Effectiveness of levofloxacin for adult community-acquired pneumonia caused by macrolide-resistant Streptococcus pneumoniae: Integrated results from four open-label, multicenter, phase III clinical trials

Charles M. Fogarty, Richard N. Greenberg, Lala Dunbar, Rick Player, Thomas J. Marrie, Clare M. Kojak, Nancy Morgan, R. Rex Williams

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Background: The rate of macrolide resistance among Streptococcus pneumoniae clinical isolates is rising. Coresistance to several unrelated classes of antimicrobial agents is common and may limit the treatment options available for the management of infections caused by this pathogen. Although the fluoroquinolones appear to retain activity against macrolide-resistant pneumococci, limited clinical data exist to support their use in this setting. Objective: This study integrated data from 4 clinical trials to determine whether the fluoroquinolone levofloxacin is an effective therapeutic agent for community-acquired pneumonia (CAP) caused by macrolide-resistant S pneumoniae. Methods: Across the 4 trials, 271 adult patients with CAP were diagnosed with infections caused by S pneumoniae; these constituted the intent-to-treat population. Clinical isolates obtained from each patient at admission were tested using broth microdilution for in vitro sensitivity to the macrolide erythromycin (minimum inhibitory concentration breakpoints: susceptible, ≤0.25 μg/mL; intermediate, 0.5 μg/mL; resistant, ≥1.0 μg/mL). All patients received levofloxacin (500 mg once daily for 7-14 days) and were analyzed at a posttherapy visit (2-5 days after completion of therapy) for clinical and microbiologic outcomes; in 3 trials, patients were also examined at a poststudy visit (14-28 days after completion of treatment). Clinical and microbiologic outcomes were analyzed in patients infected with macrolide-resistant and macrolide-susceptible S pneumoniae. Results: A total of 235 evaluable patients infected with S pneumoniae were identified from the 4 trials. Twenty-seven (11.5%) patients were infected with isolates resistant to erythromycin, of whom 26 (96.3%) were clinical successes. By comparison, the clinical success rate in patients infected with erythromycin-susceptible isolates was 97.7%. Conclusions: These results suggest that if future studies demonstrate the clinical relevance of macrolide resistance, levofloxacin may be a useful therapeutic option in patients with CAP caused by macrolide-resistant S pneumoniae. However, caution may be warranted to prevent overprescription of levofloxacin and other fluoroquinolones, given the potential for the development of resistance in S pneumoniae.

Original languageEnglish
Pages (from-to)425-439
Number of pages15
JournalClinical Therapeutics
Volume23
Issue number3
DOIs
StatePublished - 2001

Bibliographical note

Funding Information:
This study integratedd ataf rom 4 phase III clinical trials conductedi n the United States and Canada and sponsoredb y the R.W. Johnson Pharmaceutical Research Institute, Raritan, New Jersey.‘9,20q23*24

Funding Information:
This researchw as supportedb y the R.W. Johnson PharmaceuticaRl esearchI nstitute, Raritan, New Jersey.

Keywords

  • Fluoroquinolones
  • Macrolides
  • Pneumonia
  • Resistance
  • Streptococcus pneumoniae

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Fingerprint

Dive into the research topics of 'Effectiveness of levofloxacin for adult community-acquired pneumonia caused by macrolide-resistant Streptococcus pneumoniae: Integrated results from four open-label, multicenter, phase III clinical trials'. Together they form a unique fingerprint.

Cite this