Sitafloxacin-containing regimen for the treatment of refractory mycobacterium avium complex lung disease

Takanori Asakura, Shoji Suzuki, Hanako Fukano, Satoshi Okamori, Tatsuya Kusumoto, Yoshifumi Uwamino, Takunori Ogawa, Matsuo So, Shunsuke Uno, Ho Namkoong, Mitsunori Yoshida, Hirofumi Kamata, Makoto Ishii, Tomoyasu Nishimura, Yoshihiko Hoshino, Naoki Hasegawa

Research output: Contribution to journalArticle

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 STFXcontaining 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.

Original languageEnglish
Article numberofz108
JournalOpen Forum Infectious Diseases
Volume6
Issue number4
DOIs
Publication statusPublished - 2019 Apr 1

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Mycobacterium avium Complex
Lung Diseases
Sputum
Therapeutics
Macrolides
Microbial Sensitivity Tests
sitafloxacin
Clarithromycin
National Cancer Institute (U.S.)
Terminology
Logistic Models
Regression Analysis
Prospective Studies
Safety

Keywords

  • clarithromycin (CLR) resistance
  • difficult to treat
  • fluoroquinolone
  • Mycobacterium avium complex (MAC)
  • nontuberculous mycobacteria (NTM)

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology

Cite this

Sitafloxacin-containing regimen for the treatment of refractory mycobacterium avium complex lung disease. / 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.

In: Open Forum Infectious Diseases, Vol. 6, No. 4, ofz108, 01.04.2019.

Research output: Contribution to journalArticle

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. / Sitafloxacin-containing regimen for the treatment of refractory mycobacterium avium complex lung disease. In: Open Forum Infectious Diseases. 2019 ; Vol. 6, No. 4.
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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 STFXcontaining 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.",
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AU - Asakura, Takanori

AU - Suzuki, Shoji

AU - Fukano, Hanako

AU - Okamori, Satoshi

AU - Kusumoto, Tatsuya

AU - Uwamino, Yoshifumi

AU - Ogawa, Takunori

AU - So, Matsuo

AU - Uno, Shunsuke

AU - Namkoong, Ho

AU - Yoshida, Mitsunori

AU - Kamata, Hirofumi

AU - Ishii, Makoto

AU - Nishimura, Tomoyasu

AU - Hoshino, Yoshihiko

AU - Hasegawa, Naoki

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N2 - 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 STFXcontaining 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.

AB - 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 STFXcontaining 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.

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KW - Mycobacterium avium complex (MAC)

KW - nontuberculous mycobacteria (NTM)

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