Management of Drug Toxicity in Mycobacterium avium Complex Pulmonary Disease: An Expert Panel Survey.
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ABSTRACT:
SUBMITTER: van Ingen J
PROVIDER: S-EPMC8491833 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Pirfenidone is currently the only approved therapy for idiopathic pulmonary fibrosis, following studies demonstrating that treatment reduces the decline in lung function and improves progression-free survival. Although generally well tolerated, a minority of patients discontinue therapy due to gastrointestinal and skin-related adverse events (AEs). This review summarizes recommendations based on existing guidelines, research evidence, and consensus opinions of expert authors, with the aim of providing practicing physicians with the specific clinical information needed to educate the patient and better manage pirfenidone-related AEs with continued pirfenidone treatment. The main recommendations to help prevent and/or mitigate gastrointestinal and skin-related AEs include taking pirfenidone during (or after) a meal, avoiding sun exposure, wearing protective clothing, and applying a broad-spectrum sunscreen with high ultraviolet (UV) A and UVB protection. These measures can help optimize AE management, which is key to maintaining patients on an optimal treatment dose.
| S-EPMC4003341 | biostudies-literature
Project description:BackgroundIn Japan, Mycobacterium avium complex lung disease (MAC-LD) is the most common in nontuberculous mycobacterial lung disease. Patients often experience adverse events, resulting in the discontinuation of treatment, which causes treatment failure. The JADER (Japanese Adverse Drug Event Report) database is a database of adverse events that allows us to collect real-world data on adverse events. We can collect large-scale data cost-effectively and detect signals of potential adverse events such as reporting odds ratio (ROR) by using spontaneous reporting systems. In this study, we aimed to elucidate the adverse events of clarithromycin (CAM), ethambutol (EB), and rifampicin (RFP) using the JADER database.MethodsWe included cases of MAC-LD between April 2004 and June 2017. We investigated sex, age, and medications that may have caused the adverse events, outcomes, and time of onset. We calculated the safety signal index as the ROR. Time-to-event analysis was performed using the Weibull distribution.ResultsThe total number of adverse events of CAM, EB, and RFP was 2780, with 806 patients. In the overall adverse events, hematologic and lymphatic disorders were the most common adverse events, with 17.3%, followed by eye disorders (16.6%), and hepatobiliary disorders (14.0%). The outcomes were as follows: recovery, 40.0%; remission, 27.1%; non-recovery, 11.2%; and death, 7.1%. Regarding the most common onset time of CAM, EB, and RFP was within 120 days at 40%, 181-300 days at 43.6%, and within 120 days at 88.5%. For CAM, the RORs of infections and infestations, hepatobiliary system disorders, and immune system disorders were 4.13 (95% confidence interval [CI], 2.3-7.44), 2.61 (95% CI, 1.39-4.91), and 2.38 (95% CI, 1.04-5.44). For EB, the ROR of eye disorders was 215.79 (95% CI, 132.62-351.12). For RFP, the RORs of renal and urinary tract disorders and investigations were 7.03 (95% CI, 3.35-14.77) and 6.99 (95% CI, 3.22-15.18). The β value of EB was 2.07 (95% CI, 1.48-2.76), which was classified as a wear-out failure type.ConclusionsFor MAC-LD, the adverse event which has the highest ROR is infections and infestations in CAM, eye disorders in EB, renal and urinary tract disorders in RFP. Adverse events of EB occur after 180 days, whereas the adverse events of CAM and RFP occur early in the course of treatment.
| S-EPMC9241207 | biostudies-literature
Project description:Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and an important cause of disease. The most common species causing pulmonary disease are members of Mycobacterium avium complex (MAC). MAC pulmonary disease (MAC-PD) can be chronic, debilitating, costly, and associated with a high mortality. However, MAC diagnoses are often delayed due to the nonspecific presentation of MAC-PD and radiological findings that overlap with other pulmonary diseases. Patients with risk factors and who meet the diagnostic criteria-which include clinical, radiological, and microbiologic criteria-should be considered for treatment. Diagnosis requires 2 or more positive sputum cultures or 1 bronchoscopic specimen culture. The recommendation for those who are treated is a 3-drug regimen including macrolide, rifamycin, and ethambutol that is continued for 12 months beyond sputum culture conversion to negative. MAC-PD is difficult to treat, with frequent drug-related side effects and suboptimal treatment outcomes. Refractory and recurrent disease is common, leading to lifelong follow-up of patients. There are limited treatment options for patients with macrolide-resistant or refractory disease. Amikacin liposome inhalation suspension is recommended for treatment-refractory patients whose cultures remain positive after 6 months of guideline-based therapy. Among the research priorities to improve patient outcomes and quality of life are developing new, more rapid diagnostic tests, investigating biomarkers associated with disease progression, and identifying new drugs and routes of administration as well as new, shorter, and better-tolerated regimens.
| S-EPMC7566660 | biostudies-literature
Project description:BACKGROUND:Multidrug therapy is essential for preventing respiratory failure in patients with highly progressive Mycobacterium avium complex pulmonary disease (MAC-PD). However, the prognosis and long-term outcome following combination therapy is poorly understood. METHODS:We retrospectively evaluated the clinical characteristics and long-term outcomes in patients with chemo-naïve progressive MAC-PD, hospitalized for first-line multidrug therapy. RESULTS:Among 125 patients, 86 (68.8%) received standardized treatment (rifampicin, ethambutol, clarithromycin), 25 (20.0%) received a fluoroquinolone (FQ)-containing regimen, and 53 (42.4%) received aminoglycoside injection. The sputum conversion rate was 80.0%, and was independently associated with standardized treatment. The incidence of refractory disease (45.6%) was independently and negatively associated with standardized regimen and aminoglycoside use. Choice of an FQ-containing regimen was not associated with positive outcome. Clarithromycin resistance occurred in 16.8% and was independently associated with refractory disease. MAC-PD-associated death occurred in 3.3% of patients with non-cavitary nodular bronchiectasis (NB) and 21.3% with cavitary MAC-PD over a median follow-up period of 56.4 months. The rates of MAC-PD-associated death were comparable between cavitary-NB and fibrocavitary disease. Concurrent chronic pulmonary aspergillosis (CPA) occurred in 13 (17.3%) patients with cavitary MAC-PD, and age, diabetes mellitus, and CPA were independent risk factors for mortality. CONCLUSIONS:Standardized intensive multidrug treatment reduces disease progression and persistence in progressive MAC-PD. Cavitary NB may differ from, rather than being just an advanced stage of, non-cavitary NB. The high incidence and significant mortality of CPA in cavitary MAC-PD highlight the need for early diagnosis and treatment.
| S-EPMC7291046 | biostudies-literature
Project description: Not available
| S-EPMC8266509 | biostudies-literature
Project description:The Mycobacterium abscessus complex (MABC) comprises rapidly growing mycobacteria and has received increasing attention recently, with an increasing number of associated infections reported worldwide. However, the clinical features of MABC pulmonary disease (MABC-PD), especially in terms of the chest computed tomography (CT) findings, are not fully understood. Thus, this retrospective, cross-sectional study aimed to evaluate the clinical background and chest high-resolution CT (HRCT) findings of MABC-PD in comparison with those of Mycobacterium avium complex PD (MAC-PD). Accordingly, 36 patients with MABC-PD and 65 patients with MAC-PD (defined according to the American Thoracic Society criteria), who were newly diagnosed at four major hospitals in Okinawa (Japan) between January 2012 and December 2017, were analyzed. With respect to their clinical background, only cardiovascular diseases were significantly more common in patients with MABC-PD than in those with MAC-PD (38.9% vs. 18.5%, p = 0.0245). HRCT revealed a significantly higher incidence of low attenuation in patients with MABC-PD than in those with MAC-PD (63.9% vs. 10.8%, p<0.0001). On analyzing only never-smokers (20 and 47 patients with MABC-PD and MAC-PD, respectively), this significant difference remained (65.0% vs. 8.5%, p<0.0001), suggesting MABC infection itself caused low attenuation. In terms of the distribution of abnormal shadows, the involvement of the right lower, left upper, and left lower lobes was more common in patients with MABC-PD than in those with MAC-PD. Furthermore, the mean number of involved lung lobes was significantly higher in patients with MABC-PD than in those with MAC-PD (5.6 vs. 4.7, p<0.001). Although further studies are needed, we assume that the aforementioned radiological features of MABC-PD are due to the high virulence of MABC.
| S-EPMC9302740 | biostudies-literature
Project description:An enzyme immunoassay kit that detects serum IgA antibody reacting to glycopeptidolipid core antigen derived from Mycobacterium avium complex (MAC) was not useful for differentiating MAC pulmonary disease (PD) from Mycobacterium abscessus complex PD (MAB-PD). However, this assay could be useful for differentiating MAC- and MAB-PD from pulmonary tuberculosis. (This study has been registered at ClinicalTrials.gov under registration no. NCT00970801.).
| S-EPMC3719614 | biostudies-literature
Project description:Limited data are available regarding the impact of the antibiotic maintenance period on the redevelopment of nontuberculous mycobacteria-pulmonary disease (NTM-PD) after microbiological cure of Mycobacterium avium complex (MAC)-PD. This retrospective study included 631 MAC-PD patients who achieved microbiological cure between 1994 and 2021. Data on the antibiotic maintenance period, defined as the time between culture conversion and treatment completion, were collected. Redevelopment, the subsequent diagnosis of NTM-PD regardless of causative organism after microbiological cure, was investigated. Factors associated with redevelopment were analyzed after adjusting for disease severity using the body mass index, age, cavity, erythrocyte sedimentation rate, and sex (BACES) scoring system. In total, 205 (33%) patients experienced redevelopment, with a median maintenance period after culture conversion of 15.0 months (interquartile range, 13.0 to 22.0 months). A greater proportion of patients with the nodular bronchiectatic form of MAC-PD (87% versus 80%, P = 0.033) and a longer maintenance period (median 15.0 versus 14.0 months, P < 0.001) were noted in the redevelopment group compared with the nonredevelopment group. The cumulative rate of redevelopment according to the maintenance period did not differ between the >12-month and ≤12-month groups in the total patient population or the subgroups sorted according to BACES severity. No association between a maintenance period >12 months and redevelopment was identified in multivariate models. Extending the antibiotic maintenance period more than 12 months did not reduce the redevelopment rate even with adjustment for disease severity, suggesting the need to further optimize the duration of the antibiotic maintenance period. IMPORTANCE Limited data are available regarding the impact of the antibiotic maintenance period on the redevelopment of Mycobacterium avium complex-pulmonary (MAC-PD) disease after microbiological cure. To improve treatment outcomes and reduce the recurrence rate, current guidelines recommend maintenance of antibiotics for a minimum of 12 months after achievement of negative culture conversion. However, the optimal duration of antibiotic therapy for MAC-PD is not currently known. Moreover, in real-world clinical practice, total antibiotic duration is mainly impacted by the length of the maintenance period; however, it is unknown whether extending the maintenance period is beneficial for preventing redevelopment of NTM-PD. Our study may help to address concerns regarding the antibiotic maintenance period after achievement of negative culture conversion in patients with MAC-PD.
| S-EPMC9431257 | biostudies-literature
Project description:Although the isolation of clarithromycin (CAM)-resistant Mycobacterium avium complex (MAC) indicates a poor treatment outcome and increased mortality, there have been only a few reports on drug treatment for CAM-resistant MAC lung disease. We aimed to reveal the effectiveness of the continuation of a macrolide and the use of a multidrug regimen in the treatment of CAM-resistant MAC lung disease.Among patients with MAC pulmonary disease as defined by the 2007 criteria of the American Thoracic Society and the Infectious Diseases Society of America statement, those with CAM-resistant MAC (minimum inhibitory concentration ≥32 μg/ml) isolated, newly diagnosed and treated from January 2009 to June 2013 were analysed in this study. Effectiveness was measured based on culture conversion rate and improvement of radiological findings.Thirty-three HIV-negative patients were analysed in this study. Twenty-six were treated with a regimen containing CAM or azithromycin (AZM), and 21 patients were treated with three or more drugs except macrolide. The median duration to be evaluated was 10.4 months after beginning the treatment regimen. Sputum conversion (including cases of inability to expectorate sputum) was achieved in 12 (36%) patients. Radiological effectiveness improved in 4 (12%) patients, was unchanged in 11 (33%) patients and worsened in 18 (55%) patients. In the multivariate analysis, CRP <1.0 mg/dl (p = 0.017, odds ratio 12, 95% confidence interval (CI) 1.6-95) was found to be the only significant risk factor for radiological non-deterioration, and no significant risk factors for microbiological improvement were found.Our results suggested that continuation of macrolides or the addition of a new quinolone or injectable aminoglycoside to therapy with rifampicin and ethambutol would not improve clinical outcome after the emergence of CAM-resistant MAC. However, further prospective study is required to evaluate the precise clinical efficacy and effectiveness of these drugs.
| S-EPMC4730784 | biostudies-other
Project description:BackgroundA three-drug regimen (macrolide, ethambutol, and rifampicin) is recommended for the treatment of Mycobacterium avium complex pulmonary disease (MAC-PD). Although macrolide has proven efficacy, the role of ethambutol and rifampicin in patients without acquired immune deficiency syndrome is not proven with clinical studies. We aimed to clarify the roles of ethambutol and rifampicin in the treatment of MAC-PD.MethodsPatients treated for MAC-PD between March 1st, 2009 and October 31st, 2018 were reviewed retrospectively. Rates of culture conversion, microbiological cure, treatment failure, and recurrence were compared according to the maintenance (?6?months) of ethambutol or rifampicin with macrolide.ResultsAmong the 237 patients, 122 (51.5%) maintained ethambutol and rifampicin with macrolide, 58 (24.5%) maintained ethambutol and macrolide, 32 (13.5%) maintained rifampicin and macrolide, and 25 (10.6%) maintained macrolide only. Culture conversion was reached for 190/237 (80.2%) patients and microbiological cure was achieved for 129/177 (72.9%) who completed the treatment. Treatment failure despite ?12?months of treatment was observed in 66/204 (32.4%), and recurrence was identified in 16/129 (12.4%) who achieved microbiological cure. Compared with maintenance of macrolide only, maintenance of ethambutol, rifampicin or both with macrolide were associated with higher odds of culture conversion [odds ratio (OR), 95% confidence interval (CI): 18.06, 3.67-88.92; 15.82, 2.38-105.33; and 17.12, 3.93-74.60, respectively]. Higher odds of microbiological cure were associated with maintenance of both ethambutol and rifampicin with macrolide (OR, 95% CI: 5.74, 1.54-21.42) and macrolide and ethambutol (OR, 95% CI: 5.12, 1.72-15.24) but not macrolide and rifampicin. Maintenance of both ethambutol and rifampicin with macrolide was associated with lower odds of treatment failure (OR, 95% CI: 0.09, 0.01-0.53) compared with macrolide only, while maintenance of one of these with macrolide was not. Maintenance of both ethambutol and rifampicin or one of these with macrolide did not decrease the probability of recurrence when compared with macrolide only.ConclusionsMaintenance (?6?months) of ethambutol and rifampicin with macrolide was associated with the most favorable treatment outcomes among patients with MAC-PD. Given the association between ongoing ethambutol use and microbiological cure, clinicians should maintain ethambutol unless definite adverse events develop.
| S-EPMC6849249 | biostudies-literature