Sitafloxacin-Containing Regimen for the Treatment of Refractory Mycobacterium avium Complex Lung Disease. (7th March 2019)

• Record Type: Journal Article
• Authors: Asakura, Takanori; Suzuki, Shoji; Fukano, Hanako; Okamori, Satoshi; Kusumoto, Tatsuya; Uwamino, Yoshifumi; Ogawa, Takunori; So, Matsuo; Uno, Shunsuke; Namkoong, Ho; Yoshida, Mitsunori; Kamata, Hirofumi; Ishii, Makoto; Nishimura, Tomoyasu; Hoshino, Yoshihiko; Hasegawa, Naoki
• Is Part Of: Open forum infectious diseases. Volume 6:Number 4(2019)
• Publication Date: 2019-03-07
• Subjects: clarithromycin (CLR) resistance -- difficult to treat -- fluoroquinolone -- Mycobacterium avium complex (MAC) -- nontuberculous mycobacteria (NTM); Communicable diseases -- Periodicals; Medical microbiology -- Periodicals; Infection -- Periodicals; 616.9
• DOI: 10.1093/ofid/ofz108
• Languages: English
• ISSNs: 2328-8957

Abstract

Abstract: Background: Sitafloxacin (STFX) exhibits potent activity against Mycobacterium avium complex (MAC) in both in vitro and in vivo experiments. However, limited data are available for the clinical efficacy and adverse effects of STFX and the susceptibility of refractory MAC lung disease (MAC-LD) to the drug. Therefore, this study was aimed at evaluating the clinical efficacy and safety of an STFX-containing regimen for the treatment of refractory MAC-LD. Methods: We retrospectively evaluated treatment outcomes of 31 patients with refractory MAC-LD, who received an STFX-containing regimen for ≥4 weeks between January 2010 and July 2017. Refractory MAC-LD was defined as persistent positive sputum cultures for >6 months of macrolide-based standard therapy. Results: Clarithromycin resistance (minimum inhibitory concentration [MIC] ≥32 μg/mL) was identified in 15 patients (48%). Twelve months after receiving the STFX-containing regimen, 26% and 19% of patients showed symptomatic and radiological responses, respectively. Although STFX-associated adverse effects were noted in 9 patients, their severity was grade 1 (National Cancer Institute Common Terminology Criteria); only 1 patient discontinued STFX because of suspected gastrointestinal disturbance. Negative sputum culture conversion was achieved in 7 patients (23%). Both univariate and multivariate logistic regression analyses revealed that surgery, low STFX MIC (≤1 μg/mL), and macrolide resistance were significant predictors of negative sputum culture conversion. Conclusions: Our results demonstrate that STFX may be effective in one-fourth of patients with refractory MAC-LD. Prospective larger studies that include the analyses of MAC are needed to determine the clinical efficacy of STFX against refractory MAC-LD. Abstract : Our results demonstrate that sitafloxacin (STFX) may be effective in one-fourth of patients with refractory Mycobacterium avium complex lung disease. Surgery, low minimum inhibitory concentration of STFX, and clarithromycin resistance were predictors of negative sputum culture conversion.