Moxifloxacin resistance and genotyping of Mycobacterium avium and Mycobacterium intracellulare isolates in Japan

Yusuke Yamaba, Yutaka Ito, Katsuhiro Suzuki, Toshiaki Kikuchi, Kenji Ogawa, Satoru Fujiuchi, Naoki Hasegawa, Atsuyuki Kurashima, Takeshi Higuchi, Kei ichi Uchiya, Akira Watanabe, Akio Niimi

Research output: Contribution to journalArticle

Abstract

Background: Although fluoroquinolones are considered as alternative therapies of pulmonary Mycobacterium avium complex (MAC) disease, the association between fluoroquinolone resistance and MAC genotypes in clinical isolates from individuals not previously treated for MAC infection is not fully clear. Methods: Totals of 154 M. avium isolates and 35 Mycobacterium intracellulare isolates were obtained from treatment-naïve patients with pulmonary MAC disease at the diagnosis of MAC infection at 8 hospitals in Japan. Their susceptibilities of moxifloxacin were determined by broth microdilution methods. Moxifloxacin-resistant isolates were examined for mutations of gyrA and gyrB. Variable numbers of tandem repeats (VNTR) assay was performed using 15 M. avium VNTR loci and 16 M. intracellulare VNTR loci. Results: Moxifloxacin susceptibility was categorized as resistant and intermediate for 6.5% and 16.9%, respectively, of M. avium isolates and 8.6% and 17.1% of M. intracellulare isolates. Although the isolates of both species had amino acid substitutions of Thr 96 and Thr 522 at the sites corresponding to Ser 95 in the M. tuberculosis GyrA and Gly 520 in the M. tuberculosis GyrB, respectively, these substitutions were observed irrespective of susceptibility and did not confer resistance. The VNTR assays showed revealed three clusters among M. avium isolates and two clusters among M. intracellulare isolates. No significant differences in moxifloxacin resistance were observed among these clusters. Conclusions: Although resistance or intermediate resistance to moxifloxacin was observed in approximately one-fourth of M. avium and M. intracellulare isolates, this resistance was not associated with mutations in gyrA and gyrB or with VNTR genotypes.

Original languageEnglish
JournalJournal of Infection and Chemotherapy
DOIs
Publication statusPublished - 2019 Jan 1

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Mycobacterium avium Complex
Japan
Minisatellite Repeats
Mycobacterium avium
Fluoroquinolones
Tuberculosis
Genotype
moxifloxacin
Lung
Mutation
Amino Acid Substitution
Mycobacterium
Complementary Therapies
Infection

Keywords

  • gyrA
  • gyrB
  • Moxifloxacin
  • Mycobacterium avium complex
  • Variable numbers of tandem repeats

ASJC Scopus subject areas

  • Microbiology (medical)
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Moxifloxacin resistance and genotyping of Mycobacterium avium and Mycobacterium intracellulare isolates in Japan. / Yamaba, Yusuke; Ito, Yutaka; Suzuki, Katsuhiro; Kikuchi, Toshiaki; Ogawa, Kenji; Fujiuchi, Satoru; Hasegawa, Naoki; Kurashima, Atsuyuki; Higuchi, Takeshi; Uchiya, Kei ichi; Watanabe, Akira; Niimi, Akio.

In: Journal of Infection and Chemotherapy, 01.01.2019.

Research output: Contribution to journalArticle

Yamaba, Y, Ito, Y, Suzuki, K, Kikuchi, T, Ogawa, K, Fujiuchi, S, Hasegawa, N, Kurashima, A, Higuchi, T, Uchiya, KI, Watanabe, A & Niimi, A 2019, 'Moxifloxacin resistance and genotyping of Mycobacterium avium and Mycobacterium intracellulare isolates in Japan', Journal of Infection and Chemotherapy. https://doi.org/10.1016/j.jiac.2019.05.028
Yamaba, Yusuke ; Ito, Yutaka ; Suzuki, Katsuhiro ; Kikuchi, Toshiaki ; Ogawa, Kenji ; Fujiuchi, Satoru ; Hasegawa, Naoki ; Kurashima, Atsuyuki ; Higuchi, Takeshi ; Uchiya, Kei ichi ; Watanabe, Akira ; Niimi, Akio. / Moxifloxacin resistance and genotyping of Mycobacterium avium and Mycobacterium intracellulare isolates in Japan. In: Journal of Infection and Chemotherapy. 2019.
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abstract = "Background: Although fluoroquinolones are considered as alternative therapies of pulmonary Mycobacterium avium complex (MAC) disease, the association between fluoroquinolone resistance and MAC genotypes in clinical isolates from individuals not previously treated for MAC infection is not fully clear. Methods: Totals of 154 M. avium isolates and 35 Mycobacterium intracellulare isolates were obtained from treatment-na{\"i}ve patients with pulmonary MAC disease at the diagnosis of MAC infection at 8 hospitals in Japan. Their susceptibilities of moxifloxacin were determined by broth microdilution methods. Moxifloxacin-resistant isolates were examined for mutations of gyrA and gyrB. Variable numbers of tandem repeats (VNTR) assay was performed using 15 M. avium VNTR loci and 16 M. intracellulare VNTR loci. Results: Moxifloxacin susceptibility was categorized as resistant and intermediate for 6.5{\%} and 16.9{\%}, respectively, of M. avium isolates and 8.6{\%} and 17.1{\%} of M. intracellulare isolates. Although the isolates of both species had amino acid substitutions of Thr 96 and Thr 522 at the sites corresponding to Ser 95 in the M. tuberculosis GyrA and Gly 520 in the M. tuberculosis GyrB, respectively, these substitutions were observed irrespective of susceptibility and did not confer resistance. The VNTR assays showed revealed three clusters among M. avium isolates and two clusters among M. intracellulare isolates. No significant differences in moxifloxacin resistance were observed among these clusters. Conclusions: Although resistance or intermediate resistance to moxifloxacin was observed in approximately one-fourth of M. avium and M. intracellulare isolates, this resistance was not associated with mutations in gyrA and gyrB or with VNTR genotypes.",
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T1 - Moxifloxacin resistance and genotyping of Mycobacterium avium and Mycobacterium intracellulare isolates in Japan

AU - Yamaba, Yusuke

AU - Ito, Yutaka

AU - Suzuki, Katsuhiro

AU - Kikuchi, Toshiaki

AU - Ogawa, Kenji

AU - Fujiuchi, Satoru

AU - Hasegawa, Naoki

AU - Kurashima, Atsuyuki

AU - Higuchi, Takeshi

AU - Uchiya, Kei ichi

AU - Watanabe, Akira

AU - Niimi, Akio

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Although fluoroquinolones are considered as alternative therapies of pulmonary Mycobacterium avium complex (MAC) disease, the association between fluoroquinolone resistance and MAC genotypes in clinical isolates from individuals not previously treated for MAC infection is not fully clear. Methods: Totals of 154 M. avium isolates and 35 Mycobacterium intracellulare isolates were obtained from treatment-naïve patients with pulmonary MAC disease at the diagnosis of MAC infection at 8 hospitals in Japan. Their susceptibilities of moxifloxacin were determined by broth microdilution methods. Moxifloxacin-resistant isolates were examined for mutations of gyrA and gyrB. Variable numbers of tandem repeats (VNTR) assay was performed using 15 M. avium VNTR loci and 16 M. intracellulare VNTR loci. Results: Moxifloxacin susceptibility was categorized as resistant and intermediate for 6.5% and 16.9%, respectively, of M. avium isolates and 8.6% and 17.1% of M. intracellulare isolates. Although the isolates of both species had amino acid substitutions of Thr 96 and Thr 522 at the sites corresponding to Ser 95 in the M. tuberculosis GyrA and Gly 520 in the M. tuberculosis GyrB, respectively, these substitutions were observed irrespective of susceptibility and did not confer resistance. The VNTR assays showed revealed three clusters among M. avium isolates and two clusters among M. intracellulare isolates. No significant differences in moxifloxacin resistance were observed among these clusters. Conclusions: Although resistance or intermediate resistance to moxifloxacin was observed in approximately one-fourth of M. avium and M. intracellulare isolates, this resistance was not associated with mutations in gyrA and gyrB or with VNTR genotypes.

AB - Background: Although fluoroquinolones are considered as alternative therapies of pulmonary Mycobacterium avium complex (MAC) disease, the association between fluoroquinolone resistance and MAC genotypes in clinical isolates from individuals not previously treated for MAC infection is not fully clear. Methods: Totals of 154 M. avium isolates and 35 Mycobacterium intracellulare isolates were obtained from treatment-naïve patients with pulmonary MAC disease at the diagnosis of MAC infection at 8 hospitals in Japan. Their susceptibilities of moxifloxacin were determined by broth microdilution methods. Moxifloxacin-resistant isolates were examined for mutations of gyrA and gyrB. Variable numbers of tandem repeats (VNTR) assay was performed using 15 M. avium VNTR loci and 16 M. intracellulare VNTR loci. Results: Moxifloxacin susceptibility was categorized as resistant and intermediate for 6.5% and 16.9%, respectively, of M. avium isolates and 8.6% and 17.1% of M. intracellulare isolates. Although the isolates of both species had amino acid substitutions of Thr 96 and Thr 522 at the sites corresponding to Ser 95 in the M. tuberculosis GyrA and Gly 520 in the M. tuberculosis GyrB, respectively, these substitutions were observed irrespective of susceptibility and did not confer resistance. The VNTR assays showed revealed three clusters among M. avium isolates and two clusters among M. intracellulare isolates. No significant differences in moxifloxacin resistance were observed among these clusters. Conclusions: Although resistance or intermediate resistance to moxifloxacin was observed in approximately one-fourth of M. avium and M. intracellulare isolates, this resistance was not associated with mutations in gyrA and gyrB or with VNTR genotypes.

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KW - Mycobacterium avium complex

KW - Variable numbers of tandem repeats

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