Variability of macrolide-resistant profile in Mycobacterium avium complex pulmonary disease

Kiyoharu Fukushima^#^{1

2

3

4

5}, Yuki Matsumoto^#⁶, Yuko Abe^#², Kazuki Hashimoto², Daisuke Motooka^{6

7}, Seigo Kitada⁸, Haruko Saito⁹, Sho Komukai^{7

10}, Eriko Fukui¹¹, Takayuki Niitsu², Hiroshi Nabeshima⁴, Yasuharu Nagahama⁴, June Yamauchi⁹, Tadayoshi Nitta⁹, Takuro Nii¹, Takanori Matsuki¹, Kazuyuki Tsujino¹, Keisuke Miki¹, Yasushi Shintani¹¹, Atsushi Kumanogoh^{2

7

12}, Shizuo Akira^{3

4}, Shota Nakamura^{6

7

12}, Hiroshi Kida¹

Affiliations

¹ Department of Respiratory Medicine, National Hospital Organization, Osaka Toneyama Medical Center, Toyonaka, Osaka, Japan.
² Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
³ Department of Host Defense, Research Institute for Microbial Diseases (RIMD), Osaka University, Suita, Osaka, Japan.
⁴ Laboratory of Host Defense, World Premier Institute Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Osaka, Japan.
⁵ Global Center for Medical Engineering and Informatics, Suita, Osaka, Japan.
⁶ Department of Infection Metagenomics, Genome Information Research Center, Research Institute for Microbial Diseases (RIMD), Osaka University, Suita, Osaka, Japan.
⁷ Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Osaka, Japan.
⁸ Kitada Respiratory Clinic, Yao, Osaka, Japan.
⁹ Department of Clinical Laboratory, National Hospital Organization, Osaka Toneyama Medical Centre, Toyonaka, Osaka, Japan.
¹⁰ Department of Biomedical Statistics, Graduate School of Medicine, Osaka University, Osaka, Japan.
¹¹ Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
¹² Center for Infectious Disease Education and Research, Osaka University, Japan for Infectious Disease Education and Research, Osaka University, Toyonaka, Osaka, Japan.

^# Contributed equally.

PMID: 39377582
PMCID: PMC11539230
DOI: 10.1128/aac.01213-24

Variability of macrolide-resistant profile in Mycobacterium avium complex pulmonary disease

Kiyoharu Fukushima et al. Antimicrob Agents Chemother. 2024.

. 2024 Nov 6;68(11):e0121324.

doi: 10.1128/aac.01213-24. Epub 2024 Oct 8.

Authors

Affiliations

¹ Department of Respiratory Medicine, National Hospital Organization, Osaka Toneyama Medical Center, Toyonaka, Osaka, Japan.
² Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
³ Department of Host Defense, Research Institute for Microbial Diseases (RIMD), Osaka University, Suita, Osaka, Japan.
⁴ Laboratory of Host Defense, World Premier Institute Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, Osaka, Japan.
⁵ Global Center for Medical Engineering and Informatics, Suita, Osaka, Japan.
⁶ Department of Infection Metagenomics, Genome Information Research Center, Research Institute for Microbial Diseases (RIMD), Osaka University, Suita, Osaka, Japan.
⁷ Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Osaka, Japan.
⁸ Kitada Respiratory Clinic, Yao, Osaka, Japan.
⁹ Department of Clinical Laboratory, National Hospital Organization, Osaka Toneyama Medical Centre, Toyonaka, Osaka, Japan.
¹⁰ Department of Biomedical Statistics, Graduate School of Medicine, Osaka University, Osaka, Japan.
¹¹ Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
¹² Center for Infectious Disease Education and Research, Osaka University, Japan for Infectious Disease Education and Research, Osaka University, Toyonaka, Osaka, Japan.

^# Contributed equally.

PMID: 39377582
PMCID: PMC11539230
DOI: 10.1128/aac.01213-24

Abstract

This single-center retrospective study aimed to analyze the variability of macrolide resistance (MR) in 68 patients with Mycobacterium avium complex pulmonary disease. Among 25 patients treated without macrolides, 13 (52%) reverted to macrolide-susceptible (MS) profiles. Only one (2%) of 43 patients who continued macrolide treatment showed this change. We compared 30 MR isolates with recent specimens. Among them, seven shifted to MS (five attributed to clonally related strains; two resulting from reinfection or polyclonal infection).

Keywords: Mycobacterium avium complex; drug resistance; macrolide resistance; non-tuberculous mycobacteria; variable number tandem repeat; whole-genome sequence.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**FIG 1**
The drug regimen before and after macrolide resistance (MR) profile detection and the time course of the drug susceptibility test (DST) after MR detection. (A) Drugs used in the initial treatment and treatment prior to MR detection. Closed cells indicate drugs administered for treatment. Treatment duration from the start of initial treatment to the MR detection is also shown. (B) Drugs used in the treatment and treatment duration after MR detection. (C) Time course of DST results for CLR from MR detection. Abbreviations: CLR, clarithromycin; EB, ethambutol; EM, erythromycin; FQ, fluoroquinolone; I, intermediate; R, resistant; RFP, rifampicin; S, susceptible. ^#One patient (#11) had a history of occasional prescription of CLR for symptom aggravation, and another (#17) had a history of multidrug treatment with CLR + levofloxacin.

**FIG 2**
Examination of the growth rate of paired clinical isolates. (A) Isolates with reappearance of the macrolide-susceptible profile (n = 7). Isolates obtained during macrolide resistance profile (MR) detection and the most recently available isolate are compared among patients who regained macrolide susceptibility. (B) Isolates obtained at MR detection and the most recently available isolate are compared among patients who remained MR (n = 8). CLR, clarithromycin.

See this image and copyright information in PMC

References

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Variability of macrolide-resistant profile in Mycobacterium avium complex pulmonary disease

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Variability of macrolide-resistant profile in Mycobacterium avium complex pulmonary disease

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