title: Therapeutic efficacy of azithromycin, clarithromycin, minocycline and tosufloxacin against macrolide-resistant and macrolide-sensitive Mycoplasma pneumoniae pneumonia in pediatric patients.
abstract: OBJECTIVE
  To clarify therapeutic effects of azithromycin, clarithromycin, minocycline and tosufloxacin against macrolide-resistant Mycoplasma pneumoniae (MRMP) pneumonia and against macrolide-sensitive Mycoplasma pneumoniae (MSMP) pneumonia in pediatric patients.
  
  
  METHODS
  A prospective, multicenter observational study was conducted from July 2013 to August 2015. The therapeutic effects of azithromycin, clarithromycin, minocycline and tosufloxacin were evaluated in 59 patients with pneumonia caused by MRMP and in 50 patients with pneumonia caused by MSMP. In vitro activities of antimicrobial agents against isolates of Mycoplasma pneumoniae were also measured.
  
  
  RESULTS
  Mean durations of fever following commencement of treatment in patients infected with MRMP and MSMP were 5.2 and 1.9 days, respectively (log-rank test, P < 0.0001). Among patients infected with MRMP, mean durations of fever were 4.6, 5.5, 1.0 and 7.5 days for patients treated with azithromycin, clarithromycin, minocycline and tosufloxacin, respectively (log-rank test, P < 0.0001). Among patients infected with MSMP, mean durations of fever were 2.5, 1.7, 0.9 and 4.3 days for patients treated with azithromycin, clarithromycin, minocycline and tosufloxacin, respectively (log-rank test, P = 0.0162). The MIC90s of azithromycin and clarithromycin among the 27 isolates of MRMP were 64 and 256 μg/ml, respectively, and those among the 23 isolates of MSMP were <0.000125 and 0.001 μg/ml, respectively. The MIC90s of minocycline and tosufloxacin among the 27 isolates of MRMP were 1.0 and 0.25 μg/ml, respectively, and those among the 23 isolates of MSMP were 1.0 and 0.5 μg/ml, respectively.
  
  
  CONCLUSIONS
  Both minocycline and tosufloxacin showed good in vitro activities against MRMP. Minocycline, but not tosufloxacin, shortened the duration of fever in pediatric patients infected with MRMP compared to the duration of fever in patients treated with macrolides.
authors.affiliation: Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.
authors.forename: Nobuhisa
authors.identifier: http://orcid.org/0000-0001-8594-6345
authors.initials: N
authors.lastname: Ishiguro
authors.affiliation: Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Koseki
authors.affiliation: Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Kaiho
authors.affiliation: Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ariga
authors.affiliation: Pediatric Clinic, Touei Hospital, Sapporo, Hokkaido, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kikuta
authors.affiliation: Hokkaido Anti-Tuberculosis Association Sapporo Fukujuji Clinic, Sapporo, Hokkaido, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Togashi
authors.affiliation: Department of Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.|Interfaculty Initiative in Information Studies, The University of Tokyo, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Oba
authors.affiliation: Department of Pediatrics, Asahikawa Red Cross Hospital, Asahikawa, Hokkaido, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Morita
authors.affiliation: Nagano Pediatric Clinic, Asahikawa, Hokkaido, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Nagano
authors.affiliation: Deparment of Pediatrics, Kushiro Red Cross Hospital, Kushiro, Hokkaido, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakanishi
authors.affiliation: Deparment of Pediatrics, Kushiro Red Cross Hospital, Kushiro, Hokkaido, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Hara
authors.affiliation: Hazama Pediatric Clinic, Muroran, Hokkaido, Japan.
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Hazama
authors.affiliation: Watanabe Pediatric Allergy Clinic, Sapporo, Hokkaido, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Yamanaka Tatsuru Pediatric Clinic, Sapporo, Hokkaido, Japan.
authors.forename: Tatsuru
authors.initials: T
authors.lastname: Yamanaka
authors.affiliation: Department of Pediatrics, Aiiku Hospital, Sapporo, Hokkaido, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sasaki
authors.affiliation: Deparment of Pediatrics, Japan Community Healthcare Organization Hokkaido Hospital, Sapporo, Hokkaido, Japan.
authors.forename: Hideto
authors.initials: H
authors.lastname: Furuyama
authors.affiliation: Department of Pediatrics, Health Sciences University of Hokkaido, Sapporo, Hokkaido, Japan.
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Shibata
authors.affiliation: Deparment of Pediatrics, Ebetsu Municipal Hospital, Ebetsu, Hokkaido, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Shida
authors.affiliation: Sumiyoshi Kodomo Clinic, Chitose, Hokkaido, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Ishizaka
authors.affiliation: Iwamizawa Pediatric and Gynecology Clinic, Iwamizawa, Hokkaido, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tabata
authors.affiliation: Deparment of Pediatrics, Obihiro Kyokai Hospital, Obihiro, Hokkaido, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Aoyagi
authors.affiliation: Deparment of Pediatrics, Chitose City Hospital, Chitose, Hokkaido, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Naito
authors.affiliation: Deparment of Pediatrics, KKR Sapporo Medical Center, Sapporo, Hokkaido, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Yoshioka
authors.affiliation: Department of Bacteriology II, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Horino
authors.affiliation: Department of Bacteriology II, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kenri
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017963:Azithromycin / Q000627:therapeutic use; D002648:Child; D017291:Clarithromycin / Q000627:therapeutic use; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D005260:Female; D024841:Fluoroquinolones / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000627:therapeutic use; D009177:Mycoplasma pneumoniae / Q000187:drug effects* / Q000235:genetics; D009287:Naphthyridines / Q000627:therapeutic use; D011019:Pneumonia, Mycoplasma / Q000188:drug therapy* / Q000209:etiology; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; D017963:Azithromycin; D008911:Minocycline; C055185:tosufloxacin; D017291:Clarithromycin