Levofloxacin for the treatment of pneumonia caused by Streptococcus pneumoniae including multidrug-resistant strains: pooled analysis

ABSTRACT

Objective: To determine the clinical and microbiologic efficacy of levofloxacin for the treatment of subjects with pneumonia caused by multidrug-resistant (MDR) Streptococcus pneumoniae (MDRSP) and non-MDRSP strains.

Research design and methods: A pooled analysis was conducted using data from ten clinical studies in pneumonia: five comparative studies and five noncomparative studies conducted from 1992 to 2002. This analysis included data from levofloxacin-treated subjects with S. pneumoniae isolated at study entry. Susceptibility of S. pneumoniae isolated from subjects at study entry was determined against representative agents from five antimicrobial classes: tetracyclines, sulfonamides, second-generation cephalosporins, penicillins, and macrolides. Isolates were classified as MDRSP (based on resistance to two or more antimicrobial classes) or non-MDRSP (intermediate resistance or susceptible to all classes or resistant to 1 antimicrobial class). Clinical and microbiologic efficacy of levofloxacin (i.v., p.o., or i.v./p.o. for 5 to 14 days) in the microbiologically evaluable population was determined at post-therapy; a test for homogeneity of the odds ratio of the difference in clinical success for comparative versus noncomparative studies was performed.

Main outcome measures and results: The main outcome measures were clinical success rates and microbiologic eradication rates of 419 microbiologically evaluable levofloxacin-treated subjects with MDRSP or non-MDRSP. Clinical success rates were 96.3% (52/54) and 95.1% (347/365), respectively (difference −1.2; 95% confidence interval [CI]: −6.7, 4.3). Similarly, per pathogen microbiologic eradication rates for MDRSP and non-MDRSP were 96.3% (52/54) and 95.6% (350/366), respectively (difference −0.7; 95% CI: −6.1, 4.8). Study limitations include the use of data from comparative and noncomparative studies. A test for homogeneity of the odds ratios for clinical success in comparative versus noncomparative studies showed no significant difference (p = 0.27).

Conclusions: These data support the use of levofloxacin for patients with community-acquired pneumonia caused by S. pneumoniae, including MDR strains.

Key words: :

• Fluoroquinolone
• Infection
• Levofloxacin
• Multidrug-resistant Streptococcus pneumoniae (MDRSP)
• Pooled analysis
• Streptococcus pneumoniae

Acknowledgments

Declaration of interest: The studies utilized in this analysis were funded and conducted by Ortho-McNeil, Inc. and Johnson & Johnson Pharmaceutical Research & Development, LLC. The analysis was conducted by employees of Ortho-McNeil Janssen Scientific Affairs and Johnson & Johnson. The authors acknowledge the contributions of numerous colleagues at Johnson & Johnson and Ortho-McNeil who, over a decade, planned and conducted the individual studies and who conducted the original analysis of S. pneumoniae that formed the basis for the current analysis. The authors also wish to acknowledge writing and editorial assistance from Ira Mills, PhD and Craig Ornstein, PhD of Advogent.