Multidrug-resistant Tuberculosis Treatment Outcomes Research Articles

Association between Directly Observed Therapy and Treatment Outcomes in Multidrug-Resistant Tuberculosis: A Systematic Review and Meta-Analysis

BackgroundMultidrug-resistant tuberculosis (MDR-TB) represents a major obstacle towards successful TB control. Directly observed therapy (DOT) was recommended by WHO to improve adherence and treatment outcomes of MDR-TB patients, however, the effectiveness of DOT on treatment outcomes of MDR-TB patients was mixed in previous studies. We conducted this systematic review and meta-analysis to assess the association between DOT and treatment outcomes and to examine the impact of different DOT providers and DOT locations on successful treatment outcomes in MDR-TB patients.MethodsWe searched studies published in English between January 1970 and December 2015 in major electronic databases. Two reviewers independently screened articles and extracted information of DOT, treatment success rate and other characteristics of studies. Random effects model was used to calculate the pooled treatment success rate and 95% confidence interval (CI). Sub-group analyses were conducted to access factors associated with successful treatment outcomes.ResultsA total of 31 articles 7,466 participants were included. Studies reporting full DOT (67.4%, 95% CI: 61.4–72.8%) had significantly higher pooled treatment success rates than those reporting self-administration therapy (46.9%, 95% CI: 41.4–52.4%). No statistically difference was found among DOT provided by healthcare providers (65.8%, 95% CI: 55.7–74.7%), family members (72.0%, 95% CI: 31.5–93.5%) and private DOT providers (69.5%, 95% CI: 57.0–79.7%); and neither did we find significantly difference on pooled treatment success rates between patients having health facility based DOT (70.5%, 95% CI: 61.5–78.1%) and home-based DOT (68.4%, 95% CI: 51.5–81.5%).ConclusionProviding DOT for a full course of treatment associated with a higher treatment success rate in MDR-TB patients.

Management of multidrug resistant tuberculosis (MDR-TB) – Monitoring is the key to successful outcome

ContextTreatment of multidrug resistant tuberculosis (MDR-TB) is challenging. In India, standard treatment regimen is established by Revised National Tuberculosis Control Programme (RNTCP). Adequate follow-up of patients during the treatment period is a challenging task under programmatic conditions. We did a retrospective analysis of patients enrolled and treated under the national programme to study the outcome. AimsTo study the treatment outcome of MDR-TB and the factors affecting it. Settings and designRetrospective analysis of 69 patients treated with standard regimen for MDR-TB, as per RNTCP guidelines. Methods and materialRetrospective analysis of 69 MDR-TB patients for the clinical and demographic profile. Treatment outcome is defined as cure rate, default rate, death rate and failure. The factors affecting this outcome are also studied. ResultsSputum culture conversion rate was 33.9% and 62.5% at 3rd and 6th month of treatment respectively. Cure rate was 47.8%, death rate 27.5%, default rate 14.5% and failure 7.3%. ConclusionsThe major hindrance in achieving a good cure-rate was a high death rate and default. Early diagnosis of MDR-TB and adequate clinical monitoring during treatment is essential. Identifying adverse drug reactions, other co morbidities and their optimal management is the key to success.

Risk Factors of Treatment Outcomes for Multi-drug Resistant Tuberculosis in Shanghai, 2009-2012

Background: Multi-drug resistant tuberculosis (MDR-TB), defined as resistant to at least isoniazid and rifampicin, has imposed serious risks on public health globally. China has the largest number of MDR-TB patients, and a prevalence rate two times of the world average. The study investigated the association between MDR-TB treatment outcome and patient risk factors, including physical accessibility to TB hospitals.Methods: We collected all the 336 MDR-TB cases reported in Shanghai between 2009 and 2012 from Shanghai CDC regarding information on age, gender, resident status, treatment history, and outcomes. Using the Geographical Information System (GIS), TB hospitals and study subjects’ locations were geocoded on digital maps. To identify the statistically significant geographical clusters, kernel density estimation (KDE) and Average Nearest Neighbor (ANN) index were used. Logistic regression analysis was employed to determine the association of spatial and non-spatial variables on the occurrence of poor treatment outcomes.Results: The spatial clusters of MDR-TB cases were concentrated in the most densely populated central urban areas. There was a tendency toward higher odds of poor treatment outcomes among aged>45 years old (aOR 3.251; 95%CI 1.527-7.21), residential (aOR 2.566; 95%CI 1.154-5.88), retreated (aOR 2.566; 95%CI 1.154-5.88) and sputum smear positive (aOR 3.286; 95%CI 1.154-11.66) MDR-TB cases. Both the straight-line distance and the road distance from a patient's home to the related TB hospital were significantly associated with poor treatment outcome with an odds ratio of 1.04 (95%CI 1.009-1.08) and 1.029 (95%CI 1.005-1.06) respectively.Conclusion: This study highlights the effect of spatial and non-spatial determinants of MDR-TB treatment outcome, particularly with regard to physical accessibility to the TB hospitals. Accordingly, non-spatial factors in terms of previous treated status need for more attention by public health policy makers, and then more focus should be placed on the health delivery system, particularly in elderly patients. In addition, using the GIS application with a view to MDR-TB distribution and physical accessibility to hospitals is a novel method in Shanghai and it can be developed to reach other related public health disciplines.

Multidrug-Resistant Tuberculosis Treatment Outcomes in Relation to Treatment and Initial Versus Acquired Second-Line Drug Resistance.

Resistance to second-line drugs develops during treatment of multidrug-resistant (MDR) tuberculosis, but the impact on treatment outcome has not been determined. Patients 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. Of 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. Increasing 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.

Management and treatment outcomes of MDR-TB: results from a setting with high rates of drug resistance.

Although Pakistan has a high burden of multidrug-resistant tuberculosis (MDR-TB), little is known about the management and treatment outcomes of MDR-TB patients in Pakistan. To evaluate management and predictors of unsuccessful treatment outcomes among MDR-TB patients. In this observational cohort study, 196 MDR-TB patients enrolled at the Programmatic Management Unit for drug-resistant TB of Lady Reading Hospital, Peshawar, Pakistan, between 1 January 2012 and 28 February 2013 were included. Patients were followed until an outcome was recorded or 31 January 2015. Extensive concurrent resistance to ofloxacin (OFX) and pyrazinamide (54.6%) was observed. Among 181 patients for whom treatment outcome was available, 135 (74.6%) were cured, 1 (0.6%) completed treatment, 35 (19.3%) died, 8 (4.4%) failed treatment and 2 (1.1%) defaulted. In multivariate analysis, predictors of unsuccessful treatment outcome (death, failure and default) were age >40 years (OR 3.412, P = 0.009), baseline body weight <40 kg (OR 2.966, P = 0.020), concurrent comorbidity (OR 3.785, P = 0.023), resistance to OFX (OR 2.777, P = 0.023), lung cavitations at baseline chest X-ray (OR 5.253, P < 0.001) and regimen modification due to adverse events (OR 3.492, P = 0.037). The treatment outcome results were encouraging. Patients with identifiable predictors of poor treatment outcome should receive enhanced clinical management. Early detection and management of mild adverse effects can help prevent regimen modification and may improve treatment outcomes.

Treatment outcomes for HIV and MDR-TB co-infected adults and children: systematic review and meta-analysis.

The incidence of multidrug-resistant tuberculosis (MDR-TB) is increasing in high human immunodeficiency virus (HIV) prevalence settings, with high associated mortality. Treatment outcomes in HIV-co-infected adults and children are poorly documented. To systematically assess treatment outcomes among HIV-MDR-TB co-infected patients. We searched two databases and the proceedings of an annual international conference up to November 2014 for studies reporting on major clinical outcomes among HIV-MDR-TB-co-infected adults and children, and pooled the results using random-effects meta-analysis. Of 4812 abstracts and articles screened, 30 studies providing data on 2578 adults and 147 children were included. Overall pooled treatment success was 56.9% (95% confidence interval [CI] 46.2-67.6), 49.9% (95%CI 38.5-61.2) among adults and 83.4% (95%CI 74.7-92) among children. Mortality was 38% in adults (95%CI 28-48.1) and 11.4% (95%CI 5.8-17.1) in children. Loss to follow-up was higher among adults (16.1%, 95%CI 9-23.2) than among children (3.9%, 95%CI 0.9-6.9). Adverse events were experienced by the majority of patients; however, this was inconsistently documented. The use of fluoroquinolones, aminoglycosides and Group IV drugs appeared to be associated with treatment success. The proportion of HIV-MDR-TB-co-infected patients achieving treatment success was similar to success rates reported among MDR-TB patients in general, regardless of HIV status; however, mortality was higher, particularly among adults, highlighting the need for early diagnosis and more effective treatment regimens.

Host-Directed Therapies for Tackling Multi-Drug Resistant Tuberculosis: Learning From the Pasteur-Bechamp Debates.

Tuberculosis remains a global emergency causing an estimated 1.5 million deaths annually. For several decades the major focus of tuberculosis treatment has been on antibiotic development targeting Mycobacterium tuberculosis. The lengthy tuberculosis treatment duration and poor treatment outcomes associated with multi-drug resistant tuberculosis (MDR-TB) are of major concern. The sparse new tuberculosis drug pipeline and widespread emergence of MDR-TB signal an urgent need for more innovative interventions to improve treatment outcomes. Building on the historical Pasteur-Bechamp debates on the role of the "microbe" vs the "host internal milieu" in disease causation, we make the case for parallel investments into host-directed therapies (HDTs). A range of potential HDTs are now available which require evaluation in randomized controlled clinical trials as adjunct therapies for shortening the duration of tuberculosis therapy and improving treatment outcomes for drug-susceptible tuberculosis and MDR-TB. Funder initiatives that may enable further research into HDTs are described.

Loss-To-Follow-Up on Multidrug Resistant Tuberculosis Treatment in Gujarat, India: The WHEN and WHO of It.

BackgroundMultidrug-resistant Tuberculosis (MDR-TB) is a rising global threat to public health and concerted efforts for its treatment are diluted if the outcomes are not successful, loss to follow up (LFU) being one of them. It is therefore necessary to know the proportion and the associated reasons for LFU and devise effective patient-centered strategies to improve retention in care.MethodsA retrospective cohort study was conducted at the MDR-TB treatment site (DR-TB Site)in Central Gujarat among all patients registered from February 2010 to June 2013.LFU patients were defined as those whose treatment was interrupted for two or more consecutive months for any reason. Descriptive statistics, survival analysis and multivariate modeling were used to determine the proportion of patients LFU and to assess associations between LFU and selected demographic and clinical factors.ResultsA total of 796 patients were enrolled during the study period; 71.9% were male and the median age was 35 years [Interquartile range (IQR) 27-45].The overall proportion of LFU patients was 153/796 (19.2%).The majority of LFU patients (133/153 i.e.87%) were lost within the first 6 months of treatment. Ambulatory treatment initiation (adjusted Hazards ratio aHR=2.63, CI:1.01-6.86), different providers in IP and CP ( aHR=1.27, CI:1.18-1.38)and culture conversion after more than 4 months of treatment(aHR=1.34, CI: 1.21-1.49)were found to be significantly associated with LFU in multivariate models.ConclusionsA high proportion of LFU among patients on MDR-TB treatment was found in a programmatic setting in India. Clinical but equally important programmatic factors were associated with LFU, accounting for one-fifth of all the outcomes of MDR-TB treatment. Proper training for DOT providers and aggressive counseling and health system strengthening with patient friendly follow up services may help reduce LFU.

Reply: How Do the New Definitions for Multidrug-Resistant Tuberculosis Treatment Outcomes Really Perform?

Reply: How Do the New Definitions for Multidrug-Resistant Tuberculosis Treatment Outcomes Really Perform?

Highly successful treatment outcome of multidrug-resistant tuberculosis in the Netherlands, 2000–2009

Resistance to the two key anti-tuberculosis drugs isoniazid and rifampicin is a characteristic of multidrug-resistant tuberculosis (MDR-TB). MDR-TB is a scourge requiring toxic, prolonged treatment and is associated with poor outcomes. The Netherlands is a country with a long-standing, integrated, well-resourced TB service where all patients are offered culture-confirmed diagnosis by a central reference laboratory. To assess the treatment outcomes of MDR-TB patients over a period of 10 years in The Netherlands. Demographic, clinical and microbiological features of all patients with MDR-TB who started treatment in 2000-2009 in the Netherlands were analysed from national registry and patient records. Characteristics of the 113 MDR-TB patients were as follows: male/female ratio 1.57, 96% foreign born, median age 29 years, 96 (85%) pulmonary TB, 56 (50%) smear-positive, 14 (12%) human immunodeficiency virus (HIV) co-infected. Of the 104 (92%) patients who started MDR-TB treatment, 86% had a successful outcome using a median of six active drugs; eight underwent pulmonary surgery. HIV negativity was associated with successful outcome (adjusted OR 2.1, 95%CI 1.1-3.8). High success rates for MDR-TB treatment were achieved with close collaboration of all stakeholders, reaching the targets set for drug-susceptible TB. HIV remained an independent risk factor for unsuccessful treatment outcome.

Predictors of cure among HIV co-infected multidrug-resistant TB patients at Sizwe Tropical Disease Hospital Johannesburg, South Africa.

The global incidence of multidrug-resistant tuberculosis (MDR-TB) is rising, especially among HIV infected patients, despite intervention programs. Limited data are available on outcomes of MDR-TB treatment, specifically in a cohort of HIV co-infected patients in sub-Saharan Africa. The objective of this study was to determine the predictors of cure among MDR-TB HIV co-infected patients. A retrospective review of 1200 medical records of HIV co-infected MDR-TB patients was performed at Sizwe Tropical Disease Hospital, Johannesburg covering the period 2007 to 2010. Logistic regression analysis was done to identify predictors of cure. Of 1137 patients included in the analysis, 29.8% (339/1137) were cured, 16.5% (188/1137) completed treatment, 22.3% (254/1137) defaulted treatment, 2.9% (33/1137) failed treatment and 22.7% (258/1137) died while on treatment. The remaining 5.7% (65/1137) were transferred-out or still-on-treatment. There was a significant interaction between sex and timing of antiretroviral treatment (ART) initiation (p=0.008). Factors predicting cure were male patients on ART prior to commencing MDR-TB treatment (OR 1.87, [1.11-3.13]), CD4(+) cell counts between 201-349 (OR 2.06, [1.10-3.84]) and ≥ 350 cells/mm³ (OR 1.98, [0.98-3.97]). Negative predictors of cure included the presence of cavitary lesions on chest x-rays (OR 0.55, [0.38-0.78]) and modified individualised regimen at baseline (OR 0.62, [0.42-0.92]). Cure was higher in males on ART prior to initiating MDR-TB treatment compared with males on ART after initiating MDR-TB treatment. The inverse was the case among females. Therefore, future research should explore the biological and behavioural mechanisms that may possibly be responsible for this observed trend. This will help improve MDR-TB treatment outcomes in HIV co-infected patients on ART.

Treatment outcomes of multidrug-resistant tuberculosis in Switzerland.

To assess outcomes 24 months after treatment start for multidrug-resistant tuberculosis (MDR-TB). Cohort study of all culture-positive MDR-TB cases notified in Switzerland from 01/2003 to 07/2010. Fifty-one cases were observed, with a median age of 26 years (range 2-56). Twenty-seven were male, five of Swiss origin, 46 of foreign origin (Asia 18, Africa 13, former Soviet Union 8), including 21 asylum seekers and refugees. Twelve had received a previous treatment for TB and 24 had not (15 unknown). Forty-four cases were pulmonary of which 25 were known to be sputum smear positive. All but two strains showed additional resistances: 29 to ethambutol, 27 to pyrazinamide, 6 to a fluoroquinolone, 5 to amikacin. None was resistant to both of the latter two classes. Molecular analyses showed three pairs of identical strains. Fluoroquinolones were used in 48 patients and second-line injectable drugs in 37. The median duration of MDR treatment was 18 months (range 1-26). The outcome after 24 months was successful in 39 (76%) and unsatisfactory in 12 (24%) patients: two deaths from TB; two treatments terminated owing to side effects of drugs and one owing to pregnancy; four defaults from treatment at months 0, 4, 8, and 21; two transfers abroad with unknown outcome; one outcome unknown. There was no significant association of unfavourable outcomes with age, sex, origin, previous treatment, treatment delay, resistance pattern, and classes of drugs used. MDR-TB in Switzerland occurs mostly in persons of foreign origin. Results of decentralised treatments were satisfactory.

The Effect of Smoking on Treatment Outcome of Multidrug-Resistant Tuberculosis

The Effect of Smoking on Treatment Outcome of Multidrug-Resistant Tuberculosis

Aggressive Regimens for Multidrug-Resistant Tuberculosis Decrease All-Cause Mortality

RationaleA better understanding of the composition of optimal treatment regimens for multidrug-resistant tuberculosis (MDR-TB) is essential for expanding universal access to effective treatment and for developing new therapies for MDR-TB. Analysis of observational data may inform the definition of an optimized regimen.ObjectivesThis study assessed the impact of an aggressive regimen–one containing at least five likely effective drugs, including a fluoroquinolone and injectable–on treatment outcomes in a large MDR-TB patient cohort.MethodsThis was a retrospective cohort study of patients treated in a national outpatient program in Peru between 1999 and 2002. We examined the association between receiving an aggressive regimen and the rate of death.Measurements and Main ResultsIn total, 669 patients were treated with individualized regimens for laboratory-confirmed MDR-TB. Isolates were resistant to a mean of 5.4 (SD 1.7) drugs. Cure or completion was achieved in 66.1% (442) of patients; death occurred in 20.8% (139). Patients who received an aggressive regimen were less likely to die (crude hazard ratio [HR]: 0.62; 95% CI: 0.44,0.89), compared to those who did not receive such a regimen. This association held in analyses adjusted for comorbidities and indicators of severity (adjusted HR: 0.63; 95% CI: 0.43,0.93).ConclusionsThe aggressive regimen is a robust predictor of MDR-TB treatment outcome. TB policy makers and program directors should consider this standard as they design and implement regimens for patients with drug-resistant disease. Furthermore, the aggressive regimen should be considered the standard background regimen when designing randomized trials of treatment for drug-resistant TB.

Impact of the human immunodeficiency virus on early multidrug-resistant tuberculosis treatment outcomes in Botswana

The impact of the human immunodeficiency virus (HIV) on multidrug-resistant tuberculosis (MDR-TB) treatment outcomes in sub-Saharan Africa, where extensive rollout of highly active antiretroviral therapy (HAART) has occurred, remains unclear. To compare the time to initial culture conversion among patients with and those without HIV infection in a setting of individualized MDR-TB care in Botswana. Prospective cohort study of MDR-TB patients receiving ambulatory, integrated TB-HIV care at two public clinics in Botswana. The time to culture conversion was compared by HIV status using Cox proportional hazard ratios (HRs). A total of 40 HIV-infected and 30 non-HIV-infected patients with MDR-TB and follow-up cultures were identified. The median time to initial culture conversion was 78 days (interquartile range [IQR] 42-186) for HIV-infected and 95 days (IQR 70-133) for non-HIV-infected individuals (log rank P > 0.5; unadjusted HR 0.9, 95%CI 0.5-1.5). Adjusting for age, sex, treatment history and number of active anti-tuberculosis drugs did not change this result (adjusted HR 0.8, 95%CI 0.4-1.4). We found no difference in the proportion of or time to initial sputum culture conversion between an HIV-infected and a non-infected cohort of MDR-TB patients in Botswana, suggesting that outcomes may be comparable in similar settings with access to individualized anti-tuberculosis treatment and HAART.

Outcomes of Multidrug-Resistant Tuberculosis Treatment with Early Initiation of Antiretroviral Therapy for HIV Co-Infected Patients in Lesotho

BackgroundAlthough the importance of concurrent treatment for multidrug-resistant tuberculosis (MDR-TB) and HIV co-infection has been increasingly recognized, there have been few studies reporting outcomes of MDR-TB and HIV co-treatment. We report final outcomes of comprehensive, integrated MDR-TB and HIV treatment in Lesotho and examine factors associated with death or treatment failure.MethodsWe reviewed clinical charts of all adult patients who initiated MDR-TB treatment in Lesotho between January 2008 and September 2009. We calculated hazard ratios (HR) and used multivariable Cox proportional hazards regression to identify predictors of poor outcomes.ResultsOf 134 confirmed MDR-TB patients, 83 (62%) were cured or completed treatment, 46 (34%) died, 3 (2%) transferred, 1 (1%) defaulted, and 1 (1%) failed treatment. Treatment outcomes did not differ significantly by HIV status. Among the 94 (70%) patients with HIV co-infection, 53% were already on antiretroviral therapy (ART) before MDR-TB treatment initiation, and 43% started ART a median of 16 days after the start of the MDR-TB regimen. Among HIV co-infected patients who died, those who had not started ART before MDR-TB treatment had a shorter median time to death (80 days vs. 138 days, p = 0.065). In multivariable analysis, predictors of increased hazard of failure or death were low and severely low body mass index (HR 2.75, 95% confidence interval [CI] 1.27–5.93; HR 5.50, 95% CI 2.38–12.69), and a history of working in South Africa (HR 2.37, 95% CI 1.24–4.52).ConclusionsFavorable outcomes can be achieved in co-infected patients using a community-based treatment model when both MDR-TB and HIV disease are treated concurrently and treatment is initiated promptly.

Integrated, home-based treatment for MDR-TB and HIV in rural South Africa: an alternate model of care.

Treatment outcomes for multidrug-resistant tuberculosis (MDR-TB) in South Africa have suffered as centralized, in-patient treatment programs struggle to cope with rising prevalence and human immunodeficiency virus (HIV) co-infection rates. A new treatment model is needed to expand treatment capacity and improve MDR-TB and HIV outcomes. To describe the design and preliminary results of an integrated, home-based MDR-TB-HIV treatment program created in rural KwaZulu-Natal. In 2008, a decentralized center was established to provide out-patient MDR-TB and HIV treatment. Nurses, community health workers and family supporters have been trained to administer injections, provide adherence support and monitor adverse reactions in patients' homes. Physicians assess clinical response, adherence and the severity of adverse reactions to MDR-TB and HIV treatment at monthly follow-up visits. Treatment outcomes are assessed by monthly cultures and CD4 and viral load every 6 months. Of 80 patients initiating MDR-TB treatment from February 2008 to April 2010, 66 were HIV-co-infected. Retention has been high (only 5% defaults, 93% of visits attended), and preliminary outcomes have been favorable (77% cured/still on treatment, 82% undetectable viral load). Few patients have required escalation of care (9%), had severe adverse events (8%) or died (6%). Integrated, home-based treatment for MDR-TB and HIV is a promising treatment model to expand capacity and achieve improved outcomes in rural, resource-poor and high HIV prevalent settings.

Treatment Outcome of Multidrug-Resistant Mycobacterium tuberculosis in Nepal

The purpose of this study was to examine factors associated with treatment outcome of multidrug-resistant tuberculosis (MDR-TB) cases in Nepal. A retrospective analysis of MDR-TB cases by demographic determinants and treatment was conducted. A total of 494 MDR-TB cases were registered from 2005 to 2008, with data obtained from the National Tuberculosis Center. Chi-squared tests were used to assess statistically the association between smear and culture conversion and treatment outcome. Determinants were analyzed with the use of Kaplan-Meier curves and Cox proportional hazards models to generate estimates of the associations with the time to treatment outcome. Sputum conversion status and culture conversion status were positively associated with treatment outcome for MDR-TB. In a multiple Cox proportional hazards regression model, no determinants were found to be associated with time to cure.

Concordance of programmatic and laboratory-based multidrug-resistant tuberculosis treatment outcomes in Peru

Confirmation of cure for multidrug-resistant tuberculosis (MDR-TB) patients requires laboratory tests for Mycobacterium tuberculosis growth on culture media. Outcome decisions dictate patient management, and inaccuracies place patients at an increased risk of morbidity and mortality, and may contribute to continued transmission of MDR-TB. To examine concordance between programmatic and laboratory-based MDR-TB treatment outcomes. The study population included 1658 MDR-TB patients in Peru treated between 1996 and 2002 with both program and laboratory-based outcomes. Laboratory-based outcomes were assigned according to international standards requiring at least five consecutive negative cultures in the last 12 months of treatment to confirm cure. Compared to the global culture-defined standard classification, only 1.1% of treatment successes, but 54.3% of failures, were misclassified programmatically. Overall, 10.4% of patients identified by a clinician as having a successful treatment outcome still had cultures positive for MDR-TB. Most patients with successful treatment outcomes by strict culture definitions were also classified by clinicians as having successful outcomes. However, many culture-confirmed failures were missed. In light of delays and incomplete access to culture in MDR-TB programs, efforts should be made to improve the accuracy of programmatically determined treatment outcomes.

Comparing early treatment outcomes of MDR-TB in decentralised and centralised settings in KwaZulu-Natal, South Africa

In KwaZulu-Natal, South Africa, a setting endemic for tuberculosis (TB) and the human immunodeficiency virus (HIV), prolonged hospitalisation for the treatment of the growing number of multidrug-resistant TB (MDR-TB) patients is neither possible nor effective. To compare early treatment outcomes in patients with MDR-TB with and without HIV co-infection at four decentralised rural sites with a central urban referral hospital. This is an operational, prospective cohort study of patients between 1 July 2008 and 30 November 2009, where culture conversion, time to culture conversion, survival and predictors of these outcomes were analysed. Of 860 patients with MDR-TB, 419 were at the decentralised sites and 441 at the central hospital. Overall, 71% were HIV co-infected. In the 17-month study period, there was a higher proportion of culture conversion at the decentralised sites compared with the centralised hospital (54% vs. 24%, P < 0.001, OR 3.76, 95%CI 2.81-5.03). The median time to treatment initiation was significantly shorter at the decentralised sites compared with the centralised hospital (72 vs. 93 days, P < 0.001). There was no significant difference in survival following treatment initiation. In this study, early treatment outcomes suggest that decentralised care for MDR-TB patients is superior to that in a centralised setting.