; 95% CI 0.78-2.13; p = 0.326). CONCLUSION: The majority of people living with HIV and DRTB achieve ECC. However, ECC does not predict cure, death, or treatment success. Moreover, it may require six or more drugs to achieve ECC. ECC is not an excellent indicator of the effectiveness of DRTB regimens among people living with HIV.

Challenges of diabetes in elderly TB patients.

Diabetes mellitus (DM) and tuberculosis (TB) are worldwide health burdens post-COVID-19. TB is the second-leading cause of death by a single infectious microbe. There is much evidence around the world about the responsibility of TB-DM co-morbidity. Both TB and DM prevalence is high in low- and middle-income countries. Especially the elderly with diabetes are more prone to TB infection due to compromised immune systems. Diabetic patients are three times as likely to develop tuberculosis as non-diabetic patients. DM interferes with the status of TB and leads to undesirable outcomes in the treatment of TB. This may later lead to the development of multidrug-resistant tuberculosis (MDR-TB). The coexistence of TB and DM leads to a high mortality rate and therefore becomes an enormous challenge for the medical field. This viewpoint includes the most current information about TB and DM, disease complications, treatment strategies, challenges to be faced in disease management and the importance of TB-DM bidirectional screening in older adults, which helps in early detection and better treatment programme.

Risk factors for multidrug resistance in tuberculosis patients with diabetes mellitus.

OBJECTIVE: To study the risk factors and prediction models of multidrug resistance in patients with tuberculosis and diabetes and those with a history of tuberculosis treatment. METHODS: A total of 256 tuberculosis patients with diabetes who were registered in Luoyang city, Henan Province, from January 2018 to December 2021. Logistic regression analysis was performed to analyse the risk factors for multidrug resistance. ROC curves were used to analyse the predictive model for multidrug resistance. RESULTS: Age < 65 years old, HbA1c, and a history of tuberculosis treatment were independent risk factors for multidrug resistance in patients with tuberculosis and diabetes (P < 0.05). The area under the ROC curve of predictive model for MDR was 0.878 (95% CI (0.824, 0.932)). Age < 65 years old and HbA1c were independent risk factors for MDR in patients with TB and diabetes with a history of TB treatment. The area under the ROC curve of predictive model for MDR was 0.920 [95% CI (0.831, 0.999)]. CONCLUSION: The predictive model had certain prediction value for the risk of multidrug resistance in patients with tuberculosis and diabetes.

Evidence for Implementation: Management of TB in HIV and Pregnancy.

PURPOSE OF REVIEW: Pregnant people living with HIV (PLWH) are at especially high risk for progression from latent tuberculosis infection (LTBI) to active tuberculosis (TB) disease. Among pregnant PLWH, concurrent TB increases the risk of complications such as preeclampsia, intrauterine fetal-growth restriction, low birth weight, preterm-delivery, perinatal transmission of HIV, and admission to the neonatal intensive care unit. The grave impact of superimposed TB disease on maternal morbidity and mortality among PLWH necessitates clear guidelines for concomitant therapy and an understanding of the pharmacokinetics (PK) and potential drug-drug interactions (DDIs) between antitubercular (anti-TB) agents and antiretroviral therapy (ART) in pregnancy. RECENT FINDINGS: This review discusses the currently available evidence on the use of anti-TB agents in pregnant PLWH on ART. Pharmacokinetic and safety studies of anti-TB agents during pregnancy and postpartum are limited, and available data on second-line and newer anti-TB agents used in pregnancy suggest that several research gaps exist. DDIs between ART and anti-TB agents can decrease plasma concentration of ART, with the potential for perinatal transmission of HIV. Current recommendations for the treatment of LTBI, drug-susceptible TB, and multidrug-resistant TB (MDR-TB) are derived from observational studies and case reports in pregnant PLWH. While the use of isoniazid, rifamycins, and ethambutol in pregnancy and their DDIs with various ARTs are well-characterized, there is limited data on the use of pyrazinamide and several new and second-line antitubercular drugs in pregnant PLWH. Further research into treatment outcomes, PK, and safety data for anti-TB agent use during pregnancy and postpartum is urgently needed.

Population Pharmacokinetic Modeling of Bedaquiline among Multidrug-Resistant Pulmonary Tuberculosis Patients from China.

Bedaquiline has been widely used as a part of combination dosage regimens for the treatment of multidrug-resistant tuberculosis (MDR-TB) patients with limited options. Although the effectiveness and safety of bedaquiline have been demonstrated in clinical trials, limited studies have investigated the significant pharmacokinetics and the impact of genotype on bedaquiline disposition. Here, we developed a population pharmacokinetic model of bedaquiline to describe the concentration-time data from Chinese adult patients diagnosed with MDR-TB. A total of 246 observations were collected from 99 subjects receiving the standard recommended dosage. Bedaquiline disposition was well described by a one-compartment model with first-order absorption. Covariate modeling identified that gamma-glutamyl transferase (GGT) and the single-nucleotide polymorphism (SNP) rs319952 in the AGBL4 gene were significantly associated with the apparent clearance of bedaquiline. The clearance (CL/F) was found to be 1.4 L/h lower for subjects with allele GG in SNP rs319952 than for subjects with alleles AG and AA and to decrease by 30% with a doubling in GGT. The model-based simulations were designed to assess the impact of GGT/SNP rs319952 on bedaquiline exposure and showed that patients with genotype GG in SNP rs319952 and GGT ranging from 10 to 50 U/L achieved the targeted maximum serum concentration at steady state (Cmax,ss). However, when GGT was increased to 100 U/L, Cmax,ss was 1.68-fold higher than the highest concentration pursued. The model developed provides the consideration of genetic polymorphism and hepatic function for bedaquiline dosage in MDR-TB adult patients.

Hepatocellular Injury in Children Treated for Rifampicin-resistant Tuberculosis: Incidence, Etiology and Outcome.

BACKGROUND: Hepatocellular injury has been reported commonly in adults on rifampicin-resistant and multidrug-resistant tuberculosis (RR/MDR-TB) treatment. However, there are limited data in children. METHODS: Two pharmacokinetic studies of children (0-17 years) routinely treated for RR/MDR-TB were conducted in Cape Town, South Africa between October 2011 and February 2020. Hepatocellular injury adverse events (AEs; defined as elevated alanine aminotransferase [ALT]) were documented serially. Data were analyzed to determine the incidence, etiology, risk factors, management and outcome of ALT elevation. RESULTS: A total of 217 children, median age 3.6 years (interquartile range, 1.7-7.1 years) at enrollment were included. The median follow-up time was 14.0 months (interquartile range, 9.8-17.2 months). Fifty-five (25.3%) patients developed an ALT AE. Of these, 43 of 55 (78%) patients had 54 ALT AEs attributed to their RR/MDR-TB treatment. The incidence rate of ALT AEs related to RR-TB treatment was 22.4 per 100 person-years. Positive HIV status and having an elevated ALT at enrollment were associated with time to ALT AE attributed to RR/MDR-TB treatment, with P values 0.0427 and P < 0.0001, respectively. Hepatitis A IgM was positive in 11 of 14 (78.6%) severe (grade ≥3) cases of ALT AEs. In 8 of 14 (57%) severe ALT AEs, hepatotoxic drugs were stopped or temporarily interrupted. None had a fatal or unresolved outcome. CONCLUSIONS: Hepatocellular injury in children on RR/MDR-TB treatment is common, although usually mild; having elevated ALT early in treatment and HIV-positive status are possible risk factors. Hepatitis A was a common etiology of severe ALT AE in children treated for RR/MDR-TB.

Factors associated with screening failure and study withdrawal in multidrug-resistant TB.

SETTING: Multidrug-resistant TB (MDR-TB) clinical trial in Lima, Peru and Cape Town, South Africa.OBJECTIVE: To identify baseline factors associated with screening failure and study withdrawal in an MDR-TB clinical trial.DESIGN: We screened patients for a randomized, blinded, Phase II trial which assessed culture conversion over the first 6 months of treatment with varying doses of levofloxacin plus an optimized background regimen (ClinicalTrials.gov: NCT01918397). We identified factors for screening failure and study withdrawal using Poisson regression to calculate prevalence ratios and Cox proportional hazard regression to calculate hazard ratios. We adjusted for factors with P < 0.2.RESULTS: Of the 255 patients screened, 144 (56.5%) failed screening. The most common reason for screening failure was an unsuitable resistance profile on sputum-based molecular susceptibility testing (n = 105, 72.9%). No significant baseline predictors of screening failure were identified in the multivariable model. Of the 111 who were enrolled, 33 (30%) failed to complete treatment, mostly for non-adherence and consent withdrawal. No baseline factors predicted study withdrawal in the multivariable model.CONCLUSION: No baseline factors were independently associated with either screening failure or study withdrawal in this secondary analysis of a MDR-TB clinical trial.

Case-control study of vitamin D status and adult multidrug-resistant pulmonary TB.

BACKGROUND: India has the highest prevalence of multidrug-resistant TB (MDR-TB) globally. Vitamin D deficiency is potentially an important risk factor for MDR-TB.METHODS: We conducted a case-control study of 90 newly diagnosed adult MDR-TB cases, 180 household controls and 82 non-household controls in Mumbai, India. Serum 25-hydroxyvitamin D (25(OH)D), anthropometry, clinical status and history, dietary data and sociodemographic data were collected from each participant. Interferon-gamma release assay (IGRA) was also performed in controls to assess latent TB. Multivariable regression was performed to estimate associations between 25(OH)D vs. case status and IGRA positivity.RESULTS: Mean participant age was 33.8 ± 12.0 years; 72.8% had 25(OH)D <20 ng/ml. Mean 25(OH)D was significantly (P < 0.05) lower in cases (12.5 ± 7.9) than both household (17.5 ± 11.2) and non-household controls (16.4 ± 9.1). In multivariable models, 25(OH)D concentration was inversely associated with MDR-TB case status among cases and household controls (OR 0.95 per 1 ng/ml, 95% CI 0.92-0.99; P = 0.015), and among cases and non-household controls (OR 0.94 per 1 ng/ml, 95% CI 0.89-1.00; P = 0.033); 53.6% of controls were IGRA-positive. 25(OH)D status was not associated with IGRA positivity.CONCLUSION: Vitamin D status was independently associated with MDR-TB case status. Research should evaluate the effectiveness of vitamin D supplementation in prevention and adjunctive treatment of MDR-TB.

Bedaquiline and Linezolid improve anti-TB treatment outcome in drug-resistant TB patients with HIV: A systematic review and meta-analysis.

OBJECTIVES: We aimed to assess the effect of second-line anti-TB treatment and determine which drugs can achieve the greatest clinical benefit for DR-TB-HIV patients by comparing multiple chemotherapy regimens, to provide a basis for evidence-based practice. METHODS: We searched three electronic databases (PubMed, Web of Science and Cochrane) for related English studies published since 2010. A random-effect model was used to estimate the pooled result for the treatment outcomes. Subgroup analysis based on possible factors, such as ART, baseline CD4 T-cell count, treatment regimens, and profiles of drug resistance, was also conducted to assess factors for favorable outcome. Outcomes were treatment success and mortality. RESULTS: 38 studies, 40 cohorts with 9279 patients were included. The pooled treatment success, mortality, treatment failure, and default rates were 57.5 % (95 % CI 53.1-61.9), 21 % (95 % CI 17.8-24.6), 4.8 % (95 % CI 3.5-6.5), and 10.7 % (95 % CI 8.7-13.1), respectively, in patients with DR-TB and HIV co-infection. Subgroup analysis showed that BDQ and LZD based regimen, and ≥ 2 Group A drugs were associated with a higher treatment success rate. Besides, higher CD4 T-cell count at baseline was also correlated with higher treatment success rate, too. CONCLUSIONS: Suboptimal anti-TB outcomes underlining the need to expand the application of effective drugs and better regimen in high HIV setting. BDQ and LZD based all-oral regimen and early ART could contribute to higher treatment success, particularly among XDR-TB-HIV patients. Given that all included studies were observational, our findings emphasize the need for high-quality studies to further investigate the optimal treatment regimen for DR-TB-HIV.

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

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.

Recurrent pneumothorax in a human immunodeficiency virus-positive patient with multidrug-resistant tuberculosis: a rare case of bronchopleural fistula: a case report.

BACKGROUND: Human immunodeficiency virus/tuberculosis coinfections have amplified the multidrug-resistant tuberculosis pandemic in many countries in Sub-Saharan Africa, and multidrug-resistant tuberculosis has become a major public health threat. There is a paucity of data on severe complications of multidrug-resistant tuberculosis in the context of human immunodeficiency virus coinfection despite the increasing prevalence of multidrug-resistant tuberculosis/human immunodeficiency virus coinfection and the complexity of multidrug-resistant tuberculosis treatment. This report describes a rare case of complicated multidrug-resistant tuberculosis in a human immunodeficiency virus-positive individual. CASE PRESENTATION: A 39-year-old human immunodeficiency virus-positive Ugandan male on anti-retroviral therapy for 6 years, who had recently completed treatment for drug-susceptible tuberculosis from a public hospital, presented to the tuberculosis ward of Mulago National Referral Hospital with worsening respiratory symptoms including persistent cough with purulent sputum, fever, right chest pain, and shortness of breath. On admission, a diagnosis of drug-resistant tuberculosis was made following a positive sputum Xpert MTB/Rif test with rifampicin resistance. Culture-based tuberculosis tests and line probe assay confirmed multidrug-resistant tuberculosis. The patient was given multidrug-resistant tuberculosis treatment that included bedaquiline, isoniazid, prothionamide, clofazimine, ethambutol, levofloxacin, and pyrazinamide and switched to second-line anti-retroviral therapy that included tenofovir/lamivudine/lopinavir/ritonavir. Chest X-ray revealed a hydro-pneumothorax, following which a chest tube was inserted. With persistent bubbling from the chest tube weeks later and a check chest X-ray that showed increasing pleural airspace (pneumothorax) and appearance of a new air-fluid level, chest computed tomography scan was performed, revealing a bronchopleural fistula in the right hemithorax. The computed tomography scan also revealed a pyo-pneumothorax and lung collapse involving the right middle and lower lobes as well as a thick-walled cavity in the right upper lobe. With the pulmonary complications, particularly the recurrent pneumothorax, bronchopleural fistula, and empyema thoracis, cardiothoracic surgeons were involved, who managed the patient conservatively and maintained the chest tube. The patient continued to be ill with recurrent pneumothorax despite the chest tube, until relatives opted for discharge against medical advice. CONCLUSIONS: Complicated human immunodeficiency virus-related multidrug-resistant tuberculosis is not uncommon in settings of high human immunodeficiency virus/tuberculosis prevalence and is often associated with significant morbidity and mortality. Early diagnosis and treatment of multidrug-resistant tuberculosis, with rigorous monitoring for human immunodeficiency virus-positive individuals, is necessary to prevent debilitating complications.