XDR-TB Patients Research Articles

Clinical outcomes for multi- and extensively drug resistant tuberculosis patients with adjunctive resectional lung surgery in Beijing, China.

The objective of this study was to assess the performance of adjective resectional lung surgery for multidrug resistant (MDR-) and extensively drug resistant tuberculosis (XDR-TB) patients in Beijing, China. Between October 1992 and October 2012, 21 MDR/XDR patients undergoing pulmonary resection at Beijing Chest Hospital were enrolled in this study. The clinical outcomes of MDR- and XDR-TB patients were analyzed with a 3-year surgical follow-up. Out of 21 patients enrolled in this study, 20 patients (95.2%) had unilateral cavitary disease, and 1 patient (4.8%) exhibited bilateral cavitary disease. The most frequent cavitation was located in the left upper lung (38.1%, 8/21). In addition, 19 (90.5%) underwent lobectomy, and the other two (9.5%) underwent pneumonectomy due to obvious cavitation in both upper and lower fields of unilateral lung. After 3-year follow-up, eight patients (38.1%) were cured and 13 patients (61.9%) suffered from unfavorable outcomes. Of 13 patients with unfavorable outcomes, 5 patients (38.5%) died of further progression of TB disease, and 8 patients (61.5%) relapsed. Only 1 (14.3%) out of 7 XDR-TB patients was cured, compared with 7 (50.0%) out of 14 multidrug-resistant tuberculosis (MDR-TB) patients. In conclusion, our data demonstrate that if available, surgical treatment should be considered in MDR/XDR-TB patients in China. The subsequent treatment with second-line drugs may play the most important role in determining the final clinical outcome for MDR/XDR-TB patients.

Correlations between Gene Resistant Markers and Second-Line Anti-TB Drug Resistance in Pre-XDR and XDR-TB Patients

Background: Extensively drug resistant tuberculosis (XDR-TB) is a serious problem in public health and XDR-TB patients usually develop from multi-drug resistance tuberculosis (MDR-TB) and pre-XDR-TB. The rapid molecular test for drug susceptibility testing (DST) can be used for early detection to prevent XDR-TB. Methods: We examined 34 clinical Mycobacterium tuberculosis (M. tuberculosis) isolates from MDR/XDR-TB patients in the upper north of Thailand that were identified with drug susceptibility profiles by indirect agar proportion method from 2005-2012. Our study investigated the genetic mutations in gyrA for ofloxacin resistance and rrs for kanamycin resistance. The genetic mutations and drug susceptibility test results were analyzed using the exact test. Results: The majority of the ofloxacin resistance was detected in gyrA 21, gyrA 70, gyrA 87, gyrA 102, gyrA 162, and gyrA 187 were at 0%, 12.5%, 37.5%, 0%, 50.0% and 25.0% sensitivity, respectively, and at 96.2, 96.2%, 20.1%, 96.2%, 57.7% and 61.5% specificity, respectively. Kanamycin resistance was found in rrs 512, rrs 241, rrs 223, rrs 414 and rrs 408 at 16.7%, 0%, 0%, 16.7% and 16.7% sensitivity, respectively, and at 96.4%, 92.9%, 82.1%, 82.1% and 71.4% specificity, respectively. This study found no significant correlation between gyrA mutations and ofloxacin resistance and also no correlation between the rrs gene and kanamycin resistance. Conclusion: These primer sequences and PCR products in our study such as gyrA and rrs might be unsuitable to detect ofloxacin and kanamycin resistance in the upper north of Thailand.

Treatment outcome of patients having extensively drug-resistant tuberculosis in Gujarat, India.

To investigate the factors affecting treatment outcome of extensively drug resistant tuberculosis (XDR-TB) in Gujarat, India. A prospective, observational study was conducted on patients with XDR TB from January 2012 to October 2016. Details of demography, clinical symptoms, sputum/culture and radiological examination, drug treatment, adverse drug reactions (ADRs) and treatment outcome were recorded in pretested case record form (CRF). Data was analyzed using Fisher's exact test and paired student's t test. Out of 112 patients, 83 (74%) were men and 29 (26%) were women and majority of belonged to age group of 16 - 45 years. Majority of patients (79%) received standardized treatment. A total of 61 (54%) patients converted to sputum culture negative by 12 months and out of these, 49 turned sputum culture negative within initial 6 months of treatment. Successful treatment outcome was seen in 29 (25.89 %). Age ≤40 years (P<0.05), body mass index > 18.5 (P<0.05) and sputum/culture conversion at three month (P<0.001) were positive predictors for successful treatment outcome, while tobacco chewing habit (P<0.05) and alcohol consumption (P<0.05) were negative predictors for the successful treatment outcome. Out of 83 (74.1 %) patients with unsuccessful treatment outcome, 58 (51.78 %) died, 11 (9.82 %) were defaulter and 10 (8.92 %) were treatment failure. Factors positively associated with death were very low BMI (< 18.5), concomitant diseases and harmful personal habits. Treatment outcome of XDR TB patients is extremely poor with high mortality rate.

Whole-Genome Sequencing Analysis of Serially Isolated Multi-Drug and Extensively Drug Resistant Mycobacterium tuberculosis from Thai Patients.

Multi-drug and extensively drug-resistant tuberculosis (MDR and XDR-TB) are problems that threaten public health worldwide. Only some genetic markers associated with drug-resistant TB are known. Whole-genome sequencing (WGS) is a promising tool for distinguishing between re-infection and persistent infection in isolates taken at different times from a single patient, but has not yet been applied in MDR and XDR-TB. We aim to detect genetic markers associated with drug resistance and distinguish between reinfection and persistent infection from MDR and XDR-TB patients based on WGS analysis. Samples of Mycobacterium tuberculosis (n = 7), serially isolated from 2 MDR cases and 1 XDR-TB case, were retrieved from Siriraj Hospital, Bangkok. The WGS analysis used an Illumina Miseq sequencer. In cases of persistent infection, MDR-TB isolates differed at an average of 2 SNPs across the span of 2–9 months whereas in the case of reinfection, isolates differed at 61 SNPs across 2 years. Known genetic markers associated with resistance were detected from strains susceptible to streptomycin (2/7 isolates), p-aminosalicylic acid (3/7 isolates) and fluoroquinolone drugs. Among fluoroquinolone drugs, ofloxacin had the highest phenotype-genotype concordance (6/7 isolates), whereas gatifloxcain had the lowest (3/7 isolates). A putative candidate SNP in Rv2477c associated with kanamycin and amikacin resistance was suggested for further validation. WGS provided comprehensive results regarding molecular epidemiology, distinguishing between persistent infection and reinfection in M/XDR-TB and potentially can be used for detection of novel mutations associated with drug resistance.

Community-based management versus traditional hospitalization in treatment of drug-resistant tuberculosis: a systematic review and meta-analysis.

BackgroundMultidrug drug resistant Tuberculosis (MDR-TB) and extensively drug resistant Tuberculosis (XDR-TB) have emerged as significant public health threats worldwide. This systematic review and meta-analysis aimed to investigate the effects of community-based treatment to traditional hospitalization in improving treatment success rates among MDR-TB and XDR-TB patients in the 27 MDR-TB High burden countries (HBC).MethodsWe searched PubMed, Cochrane, Lancet, Web of Science, International Journal of Tuberculosis and Lung Disease, and Centre for Reviews and Dissemination (CRD) for studies on community-based treatment and traditional hospitalization and MDR-TB and XDR-TB from the 27 MDR-TB HBC. Data on treatment success and failure rates were extracted from retrospective and prospective cohort studies, and a case control study. Sensitivity analysis, subgroup analyses, and meta-regression analysis were used to explore bias and potential sources of heterogeneity.ResultsThe final sample included 16 studies involving 3344 patients from nine countries; Bangladesh, China, Ethiopia, Kenya, India, South Africa, Philippines, Russia, and Uzbekistan. Based on a random-effects model, we observed a higher treatment success rate in community-based treatment (Point estimate = 0.68, 95 % CI: 0.59 to 0.76, p < 0.01) compared to traditional hospitalization (Point estimate = 0.57, 95 % CI: 0.44 to 0.69, p < 0.01). A lower treatment failure rate was observed in community-based treatment 7 % (Point estimate = 0.07, 95 % CI: 0.03 to 0.10; p < 0.01) compared to traditional hospitalization (Point estimate = 0.188, 95 % CI: 0.10 to 0.28; p < 0.01). In the subgroup analysis, studies without HIV co-infected patients, directly observed therapy short course-plus (DOTS-Plus) implemented throughout therapy, treatment duration > 18 months, and regimen with drugs >5 reported higher treatment success rate. In the meta-regression model, age of patients, adverse events, treatment duration, and lost to follow up explains some of the heterogeneity of treatment effects between studies.ConclusionCommunity-based management improved treatment outcomes. A mix of interventions with DOTS-Plus throughout therapy and treatment duration > 18 months as well as strategies in place for lost to follow up and adverse events should be considered in MDR-TB and XDR-TB interventions, as they influenced positively, treatment success.

Rapid detection of extensively drug-resistant (XDR-TB) strains from multidrug-resistant tuberculosis (MDR-TB) cases isolated from smear-negative pulmonary samples in an Intermediate Reference Laboratory in India

BackgroundDirect sputum smear microscopy is commonly used for diagnosing tuberculosis (TB). The objectives of the study were first, to determine the recovery of Mycobacterium tuberculosis in smear-negative sputum samples through liquid culture (using MGIT 960) and solid culture (using LJ slant) and second, to screen multidrug-resistant isolates through line probe assay and further third, to identify XDR isolates through MGIT second-line DST from these positive MDR cultures in Delhi region. MethodsIn this study, the sample size was 717 (sputum smear AFB negative and culture positive for M. tuberculosis complex by both solid and liquid culture methods) MDRTB suspects who were enrolled from January 2014 to December 2014 at the Intermediate Reference Laboratory in New Delhi Tuberculosis Centre, New Delhi. Rapid line probe assay was performed on all culture-positive samples, which were direct smear-negative specimens, and LPA-confirmed MDR samples were tested on MGIT 960 second-line DST for identification of XDR strains. ResultsAn overall increase in the culture positivity (9.4%) among these smear-negative cases shows a good sign of recovery from M. tuberculosis infection in these samples. 717 (9.4%) positive cultures (MGIT+LJ) were subjected to line probe assay. Out of these 717 cultures, 9 (1.2%) were confirmed as NTM, 50 (7%) were MDR, 4 (0.6%) were mono-rifampicin resistant and 654 (91.2%) cultures were sensitive to both drugs Rif and Inh, respectively. Out of these 54 (50 MDR +4 mono-RIF resistant) cultures as screened by LPA, 1 (1.8%) was XDR, 10 (18.6%) were mono-ofloxacin resistant and 1 (1.8%) was mono-Kanamycin resistant. Sensitivity to both drugs KAN and OFX was seen in 42 (77.8%) cultures. ConclusionsSince the bacterial load in direct smear-negative suspected MDR samples is less, it is important to recover mycobacteria by rapid liquid culture method in such samples. Initial screening for MDRTB is to be done in such cases by performing rapid molecular genotypic drug susceptibility test such as LPA. Baseline second-line DST is also done to rule out the XDR cases among them for rapid and better management of XDRTB patients.

Efficacy and safety profile of linezolid in the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis: a systematic review and meta-analysis.

BackgroundTreatment options for drug-resistant tuberculosis are still limited. Linezolid has been recommended for treatment of patients with multidrug-resistant (MDR) or extensively-drug-resistant (XDR) tuberculosis, although uncertainties remain regarding its safety and tolerability in these circumstances.ObjectiveTo systematically evaluate the existing evidence regarding the efficacy and tolerability of linezolid in the treatment of MDR or XDR tuberculosis.MethodsWe conducted a systematic review and meta-analysis in accordance with the PRISMA guidelines. Searches were conducted in PubMed, Web of Science and EMBASE followed by direct search of abstracts in the International Journal of Tuberculosis and Lung Disease to retrieve primary studies published between January 2000 and January 2016 assessing linezolid efficacy and safety in the treatment of drug-resistant TB. We evaluated the occurrence of outcomes including culture conversion, treatment success and incidence of adverse events such as myelosuppression and neuropathy.ResultsTwenty-three (23) studies conducted in fourteen (14) countries and involving 507 patients were retrieved. Only 1 randomized controlled trial was identified and none of the identified studies involved participants from Africa. The pooled proportion for treatment success was 77.36 % (95 % CI = 71.38–82.83 %, I2 = 37.6 %) with culture conversion rate determined as 88.45 % (95 % CI = 83.82–92.38 %, I2 = 45.4 %). There was no strong evidence for both culture conversion (p = 0.0948) and treatment success (p = 0.0695) between linezolid daily doses ≤ 600 and > 600 mg. Only myelosuppression showed a strong statistical significance (p < 0.0001) between dose comparisons. The incidence of neuropathy and other adverse events leading to permanent discontinuation of linezolid also showed no significance upon dose comparisons (p = 0.3213, p = 0.9050 respectively).ConclusionAvailable evidence presents Linezolid as a viable option in the treatment of MDR/XDR TB although patients ought to be monitored closely for the incidence of major adverse events such as myelosuppression and neuropathy. Additionally, highly powered randomized controlled trials including participants from endemic regions are urgently needed to better inform the magnitude and significance of Linezolid treatment effect in MDR and XDR TB patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12941-016-0156-y) contains supplementary material, which is available to authorized users.

Characteristics and costs of multidrug-resistant tuberculosis in-patient care in the United States, 2005-2007.

A population-based study of 135 multidrug-resistant tuberculosis (MDR-TB) patients reported to the Centers for Disease Control and Prevention (CDC) during 2005-2007 found 73% were hospitalized. We analyzed factors associated with hospitalization. We assessed statistically significant multivariable associations with US in-patient TB diagnosis, frequency of hospitalization, length of hospital stay, and in-patient direct costs to the health care system. Of 98 hospitalized patients, 83 (85%) were foreign-born. Blacks, diabetics, or smokers were more likely, and patients with disseminated disease less likely, to receive their TB diagnosis while hospitalized. Patients aged ⩾65 years, those with the acquired immune-deficiency syndrome (AIDS), or with private insurance, were hospitalized more frequently. Excluding deaths, length of stay was greater for patients aged ⩾65 years, those with extensively drug-resistant TB (XDR-TB), those residing in Texas, those with AIDS, those who were unemployed, or those who had TB resistant to all first-line medications vs. others. Average hospitalization cost per XDR-TB patient (US$285 000) was 3.5 times that per MDR-TB patient (US$81 000), in 2010 dollars. Hospitalization episode costs for MDR-TB rank third highest and those for XDR-TB highest among the principal diagnoses. Hospitalization was common and remains a critical care component for patients who were older, had comorbidities, or required complex management due to XDR-TB. MDR-TB in-patient costs are among the highest for any disease.

Linezolid as a Potentially Effective Drug for the Treatment of Multidrug-Resistant Tuberculosis in Japan.

Linezolid (LZD) is classified as a WHO group 5 drug used in the treatment of tuberculosis (TB). Although its efficacy and long-term safety have not yet been established, it is being increasingly used in the treatment of multidrug resistant tuberculosis (MDR-TB) and extensive multidrug-resistant tuberculosis (XDR-TB). The current study is a single-center retrospective clinical analysis of hospitalized M/XDR-TB patients in Fukujuji Hospital involving 26 patients (18 men and 8 women) consecutively treated with combinations of anti-TB drugs including LZD from 2009 to 2015. The sputum culture results were negative after using LZD for an average period of 28.0 ± 12.0 (average ± SD) days. LZD was reduced or withdrawn in 11 cases due to adverse effects. Nineteen cases including 3 XDR-TB patients were operated on, and their TB was treated following surgery. The average time from the initiation of LZD therapy to surgery was 87.6 ± 38.7 (average ± SD) days. Favorable clinical outcome was maintained in 23 surviving patients, while 3 patients died during treatment because of end stage cancer and aspiration pneumonia. Our study showed that LZD might be clinically effective in the treatment of M/XDR-TB patients in Japan.

Effectiveness and safety of meropenem/clavulanate-containing regimens in the treatment of MDR- and XDR-TB.

No large study has ever evaluated the efficacy, safety and tolerability of meropenem/clavulanate to treat multidrug- and extensively drug-resistant tuberculosis (MDR- and XDR-TB). The aim of this observational study was to evaluate the therapeutic contribution, effectiveness, safety and tolerability profile of meropenem/clavulanate added to a background regimen when treating MDR- and XDR-TB cases.Patients treated with a meropenem/clavulanate-containing regimen (n=96) showed a greater drug resistance profile than those exposed to a meropenem/clavulanate-sparing regimen (n=168): in the former group XDR-TB was more frequent (49% versus 6.0%, p<0.0001) and the median (interquartile range (IQR)) number of antibiotic resistances was higher (8 (6-9)versus 5 (4-6)). Patients were treated with a meropenem/clavulanate-containing regimen for a median (IQR) of 85 (49-156) days.No statistically significant differences were observed in the overall MDR-TB cohort and in the subgroups with and without the XDR-TB patients; in particular, sputum smear and culture conversion rates were similar in XDR-TB patients exposed to meropenem/clavulanate-containing regimens (88.0% versus 100.0%, p=1.00 and 88.0% versus 100.0%, p=1.00, respectively). Only six cases reported adverse events attributable to meropenem/clavulanate (four of them then restarting treatment).The nondifferent outcomes and bacteriological conversion rate observed in cases who were more severe than controls might imply that meropenem/clavulanate could be active in treating MDR- and XDR-TB cases.

Beyond multidrug-resistant tuberculosis in Europe: a TBNET study.

The emergence of drug-resistant tuberculosis (TB) is a challenge to TB control in Europe. We evaluated second-line drug susceptibility testing in Mycobacterium tuberculosis isolates from patients with multidrug-resistant, pre-extensively drug-resistant (pre-XDR-TB) and XDR-TB at 23 TBNET sites in 16 European countries. Over 30% of bacilli from patients with pre-XDR-TB showed resistance to any fluoroquinolone and almost 70% to any second-line injectable drug. Respectively >90% and >80% of the XDR-TB strains tested showed phenotypic resistance to pyrazinamide and ethambutol. Resistance to prothionamide/ethionamide was high in bacilli from pre-XDR-TB patients (43%) and XDR-TB patients (49%).

Treatment of drug-resistant tuberculosis with bedaquiline in a high HIV prevalence setting: an interim cohort analysis.

South Africa has a large burden of extensively drug-resistant tuberculosis (XDR-TB); only 15% of XDR-TB patients have successful outcomes. To describe the safety and effectiveness of bedaquiline (BDQ) in the South African BDQ Clinical Access Programme. An interim cohort analysis. Of the first 91 patients enrolled between March 2013 and July 2014 (with follow-up until August 2014), 54 (59%) were human immunodeficiency virus (HIV) infected. The median CD4 count was 239 cells/μl, and all patients were on antiretroviral therapy (ART) at initiation of BDQ; 33 had XDR-TB, 41 were pre-XDR-TB with fluoroquinolone resistance and 17 were pre-XDR-TB with resistance to an injectable. Of the 91 patients, 58 (64%) had completed 24 weeks of BDQ, 28 were still on BDQ, 3 were lost to follow-up, 1 had died and 1 had BDQ withdrawn following atrial fibrillation. Of the 63 patients with 6 months follow-up, 48 (76%) had either culture-converted or remained culture-negative after initiation of BDQ. QTcF was monitored monthly and exceeded 500 ms in three participants; this resolved in all three. Interim safety and culture conversion outcomes for patients accessing BDQ in South Africa, including HIV-infected patients on ART and patients with pre-XDR- and XDR-TB, suggest that BDQ may be both efficacious and safe.

The Relationship between Extensively Drug-Resistant Tuberculosis and Multidrug-Resistant Gram-Negative Bacilli.

ObjectiveThe relationship between extensively drug-resistant tuberculosis (XDR-TB) and multidrug-resistant Gram-negative bacilli (MDR-GNB) is unclear. Identification of the relationship between XDR-TB and MDR-GNB would have important implications for patient care.MethodsWe conducted a retrospective study reviewing the records of patients admitted with a confirmed pulmonary TB from 2011 to 2014. To identify the relationship between XDR-TB and MDR-GNB, univariable comparison and multivariable logistic regression were performed.ResultsAmong 2962 pulmonary TB patients, 45(1.5%) patients had a diagnosis of XDR-TB. A total of 165 MDR-GNB strains were detected in 143 (4.8%) pulmonary TB patients. XDR-TB patients had a significantly higher occurrence of MDR-GNB than non-XDR-TB patients (24.4% vs. 4.5%; P<0.001). Age (OR 1.02, 95% CI 1.01–1.03), hypoalbuminemia (OR 1.48, 95% CI 1.18–1.85), chronic renal failure (OR 6.67, 95% CI 1.42–31.47), chronic hepatic insufficiency (OR 1.99, 95% CI 1.15–3.43), presence of XDR-TB (OR 6.56, 95% CI 1.61–26.69), and duration of TB diagnostic delay (OR 1.01, 95% CI 1.00–1.02) were the independent risk factors for MDR-GNB infection.ConclusionsPatients with XDR-TB have a significantly higher risk of being affected by MDR-GNB pathogen. The underlying mechanism association warrant further studies.

High frequency of resistance, lack of clinical benefit, and poor outcomes in capreomycin treated South African patients with extensively drug-resistant tuberculosis.

BackgroundThere are limited data about the epidemiology and treatment-related outcomes associated with capreomycin resistance in patients with XDR-TB. Capreomycin achieves high serum concentrations relative to MIC but whether capreomycin has therapeutic benefit despite microbiological resistance remains unclear.MethodsWe reviewed the susceptibility profiles and outcomes associated with capreomycin usage in patients diagnosed with XDR-TB between August 2002 and October 2012 in two provinces of South Africa. Patients whose isolates were genotypically tested for capreomycin resistance were included in the analysis.ResultsOf 178 XDR-TB patients 41% were HIV-infected. 87% (154/178) isolates contained a capreomycin resistance-conferring mutation [80% (143/178) rrs A1401G and 6% (11/178) were heteroresistant (containing both the rrs A1401G mutation and wild-type sequences)]. Previous MDR-TB treatment, prior usage of kanamycin, or strain type was not associated with capreomycin resistance. 92% (163/178) of XDR-TB patients were empirically treated with capreomycin. Capreomycin resistance decreased the odds of sputum culture conversion. In capreomycin sensitive and resistant persons combined weight at diagnosis was the only independent predictor for survival (p=<0.001). By contrast, HIV status and use of co-amoxicillin/clavulanic acid were independent predictors of mortality (p=<0.05). Capreomycin usage was not associated with survival or culture conversion when the analysis was restricted to those whose isolates were resistant to capreomycin.ConclusionIn South Africa the frequency of capreomycin conferring mutations was extremely high in XDR-TB isolates. In those with capreomycin resistance there appeared to be no therapeutic benefit of using capreomycin. These data inform susceptibility testing and the design of treatment regimens for XDR-TB in TB endemic settings.

Consolidated Action Plan to Prevent and Combat Multidrug- and Extensively Drug-resistant Tuberculosis in the WHO European Region 2011–2015: Cost-effectiveness analysis

Drug-resistant tuberculosis (TB) has increased at an alarming rate in the WHO European Region. Of the 27 countries worldwide with a high burden of multidrug resistant-TB (MDR-TB), 15 are in the European Region. An estimated 78,000 new cases of MDR-TB occur annually in the Region, of which approximately 10% are extensively drug-resistant (XDR)-TB. In response, the WHO Regional Office for Europe developed a Consolidated Action Plan to Prevent and Combat Multidrug- and Extensively Drug-resistant Tuberculosis (2011-2015). Our objective was to analyse the cost-effectiveness of implementing the plan, with the expected achievements of diagnosing 85% of estimated MDR-TB cases and treating at least 75% successfully. A transmission model, using epidemiological data reported to WHO was developed to calculate expected achievements. WHO-CHOICE database was used for cost analyses. The highly cost-effective plan is expected to prevent the emergence of 250,000 new MDR-TB and 13,000 XDR-TB patients respectively, saving US$7 billion and 120,000 lives. The plan and accompanying Resolution were fully endorsed by the sixty-first session of the WHO Regional Committee for Europe in 2011. Member States need to continuously improve health system performance and address TB determinants. Research and development of new medicines, tools and patient-friendly services are also crucial.

Immunotherapy of patients with multiple and extreme drug-resistant pulmonary tuberculosis with autologous monocyte- and stem cell-derived dendritic cells vaccine

Aims and objectivesThis study evaluates the response of TB patients to treatment with autologous dendritic cell (DC) vaccine. MethodsThere were 25 patients with MDR⧹XDR pulmonary TB included in the study. DCs were obtained both from peripheral blood monocytes and bone marrow isolated stem cells using standard protocols. DCs were primed with either autologous M. tuberculosis lysates or CFP-10 peptides and cultured with maturation inducers. DCs were tested for immuno-phenotype, viability and sterility and injected into the patients subcutaneously three times at 2- to 3-week intervals. Clinical monitoring, sputum assessments, chest X-rays and immune status were performed before and 2–3months after the treatment. The control group (C) consisted of 25 patients with MDR⧹XDR TB matched by sex and age. ResultsDCs obtained from all patients were sterile, viable, morphologically intact and phenotypically mature (expression of CD83 and CD86 being >80%). The number of injected DCs averaged 10.2 (range: 8.3–15.6)×106.Treatment of TB patients with autologous DCs was safe and well tolerated. No significant side effects which required medical aid were noted during the study.The combination of standard treatment and DC-vaccination promoted the decrease or complete clearance of mycobacteria tuberculosis from the sputum (DC-treated patients – 69.23±12.8% versus 30.76±12.8% in C, p<0.05) and X-ray improvement (69.23±12.8% versus 30.76±12.8% in C, p<0.05).Treatment with DCs was also associated with the significant increase of antigen-specific T-cells in the blood, which reflects the accumulation of antigen-specific T-cells in peripheral blood and indicates the restoration of immune response against mycobacteria tuberculosis. ConclusionsDC-based treatment may become an effective valuable method of cellular immunotherapy for MDR- and XDR-TB patients.

Clinical outcomes of linezolid treatment for extensively drug-resistant tuberculosis in Beijing, China: a hospital-based retrospective study.

Studies have shown that linezolid achieves good clinical outcomes against multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB). However, the efficacy of linezolid for individual TB patients and its precise contribution to combination regimens remain unclear for Chinese patients. This study examined the clinical outcomes and safety of linezolid in adults with XDR pulmonary TB at the Chinese PLA 309 hospital. Sixteen XDR-TB patients received linezolid (600 mg daily) in addition to vitamin B6 (50-100 mg daily) as part of their individualized treatment regimens. Of the 16 patients, 14 had received previous treatment for tuberculosis. Sputum samples for all patients showed high colony-forming unit counts when tested by a real-time polymerase chain reaction (PCR). In addition, a high proportion of patients had cavitary lesions in the lungs. Eleven of the 16 patients (68.75%) had successfully completed therapy with documented negative quantitative PCR (qPCR) data and cultures at follow-up (mean = 12 months). Three patients (18.75%) are still receiving treatment, and all 3 have shown clinical and radiographic improvement. Linezolid was discontinued for 2 patients with persistent positive qPCR data and cultures because they developed severe, intractable diarrhea and nausea shortly after beginning treatment. Data indicated that linezolid was a well-tolerated and efficient treatment for XDB-TB in of Chinese patients.

Factores asociados a tuberculosis multidrogorresistente primaria en pacientes de Callao, Perú

Introduction: Lima and Callao are high risk areas for tuberculosis active transmission in Peru. Multidrug-resistant tuberculosis represents 5.54% of the new cases of pulmonary tuberculosis (primary MDR-TB) in Lima and Callao. Involved risk factors have not been studied in patients from Callao. Objectives: To determine risk factors for primary MDR-TB in patients attending health care facilities in Callao during 2009-2010. Design: Case-control study. Setting: Health care facilities from Callao. Participants: Twenty nine primary MDR-TB patients and 37 drug-sensitive TB patients were studied through assessment of the Tuberculosis Control Program Registries and healthcare facilities’ clinical records. Interventions: Information was obtained from secondary sources. Odds-ratios were calculated by bivariate analysis. Logistic regression models were used to calculate multivariate odd-ratios. Main outcome measures: Risk factors for primary MDR-TB. Results: Prior contact with a MDR-TB or XDR-TB patient was a significant risk factor (OR: 5.56; 95%CI: 1.05-29.27) in bivariate analysis; the same was found in multivariate analysis (OR: 14.56; 95%CI: 1.52–139.54). Being 40 or more years old was a significant protective factor in multivariate analysis (OR: 0.94; 95% CI: 0.90–0.99). Conclusions: Previous contact with a MDR-TB or XDR-TB patient was a risk factor, and being 40 or more years old was a protective factor for primary MDR-TB in Callao patients studied.

Adherence in the treatment of patients with extensively drug-resistant tuberculosis and HIV in South Africa: a prospective cohort study.

Extensively drug-resistant tuberculosis (XDR-TB)/HIV coinfection is difficult to treat with frequent adverse drug reactions and associated with high mortality. Adherence to antiretroviral therapy (ARV) and second-line TB medications may reduce mortality, prevent amplification of drug resistance, and improve outcomes. Prospective cohort study of XDR-TB patients on treatment in KwaZulu-Natal, South Africa. Adherence to ARV and TB medications was assessed separately at baseline and monthly. Knowledge, attitudes, and beliefs were assessed at baseline. Optimal adherence was defined as self-report of taking all pills in the previous 7 days; missing any pills was defined as suboptimal adherence. Primary outcome was optimal adherence 6 months after initiation of XDR-TB treatment to TB medications, ARV, and both ("dual adherence"). One hundred four XDR-TB patients (79.8% HIV coinfected, 84.3% on ARV at enrollment) were enrolled and followed monthly (median 8 visits; interquartile range: 4-12). Six-month optimal adherence was higher for ARV (88.2%) than TB medications (67.7%) (P < 0.001). Low educational attainment, male gender, and year of enrollment were independently associated with dual suboptimal adherence. At baseline, participants indicated that XDR-TB was curable (76.0%), HIV and TB were linked (81.7%), and ARV improves TB outcomes (72.1%). Baseline knowledge, attitudes, and beliefs did not predict subsequent adherence. Medication adherence was significantly higher for ARV than for TB medications in this cohort. Short-course treatment regimens for drug-resistant TB with lower pill burden may increase adherence and improve outcomes in XDR-TB/HIV. Programmatic support for dual adherence is critical in the treatment of drug-resistant TB and HIV.

Clofazimine in the treatment of extensively drug-resistant tuberculosis with HIV coinfection in South Africa: a retrospective cohort study.

Extensively drug-resistant (XDR) tuberculosis (TB) and HIV coinfection is associated with low cure rates and high mortality. Clofazimine has shown activity in vitro against Mycobacterium tuberculosis, but clinical experience with clofazimine in XDR-TB and HIV coinfection is limited. This was a retrospective cohort study of adult XDR-TB patients in KwaZulu-Natal, South Africa, treated with either a clofazimine- or non-clofazimine-containing XDR-TB treatment regimen. The primary outcome measure was TB culture conversion at 6 months. Survival analysis and multivariate logistic regression compared time to event in different strata and identified risk factors for TB culture conversion. Between August 2009 and July 2011, eligible XDR-TB patients (n = 85) were initiated on treatment for XDR-TB. Most patients (86%) were HIV-infected and receiving antiretroviral therapy (90%). Patients receiving a clofazimine-containing regimen (n = 50) had a higher percentage of culture conversion (40%) compared with patients (n = 35) receiving a non-clofazimine regimen (28.6%). On multivariate analysis, there was a 2-fold increase in TB culture conversion at 6 months (hazard rate ratio 2.54, 95% CI 0.99-6.52, P = 0.05) in the group receiving a clofazimine-containing regimen. Adverse effects due to clofazimine were minor and rarely life-threatening. Clofazimine was associated with improved culture conversion in the treatment of XDR-TB/HIV. Adverse effects were minor and non-life-threatening. Based on these preliminary data, further study of clofazimine in XDR-TB/HIV treatment is warranted. Given the present low rates of culture conversion in XDR-TB treatment, we recommend empirical inclusion of clofazimine in treatment regimens for XDR-TB.