Achieved Sputum Culture Conversion Research Articles

Body Mass Index a Forecast of Sputum Culture Conversion Among Drug-Resistant Tuberculosis Patients.

Background Drug-resistant tuberculosisis a major health issue around the world. The time it takes to find a sputum-positive patient is a major risk factor for the spread of tuberculosis, and many things can indicate a longer time to culture conversion. Also, there is strong proof that poor nutrition is linked to infectious diseases. So, this study aimed to look into the link between a person's body mass index (BMI) and the change of a sputum culture within three months in people who have rifampicin-resistant (RR)/multidrug-resistant (MDR)-tuberculosis (TB) kept on a bedaquiline-based regimen. Materials and methods The Department of Respiratory Medicine at King George's Medical University, Lucknow, hosted an observational, analytical, prospective, single-center study from May 2020 to April 2021. The study included 105 people who had been identified with RR/MDR-TB and were on an optimized background regimen that included a bedaquiline-based regimen. The result we were interested in was sputum culture conversion within three months, and we looked at how BMI related to that outcome. Analytical analyses utilized Pearson's chi-square test for categorical variables and the t-test for continuous variables. Differences with a P-value of <0.05 were considered significant. SPSS software (version 18.0, IBM Corp., Armonk, NY, USA) was used for all analyses, with missing data not replaced or credited. Results A total of 105 people who met the inclusion and exclusion criteria were analyzed. The patients had a mean age of 33.34 years and were mostly male 61 (58%). Fifty-eight (58; 55%) patients lived in rural areas. Most patients had fever 77 (73%), cough 72 (69%), and weight loss 66 (63%). Sixty-nine (69; 66%) patients had a history of TB. Fifty-seven patients had a BMI of <18.5 kg/m2, and 48 patientshad with BMI of ≥18.5. At the end ofthe study, 75/105 patients converted their sputum culture. Of the 105 patients, 57 (54%) had a low BMI (less than 18.5 kg/m2). Among the 57 patients with a BMI of <18.5 kg/m2, only 28(46%) achieved sputum culture conversion after 3 months while 29 (60%) of 48 with BMI ≥18.5 achieved sputum culture conversion after 3 months.Among the patients with a BMI <18.5, 15/57 (26%) tested positive for sputum culture after three months. In patients with a BMI of ≥18.5, only 4/48 (8%) patients tested positive for sputum culture after three months. Conclusion Inpatientswithdrug-resistant tuberculosis, lowBMI (<18.5kg/m2)wasanindependentriskfactor forfailingtoconvert sputum cultureswithinthreemonths.

Therapeutic drug monitoring and TB treatment outcomes in patients with diabetes mellitus.

BACKGROUND: Diabetes mellitus (DM) increases the risk of TB disease and poor treatment outcomes such as delayed sputum culture conversion due to inadequate drug exposure. Therapeutic drug monitoring (TDM) has improved these outcomes in some settings.METHODS: To compare treatment outcomes in programs with routine TDM vs. programs that did not use TDM, we conducted a retrospective study among people with DM and TB at health departments in four US states.RESULTS: A total of 170 patients were enrolled (73 patients in the non-TDM group and 97 patients in the TDM group). Days to sputum culture conversion and total treatment duration were significantly shorter in the TDM group vs. the non-TDM group. In adjusted analyses, patients who underwent TDM were significantly more likely to achieve sputum culture conversion at 2 months (P = 0.007).CONCLUSION: TDM hastened microbiological cure from TB among people with DM and a high risk for poor treatment outcomes in the programmatic setting.

Malnutrition is Associated with Delayed Sputum Culture Conversion Among Patients Treated for MDR-TB.

BackgroundClinicians use sputum culture conversion as an interim indicator of the efficacy of multi-drug resistant tuberculosis (MDR-TB) treatment and to determine treatment duration. Yet, limited studies have been published in Ethiopia.ObjectiveThe objective of this study was to determine the predictors of delayed culture conversion among patients receiving MDR-TB treatment at selected treatment centers in Ethiopia.Patients and MethodsA multi-center observation study was conducted among MDR-TB patients in South and Southwestern Ethiopia from April 14 to May 14, 2019. The data of patients treated from January 2013 to July 2019 were reviewed using a data abstraction tool. The data were analyzed. Descriptive statistics was computed using SPSS version 21 software program. Cox regression was used to identify predictors of delayed culture conversion. Hazard ratios with a two-sided p-value <0.05 were considered statistically significant.ResultsOf 200 included MDR-TB patients, 108 (54%) were males. Majority,159 (79.5%) of the patients had a culture conversion time of less than two months, while 15 (7.5%) had delayed culture conversion (greater than 120 days). Patient’s registration group (after loss to follow- (adjusted hazard ratio (AHR)=16.215, 95% CI [3.839, 68.498]), after treatment failure (AHR=12.161, 95% CI [2.516, 58.793]), history of previous TB treatment (AHR=4.007, 95% CI [3.115, 62.990])) and low BMI (AHR= 1.257; 95% CI [0.725,1.547] were identified as a risk factors for delayed culture conversion.ConclusionOur finding showed that nearly 80% of the patients achieve sputum culture conversion by the second month of treatment. Delayed culture conversion was more likely among patients with malnutrition (BMI<18.5kg/m2), after treatment failure, previous TB treatment, and after lost to follow-up.

Rifampin-resistant/multidrug-resistant Tuberculosis in Alberta, Canada: Epidemiology and treatment outcomes in a low-incidence setting.

Treatment of rifampin-monoresistant/multidrug-resistant Tuberculosis (RR/MDR-TB) requires long treatment courses, complicated by frequent adverse events and low success rates. Incidence of RR/MDR-TB in Canada is low and treatment practices are variable due to the infrequent experience and challenges with drug access. We undertook a retrospective cohort study of all RR/MDR-TB cases in Alberta, Canada from 2007–2017 to explore the epidemiology and outcomes in our low incidence setting. We performed a descriptive analysis of the epidemiology, treatment regimens and associated outcomes, calculating differences in continuous and discrete variables using Student’s t and Chi-squared tests, respectively. We identified 24 patients with RR/MDR-TB. All patients were foreign-born with the median time to presentation after immigration being 3 years. Prior treatment was reported in 46%. Treatment was individualized. All patients achieved sputum culture conversion within two months of treatment initiation. The median treatment duration after culture conversion was 18 months (IQR: 15–19). The mean number of drugs utilized during the intensive phase was 4.3 (SD: 0.8) and during the continuation phase was 3.3 (SD: 0.9) and the mean adherence to medications was 95%. Six patients completed national guideline-concordant therapy, with many patients developing adverse events (79%). Treatment success (defined as completion of prescribed therapy or cure) was achieved in 23/24 patients and no acquired drug resistance or relapse was detected over 1.8 years of median follow-up. Many cases were captured upon immigration assessment, representing important prevention of community spread. Despite high rates of adverse events and short treatment compared to international guidelines, success in our cohort was very high at 96%. This is likely due to individualization of therapy, frequent use of medications with high effectiveness, intensive treatment support, and early sputum conversion seen in our cohort. There should be ongoing exploration of treatment shortening with well-tolerated, efficacious oral agents to help patients achieve treatment completion.

Safety and Efficacy of Nontuberculous Mycobacteria Treatment among Elderly Patients.

Background and objectives: Incidence rates of pulmonary nontuberculous mycobacterial (NTM) disease have been increasing, especially in the elderly population. Given the limited evidence regarding the safety and efficacy of NTM treatment, this study aimed to evaluate the same among elderly patients. Material and methods: Patients diagnosed with NTM disease at a tertiary hospital from January 2007 to December 2017 were enrolled and data were then retrospectively collected. Data of elderly patients who received antimycobacterial treatment were then analyzed. Results: A total of 161 patients satisfied the diagnostic criteria for NTM disease. There were 40 elderly patients who received treatments. Of the patients, 60% received the guideline oriented standard regimens. Single drug regimens were administered to 22.5% of patients. Only 55.0% of the patients were able to continue any treatment. Treatment-related discontinuation was observed in 44.4% of discontinued or changed patients. There were no significant differences in the characteristics of patients with or without adverse events. Patients who were able to continue the treatment for >12 months had a lower proportion of activities of daily living (ADL) disability (nine in 18, 50.0% vs. three in 22, 13.6%, p = 0.018) and heart disease (six in 18, 33.3% vs. 1/22, 4.6%, p = 0.033). Sputum culture conversion was achieved in 28 out of 40 (70.0%) elderly patients treated, and those who achieved sputum culture conversion had more standard regimens prescribed than those who failed sputum culture conversion (21 in 28, 75% vs. 3 in 12, 25%; p = 0.005). Conclusion: Age may not be an obstacle for receiving the benefits of the treatment of NTM disease with a precise evaluation of patient’s comorbidities. Furthermore, elderly patients without heart disease and ADL disability may have better rate of continuing the NTM treatment. The current study suggested that selecting standard regimens to treat pulmonary NTM is important for elderly patients.

The impact of adjuvant surgical treatment of nontuberculous mycobacterial pulmonary disease on prognosis and outcome

BackgroundLung resection in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) has been reported to be associated with favorable outcomes. However, little is known regarding the risk and prognostic factors for refractory and recurrent cases. We aimed to evaluate the overall impact and benefit of adjuvant lung surgery by comparing NTM-PD patients who underwent adjuvant lung resection with those treated exclusively with antibiotics. We also investigated the efficacy of serum IgA antibody against glycopeptidolipid (GPL) core antigen (GPL core antibody) to monitor disease activity and predict the recurrence of disease after adjuvant lung resection.MethodsWe retrospectively evaluated the clinical characteristics and surgical outcomes of 35 patients surgically treated for NTM-PD. Furthermore, we compared surgically treated patients and control patients treated exclusively with antibiotics who were matched statistically 1:1 using a propensity score calculated from age, sex, body mass index, and radiologic features of disease.ResultsIn the surgically treated patients, the median age was 58 (interquartile range, 47–65) years and 65.7% were female. Twenty-eight patients had Mycobacterium avium complex. Operations comprised four pneumonectomies, two bilobectomies, one bilobectomy plus segmentectomy, 17 lobectomies, two segmentectomies, and nine lobectomies plus segmentectomies. Postoperative complications occurred in seven patients (20%), there were no operative deaths, and 33 (94.3%) patients achieved negative sputum culture conversion. Refractory and recurrent cases were associated with remnant bronchiectasis, contralateral shadows, and positive acid-fast bacilli staining or culture. Of 28 statistically matched pairs, long-term sustained negative culture conversion was observed in 23 (82.2%) surgical group patients and in 14 (50.0%) non-surgical group patients (0.0438). The mortality rate was lower in the surgical group, but did not reach statistical significance (one in the surgical group and four in the non-surgical group, p = 0.3516). GPL core antibody was correlated with disease activity and recurrence.ConclusionsNTM-PD patients who underwent adjuvant lung resection experienced overall favorable outcomes and achieved sputum culture conversion more frequently. Long-term mortality may have been reduced by this procedure, and the level of GPL core antibody was shown to be a good clinical indicator of disease activity after surgery.

Intermittent Treatment with Azithromycin and Ethambutol for Noncavitary Mycobacterium avium Complex Pulmonary Disease.

We evaluated the efficacy of intermittent azithromycin and ethambutol therapy for noncavitary Mycobacterium avium complex pulmonary disease (MAC-PD). Twenty-nine (76%) of 38 patients achieved sputum culture conversion after 12 months of treatment, and sputum smear positivity was an independent factor for failure to achieve culture conversion (adjusted odds ratio, 26.7; 95% confidence interval, 2.1 to 339.9; P = 0.011). Intermittent azithromycin and ethambutol may be an optional treatment regimen for noncavitary MAC-PD.

Bedaquiline for the Treatment of Multidrug-resistant Tuberculosis in the United States.

In 2012, the Food and Drug Administration approved use of bedaquiline fumarate as part of combination therapy for multidrug-resistant tuberculosis (MDR TB). We describe treatment outcomes, safety, and tolerability of bedaquiline in our case series. Data on patients started on bedaquiline for MDR TB between September 2012 and August 2016 were collected retrospectively through 4 TB programs using a standardized abstraction tool. Data were analyzed using univariate methods. Adverse events were graded using the Common Terminology Criteria for Adverse Events. Of 14 patients, 7 (50%) had MDR, 4 (29%) had pre-extensively drug-resistant (XDR), and 3 (21%) had XDR TB. All had pulmonary TB, 5 (36%) had pulmonary and extrapulmonary TB, and 9/13 (69%) were smear positive. One patient (7%) had HIV coinfection, 5 (36%) had diabetes mellitus, and 5/14 (36%) had previous treatment TB. All patients were non-US-born and 5/14 (36%) had private insurance. All patients achieved sputum culture conversion within a mean of 71 days (26-116); 5 after starting bedaquiline. Twelve (86%) completed treatment and 1 (7%) moved out of the country. One patient (7%) had QTc prolongation >500 milliseconds and died 20 months after discontinuing bedaquiline of a cause not attributable to the drug. Common adverse events were peripheral neuropathy 7/14 (50%), not customarily associated with bedaquiline use, and QTc prolongation 6/14 (43%). Of 14 patients, 1 (7%) had an adverse event necessitating bedaquiline discontinuation. Safety, culture conversion, and treatment completion in this series (7%) support use of bedaquiline for the treatment of MDR/XDR TB.

Computed tomographic findings of macrolide-resistant Mycobacterium massiliense pulmonary disease and changes after antibiotic treatment.

The purpose of this study was to present the computed tomographic (CT) findings of lung abnormalities in macrolide-resistant Mycobacterium massiliense pulmonary disease and its changes in follow-up CT after antibiotic treatment.Chest CT scans of patients with macrolide-resistant M massiliense pulmonary disease (n = 19) were retrospectively reviewed. Patients were treated with multidrug therapy, and sputum examinations were performed. Follow-up CT scans obtained during antibiotic treatment after detection of macrolide resistance were also reviewed, if available (n = 13). The CT scores at detection of macrolide resistance and at the last follow-up periods were also compared.Of all patients with macrolide-resistant M massiliense pulmonary disease, 2 (11%) patients achieved sputum culture conversion during the follow-up period. The most common CT findings of M massiliense pulmonary disease at detection of macrolide resistance were bronchiectasis and bronchiolitis (n = 19, 100%), followed by consolidation (n = 16, 84%), cavities (n = 11, 58%), and nodules (n = 6, 32%). On the last follow-up CT, overall CT scores were increased in 8 (62%) of 13 patients, and total mean CT score was significantly increased (P = .021). For each CT pattern, the cavity showed the greatest increase in CT score (P = .027), followed by bronchiectasis (P = .038).Common CT findings of macrolide-resistant M massiliense pulmonary disease were similar to those of pulmonary disease caused by other species of nontuberculous mycobacteria at presentation. However, in macrolide-resistant M massiliense pulmonary disease, serial CT scans showed deterioration with cavitary and bronchiectatic change in most patients despite multidrug antibiotic therapy.

Predictors of time to sputum culture conversion in multi-drug-resistant tuberculosis and extensively drug-resistant tuberculosis in patients at Tshepong-Klerksdorp Hospital

SettingKlerksdorp-Tshepong Hospital Complex MDR-TB Unit, North-West Province, South Africa.BackgroundTo determine the time to sputum culture conversion (TTSCC) and factors predictive of TTSCC in patients with multi-drug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) in the North-West Province.MethodsA retrospective cohort study, abstracting patient demographic and clinical data, laboratory results, dates of sputum testing and sputum culture conversion results, from medical records of 526 MDR-TB and 47 XDR-TB patients started on TB treatment between 01 January 2012 and 31 December 2014. Predictors of TTSCC were determined by Cox proportional hazards regression.ResultsThe median age was 38 years (interquartile range 31–47) with 64% being male. Overall, 79% (449) were Human Immunodeficiency Virus (HIV)-infected. The median TTSCC was 56.5 days and 162.5 days for MDR-TB and XDR-TB patients, respectively. In the multivariate analysis, age [hazard ratio (HR): 0.89, 95% confidence interval (CI): 0.96–0.99], being underweight (HR: 0.631.61, 95% CI: 0.451.03–0.882.51), Acid Fast Bacilli (AFB) positivity (HR: 0.72, 95 % CI: 0.51–1.01) and having XDR-TB (HR: 0.36. 95% CI: 0.19–0.69) were predictive of longer TTSCC.ConclusionPredictors of TTSC allow for MDR-TB- and XDR-TB-diagnosed patients to be identified early for effective management. Those with risk factors for delayed sputum culture conversion which are being underweight and having XDR-TB should be monitored carefully during treatment so that they can achieve sputum culture conversion early.

805. Amikacin Liposome Inhalation Suspension (ALIS) Add-on Therapy for Refractory Mycobacterium avium Complex (MAC) Lung Disease: Effect of In Vitro Amikacin Susceptibility on Sputum Culture Conversion

BackgroundALIS (590 mg amikacin base) is liposome-encapsulated amikacin for inhalation, which delivers amikacin directly to the lung and limits systemic exposure. In the CONVERT phase 3 trial, significantly more adults with treatment-refractory MAC lung disease receiving ALIS plus guideline-based therapy (GBT) vs. GBT alone achieved sputum culture conversion by month 6 (29.0% vs. 8.9%, P < 0.0001). Amikacin treatment failure has previously been reported in patients with amikacin minimum inhibitory concentrations (MIC) >64 µg/mL. We analyzed the impact of amikacin MIC on culture conversion during treatment with add-on ALIS.MethodsIn CONVERT, patients were randomly assigned (2:1) to receive once daily ALIS+GBT (n = 224) or GBT alone (n = 112). Patients with amikacin-resistant MAC isolates (MICs >64 μg/mL by broth microdilution) were excluded prior to randomization. The primary endpoint was culture conversion, defined as 3 consecutive monthly MAC-negative sputum cultures by month 6. Amikacin MICs were correlated with culture conversion rates.ResultsAmikacin MIC distributions at baseline (day 1) were similar in both groups (Figure 1). Conversion rates in the ALIS+GBT arm were 28.6–34.5% for MAC with amikacin MICs of 8–64 µg/mL (Figure 2). Overall, 28 patients developed post-screening amikacin MIC >64 µg/mL, 4/112 in the GBT alone arm (post-baseline), and 24/224 in the ALIS+GBT arm (1 at baseline and 23 post-baseline after adding ALIS). Most of these (18/24) had MAC isolates with persistent amikacin MIC >64 µg/mL. Only 1/24 patients in the ALIS+GBT arm with amikacin MIC >64 µg/mL achieved culture conversion. No patient with both macrolide resistance and persistent amikacin MIC >64 µg/mL (8/24) converted.ConclusionIn the ALIS+GBT arm of CONVERT, culture conversion rates were similar for amikacin MICs ranging from 8–64 µg/mL at baseline. Amikacin MIC >64 µg/mL emerged in 10.3% of patients after initiation of add-on ALIS treatment, and 3.6% in the GBT alone arm. Emergent amikacin MIC >64 µg/mL was associated with failure to convert, particularly with concurrent macrolide resistance. Determining amikacin susceptibility at both treatment initiation and during treatment may have utility for guiding treatment decisions. Disclosures B. A. Brown-Elliott, Insmed: Investigator, Research support. G. Eagle, Insmed Incorporated: Employee, Salary. R. J. Wallace, Insmed: Investigator, Research support. J. Van Ingen, Insmed: Investigator, Research support. L. J. Pennings, Insmed: Investigator, Research support. B. Berry, Insmed: Investigator, Research support. S. Pandey, Insmed: Investigator, Research support. C. Coulter, Insmed: Investigator, Research support. M. Syrmis, Insmed: Investigator, Research support. K. L. Winthrop, Insmed Incorporated: Consultant and Scientific Advisor, Consulting fee and Research grant. D. E. Griffith, Aradigm Corporation: Advisor/consultant and Speaker’s Bureau, Consulting fee and Speaker honorarium. Bayer Healthcare Pharmaceuticals: Advisor/consultant, Consulting fee. Grifols: Advisor/consultant and Speaker’s Bureau, Consulting fee and Speaker honorarium. Insmed Incorporated: Advisor/consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Grant recipient and Speaker honorarium.

Outcomes and risk factors after adjuvant surgical treatments for Mycobacterium avium complex lung disease.

Limited information is currently available on the postoperative outcomes of Mycobacterium avium complex lung disease (MAC-LD). To show the outcomes of pulmonary resection and identify risk factors after adjuvant surgical treatments for MAC-LD. One hundred and eight patients underwent adjuvant lung resection for MAC-LD at two hospitals between January 2008 and July 2016. We retrospectively evaluated outcomes and risk factors. Postoperative complications occurred in 14 patients (13%). After lung resection, 98 out of 108 patients (91%) achieved sputum culture conversion, eight (8.2%) of whom developed microbiological recurrence during the follow-up period. As a result, the success rate of adjuvant surgical treatments for MAC-LD with drug resistance was 83%. A multivariable analysis showed that a longer period from the initial medical treatment to surgery (hazard ratio, 1.01; 95% confidence interval, 1.00-1.02; p = 0.008) was independently associated with an increased risk of unfavorable outcomes after adjuvant surgery. Adjuvant surgical treatments for MAC-LD have acceptable outcomes. Better control of the disease may be achieved in some patients with drug resistance and indications for surgery through surgical treatments, and pulmonary resection needs to be performed earlier rather than continuing chemotherapy in these patients because it reduces unfavorable outcomes.

Adjuvant lung resection in the management of nontuberculous mycobacterial lung infection: A retrospective matched cohort study.

Lung resection in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) is considered when medical therapy alone fails to provide long term control. Data regarding comparative and long-term outcomes are limited. We aimed to review indications and outcomes of adjuvant lung resection for NTM-PD compared with controls. We retrospectively studied 27 surgically treated patients, matched 1:1 for age, sex, NTM species, and radiologic pattern of disease, with control patients treated exclusively with antibiotics. In the surgical group, the median (IQR) age was 55 (49-61) years and 74.1% were female. Eighteen patients had Mycobacterium avium complex, and 9 had M. xenopi. Operations included 8 pneumonectomies, 20 lobectomies, one segmentectomy and one lobectomy plus segmentectomy. Post-surgical complications occurred in 6 patients (20%), including 2 acute respiratory distress syndrome, 1 bronchopleural fistula, 1 pericardial tamponade, and 2 empyema. Complications were more common among patients operated upon for progressive disease despite medical therapy (OR 10, p = 0.025). Of 24 matched pairs followed for ≥1 year, sustained culture conversion was observed in 21 (87.5%) patients in the surgical group and in 11 (45.8%) patients in the non-surgical group (RR 2.36, 95%CI 1.37-4.03, p = 0.002). Median (IQR) percentage of follow-up time on antibiotics was 14% (0-100%) in the surgical group and 83% (10.8%-100%) in the non-surgical group (p = 0.195) during a median (IQR) follow-up of 16 (2-36) months. NTM-PD patients who underwent adjuvant lung resection experienced significant morbidity and more frequently achieved sputum culture conversion. Long term antibiotic requirements may have been reduced.

Time to sputum smear and culture conversions in multidrug resistant tuberculosis at University of Gondar Hospital, Northwest Ethiopia.

BackgroundSputum smear and culture conversions are an important indicator of treatment efficacy and help to determine treatment duration in multidrug resistant tuberculosis (MDR-TB) patients. There are no published studies of sputum smear and culture conversion of MDR-TB patients in Ethiopia. The objective of this study is to evaluate and compare time to initial sputum smear and culture conversion and to identify factors influencing time to culture conversion.MethodsA retrospective cohort study was conducted among all culture positive and rifampicin mono resistant (RR) or MDR-TB patients from September 2011 to August 2016 at University of Gondar Hospital. Sputum cultures were collected monthly and conversion was defined as two consecutive negative cultures taken at least 30 days apart. Data were entered using EpiData and exported to SPSS software for analysis. Cox proportional hazard model was used to determine the predictor variables for culture conversion.ResultsOverall, 85.5% (201/235) of the patients converted their cultures in a median of 72 days (inter-quartile range: 44–123). More than half (61.7%) of patients achieved culture conversion within three months. The median time for sputum smear conversion was 54 days (inter-quartile range: 31–72). The median time to culture conversion among HIV positive patients was significantly shorter at 67 days (95% CI, 55.4–78.6) compared to HIV negative patients, 77 days (95% CI, 63.9–90, p = 0.005). Independent predictors of significantly longer time to sputum culture conversion were underweight (aHR = 0.71, 95% CI, 0.52–0.97), HIV negative (aHR = 0.66, 95% CI, 0.47–0.94) and treatment regimen composition (aHR = 0.57, 95% CI, 0.37–0.88). Significantly higher rate of culture conversion was observed in 2015 (aHR = 1.86, 95% CI, 1.1–3.14) and in 2016 (aHR = 3.7, 95% CI, 1.88–7.35) years of treatment compared to 2011.ConclusionsMajority of patients achieved sputum culture conversion within three months and smear conversion within two months. Patients with identified risk factors were associated with delayed culture conversion. These factors should be considered during management of MDR-TB patients.

Bedaquiline and delamanid for the treatment of multidrug-resistant tuberculosis: a multicentre cohort study in Korea.

Relatively little is known about the efficacy and safety of the programmatic use of bedaquiline and delamanid in multidrug-resistant tuberculosis (MDR-TB) treatment.This study evaluated 61 patients with MDR-TB treated with bedaquiline (n=39), delamanid (n=11) or both, either sequentially (n=10) or in coadministration (n=1), for >1 month, combined with a World Health Organization-recommended regimen.Of these, 49 (80.3%) were male and 12 (19.7%) were female. The median (interquartile range (IQR)) age was 53 (38.5-61.0) years. 42 (68.9%) patients had fluoroquinolone-resistant MDR-TB and 16 (26.2%) had extensively drug-resistant TB. The median (IQR) duration of treatment with bedaquiline and/or delamanid was 168 (166.5-196.5) days, with 33 (54.1%) receiving linezolid for a median (IQR) of 673 (171-736) days. Of the 55 patients with positive sputum cultures at the start of bedaquiline and/or delamanid treatment, 39 (70.9%) achieved sputum culture conversion within a median of 119 days. Treatment was halted in four patients (6.6%) because of prolonged Fridericia's corrected QT interval.Bedaquiline and delamanid were effective and safe for treating MDR-TB, with initial evidence of sequential administration of these two drugs as a viable treatment strategy for patients when an adequate treatment regimen cannot be constructed.

Efficacy and Safety of Mycobacterium indicus pranii as an adjunct therapy in Category II pulmonary tuberculosis in a randomized trial

Prolonged treatment of tuberculosis (TB) often leads to poor compliance, default and relapse, converting primary TB patients into category II TB (Cat IITB) cases, many of whom may convert to multi-drug resistant TB (MDR-TB). We have evaluated the immunotherapeutic potential of Mycobacterium indicus pranii (MIP) as an adjunct to Anti-Tubercular Treatment (ATT) in Cat II pulmonary TB (PTB) patients in a prospective, randomized, double blind, placebo controlled, multicentric clinical trial. 890 sputum smear positive Cat II PTB patients were randomized to receive either six intra-dermal injections (2 + 4) of heat-killed MIP at a dose of 5 × 108 bacilli or placebo once in 2 weeks for 2 months. Sputum smear and culture examinations were performed at different time points. MIP was safe with no adverse effects. While sputum smear conversion did not show any statistically significant difference, significantly higher number of patients (67.1%) in the MIP group achieved sputum culture conversion at fourth week compared to the placebo (57%) group (p = 0.0002), suggesting a role of MIP in clearance of the bacilli. Since live bacteria are the major contributors for sustained incidence of TB, the potential of MIP in clearance of the bacilli has far reaching implications in controlling the spread of the disease.

Association between Body Mass Index and Sputum Culture Conversion among South Korean Patients with Multidrug Resistant Tuberculosis in a Tuberculosis Referral Hospital

BackgroundMultidrug-resistant tuberculosis (MDR-TB) is an important global health problem. Furthermore, the time to identify a positive sputum culture is an important risk factor for the spread of tuberculosis, and several factors can predict a prolonged time to culture conversion. Moreover, the relationship between poor nutritional status and infectious disease is clearly established. Therefore, the present study aimed to investigate the association between body mass index (BMI) and sputum culture conversion within 3 months among patients with MDR-TB.Materials and MethodsWe retrospectively evaluated 218 patients with MDR-TB who were treated at a large tuberculosis referral hospital in South Korea between January 2005 and December 2010. The outcome of interest was defined as sputum culture conversion within 3 months, and we analyzed the association between BMI and this outcome.ResultsAmong the 218 patients, 53 patients (24.3%) had a low BMI (<18.5 kg/m2). In the multivariate Cox proportional-hazards regression analysis, failure to achieve sputum culture conversion within 3 months was independently associated with having a low BMI (hazard ratio [HR]: 1.741, 95% confidence interval [CI]: 1.006–3.013; P = 0.047) and a positive sputum smear at the initiation of therapy (HR: 8.440, 95% CI: 1.146–62.138, P = 0.036).ConclusionLow BMI (<18.5 kg/m2) was an independent risk factor for failure to achieve sputum culture conversion within 3 months among patients with MDR-TB.

Long-term outcomes of patients with extensively drug-resistant tuberculosis in South Africa: a cohort study

Long-term treatment-related outcomes in patients with extensively drug-resistant (XDR) tuberculosis are unknown. We followed up a cohort of patients to address knowledge gaps. Between March, 2008, and August, 2012, we prospectively followed up a cohort of 107 patients from three provinces in South Africa, who had been diagnosed with XDR tuberculosis between August 2002, and February, 2008. Available isolates from 56 patients were genotyped to establish strain type and used for extended susceptibility testing. All patients were treated empirically as inpatients with a median of eight drugs (IQR six to ten). 44 patients (41%) had HIV. 36 (64%) of 56 isolates were resistant to at least eight drugs, and resistance to an increasing number of drugs was associated with the Beijing genotype (p=0·01). After 24 months of follow-up, 17 patients (16%) had a favourable outcome (ie, treatment cure or completion), 49 (46%) had died, seven (7%) had defaulted (interruption of treatment for at least 2 consecutive months), and 25 (23%) had failed treatment. At 60 months, 12 patients (11%) had a favourable outcome, 78 (73%) had died, four (4%) had defaulted, and 11 (10%) had failed treatment. 45 patients were discharged from hospital, of whom 26 (58%) had achieved sputum culture conversion and 19 (42%) had failed treatment. Median survival of patients who had failed treatment from time of discharge was 19·84 months (IQR 4·16-26·04). Clustering of cases and transmission within families containing a patient who had failed treatment and been discharged were shown with genotypic methods. Net sputum culture conversion occurred in 22 patients (21%) and median time to net culture conversion was 8·7 months (IQR 5·6-26·4). Independent predictors of probability of net culture conversion were no history of multidrug-resistant tuberculosis (p=0·0007) and use of clofazamine (p=0·0069). Independent overall predictors of survival were net culture conversion (p<0·0001) and treatment with clofazamine (p=0·021). Antiretroviral therapy was also a predictor of survival in patients with HIV (p=0·003). In South Africa, long-term outcomes in patients with XDR tuberculosis are poor, irrespective of HIV status. Because appropriate long-stay or palliative care facilities are scarce, substantial numbers of patients with XDR tuberculosis who have failed treatment and have positive sputum cultures are being discharged from hospital and are likely to transmit disease into the wider community. Testing of new combined regimens is needed urgently and policy makers should implement interventions to minimise disease spread by patients who fail treatment. European and Developing Countries Clinical Trials Partnership, South African National Research Foundation (SARChI), and the South African Medical Research Council.

Comparison of Levofloxacin versus Moxifloxacin for Multidrug-Resistant Tuberculosis

Levofloxacin (LFX) and moxifloxacin (MXF) are the two most frequently recommended fluoroquinolones for treatment of patients with multidrug-resistant tuberculosis (MDR-TB). However, studies comparing the effectiveness of LFX and MXF among patients with MDR-TB are lacking. To compare the effectiveness of LFX and MXF in terms of culture conversion after 3 months of treatment for MDR-TB. In this prospective multicenter randomized open label trial, we randomly assigned 182 patients with MDR-TB (sensitive to LFX and MXF) to receive either LFX (750 mg/day; 90 patients) or MXF (400 mg/day; 92 patients) with a background drug regimen. The primary outcome was the proportion of patients who achieved sputum culture conversion at 3 months of treatment. Secondary outcomes were time to culture conversion and time to smear conversion, with data censored at 3 months, and the proportions of adverse drug reactions. At 3 months of treatment, 68 (88.3%) of the 77 patients in the LFX group and 67 (90.5%) of the 74 in the MXF group showed conversion to negative sputum cultures (odds ratio for LFX compared with MXF, 0.78; 95% confidence interval, 0.27-2.20). Adverse drug reactions were reported in six patients (7.7%) in the LFX group and four (5.2%) in the MXF group (P = 0.75). The choice of LFX or MXF for treatment of patients with MDR-TB may not affect sputum culture conversion at 3 months of treatment. Clinical trial registered with www.clinicaltrials.gov (NCT 01055145).

Extensively Drug-Resistant Tuberculosis Treatment Disappointing Outcomes for Global Public Health

Copyright © 2013, Infectious Diseases and Tropical Medicine Research Center; Published by Kowsar Corp. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Tuberculosis (TB) is an airborne, globally common bacterial infection, easily spread by coughing, and can be fatal. It often lies dormant in the human body for many years; most of the 11 million infected people in the United States are not even aware of its existence. The only available vaccine has limited effectiveness and is not prescribed in most European and American countries. Today, the biggest risk for TB is not HIV/AIDS, which led to a surge in the late 1980s. The most challenging issues in this regard are multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) (1). Researchers followed up the South African patients with XDR-TB, who had been a part of an earlier study looking at early treatment outcomes in 2010. The study said that despite lengthy treatment with a median of eight anti-TB drugs, treatment outcomes were dismal: of 107 patients, only 17 were cured or completed the treatment after 24 months, and 12 had similar favorable outcomes five years after the treatment initiation. Forty nine patients died and in 25, the treatment was failed after 24 months of follow up. After 60 months, 79 patients died and in 11 the treatment was failed. Of the 45 patients released into the community, 19 did not achieve sputum culture conversion (2). Of the 79 patients who died, 32 were infected with HIV. “Twenty four (69%) of 53 patients living with HIV and receiving antiretroviral therapy died by the end of follow-up, compared with 46 (73%) of 63 patients not infected with HIV and all nine patients with HIV not taking antiretroviral therapy” the study said. A CD4 count of less than 200 was also associated with the increased mortality, the study reported. The use of clofazimine in the treatment regimen seemed to reduce the risk of death (2). “Long-term outcomes in patients with XDR-TB are poor, irrespective of HIV status, although antiretroviral therapy has improved survival in patients with HIV” the report stated. “Many patients in our cohort who were discharged from hospital had positive sputum cultures, failed the treatment, and had no further therapeutic options. These patients survived for long periods living in the community and were likely to contribute to the community-based spread of XDR-TB” (2). “Their study should serve as another urgent alarm for global TB control: MDR disease in all its forms is an outof-control problem with potentially vast and devastating repercussions for global public health” they announced. “Clearly, drug regimens that are more effective and better tolerated are needed to improve the adherence, decrease the mortality, and prevent the amplification of TB drug resistance on treatment” (2). As cases of XDR-TB have previously been reported in Iran, both the reports and commentaries call for policymakers and national control programs to urgently develop strategies for applying the existing public health instruments for TB control. They also argue the community-based interventions as well as creation of palliative care facilities to minimize the disease spread by patients with treatment failure (3). Since XDR-TB is resistant to firstand second-line drugs, treatment options are seriously limited. Therefore, it is vital to manage TB control programs properly to prevent further progression of MDR-TB and mitigate the emergence of XDR-TB (4). The mortality rate of patient with XDR-TB infection is about 14%-20%, which may reach to 98% in HIV coinfected patients. In a retrospective study in Iran, a successful outcome was observed in 81.2% of patients with MDR-TB in comparison with 41.6% of patients with XDRTB. These findings indicated that patients with XDR-TB had higher probability of treatment failure and mortality (5).