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Journal of Clinical Microbiology, May 2007, p. 1440-1446, Vol. 45, No. 5
0095-1137/07/$08.00+0     doi:10.1128/JCM.01430-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Genotypes and Related Factors Reflecting Macrolide Resistance in Pneumococcal Pneumonia Infections in Japan{triangledown}

Rie Isozumi,1 Yutaka Ito,1* Tadashi Ishida,2 Makoto Osawa,1 Toyohiro Hirai,1 Isao Ito,1,3 Ko Maniwa,4 Michio Hayashi,5 Hitoshi Kagioka,6 Masataka Hirabayashi,7 Koichi Onari,8 Hiromi Tomioka,9 Keisuke Tomii,5,10 Iwao Gohma,10 Seiichiro Imai,1 Shunji Takakura,11 Yoshitsugu Iinuma,11 Satoshi Ichiyama,11 Michiaki Mishima,1 and the Kansai Community Acquired Pneumococcal Pneumonia Study Group {dagger}

Department of Respiratory Medicine,1 Department of Clinical Laboratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan,11 Kurashiki Central Hospital, Okayama, Japan,2 Ono Municipal Hospital, Hyogo, Japan,3 Tenri Hospital, Nara, Japan,4 Kobe City General Hospital, Hyogo, Japan,5 Kitano Hospital, Osaka, Japan,6 Hyogo Prefectural Tsukaguchi Hospital, Hyogo, Japan,7 Sakai Municipal Hospital, Osaka, Japan,8 Nishi-Kobe Medical Center, Hyogo, Japan,9 Kobe Japan Post Hospital, Hyogo, Japan,10

Received 11 July 2006/ Returned for modification 26 August 2006/ Accepted 9 February 2007

Although macrolide-resistant Streptococcus pneumoniae strains possessing either the ermB or mefA gene are very common in Japan, clinical and microbial factors in community-acquired pneumonia (CAP) caused by different macrolide resistance genotypes have not been evaluated. A multicenter study of CAP caused by S. pneumoniae was performed in Japan from 2003 to 2005. A total of 156 isolates were tested for susceptibility to antibiotics correlated with ermB and mefA genotyping. Independent relationships between tested variables and possession of either the ermB or the mefA gene were identified. Of 156 isolates, 127 (81.4%) were resistant to erythromycin, with the following distribution of resistance genotypes: ermB alone (50.0%), mefA alone (23.7%), and both ermB and mefA (7.1%). All isolates were susceptible to telithromycin. By multivariate analysis, oxygen saturation of <90% on admission increased the risk for ermB-positive pneumococcal pneumonia (odds ratio [OR] = 11.1; 95% confidence interval [CI] = 1.30 to 95.0; P = 0.03), but there were no associations with mefA or with ermB mefA positivity. Penicillin nonsusceptibility was associated with mefA-positive and with ermB- and mefA-positive isolates (OR = 14.2; 95% CI = 4.27 to 46.9; P < 0.0001 and P < 0.0001, respectively) but not with ermB-positive isolates. The overall patient mortality was 5.1%. Mortality, the duration of hospitalization, and the resolution of several clinical markers were not associated with the different erythromycin resistance genotypes. In Japan, S. pneumoniae with erythromycin resistance or possession of ermB, mefA, or both genes was highly prevalent in patients with CAP. The risk factors for ermB-positive, mefA-positive, and double ermB-mefA-positive pneumococcal pneumonia were different, but the clinical outcomes did not differ.

* Corresponding author. Mailing address: Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, 54, Kawahara, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. Phone: 81-75-751-3830. Fax: 81-75-751-4643. E-mail: yutaka{at}kuhp.kyoto-u.ac.jp

{triangledown} Published ahead of print on 7 March 2007.

{dagger} Y. Ito, T. Ishida, T. Hirai, I. Ito, K. Maniwa, M. Hayashi, H. Kagioka, M. Hirabayashi, K. Onari, H. Tomioka, K. Tomii, I. Gohma, and M. Mishima are contributing members of the Kansai Community Acquired Pneumococcal Pneumonia Study Group.

Journal of Clinical Microbiology, May 2007, p. 1440-1446, Vol. 45, No. 5
0095-1137/07/$08.00+0     doi:10.1128/JCM.01430-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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