Culture Conversion Rate Research Articles

Cigarette smoking and culture conversion in patients with susceptible and M/XDR-TB.

Tuberculosis (TB) is a leading cause of morbidity and mortality worldwide. Active cigarette smoking may have a significant impact on treatment responses to anti-tuberculosis treatment. To ascertain the effect of smoking on Mycobacterium tuberculosis sputum culture conversion rates following treatment initiation in patients with susceptible, multidrug-resistant and extensively drug-resistant TB (M/XDR-TB). Sputum cultures of smoking and non-smoking patients with pulmonary TB (PTB) treated at a referral centre in Germany were evaluated. Between January 2012 and March 2017, 247 patients with PTB treated at the Medical Clinic of Research Center Borstel, Borstel, Germany, were included in the study. Of 247 patients, 65 (26.3%) were infected with multidrug-resistant strains of M. tuberculosis (MDR-TB). Sputum culture examinations were performed on a weekly basis. Active smoking (n = 111; time to culture conversion [TCC] 50.7 days, interquartile range [IQR] 26.5-73.0) and former smoking (n = 72; TCC 43.1 days, IQR 19.8-56.0) significantly delayed culture conversion rates (P < 0.001) when compared with never smoking (n = 64; TCC 33.2 days, IQR 8.0-50.3). Delay in TCC among smoking, non-MDR-TB patients (n = 138; TCC 47.3 days, IQR 19.0-89.0) was comparable with non-smoking, MDR-TB patients (n = 20; TCC 53.0 days, IQR 18.0-71.0). The shortest TCC was observed in non-smoking, non-MDR-TB patients (n = 44; TCC 33.0 days, IQR 10.0-48.5), whereas the longest was seen in smoking, MDR-TB patients (n = 45; TCC 60.7 days, IQR 33.3-89.0); P < 0.001). Active cigarette smoking and, to a lesser extent, former cigarette smoking, substantially delayed culture conversion in PTB.

Treatment outcome of multidrug-resistant tuberculosis with modified DOTS-plus strategy: A 2 years' experience.

Background:Multidrug-resistant tuberculosis (MDR-TB) is a global health problem with notoriously difficult and challenging treatment. This study determined treatment outcome in patients of MDR-TB with modified DOTS-Plus strategy.Methods:Ninety-eight consecutive MDR-TB patients treated with standardized regimen according to modified DOTS-Plus strategy aligned to the existing national DOTS-Plus guidelines with relevant modifications proposed by Chennai consensus were analyzed prospectively. Treatment included monthly follow-up with clinical, radiological, and bacteriological assessment (sputum smear advised monthly till conversion then quarterly; culture for Mycobacterium tuberculosis at 0, 4, 6, 12, 18, and 24 months), ensuring adherence, intense health education, and monitoring of adverse events (AEs). Patients' outcome was considered as cure when at least two of the last three cultures (all three or last two) were negative and as failure when the same were positive.Results:Favorable and unfavorable outcomes in this cohort were reported to be 71/98 (72.4%) and 27/98 (27.6%) (failure – 10 [10.2%], default – 7 [7.1%], and expiry – 10 [10.2%]), respectively. Sputum smear and culture conversion rate were 75/81 (92.5%) and 71/81 (87.7%), respectively. Major AEs were experienced in only 17.4% of patients.Conclusions:MDR-TB can be cured successfully with modified DOTS-Plus strategy and requires much effort from both the patients and health-care workers. It can be an alternative model for treating MDR-TB patients in private sector.

Bedaquiline and delamanid in the treatment of multidrug-resistant tuberculosis: Promising but challenging.

Improving treatment outcomes in multidrug‐resistant tuberculosis (MDR‐TB) is partly hampered by inadequate effective antitubercular agents. Development of bedaquiline and delamanid has potentially changed the treatment landscape for MDR‐TB. This review provides an update on the progress of these novel antitubercular agents. We review published studies aimed at evaluating clinical efficacy and effectiveness of bedaquiline and delamanid. Five prospective clinical studies and seven retrospective studies on bedaquiline showed that patients treated with a bedaquiline‐containing regimen had a high culture conversion rate ranging from 65 to 100% and a satisfactory treatment outcome. The combined use with linezolid might add to the effectiveness of bedaquiline. Controversies about bedaquiline resistance are discussed. Three clinical trials have reported outcomes on delamanid and showed that introducing delamanid to a background regimen improved culture conversion rate at 2 months from 29.6% to more than 40%. A higher favorable treatment rate was also observed among patients who received delamanid for more than 6 months, but about a quarter of patients defaulted in the control group. Seven retrospective studies were summarized and found a treatment benefit as well. More reliable evidence from randomized clinical trials reporting on the treatment outcomes is needed urgently to support a strong recommendation for the use of delamanid. Advances in the combined use of bedaquiline and delamanid are also reviewed, and the combination may be well tolerated but requires electrocardiograph monitoring.

794. Infectivity of Smear-Positive Pulmonary TB After 2 Weeks of Rifampicin-based Anti-Tuberculous Therapy

BackgroundPulmonary tuberculosis (TB) remains one of the leading infectious causes of morbidity and mortality worldwide. Most data showed that infectiousness of pulmonary TB diminishes rapidly after 2 weeks of effective anti-tuberculous therapy and the bacilli seen in the smear after 2 weeks are most likely nonviable. We aim to assess this hypothesis by doing sputum culture after 2 weeks of therapy to assess the viability of the bacilli in the smear.MethodsA prospective cohort study was conducted on patients admitted to Communicable Disease Centre (CDC), Qatar with smear positive pulmonary tuberculosis during the period November 2013–November 2014. We repeated sputum smear and culture after 2 weeks of rifampicin based regimen to assess the infectivity. Demographic and clinical characteristics of patients was evaluated and compared with smear and culture conversion rate.ResultsNinety-five cases were included in the study. All had sputum smear and culture after 2 weeks of supervised rifampicin based therapy (Table 1). Sputum culture at two weeks of treatment was positive in 91 cases (95.7%) and only four cases were culture negative after 2 weeks. Demographic and clinical characteristics were compared with the culture status after 2 weeks, found Patient from Indian subcontinent and symptoms duration more than 1 month are less likely to clear infection after 2 weeks with P-value 0.01 and 0.009, respectively (Table 2). The calculated mean for sputum smear and culture conversion rate was 4 and 8 weeks, respectively. The presence of cough and the duration of symptoms were associated significantly with rapid sputum conversion (P < 0.05); however, the presence of cavity on CXR had no statistical significant effect (Table 3). ConclusionMajority of our patients in the study have positive TB culture after two weeks of rifampicin based anti-tuberculosis therapy. So, discontinuation of the isolation after 2 weeks of treatment assuming that bacilli in the smear are nonviable may not be safe.Disclosures All authors: No reported disclosures.

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.

800. Drug-Resistant TB: An Experience From Qatar

BackgroundDrug-resistant tuberculosis (DR-TB) is an important issue for public health. This study was conducted to evaluate the characteristics, treatment outcome, and risk factors associated with 223 DR-TB cases in the State of Qatar.MethodsA descriptive records-based retrospective study was conducted on patients registered at Communicable Disease Centre (CDC), Qatar to all consecutive microbiologically confirmed tuberculosis cases for the period January 2010–March 2015. Demographic and clinical data extracted included: patient’s age, sex, and country of origin; disease site (pulmonary or extra-pulmonary); presence of comorbidities, HIV/AIDS status, previous chemoprophylaxis and/or previous treatment for TB, and anti-TB drug resistance the resistance pattern of isolated mycobacteria. The sputum culture conversion rate and treatment outcome was assessed for the patient who completed their treatment in QatarResultsOf 3,301 patients with positive M. tuberculosis culture were analyzed; 223 (6.7%) were resistant to one or more first-line drugs, to isoniazid in 3.1% (n = 102), streptomycin in 1.2% (n = 41), rifampicin in 0.2% (n = 6), ethambutol in 0.15% (n = 5), and multi-drug resistance in 1.2% (n = 38) of patients. Among the resistant TB patients, more common demographic characteristics were former resident of Indian subcontinent (64.1%). A history of anti-TB treatment was not a risk factor with drug resistance in our cohort. Only 111 (49.7%) patients were tested for HIV antibodies and the results were all negative. There was significant correlation between the type of drug-resistance and CXR finding (23.3% had cavity—P = 0.019). Sputum culture conversion to negative at 2 month of therapy was 94% (n = 101), whereas 122 cases lost follow-up. The outcome of treatment was assessed for 85 resistant cases with follow-up after completion of treatment, show cure rate of 97.6%, and relapse of 2.4%. However, 137 cases (61.4% from total) they left the country before completion of therapy.ConclusionDrug-resistant TB in Qatar is influenced by migration, especially from the Indian subcontinent, where the patients were probably infected. Rapid sputum sampling performed in the early stages of the disease, patient isolation, and drug susceptibility testing should be the standard of care to avoid further transmission and improve TB control.Disclosures All authors: No reported disclosures.

Substitution of ethambutol with linezolid during the intensive phase of treatment of pulmonary tuberculosis: a prospective, multicentre, randomised, open-label, phase 2 trial

Linezolid improves the treatment outcomes of multidrug-resistant tuberculosis substantially. We investigated whether use of linezolid instead of ethambutol increases the proportion of sputum culture conversion at 8 weeks of treatment in patients with pulmonary tuberculosis. We did a phase 2, multicentre, randomised, open-label trial for patients with pulmonary tuberculosis at the three affiliated hospitals to Seoul National University and National Medical Center (Seoul-Seongnam, South Korea). Patients, aged 20-80 years, with a positive sputum for pulmonary tuberculosis, but without resistance to rifampicin, and current treatment administered for 7 days or fewer, were randomly assigned at a 1:1:1 ratio into three groups. The control group received ethambutol (2 months) with isoniazid, rifampicin, and pyrazinamide. The second group used linezolid (600 mg/day) for 2 weeks and the third group for 4 weeks instead of ethambutol for 2 months. We used a minimisation method to randomise, and stratified according to institution, cavitation on chest radiographs, and diabetes. The primary endpoint was the proportion of patients with negative culture conversion of sputum in liquid media after 8 weeks of treatment. The results of this trial were analysed primarily in the modified intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT01994460. Between Feb 19, 2014, and Jan 13, 2017, a total of 429 patients were enrolled and 428 were randomly assigned into either the control group (142 patients), the linezolid 2 weeks group (143 patients), or the linezolid 4 weeks group (143 patients). Among them, 401 were eligible for primary efficacy analyses. In the modified intention-to-treat analyses, negative cultures in liquid media at 8 weeks of treatment were observed in 103 (76·9%) of 134 control patients, 111 (82·2%) of 135 in the linezolid 2 weeks group, and 100 (75·8%) of 132 in the linezolid 4 weeks groups. The difference from the control group was 5.4% (95% CI -4·3 to 15·0, p=0·28) for the linezolid 2 weeks group and -1·1% (-11·3 to 9·1, p=0·83) for the linezolid 4 weeks group. Numbers of patients who experienced at least one adverse event were similar across the groups (86 [62·8%] of 137 in control, 79 [57·2%] of 138 in the linezolid 2 weeks group, and 75 [62·0%] of 121 in the linezolid 4 weeks group). Resistance to linezolid was not identified in any patient. Higher rates of culture conversion at 8 weeks of treatment with short-term use of linezolid were not observed. However, safety analyses and the resistance profile suggested the potential role of linezolid in shortening of treatment for drug-susceptible tuberculosis. Ministry of Health and Welfare, South Korea.

RELATIONSHIP BETWEEN IN VITRO CLARITHROMYCIN SUSCEPTIBILITY AND SPUTUM CULTURE CONVERSION WITH ADD-ON AMIKACIN LIPOSOME INHALATION SUSPENSION (ALIS) FOR TREATMENT OF REFRACTORY MYCOBACTERIUM AVIUM COMPLEX (MAC) LUNG DISEASE

RELATIONSHIP BETWEEN IN VITRO CLARITHROMYCIN SUSCEPTIBILITY AND SPUTUM CULTURE CONVERSION WITH ADD-ON AMIKACIN LIPOSOME INHALATION SUSPENSION (ALIS) FOR TREATMENT OF REFRACTORY MYCOBACTERIUM AVIUM COMPLEX (MAC) LUNG DISEASE

Is 6 months of bedaquiline enough? Results from the compassionate use of bedaquiline in Armenia and Georgia.

Bedaquiline (BDQ) was initially only available through compassionate use programmes. To assess the effectiveness and safety of multidrug-resistant tuberculosis (MDR-TB) treatment containing BDQ. Retrospective analysis of data from patients receiving BDQ through compassionate use in Armenia and Georgia from April 2013 to April 2015. Logistic regression was used to assess the risk factors associated with unsuccessful treatment outcomes. Of 82 patients included, 84.2% (69/82) had fluoroquinolone-resistant MDR-TB and 43.4% (23/53) were seropositive for the hepatitis C virus (HCV). The culture conversion rate was 84.4% (54/64), and 18.5% (10/54) reverted back to positive. In total, 79.3% (65/82) of the patients reported at least one adverse event. Serious adverse events were reported in 14 patients, with 10/14 patients experiencing fatal outcomes-6/10 related to advanced TB and 2/10 assessed as possibly related to BDQ. Treatment outcomes were as follows: 58.5% treatment success, 12.2% deaths, 7.3% failures and 21.9% lost to follow-up. HCV coinfection was associated with unsuccessful outcomes (adjusted OR 4.45, 95%CI 1.23-16.13). BDQ through compassionate use showed relatively good success rates and safety profiles in a cohort with difficult-to-treat MDR-TB. High rates of reversion may indicate that >24 weeks of BDQ is necessary in some cases. HCV coinfection should be diagnosed and treatment considered in MDR-TB patients.

Amikacin Inhalation as Salvage Therapy for Refractory Nontuberculous Mycobacterial Lung Disease.

Although guidelines recommend amikacin (AMK) inhalation therapy for difficult-to-treat nontuberculous mycobacterial lung disease (NTM-LD), data are limited regarding the safety and clinical efficacy of this salvage therapy. We retrospectively evaluated the treatment outcomes of 77 patients with refractory NTM-LD caused by Mycobacterium abscessus complex (MABC) or M. avium complex (MAC) who initiated AMK inhalation therapy between February 2015 and June 2016. MABC was the most common etiology (n = 48, 62%), followed by MAC (n = 20, 26%) and mixed infections (n = 9, 12%). Isolates with macrolide resistance and baseline AMK resistance were identified in 63 (82%) patients and 5 (6%) patients, respectively. At 12 months after AMK inhalation therapy, 49% of patients had symptomatic improvement, whereas 42% had radiological improvement. Conversion to a negative sputum culture occurred in 14 (18%) patients, and the culture conversion rate was higher in patients infected with macrolide-susceptible isolates (7/14, 50%) than in those infected with macrolide-resistant isolates (7/63, 11%) (P = 0.003). Significant decreases in sputum semiquantitative culture positivity occurred after AMK inhalation therapy (P < 0.001). On multivariate analysis, conversion to a negative sputum culture was associated with mixed infections (P = 0.009), a forced expiratory volume in 1 s of greater than 60% (P = 0.008), and the absence of macrolide resistance (P = 0.003). Thirty-eight percent of patients experienced adverse effects, with ototoxicity (n = 15) being the most common. AMK inhalation salvage therapy may improve the treatment responses in some patients with refractory NTM-LD. However, considering the common adverse effects, further evaluation of the optimal dosage and intervals for AMK inhalation therapy is needed.

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.

Impact of integrated psycho-socio-economic support on treatment outcome in drug resistant tuberculosis – A retrospective cohort study

ObjectiveTo assess the impact of providing integrated psycho-socio-economic support to drug resistant tuberculosis (DRTB) patients on the treatment outcome under programmatic conditions. Study designRetrospective cohort study. SettingAn urban district TB centre in India under the Revised National Tuberculosis Control Programme. ParticipantsA cohort of 123 patients who started DRTB treatment between June 2010 and May 2013. MethodsPatients started on treatment for DRTB between June 2010 and May 2013 who were provided with the integrated support package for at least 3 months formed the supported group while the other patients of the cohort formed the non-supported group. The treatment outcomes and sputum culture conversion rates were compared between the two groups. ResultsThe supported group consisted of 60 patients and the non-supported group of 63 patients. The treatment success rate was found to be significantly higher in the supported group (65% vs 46.03%; p=0.0349). Support duration was significantly associated with lower incidence of death [HR 0.876, 95% CI 0.811–0.947; p=0.0009] and loss to follow up [OR: 0.752, 95% CI 0.597–0.873; p=0.0023]. The treatment failure rate was higher in the supported group (16.66% vs 4.76%) with 60% of the failures in the supported group occurring after 24 months of compliant treatment. There was no significant association found between support duration and treatment failure or sputum culture conversion. ConclusionIntegrated support seems to significantly increase the treatment success rate and improve survival and treatment adherence of DRTB patients. However, early diagnosis and effective pharmacotherapy are crucial for reducing treatment failures.

Treatment responses in multidrug-resistant tuberculosis in Germany.

Excellent treatment outcomes have recently been reported for patients with multi/extensively drug-resistant tuberculosis (M/XDR-TB) in settings where optimal resources for individualised therapy are available. To ascertain whether differences remain in treatment responses between patients with M/XDR-TB and those with non-M/XDR-TB. Patients with TB were prospectively enrolled between March 2013 and March 2016 at five hospitals in Germany. Treatment was conducted following current guidelines and individualised on the basis of drug susceptibility testing. Two-month and 6-month sputum smear and sputum culture conversion rates were assessed. A clinical and radiological score were used to assess response to anti-tuberculosis treatment. Non-M/XDR-TB (n = 29) and M/XDR-TB (n = 46) patients showed similar rates of microbiological conversion: 2-month smear conversion rate, 90% vs. 78%; culture conversion rate, 67% vs. 61%; time to smear conversion, 19 days (IQR 10-32) vs. 31 days (IQR 14-56) (P = 0.066); time to culture conversion, 39 days (IQR 17-67) vs. 39 days (IQR 6-85) (P = 0.191). Both clinical and radiological scores decreased after the introduction of anti-tuberculosis treatment. There were no significant differences in scores between the two groups until 6 months of treatment. Under optimal clinical conditions, with the availability of novel diagnostics and a wide range of therapeutic options for individualised treatment, patients with M/XDR-TB achieved 6-month culture conversion rates that were compatible with those in patients with non-M/XDR-TB.

The effect of metformin on culture conversion in tuberculosis patients with diabetes mellitus.

Background/AimsPatients with diabetes mellitus (DM) and tuberculosis (TB) have increased morbidity and a high risk of treatment failure or recurrence. It is important to manage both diseases simultaneously. Among anti-diabetic drugs, metformin inhibits intracellular growth of mycobacteria. Therefore, we examined the effects of metformin on TB treatment, especially in patients with DM.MethodsThis retrospective cohort study included patients with culture-positive pulmonary TB diagnosed between 2011 and 2012. The primary study outcome was sputum culture conversion after 2 months of treatment.ResultsOf 499 patients diagnosed with culture-positive pulmonary TB, 105 (21%) had DM at diagnosis. Among them, 62 (59.5%) were treated with metformin. Baseline characteristics, except for the presence of chronic renal disease, were not significantly different between the metformin and non-metformin groups. Metformin treatment had no significant effect on sputum culture conversion (p = 0.60) and recurrence within 1 year after TB treatment completion (p = 0.39). However, metformin improved the sputum culture conversion rate in patients with cavitary pulmonary TB, who have higher bacterial loads (odds ratio, 10.8; 95% confidence interval, 1.22 to 95.63).ConclusionsAmong cavitary pulmonary TB patients with DM, metformin can be an effective adjunctive anti-TB agent to improve sputum culture conversion after 2 months of treatment.

Factors affecting time to sputum culture conversion and treatment outcome of patients with multidrug-resistant tuberculosis in China

BackgroundFew prospective cohort studies, none in China, have investigated the relationship between treatment outcomes of multidrug-resistant tuberculosis (MDR-TB) patients and sputum culture conversion. Factors affecting the time of the culture conversion throughout the whole course of the treatment have rarely been investigated.MethodsThis study was performed in four cities in Jiangsu province, China. MDR-TB patients were consecutively enrolled between December 2011 and March 2014. Rates of sputum culture conversion were calculated and Cox proportional-hazards model was performed. Factors contributing to sputum culture conversion were investigated.ResultsIn all, 139 MDR-TB patients with treatment outcomes were enrolled. Median time to culture conversion among those who converted was 91.5 days (interquartile range, 34.0–110.8 days). After multivariable analysis, smoking (HR = 0.44; 95% CI: 0.23–0.83), drinking (HR = 0.41; 95% CI: 0.21–0.81), ofloxacin resistance (HR = 0.43; 95% CI: 0.24–0.76) and sputum smear grade > 1 (HR = 0.51; 95% CI: 0.31–0.83) were less likely to have culture conversion.ConclusionsMDR-TB patients who smoke, drink, have ofloxacin resistance, or a high smear grade are less likely to respond to treatment and should be meticulously followed up.

Intermittent Antibiotic Therapy for Recurrent Nodular Bronchiectatic Mycobacterium avium Complex Lung Disease.

Intermittent, three-times-weekly oral antibiotic therapy is recommended for the initial treatment of noncavitary nodular bronchiectatic (NB) Mycobacterium avium complex (MAC) lung disease. However, intermittent therapy is not recommended for patients who have been previously treated. We evaluated 53 patients with recurrent noncavitary NB MAC lung disease who underwent antibiotic treatment for ≥12 months with daily therapy (n = 26) or intermittent therapy (n = 27) between January 2008 and December 2015. Baseline characteristics were comparable between daily therapy and intermittent therapy groups. Sputum culture conversion rates did not differ between daily therapy (21/26, 81%) and intermittent therapy (22/27, 82%) groups. Compared to the etiologic organism at the time of previous treatment, recurrent MAC lung disease was caused by the same MAC species in 38 patients (72%) and by a different MAC species in 15 patients (28%). Genotype analysis in patients with sequenced paired isolates revealed that 86% (12/14) of cases with same species recurrence were due to reinfection with a new MAC genotype. In conclusion, most recurrent noncavitary NB MAC lung disease cases were caused by reinfection rather than relapse. Intermittent antibiotic therapy is a reasonable treatment strategy for recurrent noncavitary NB MAC lung disease.

Evaluation of treatment outcome and adverse drug reaction of directly observed treatment (DOT) plus regimen in multidrug-resistant tuberculosis (MDR-TB) patients at district tuberculosis centre Rajkot.

Background:The emergence of drug-resistant mycobacteria becomes a significant public health problem globally creating an obstacle to effective tuberculosis (TB) control. Gujarat, Maharashtra, and Andhra Pradesh DRS survey estimated that the proportion of multidrug-resistant TB (MDR-TB) is 2.1% (in new TB cases) and 15% (in previously treated cases). Programmatic management of MDR-TB implemented under Revised National Tuberculosis Control Programme in India in 2007.Objectives:The objective of this study is to evaluate treatment outcome and adverse drug reactions (ADRs) of category IV.Materials and Methods:A total of 108 MDR-TB patients were analyzed retrospectively who registered and received treatment during the year of 2014 and 2015 at district TB centre, Rajkot. MDR patients who died or transferred out or defaulter before completion of intensive phase were excluded from the analysis.Results:Of total 108 patients majority patients (64.81%) were in young (20–39 years) with m:f: 2:1. All MDR-TB patients were retreated cases and 69.44% were “undernutrition category”. Culture conversion rate was 86.91% at 4 months of treatment. Cure rate was 50.93% while defaulter rate and died rate was same (17.59%). Failure rate was 18.51%. Weight improvement was significantly associated with cure rate. The incidence of ADR was 32.71%. Most frequent ADRs were related to gastrointestinal system (34.42%), ototoxicity (13.11%), and central nervous system (8.1%). Aminoglycosides, cycloserine, and ethambutol were discontinued due to ADR. Majority ADRs (77.04%) were “possible” category by causality assessment and “mild” in severity assessment. Ototoxicity was only severe ADRs observed.Conclusion:Cure rate was improved than previous years at same center. Attention should be paid for defaulters.

Sputum Smear and Culture Conversion in Multidrug Resistance Tuberculosis Patients in Seven Districts of Central Gujarat, India: A Longitudinal Study.

Objectives:To know the sputum smear and culture conversion among multidrug resistance tuberculosis (MDR-TB) patients.Materials and Methods:The longitudinal cohort study was conducted for 142 MDR-TB patients registered in 2010 under Revised National Tuberculosis Control Programme of Vadodara region. Three follow-ups were taken for sputum and culture examination, at completion of 6, 12, and 24 months of treatment. Individuals were interviewed to know the reasons for missed dose and default.Results:The sputum smear and culture conversion rate was 43.4%, 47.7%, and 57% at 6 months, 12 months, and 24 months of follow-up, respectively. Treatment default rate was highest (15.2%) within initial 6 months of therapy. The mean time to sputum smear and culture conversion was 120.27 days and 125.02 days, respectively.Conclusions:Most of patients who were culture positive at 6 months remained so even after 12 months. There was not much difference in the time taken for culture and sputum conversion.

Treatment outcomes of macrolide-susceptible Mycobacterium abscessus lung disease

Mycobacterium abscessus lung disease is difficult to treat due to inducible resistance to macrolides. However, 15%–20% of isolates are macrolide susceptible. In 14 patients with macrolide-susceptible M. abscessus lung disease, all isolates had nonfunctional erm(41) gene, and sputum culture conversion rate was achieved in 93% (13/14) following antibiotic therapy.

Isoniazid Monoresistance and Rate of Culture Conversion among Patients in the State of Georgia with Confirmed Tuberculosis, 2009-2014.

Isoniazid-monoresistant tuberculosis (INH-monoresistant TB) is the most common drug-resistant TB type in the United States; however, its impact on TB treatment outcomes is not clear. This study aims to understand 1) factors associated with INH-monoresistant TB and 2) the association between INH monoresistance and response to TB treatment. We studied all patients with TB (age, ≥15 yr) reported to the Georgia State Electronic Notifiable Disease Surveillance System (SENDSS) from 2009 to 2014. INH-monoresistant TB was defined as a Mycobacterium tuberculosis isolate resistant to isoniazid only. Time to sputum culture conversion was defined as the time (measured in days) from TB treatment initiation to the date of the first consistently negative culture result reported to the SENDSS. Logistic regression and Cox proportional hazard models were used to estimate the odds and hazard rate of sputum culture conversion, all-cause mortality, and poor TB outcome among patients with INH-monoresistant TB. Among 1,141 culture-confirmed patients with available drug susceptibility testing results, 998 (87.5%) were susceptible to TB first-line drugs, and 143 (12.5%) were patients with INH-monoresistant TB. In multivariable analysis, male sex (adjusted odds ratio [aOR], 1.62; 95% confidence interval [CI], 1.01-2.67) and homelessness (aOR, 5.55; 95% CI, 3.38-9.17) were associated with higher odds of INH-monoresistant TB. In the same multivariable model, older age (≥65 yr old) (aOR, 0.21; 95% CI, 0.07-0.55) and miliary disease (aOR, 0.19; 95% CI, 0.01-0.96) were associated with lower odds of INH-monoresistant TB. Among 1,116 patients with pulmonary TB, the median time to sputum culture conversion was 30 days (interquartile range, 13-58). The rate of culture conversion was similar among patients with and without INH monoresistance (adjusted cause-specific hazard ratio, 1.15; 95% CI, 0.95-1.40). INH-monoresistant TB was not significantly associated with poor TB treatment outcomes (aOR, 1.61; 95% CI, 0.67-3.70) or mortality during TB treatment (aOR, 1.72; 95% CI, 0.58-4.94). Our findings suggest that compared with drug-susceptible TB, patients in Georgia with INH-monoresistant TB have a similar response to TB treatment including culture conversion rate, final TB treatment outcome, and all-cause mortality.