[Multicenter study on clinical features and genetic characteristics of Mycobacterium avium strains from patients in Japan with lung disease caused by M. avium].
BACKGROUND
The pulmonary disease caused by Mycobacterium avium shows diverse clinical manifestations. Little is known about the potential association between the genetic characteristics of M. avium strains and disease progression.


METHODS
We enrolled 89 patients with disease caused by M. avium, from 12 hospitals in Japan and collected the corresponding M. avium isolates and clinical data. We divided the 89 patients into 2 groups: one group comprising 43 patients with progressive disease despite chemotherapy ("progressive"), and the other group comprising 46 patients with untreated disease ("untreated"). We compared clinical and bacteriological characteristics between these groups. The bacteriological characteristics that we examined were drug susceptibility, variable-number tandem-repeat (VNTR) typing, and presence of the insertion sequence ISMav6. Seventeen patients in the "untreated" group were started on chemotherapy because their condition had clinically deteriorated during follow-up.


RESULTS
The result of VNTR typing showed that there was no specific clustering according to geographical region or clinical group in the "untreated" or "progressive" groups. Six out of eight cases those of polyclonal infection, and 11 of 12 isolates that were highly resistant to clarithromycin were isolated from patients with progressive disease. The frequency of isolates with ISMav6 inserted into upstream region of the cfp29 gene, which is involved in the induction of interferon-gamma production, was significantly higher in patients with deteriorating disease than in stable patients in the "untreated" group (p = 0.002).


CONCLUSIONS
Polyclonal infection and clarithromycin resistance may be involved in disease progression. ISMav6 inserted into the cfp29 gene is also suggested to be a factor related to the deterioration of pulmonary Mycobacterium avium complex disease.
Department of Respiratory Medicine, National Hospital Organization (NHO) Higashi Nagoya National Hospital, Japan. nkgwtk@toumei.hosp.go.jp
Taku
T
Nakagawa
Hiroyasu
H
Takahashi
Kazuya
K
Ichikawa
Takayuki
T
Inagaki
Kei-Ichi
K
Uchiya
Toshiaki
T
Nikai
Tetsuya
T
Yagi
Kenji
K
Ogawa
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017291:Clarithromycin / Q000494:pharmacology; D004269:DNA, Bacterial; D018432:Drug Resistance, Multiple; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D016254:Mutagenesis, Insertional; D009162:Mycobacterium avium / Q000235:genetics*; D014397:Tuberculosis, Pulmonary / Q000382:microbiology / Q000503:physiopathology*
D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D017291:Clarithromycin