title: Long-term, low-dose erythromycin monotherapy for Mycobacterium avium complex lung disease: a propensity score analysis.
abstract: Multidrug regimens are initially withheld in mild cases of pulmonary Mycobacterium avium complex (MAC) disease. Based on the anti-inflammatory effects of macrolides, some patients are treated with erythromycin, which does not appear to exhibit cross-resistance with clarithromycin in MAC. The aim of this study was to evaluate the effects and adverse events of erythromycin monotherapy in patients with pulmonary MAC disease. This was a retrospective propensity score analysis consisting of 31 patients treated with erythromycin alone and 72 patients on conservative therapy, all of whom met the ATS/IDSA criteria for pulmonary MAC disease. The primary outcome was exacerbation requiring administration of a multidrug regimen. The secondary outcome was the rate of response to the multidrug regimens after exacerbation as a surrogate variable for cross-resistance to clarithromycin. As a result, erythromycin monotherapy was found to be likely to suppress exacerbation throughout the 7-year observation period after the diagnosis of pulmonary MAC disease (P=0.045, Breslow test). Multivariate analysis showed that erythromycin tended to prevent exacerbation, albeit statistically insignificantly (hazard ratio=0.495, 95% confidence interval 0.198-1.235; P=0.132). In addition, the rate of response to the multidrug regimens after exacerbation in the erythromycin group (56%; 5/9) was similar to that observed in the control group (62%; 13/21) (P=0.528). Erythromycin monotherapy for patients with pulmonary MAC disease may have the potential to suppress exacerbation without inducing cross-resistance to clarithromycin. However, further prospective studies are needed to microbiologically verify the effectiveness and potential for cross-resistance of these drugs.
authors.affiliation: Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama, Yufu, Oita 879-5593, Japan; Clinical Research Center of Respiratory Medicine, Tenshindo Hetsugi Hospital, 5956 Nihongi, Nakahetsugi, Oita 879-7761, Japan. Electronic address: komiyakh1@oita-u.ac.jp.
authors.forename: Kosaku
authors.initials: K
authors.lastname: Komiya
authors.affiliation: Respiratory Medicine, Fukujuji Hospital, 1-24 Matsuyama, Kiyose, Tokyo 204-0022, Japan; Center of Respiratory Medicine, National Hospital Organization Tokyo Hospital, 3-1-1 Takeoka, Kiyose, Tokyo 204-0023, Japan.
authors.forename: Atsuyuki
authors.initials: A
authors.lastname: Kurashima
authors.affiliation: Respiratory Medicine, National Hospital Organization Miyazaki Higashi Hospital, 4374-1, Tayoshi, Miyazaki 880-0911, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Ihi
authors.affiliation: Center of Respiratory Medicine, National Hospital Organization Tokyo Hospital, 3-1-1 Takeoka, Kiyose, Tokyo 204-0023, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nagai
authors.affiliation: Respirology, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: Respiratory Medicine, Oita Prefectural Hospital, 476 Bunyo, Oita 870-8511, Japan.
authors.forename: Shunji
authors.initials: S
authors.lastname: Mizunoe
authors.affiliation: Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama, Yufu, Oita 879-5593, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishii
authors.affiliation: Center for Clinical Epidemiology, St Luke's Life Science Institute, 10-1 Akashi-machi, Chuo-ku, Tokyo 104-0044, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Takahashi
authors.affiliation: Center of Respiratory Medicine, National Hospital Organization Tokyo Hospital, 3-1-1 Takeoka, Kiyose, Tokyo 204-0023, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Ohta
authors.affiliation: Respiratory Medicine, Fukujuji Hospital, 1-24 Matsuyama, Kiyose, Tokyo 204-0022, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Kudoh
authors.affiliation: Respiratory Medicine and Infectious Diseases, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama, Yufu, Oita 879-5593, Japan.
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Kadota
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D017291:Clarithromycin / Q000494:pharmacology; D015331:Cohort Studies; D024881:Drug Resistance, Bacterial; D004917:Erythromycin / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008171:Lung Diseases / Q000188:drug therapy* / Q000382:microbiology*; D008297:Male; D008875:Middle Aged; D015269:Mycobacterium avium Complex / Q000187:drug effects / Q000302:isolation & purification*; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy*; D057216:Propensity Score; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D004917:Erythromycin; D017291:Clarithromycin
keywords: Erythromycin; Macrolide; Mycobacterium avium complex