Efficacy and safety of fluoroquinolone-containing regimens in treating pulmonary Mycobacterium avium complex disease: A propensity score analysis.

BACKGROUND: Although combination therapy using clarithromycin, rifampicin, and ethambutol is recommended for patients with pulmonary Mycobacterium avium complex (MAC) disease, some patients do not tolerate it because of adverse effects or underlying diseases. The efficacy and safety of fluoroquinolone-containing combination regimens as an alternative remain uncertain. This study aimed to compare the efficacy and safety of fluoroquinolone-containing regimens with those of the standard regimens for treating pulmonary MAC disease. METHODS: We retrospectively included consecutive MAC patients who were treated in our hospital between January 2011 and May 2019. Patients treated with fluoroquinolone-containing regimens who had relapsed after treatment with standard regimens were excluded. A propensity score analysis was conducted to reduce selection bias, and the proportions of clinical improvement, defined by chest imaging findings and sputum conversion, were compared between the fluoroquinolone-containing regimen and standard regimen groups. RESULTS: We analyzed 28 patients who received fluoroquinolone-containing regimens and 46 who received the standard regimen. Fluoroquinolone-containing regimens were more likely selected for patients with cavitary lesions, diabetes mellitus, culture negativity, a low daily physical activity level, a decreased lymphocyte count and an increased CRP level. The propensity score was calculated using these variables (C-statistic of the area under the receiver operating characteristic curve of the propensity score: 0.807, p < 0.0001). The fluoroquinolone-containing regimens were significantly inferior to the standard regimen in clinical improvements (p = 0.002, Log-rank test) in the univariate analysis, but the significance was lost after adjusting for the propensity score (HR 0.553, 95% CI 0.285-1.074, p = 0.080). Six (21%) patients in the fluoroquinolone-containing regimen group and ten (22%) patients in the standard regimen group experienced low-grade adverse effects. CONCLUSIONS: There was no significant difference in clinical improvement between these regimens after propensity score adjustment. A large-scale prospective study is required to validate these results.

Mycobacterium abscessus subsp. abscessus empyema complicated with subcutaneous abscess.

There have been no case reports of thoracic subcutaneous abscess after surgery for Mycobacterium abscessus complex associated empyema. We herein report a case of Mycobacterium abscessus subsp. abscessus (M. abscessus subsp. abscessus) induced subcutaneous abscesses following surgical treatment for concurrent M. abscessus subsp. abscessus -associated empyema and pneumothorax. A 75-year-old woman had M. abscessus subsp. abscessus -associated empyema and pneumothorax. She underwent surgical treatment of decortication and fistulectomy and suffered from M. abscessus subsp. abscessus -associated subcutaneous abscesses after thoracentesis/drainage. A multidisciplinary approach combined with surgical care, thermal therapy, and multidrug chemotherapy contributed to a successful result. An early multidisciplinary approach is believed to be important in cases of M. abscessus subsp. abscessus -associated empyema and subcutaneous abscess.

Current status and future perspective on preclinical pharmacokinetic and pharmacodynamic (PK/PD) analysis: Survey in Japan pharmaceutical manufacturers association (JPMA).

Preclinical pharmacokinetic/pharmacodynamic (PK/PD) analysis is an efficient tool for the translational research and proof of mechanism/concept in animals. The questionnaire survey on the practice of preclinical PK/PD analysis was conducted in the member companies of the Japan Pharmaceutical Manufacturers Association (JPMA). According to the survey, 60% of companies conducted preclinical PK/PD analysis and its impact for drug development was different between each of the companies. The frequently analyzed therapeutic areas of preclinical PK/PD analysis were neurology, inflammation and metabolic disease, and those are different from the therapeutic area (infectious disease and oncology) in which PK/PD analysis was considered as effective by the present survey. Many companies which have used preclinical PK/PD analysis for the translation to human PK/PD and for the prediction of dose/regimen had good communication with other research & development (R&D) departments (e.g. pharmacology/clinical pharmacology). The increase in resources for preclinical PK/PD analysis including education was highly demanded. As a future perspective, the closer collaboration between pharmacokinetics scientists, pharmacologists, toxicologists and clinical pharmacologists and the increase in resources including upskilling and the comprehension of preclinical PK/PD analysis by the project team are considered to lead to efficient contributions to improve the success ratio of drug discovery and development.