Therapeutic efficacy of azithromycin, clarithromycin, minocycline and tosufloxacin against macrolide-resistant and macrolide-sensitive Mycoplasma pneumoniae pneumonia in pediatric patients

PLoS One. 2017 Mar 13;12(3):e0173635. doi: 10.1371/journal.pone.0173635. eCollection 2017.

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.

Conclusion: 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.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Adolescent
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Azithromycin / therapeutic use
  • Child
  • Clarithromycin / therapeutic use
  • Drug Resistance, Bacterial / drug effects
  • Female
  • Fluoroquinolones / therapeutic use
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Minocycline / therapeutic use
  • Mycoplasma pneumoniae / drug effects*
  • Mycoplasma pneumoniae / genetics
  • Naphthyridines / therapeutic use
  • Pneumonia, Mycoplasma / drug therapy*
  • Pneumonia, Mycoplasma / etiology
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Fluoroquinolones
  • Naphthyridines
  • Azithromycin
  • Minocycline
  • tosufloxacin
  • Clarithromycin

Grants and funding

This research was funded in part by a Grant-in-Aid for Scientific Research (C), 2013 (25461577), from the Ministry of Education, Science, Sports and Culture of Japan and by a Health Science Research Grant (H24-Shinkou-Ippan-014) for Research on Emerging and Re-emerging Infectious Diseases, Labour and Welfare Programs from the Ministry of Health, Labour and Welfare of Japan. Pfizer Inc. provided grants for this study (A Prospective Observational Study of Antibiotic Treatment against Macrolide-Resistant Mycoplasma Pneumoniae Infections in Pediatric Patients, WS2419287) but was not involved in the design of the study or in enrollment of patients, data collection, analysis and interpretation, or preparation of the manuscript.