Sputum Culture Conversion Rate Research Articles

Effectiveness and safety of regimens containing linezolid for treatment of Mycobacterium abscessus pulmonary Disease

ObjectiveTo evaluate the effectiveness and safety of linezolid-containing regimens for treatment of M. abscessus pulmonary disease.MethodsThe records of 336 patients with M. abscessus pulmonary disease who were admitted to Shanghai Pulmonary Hospital from January 2018 to December 2020 were retrospectively analyzed. A total of 164 patients received a linezolid-containing regimen and 172 controls did not. The effectiveness, safety, antibiotic susceptibility profiles, outcomes, culture conversion, cavity closure, and adverse reactions were compared in these two groups.ResultsThe two groups had similar treatment success (56.1% vs. 48.8%; P > 0.05), but treatment duration was shorter in the linezolid group (16.0 months [inter-quartile ranges, IQR: 15.0–17.0] vs. 18.0 months [IQR: 16.0–18.0]; P < 0.01). The rates of sputum culture conversion were similar (53.7% vs. 46.5%, P > 0.05), but time to conversion was shorter in the linezolid group (3.5 months [IQR: 2.5–4.4] vs. 5.5 months [IQR: 4.0–6.8]; P < 0.01). The linezolid group had a higher rate of cavity closure (55.2% vs. 28.6%, P < 0.05) and a shorter time to cavity closure (3.5 months [IQR: 2.5–4.4] vs. 5.5 months [IQR: 4.0–6.8]; P < 0.01). Anemia and peripheral neuropathy were more common in the linezolid group (17.7% vs. 1.7%, P < 0.01; 12.8% vs. 0.6%, P < 0.01).ConclusionsThe linezolid and control groups had similar treatment success rates. The linezolid group had a shorter treatment duration, shorter time to sputum culture conversion, and higher rate and shorter time to lung cavity closure. More patients receiving linezolid developed anemia and peripheral neuropathy.

Impact of Prior Tuberculosis Treatment With New/Companion Drugs on Clinical Outcomes in Patients Receiving Concomitant Bedaquiline and Delamanid for Multidrug- and Rifampicin-Resistant Tuberculosis.

There are scarce data on the clinical outcomes of persons retreated with new/companion anti-tuberculosis (TB) drugs for multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB). We sought to evaluate the efficacy and safety of bedaquiline and delamanid containing regimens among patients with and without prior exposure to the new/companion drugs (bedaquiline, delamanid, linezolid, clofazimine, and fluoroquinolones). We conducted a retrospective cohort study among patients with pulmonary MDR/RR-TB in Georgia who received bedaquiline and delamanid combination as a part of a salvage regimen from November 2017 to December 2020 in a programmatic setting. Among 106 persons with a median age of 39.5 years, 44 (41.5%) were previously treated with new/companion TB drugs. Patients with prior exposure to new/companion drugs had higher rates of baseline resistance compared to those without exposure to new/companion TB drugs (bedaquiline 15.2% vs 1.8%, linezolid 22.2% vs 16.7%). Sputum culture conversion rates among patients exposed and not exposed to new/companion drugs were 65.9% vs 98.0%, respectively (P < .001). Among patients with and without prior new/companion TB drug use, favorable outcome rates were 41.0% and 82.3%, respectively (P < .001). Treatment adherence in 32 (30.2%) patients was ≤80%. Five of 21 patients (23.8%) who had a baseline and repeat susceptibility test had acquired bedaquiline resistance. QTC/F prolongation (>500 ms) was rare (2.8%). Prior exposure to new/companion TB drugs was associated with poor clinical outcomes and acquired drug resistance. Tailoring the TB regimen to each patient's drug susceptibility test results and burden of disease and enhancing adherence support may improve outcomes.

OPTIMA: An Open-Label, Noncomparative Pilot Trial of Inhaled Molgramostim in Pulmonary Nontuberculous Mycobacterial Infection.

Rationale: Inhaled granulocyte-macrophage colony-stimulating factor (GM-CSF) has been proposed as a potential immunomodulatory treatment for nontuberculous mycobacterial (NTM) infection.Objectives: This open-label, noncomparative pilot trial investigated the efficacy and safety of inhaled GM-CSF (molgramostim nebulizer solution) in patients with predominantly treatment-refractory pulmonary NTM infection (Mycobacterium avium complex [MAC] and M. abscessus [MABS]), either in combination with ongoing guideline-based therapy (GBT) or as monotherapy in patients who had stopped GBT because of lack of efficacy or intolerability.Methods: Thirty-two adult patients with refractory NTM infection (MAC, n = 24; MABS, n = 8) were recruited into two cohorts: those with (n = 16) and without (n = 16) ongoing GBT. Nebulized molgramostim 300 μg/d was administered over 48 weeks. Sputum cultures and smears and clinical assessments (6-min-walk distance, symptom scores, Quality of Life-Bronchiectasis Questionnaire score, and body weight) were collected every 4 weeks during treatment and 12 weeks after the end of treatment. The primary endpoint was sputum culture conversion, defined as three consecutive monthly negative cultures during the treatment period.Results: Eight patients (25%) achieved culture conversion on treatment (seven [29.2%] patients with MAC infection, one [12.5%] patient with MABS infection); in four patients, this was durable after the end of treatment. Of the 24 patients with MAC infection, an additional 4 patients had a partial response, converting from smear positive at baseline to smear negative at the end of treatment, and time to positivity in liquid culture media increased. Two of these patients sustained negative cultures from the end of treatment. Other clinical endpoints were unchanged. Serious adverse events were mainly pulmonary exacerbations or worsening NTM infection. Three deaths, not treatment related, were reported.Conclusions: In this population of patients with severe NTM disease, molgramostim was safe and well tolerated. Sputum culture conversion rates for patients with MAC infection (29.2%) were greater than reported for similar refractory MAC cohorts managed with GBT alone. Less benefit was seen for MABS infection. No serious safety concerns were identified. Further evaluation in a larger cohort is warranted.Clinical trial registered with www.clinicaltrials.gov (NCT03421743).

Sarecycline pharmacokinetics/pharmacodynamics in the hollow-fibre model of Mycobacterium avium complex: so near and yet so far.

Poor sustained sputum culture conversion rates with the standard-of-care therapy highlight the need for better drugs to treat Mycobacterium avium complex pulmonary disease (MAC-PD). To determine the pharmacokinetics/pharmacodynamics (PK/PD)-optimized exposure of sarecycline and its potential role in treating MAC-PD. We performed MIC studies with MAC ATCC 700898 and 19 clinical isolates and test-tube static concentration-response studies. A dynamic hollow-fibre system model of intracellular MAC (HFS-MAC) study was performed mimicking six human-equivalent sarecycline dose concentration-time profiles to identify the PK/PD optimal exposure of sarecycline for MAC kill. The inhibitory sigmoid maximal effect (Emax) model was used for PK/PD analysis. The sarecycline MIC of MAC ATCC 700898 was 1 mg/L, while the MIC for the 19 clinical strains ranged between 32 and >256 mg/L. The concentration mediating 50% of Emax (EC50) was similar between intracellular and extracellular MAC. In the HFS-MAC, all six sarecycline doses killed intracellular MAC, with an Emax of 1.0 log10 cfu/mL below Day 0 burden (stasis). The sarecycline EC80 (optimal) exposure was identified as AUC0-24/MIC = 139.46. Sarecycline demonstrated anti-MAC Emax in the HFS-MAC model better than ethambutol but worse than omadacycline (>5 log10 cfu/mL below stasis) in HFS-MAC. However, since currently approved highest oral sarecycline dose achieves an AUC0-24 of 48.2 mg·h/L and MAC MICs are >32 mg/L, the target AUC0-24/MIC of 139.46 is unlikely to be achieved in patients.

Treatment outcomes and relapse in patients with Mycobacterium avium-intracellulare complex pulmonary disease.

The treatment responses and outcomes in patients with Mycobacterium avium-intracellulare complex pulmonary disease (MAC-PD) remain uncertain. This retrospective study was conducted in Taiwan between 2011 and 2020. A microbiological cure was defined as the requirement for a minimum of three consecutive negative cultures following culture conversion that continued until the completion of anti-MAC treatment. A total of 97 patients with MAC-PD were enrolled in this study. The sputum smear-negative conversion rate was 40% (19/47). Thirty (31%) patients achieved sputum culture-negative conversion rates within 3 years after treatment initiation. All patients with negative sputum culture conversion rates achieved microbiological cure. Patients treated with a macrolide + rifamycin + ethambutol (M + R + EMB)-based regimen had a higher microbiological cure rate than the other patients (39% vs 17%, P = 0.023). Patients with persistently positive sputum smears after 6 months of treatment had a lower microbiological cure rate than those with negative sputum smears (6% vs 44%, P < 0.001). Among 30 patients with microbiological cure, the median time from sputum culture conversion to treatment completion was 221.5 (0-483) days, and the 1-year relapse rate was 17%. Treatment with the M + R + EMB-based regimen was associated with a higher microbiological cure rate, and patients with persistently positive sputum smears after 6 months of treatment had a lower microbiological cure rate. IMPORTANCE The treatment responses and outcomes in patients with Mycobacterium avium-intracellulare complex pulmonary disease (MAC-PD) remain uncertain. In this study, patients with MAC-PD treated with a macrolide + rifamycin + ethambutol (M + R + EMB)-based regimen had a higher microbiological cure rate than those treated with other regimens. After 6 months of treatment, patients with persistently positive sputum smears had a lower microbiological cure rate than those with negative sputum smears. Among patients with microbiological cure, the median time from sputum culture conversion to treatment completion was 221.5 days (range, 0-483), and the 1-year relapse rate was 17%.

The Efficacy and Safety of Bedaquiline in the Treatment of Pulmonary Tuberculosis Patients: A Systematic Review and Meta-Analysis.

Bedaquiline (BDQ) has been designated as a Group A drug by the World Health Organization (WHO) for the management of multi-drug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). This systematic review and meta-analysis aim to evaluate the efficacy and safety of BDQ-containing regimens for the treatment of patients with pulmonary TB. PubMed (MEDLINE), Elton B. Stephens Company (EBSCO) database, the Cochrane Register of Controlled Trials, and the China National Knowledge Infrastructure (CNKI) database were initially searched on 15 June 2022 and again on 20 March 2023. We included randomized controlled trials (RCTs) and non-randomized studies (NRSs) that administered BDQ to TB patients. The outcomes of interest were as follows: (1) efficacy, including the rate of sputum culture conversion at 8 weeks, 24 weeks, and during follow-up, as well as the rates of completion cure, death, treatment failure, and loss at follow-up and at the end of the treatment; and (2) safety, which encompassed the incidences of cardiotoxicity, hepatotoxicity, and grade 3-5 adverse events during the treatment period. A total of 29 articles were included in this meta-analysis, representing 23,358 individuals. Patients who were treated with BDQ were compared with patients who were not exposed to BDQ. The use of BDQ-containing regimens demonstrated improved rates of sputum conversion in RCTs at 24 weeks (RR = 1.27, 95% CI: 1.10 to 1.46) and during follow-up (RR = 1.33, 95% CI: 1.06 to 1.66). Additionally, BDQ-containing regimens showed increased cure rates (RR = 1.60, 95% CI: 1.13 to 2.26) and decreased failure rates (RR = 0.56, 95% CI: 0.56 to 0.88). In NRSs, BDQ-containing regimens improved the sputum culture conversion rate during follow-up (RR = 1.53, 95% CI: 1.07 to 2.20), increased the rate of cure (RR = 1.86, 95% CI: 1.23 to 2.83), reduced deaths from all causes (RR = 0.68, 95% CI: 0.48 to 0.97), and reduced failure rates (RR = 0.57, 95% CI: 0.46 to 0.71). However, the use of BDQ-containing regimens was associated with increased incidences of cardiotoxicity (RR = 4.54, 95% CI: 1.74 to 11.87) and grade 3-5 adverse events (RR = 1.42, 95% CI: 1.17 to 1.73) in RCTs. NRSs also showed an association between BDQ-containing regimens and cardiotoxicity (RR = 6.00, 95% CI: 1.32 to 27.19). No significant differences were observed between intervention groups and control groups with respect to other outcomes. Data from both RCTs and NRSs support the efficacy of BDQ for the treatment of pulmonary tuberculosis. However, the use of BDQ is associated with a higher incidence of cardiotoxicity and serious adverse events. Comparative data on efficacy and safety are limited, and further confirmation is required, due to potential bias and discrepancies in the available studies.

Cost-Effectiveness Analysis of Combined Chemotherapy Regimen Containing Bedaquiline in the Treatment of Multidrug-Resistant Tuberculosis in China*

ObjectiveThis study aims to estimate the cost-effectiveness of the combined chemotherapy regimen containing Bedaquiline (BR) and the conventional treatment regimen (CR, not containing Bedaquiline) for the treatment of adults with multidrug-resistant tuberculosis (MDR-TB) in China. MethodsA combination of a decision tree and a Markov model was developed to estimate the cost and effects of MDR patients in BR and CR within ten years. The model parameter data were synthesized from the literature, the national TB surveillance information system, and consultation with experts. The incremental cost-effectiveness ratio (ICER) of BR vs. CR was determined. ResultsBR (vs. CR) had a higher sputum culture conversion rate and cure rate and prevented many premature deaths (decreased by 12.8%), thereby obtaining more quality-adjusted life years (QALYs) (increased by 2.31 years). The per capita cost in BR was as high as 138,000 yuan, roughly double that of CR. The ICER for BR was 33,700 yuan/QALY, which was lower than China’s 1× per capita Gross Domestic Product (GDP) in 2020 (72,400 yuan). ConclusionBR is shown to be cost effective. When the unit price of Bedaquiline reaches or falls below 57.21 yuan per unit, BR is expected to be the dominant strategy in China over CR.

Omadacycline pharmacokinetics/pharmacodynamics in the hollow fiber model and clinical validation of efficacy to treat pulmonary Mycobacterium abscessus disease

BackgroundGuideline-based therapy (GBT) for pulmonary Mycobacterium abscessus (Mab) disease achieves sustained sputum culture conversion (SSCC) rates of 30%; this is reflected by poor efficacy of GBT in the hollow fiber system model of Mab (HFS-Mab), which killed ∼1.22 log10 CFU/mL. This study was performed to determine which clinical dose of omadacycline, a tetracycline antibiotic, should be used in combination therapy to treat pulmonary Mab disease for relapse-free cure. MethodsFirst, omadacycline intrapulmonary concentration-time profiles of seven daily doses were mimicked in the HFS-Mab model and exposures associated with optimal efficacy were identified. Second, 10,000 subject Monte-Carlo simulations were performed to determine whether oral omadacycline 300 mg/day achieved these optimal exposures. Third, a retrospective clinical study on omadacycline vs. primarily tigecycline-based salvage therapy was conducted to assess rates of SSCC and toxicity. Fourth, a single patient was recruited to validate the findings. ResultsOmadacycline efficacy in the HFS-Mab was 2.09 log10 CFU/mL at exposures achieved in >99% of patients on 300 mg/day omadacycline. In the retrospective study of omadacycline 300 mg/day-based combinations vs. comparators, SSCC was achieved in 8/10 vs. 1/9 (P=0.006), symptom improvement in 8/8 vs. 5/9 (P=0.033), toxicity in 0 vs. 9/9 (P<0.001), and therapy discontinuation due to toxicity in 0 vs. 3/9 (P<0.001) cases, respectively. In one prospectively recruited patient, omadacycline 300 mg/day salvage therapy achieved SSCC and symptom-resolution in 3 months. ConclusionBased on the preclinical and clinical data, omadacycline 300 mg/day in combination regimens could be appropriate for testing in Phase III trials in patients with Mab pulmonary disease.

Efficacy and safety of an innovative short-course regimen containing clofazimine for treatment of drug-susceptible tuberculosis: a clinical trial

ABSTRACT In preclinical studies, a new antituberculosis drug regimen markedly reduced the time required to achieve relapse-free cure. This study aimed to preliminarily evaluate the efficacy and safety of this four-month regimen, consisting of clofazimine, prothionamide, pyrazinamide and ethambutol, with a standard six-month regimen in patients with drug-susceptible tuberculosis. An open-label pilot randomized clinical trial was conducted among the patients with newly diagnosed bacteriologically-confirmed pulmonary tuberculosis. The primary efficacy end-point was sputum culture negative conversion. Totally, 93 patients were included in the modified intention-to-treat population. The rates of sputum culture conversion were 65.2% (30/46) and 87.2% (41/47) for short-course and standard regimen group, respectively. There was no difference on two-month culture conversion rates, time to culture conversion, nor early bactericidal activity (P > 0.05). However, patients on short-course regimen were observed with lower rates of radiological improvement or recovery and sustained treatment success, which was mainly attributed to higher percent of patients permanently changed assigned regimen (32.1% vs. 12.3%, P = 0.012). The main cause for it was drug-induced hepatitis (16/17). Although lowering the dose of prothionamide was approved, the alternative option of changing assigned regimen was chosen in this study. While in per-protocol population, sputum culture conversion rates were 87.0% (20/23) and 94.4% (34/36) for the respective groups. Overall, the short-course regimen appeared to have inferior efficacy and higher incidence of hepatitis but desired efficacy in per-protocol population. It provides the first proof-of-concept in humans of the capacity of the short-course approach to identify drug regimens that can shorten the treatment time for tuberculosis.

A prospective patient registry to monitor safety, effectiveness, and utilisation of bedaquiline in patients with multidrug-resistant tuberculosis in South Korea

BackgroundMultidrug-resistant tuberculosis (MDR-TB) represents a major public health concern, with an ongoing need for new effective treatments. Bedaquiline is an oral diarylquinoline that has shown encouraging treatment success and culture conversion rates in MDR-TB.MethodsA South Korean patient registry was set up across 19 centres between 2016 and 2018 for the prospective collection of data from patients with MDR-TB who received either a bedaquiline-containing or a non-bedaquiline-containing regimen. Treatment was at the physician’s discretion (bedaquiline use requiring approval by special committee) and was based on patient characteristics, disease status, and local treatment guidelines.ResultsThe safety population included 172 patients (88 bedaquiline and 84 non-bedaquiline). The mean (standard deviation, SD) duration of follow-up was 24.3 (9.5) months. Mean (SD) durations of treatment were 5.4 (1.8) months in bedaquiline-treated patients and 15.7 (6.7) months in the non-bedaquiline group. Treatment success (cured and treatment completed according to WHO 2013 treatment outcome definitions) was achieved by 56.3% of bedaquiline-treated and 45.2% of non-bedaquiline-treated patients. Sputum culture conversion rates were 90.4% and 83.7% with and without bedaquiline, respectively. Diarrhoea and nausea were the most frequently reported treatment-emergent adverse events (TEAEs) in the bedaquiline group (27.3% [24/88] and 22.7% [20/88], respectively). The most frequent bedaquiline-related TEAEs were prolonged QT interval (10.2%; 9/88), and diarrhoea and nausea (9.1% each; 8/88). QT interval prolongation was reported in 19.3% (17/88) of bedaquiline-treated and 2.4% (2/84) of non-bedaquiline-treated patients, but bedaquiline was not discontinued for any patient for this reason. There were 13 (14.7%) and three (3.6%) deaths in the bedaquiline-treated and non-bedaquiline groups, respectively. Review of fatal cases revealed no unexpected safety findings, and no deaths were bedaquiline-related. The most common cause of death was worsening cancer (three patients). Patients in the bedaquiline group tended to have poorer baseline risk profiles than non-bedaquiline patients and were more likely to have relapsed or already failed second-line treatment. Interpretation of mortality data was complicated by high rates of loss to follow-up in both groups.ConclusionsThe South Korean registry findings support previous risk/benefit observations and the continued use of bedaquiline as part of combination therapy in patients with MDR-TB.

Efficacy and Tolerability of Concomitant Use of Bedaquiline and Delamanid for Multidrug- and Extensively Drug-Resistant Tuberculosis: A Systematic Review and Meta-Analysis.

The introduction of two novel drugs, bedaquiline and delamanid, has given hope for better and shorter treatments of drug-resistant tuberculosis. A systematic review was conducted to evaluate the efficacy and safety of concomitant bedaquiline and delamanid administration. Pooled estimates of World Health Organization-defined favorable treatment outcome and significant QTc-interval prolongation (QTc ≥500 ms or ≥60 ms increase from baseline) were calculated using a random-effects model. Thirteen studies including a total of 1031 individuals with multidrug-resistant/rifampicin-resistant tuberculosis who received bedaquiline and delamanid were included. The pooled estimate of favorable treatment outcome was 73.1% (95% confidence interval [CI]: 64.3-81.8%). Sputum culture conversion at 6 months ranged from 61% to 95%. Overall, the pooled proportion of QTc-prolongation was 7.8% (95% CI: 4.1-11.6%) and few cardiac events were reported (0.8%; n = 6/798). Rates of sputum culture conversion and favorable treatment outcome were high in patients treated concomitantly with bedaquiline and delamanid, and the treatment seemed tolerable with low rates of clinically significant cardiac toxicity.

Comparative effectiveness of individualized longer and standardized shorter regimens in the treatment of multidrug resistant tuberculosis in a high burden country.

Objective: To compare the effectiveness of second line injectables containing shorter (duration 9–12 months) and longer treatment regimens (LTR, duration ≥ 20 months) among multidrug-resistant tuberculosis (MDR-TB) patients with no documented resistance and history of treatment with any second-line anti-TB drug (SLD) for ≥ 1 month. Methods: This was an observational cohort study of MDR-TB patients treated at eight PMDT units in Pakistan. Patients’ data from baseline until treatment outcomes were collected from Electronic Nominal Recording and Reporting System. The treatment outcomes of “cured” and “treatment completed” were grouped together as successful, whereas “death,” “treatment failure,” and “lost to follow-up” were collectively grouped as unsuccessful outcomes. Time to sputum culture conversion (SCC) was analyzed using the Kaplan–Meier method and the differences between groups were compared through the log-rank test. Multivariate Cox proportional hazards and binary logistic regression analyses were used to find predictors of time to SCC and unsuccessful treatment outcomes. A p-value < 0.05 was considered statistically significant. Results: A total 701 eligible MDR-TB patients [313 treated with shorter treatment regimen (STR) and 388 treated with LTR at eight centres in Pakistan were evaluated]. Time to achieve SCC was significantly shorter in STR group [mean: 2.03 months, 95% confidence interval (CI):1.79–2.26] than in LTR group (mean: 2.69 months, 95% CI: 2.35–3.03) (p-value<0.001, Log-rank test). Treatment success was higher in STR (83.7%) than in LTR (73.2%) group (p-value <0.001) due to high cure (79.9% vs. 70.9%, p-value = 0.006) and low death (9.9% vs. 18.3%, p-value = 0.002) rates with STR. Treatment with STR emerged the only predictor of early SCC [adjusted Hazards ratio (aHR) = 0.815, p-value = 0.014], whereas, patient’s age of 41–60 (OR = 2.62, p-value<0.001) and >60 years (OR = 5.84, p-value<0.001), baseline body weight of 31–60 (OR = 0.36, p-value = 0.001) and >60 kg (OR = 0.23, p-value <0.001), and treatment with LTR (OR = 1.88, p-value = 0.001) had statistically significant association with unsuccessful treatment outcomes. Conclusion: STR exhibited superior anti-microbial activity against MDR-TB. When compared LTR, treatment with STR resulted in significantly early SCC, high cure, and lower death rates among MDR-TB patients who had no documented resistance and history of treatment with any SLD ≥ 1 month.

Endobronchial Valve Treatment of Tuberculous Cavities in Patients with Multidrug-Resistant Pulmonary Tuberculosis: A Randomized Clinical Study.

Background: Multidrug-resistant pulmonary tuberculosis (MDR-PTB) has become a major cause of high morbidity and mortality related to TB. Conventional drug regimens are ineffective for the treatment of MDR-PTB patients with cavities. This study aimed to evaluate the clinical efficacy and safety of one-way endobronchial valves (EBVs) for the treatment of cavities in MDR-PTB patients. Methods: MDR-PTB patients with positive sputum cultures, sputum smears, and cavities were treated with EBVs in the drainage bronchus of the pulmonary cavity between November 2013 and March 2018. The participants comprised those who had failed previous anti-tuberculosis therapy, as determined by drug susceptibility testing. Results: Thirty-five MDR-PTB patients were included, three of whom were lost during follow-up. The size of the lung cavity was reduced in all of the patients after EBV implantation, including the three lost to follow-up. In the remaining 32 patients, the sputum culture conversion (SCC) rate reached 100%, and the cavity closure rate was 68.8%. There were no significant differences in the cavity closure rate between patients aged ≤40 and >40 years, between the upper and lower lobes, or between the use and non-use of linezolid groups (p > 0.05). Interestingly, the cavity closure rate was higher in women than in men (p = 0.005). Moreover, the cavity closure rate correlated with the time to SCC (correlation coefficient, 0.8933; p < 0.0001). There were no severe adverse events in the patients treated with EBV implantation. Conclusion: EBV installation is effective and safe for the treatment of cavities in MDR-PTB patients. The efficacy of EBV treatment may not be affected by age, disease course, or the location of the lung lobe in the cavity.

Comparison of efficacy of bedaquiline and moxifloxacin in drug resistant pulmonary tuberculosis. A prospective observational study.

Drug-resistant tuberculosis remains a major public health concern in many countries. We compared the efficacy and safety of bedaquiline plus optimized background regimen (Bdq+OBR) with high dose moxifloxacin and optimized background regimen (Mfx(h)+OBR) for the treatment of patients with multidrug-resistant tuberculosis with additional resistance to fluoroquinolones. In this prospective observational study, newly diagnosed cases of multidrug-resistant tuberculosis with additional resistance to fluoroquinolone were enrolled. They received either Bdq+OBR or Mfx(h)+OBR and were followed up for six months. The sputum culture conversion rate at the end of six months and the time to culture conversion in each group were studied. The safety profile of both regimens was also studied. The sputum culture conversion was achieved in 41 patients (100%) in the Bdq+OBR group and 36 patients (87.8%) in the Mfx(h)+OBR group at the end of 6 months. The mean time to culture conversion was found to be 3.10±0.8 months in the Bdq+OBR group and 3.32±0.9 months in the Mfx(h)+OBR group. Mortality was 6.8% in the Bdq+OBR group and 10.8 % in the Mfx(h)+OBR group at 6 months. Raised serum lipase and dark discolouration of skin were significantly more common in the Bdq+OBR group while vomiting and ototoxicity were more common in the Mfx(h)+OBR group. Bdq+OBR was associated with higher success of sputum culture conversion at 6 months and faster sputum culture conversion rate as compared to the Mfx(h)+OBR.

Factors Associated with Treatment Outcome in Patients with Nontuberculous Mycobacterial Pulmonary Disease: A Large Population-Based Retrospective Cohort Study in Shanghai.

Infectious diseases caused by nontuberculous mycobacteria (NTM) are increasingly common. This retrospective cohort study examined factors associated with outcomes in patients from Shanghai who had NTM pulmonary disease (NTMPD) from January 2014 to December 2018. The causative bacterial species, drug susceptibility test results, treatment outcomes, sputum culture conversion rate, and risk factors associated with treatment failure were determined. The most common species were Mycobacterium avium complex (MAC) (50%), M. abscessus (28%), and M. kansasii (15%). Over five years, the proportions of M. kansasii and M. abscessus increased, and that of MAC decreased. The treatment success rate was significantly greater for patients infected with M. kansasii (89.9%) than MAC (65.0%, p < 0.001) and M. abscessus (36.1%, p < 0.001). Multivariate analysis indicated the risk factors for treatment failure were pathogenic NTM species (M. abscessus: aOR = 9.355, p < 0.001; MAC: aOR = 2.970, p < 0.001), elevated ESR (>60 mm/h: aOR = 2.658, p < 0.001), receipt of retreatment (aOR = 2.074, p < 0.001), and being middle-aged or elderly (>60 years-old: aOR = 1.739, p = 0.021; 45–60 years-old: aOR = 1.661, p = 0.034). The main bacterial species responsible for NTMPD were MAC, M. abscessus, and M. kansasii. Patients who were infected by M. abscessus or MAC, with elevated ESR, received retreatment, and were middle-aged or elderly had an increased risk of treatment failure.

Surgical treatment for non-tuberculous mycobacterial pulmonary disease: analysis of prognostic factors.

BACKGROUND: The surgical treatment for non-tuberculous mycobacterial pulmonary disease (NTM-PD) has an important adjunctive role and reported outcomes have been generally good; however, the prognostic factors remain unclear.METHODS: Sixty-one patients with NTM-PD who underwent surgical resection for a therapeutic purpose from January 2000 to March 2017 at five affiliated institutions were enrolled. We explored the factors that influence complications and prognosis by retrospectively referring to the medical records.RESULTS: The mean age of the present cohort was 61.8 ± 11.4 years. The pathogen was Mycobacterium avium complex in 49 patients, M. abscessus in 5. The most common indications were refractory to medication in 39. The surgical techniques employed were lobectomy or further resection in 49, sublobar resection in 8, with video-assisted thoracoscopic surgery in 21. Sputum culture conversion rate was 95.1%. Univariate analysis of factors associated with deterioration revealed significant differences related to age (P = 0.025), pre-operative albumin level (P = 0.001) and development of postoperative complications (P = 0.037), while pre-operative albumin level alone was a significant factor in multivariate analysis (P = 0.009).CONCLUSION: Outcomes after resection were generally good in the present cases. Nutritional status, as indicated by albumin level, may affect prognosis after surgical treatment.

Effect of Health Education Combined with Dietary Guidance on Nutritional Indicator, Immune Level, and Quality of Life of Patients with Pulmonary Tuberculosis.

Objective To investigate the effects of health education combined with dietary guidance on nutritional indicators, immune level, and quality of life of patients with pulmonary tuberculosis. Method A total of 123 patients with pulmonary tuberculosis who were hospitalized to our hospital between October 2019 and October 2020 were chosen for the study and were separated into 60 control cases and 63 observation cases based on the ward they were assigned to. Patients in the two groups were compared in terms of nutritional risk, nutritional indicator levels in serum, immunological function, treatment compliance, sputum culture conversion rate, and quality of life. Result With the prolongation of patients' illness, the total NRS 2002 score gradually increased in both groups and the total NRS 2002 score of patients in the control group was higher than that of patients in the observation group at the same time point after discharge. The difference between the total NRS 2002 score of patients in both groups was significant at 3 and 6 months after discharge. After the intervention, the Hb, ALB, CD4+, and CD4+/CD8+ levels of patients in both groups were higher than those at the time of admission, and the CD8+ levels were lower than those at the time of admission. At 6 months after discharge, the Hb, ALB, CD4+, and CD4+/CD8+ levels of patients in the observation group were significantly higher than those in the control group, and the CD8+ levels were significantly lower than those in the control group. The treatment compliance rate of patients in the observation group (96.83%) was significantly higher than that of the control group (75%), and the negative sputum culture transfer rate (85.71%) was significantly higher than that in the control group (60%). The overall quality of life scores of patients in the observation group was significantly higher than that in the control group. Conclusion Health education combined with dietary guidance for patients with pulmonary tuberculosis can deepen patients' understanding of disease and nutritional knowledge, improve treatment compliance, improve their nutritional status, enhance their immune function, accelerate sputum bacterial conversion, enhance treatment effect, and improve their quality of life.

Amikacin liposome inhalation suspension as a treatment for patients with refractory mycobacterium avium complex lung infection

ABSTRACT Introduction: Amikacin liposome inhalation suspension (ALIS) contains amikacin sulfate, an aminoglycoside antibacterial drug. It has been approved in the US as a combined antibiotic treatment for refractory MAC lung disease patients. ALIS, as an inhaled antibiotic, can deliver amikacin to the infected site effectively and reduce systemic toxicity. Areas covered: This article gives a summated review of the pharmacodynamics, pharmacokinetics, therapeutic efficacy, post-marketing surveillance, and regulatory affairs of ALIS as an add-on therapy for MAC lung disease in adults by analyzing data from preclinical studies, clinical trials and original studies. We systematically searched Medline/PubMed through October 2020. Expert opinion: Studies demonstrate that ALIS as an add-on treatment significantly improve the rate of sputum culture conversion in MAC lung disease patients compare to guideline-recommended therapy only. The ALIS treatment showed a similar risk of serious adverse events and a low chance of renal adverse events. However, ALIS was associated with more respiratory adverse events than guideline-recommended therapy only. There was not sufficient data to conclude that ALIS treatment can improve clinical outcomes; however, with the significant improvement in the microbiology outcome in MAC lung disease patients, ALIS showed its potential use as an adjunct treatment for treating MAC lung disease.

Relevance of QuantiFERON-TB Gold Plus and Heparin-Binding Hemagglutinin Interferon-γ Release Assays for Monitoring of Pulmonary Tuberculosis Clearance: A Multicentered Study.

BackgroundTuberculosis (TB) is a leading infectious cause of death. To improve treatment efficacy, quicker monitoring methods are needed. The objective of this study was to monitor the response to a heparin-binding hemagglutinin (HBHA) interferon-γ (IFN-γ) release assay (IGRA) and QuantiFERON-TB Gold Plus (QFT-P) and to analyze plasma IFN-γ levels according to sputum culture conversion and immune cell counts during treatment.MethodsThis multicentered cohort study was based in Bangladesh, Georgia, Lebanon, Madagascar, and Paraguay. Adult, non-immunocompromised patients with culture-confirmed pulmonary TB were included. Patients were followed up at baseline (T0), after two months of treatment (T1), and at the end of therapy (T2). Clinical data and blood samples were collected at each timepoint. Whole blood samples were stimulated with QFT-P antigens or recombinant methylated Mycobacterium tuberculosis HBHA (produced in Mycobacterium smegmatis; rmsHBHA). Plasma IFN-γ levels were then assessed by ELISA.FindingsBetween December 2017 and September 2020, 132 participants completed treatment, including 28 (21.2%) drug-resistant patients. rmsHBHA IFN-γ increased significantly throughout treatment (0.086 IU/ml at T0 vs. 1.03 IU/ml at T2, p < 0.001) while QFT-P IFN-γ remained constant (TB1: 0.53 IU/ml at T0 vs. 0.63 IU/ml at T2, p = 0.13). Patients with low lymphocyte percentages (<14%) or high neutrophil percentages (>79%) at baseline had significantly lower IFN-γ responses to QFT-P and rmsHBHA at T0 and T1. In a small group of slow converters (patients with positive cultures at T1; n = 16), we observed a consistent clinical pattern at baseline (high neutrophil percentages, low lymphocyte percentages and BMI, low TB1, TB2, and MIT IFN-γ responses) and low rmsHBHA IFN-γ at T1 and T2. However, the accuracy of the QFT-P and rmsHBHA IGRAs compared to culture throughout treatment was low (40 and 65% respectively). Combining both tests improved their sensitivity and accuracy (70–80%) but not their specificity (<30%).ConclusionWe showed that QFT-P and rmsHBHA IFN-γ responses were associated with rates of sputum culture conversion. Our results support a growing body of evidence suggesting that rmsHBHA IFN-γ discriminates between the different stages of TB, from active disease to controlled infection. However, further work is needed to confirm the specificity of QFT-P and rmsHBHA IGRAs for treatment monitoring.

Interim Effectiveness and Safety Comparison of Bedaquiline-Containing Regimens for Treatment of Diabetic Versus Non-Diabetic MDR/XDR-TB Patients in China: A Multicenter Retrospective Cohort Study.

IntroductionDiabetes mellitus (DM), a common tuberculosis (TB) comorbidity, is associated with delayed bacillary clearance during anti-TB treatment and unfavorable outcomes. Bedaquiline (BDQ), when used as part of multidrug regimen for multidrug-resistant/extensively drug-resistant tuberculosis (MDR/XDR-TB), has been shown to be effective and safe although treatment outcome and risks for patients with MDR/XDR-TB and DM are unknown. A multicenter retrospective study was conducted to compared the safety and effectiveness of 24-week BDQ-containing anti-TB treatment for patients with MDR/XDR-TB with and without DM.MethodsThe study of patients with MDR/XDR-TB with or without DM (enrolled February 2018–September 2019, 21 Chinese hospitals) was supervised by the New Drug Introduction and Protection Program (NDIP). Of 640 patients with MDR/XDR-TB receiving BDQ-containing anti-TB treatments, two propensity score-matched groups (107 DM/107 non-DM) were compared for cumulative culture conversion rate, time to culture conversion, adverse events, and corrected QT interval.ResultsBody mass index was higher in patients with DM than patients without DM (23.29 ± 3.9 vs. 20.5 ± 3.6, P < 0.001); lung cavity prevalence (86.9% vs. 72.9%, P = 0.037) was also higher in patients with DM; the non-DM group had higher hepatitis prevalence (29.0% vs. 15.9%, P = 0.022). No significant intergroup differences were found for sputum culture conversion rate at week 8 (80.0% vs. 81.4%, P = 0.884), at week 24 (95.6% vs. 98.2%, P = 0.629), or for median time to sputum culture conversion [56 days (IQR 28–63) vs. 56 days (IQR 28–84) (P = 0.687)]. Favorable post-24-week treatment outcomes were presented by 90.7% and 93.5% in the DM group and non-DM group, respectively, without significant intergroup differences (P = 0.448). The DM adverse event rate exceeded non-DM rate (77.6% vs. 64.5%, P = 0.035).ConclusionDespite some differences in baseline characteristics, Chinese patients with MDR/XDR-TB with or without DM had similar sputum culture conversion rates and favorable treatment outcomes post-24-week BDQ-containing anti-TB treatment. Low BMI but not DM is risk factor associated with unfavorable outcome of patients with MDR/XDR-TB.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-021-00396-9.