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 language | English |
|---|---|
| Article number | ofz108 |
| Journal | Open Forum Infectious Diseases |
| Volume | 6 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2019 Apr 1 |
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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 journal › Article
}
TY - JOUR
T1 - Sitafloxacin-containing regimen for the treatment of refractory mycobacterium avium complex lung disease
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
PY - 2019/4/1
Y1 - 2019/4/1
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.
KW - clarithromycin (CLR) resistance
KW - difficult to treat
KW - fluoroquinolone
KW - Mycobacterium avium complex (MAC)
KW - nontuberculous mycobacteria (NTM)
UR - http://www.scopus.com/inward/record.url?scp=85066407651&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85066407651&partnerID=8YFLogxK
U2 - 10.1093/ofid/ofz108
DO - 10.1093/ofid/ofz108
M3 - Article
VL - 6
JO - Open Forum Infectious Diseases
JF - Open Forum Infectious Diseases
SN - 2328-8957
IS - 4
M1 - ofz108
ER -