Fluoroquinolone Pharmacodynamics and Efficacy

Abstract

To the Editor:Doern and Tillotson correctly state in their letter that the clinical success of fluoroquinolones in treating community-acquired pneumococcal pneumonia should be weighed against the fact that their marginal pharmacodynamic activity may allow resistance emergence. Obviously, the most pharmacodynamic agents should be used. We have reviewed1Karcic AA Khan FA Ciprofloxacin in the treatment of pneumococcal lower respiratory tract infections: does it work?.J Islam Med Assoc North Am. 1998; 30: 83-89Google Scholar eight reports of clinical failures caused by pneumococcus, despite the use of ciprofloxacin.Davies and colleagues2Davies BI Maesen FP Baur C Ciprofloxacin in the treatment of acute exacerbations of chronic bronchitis.Eur J Clin Microbiol. 1986; 5: 226-231Crossref PubMed Scopus (86) Google Scholar reported clinical failure in 17 of 26 patients with pneumococcal chronic bronchitis exacerbations treated with ciprofloxacin. It is possible that this study was flawed, since two lots of medications were used in four different therapeutic regimens. Lee et al3Lee BL Kimbrough RC Jones SR et al.Infectious complications with respiratory pathogens despite ciprofloxacin therapy.N Engl J Med. 1991; 25: 520-521Google Scholar reported three failures of pneumococcal upper respiratory tract infection therapy with ciprofloxacin. One patient with otitis media died. Colville et al4Colville A Knowles M Large D et al.Fluoroquinolones in chronic obstructive pulmonary disease [letter].BMJ. 1994; 308: 1437Crossref PubMed Scopus (6) Google Scholar reported two patients with pneumococcal pneumonia unsuccessfully treated with ciprofloxacin but responding to amoxicillin.During our early clinical trials,1 we were often surprised with the clinical success rate of ciprofloxacin in pneumococcal respiratory tract infections, even in the presence of high minimum inhibitory concentrations (MICs). While the reasons for this may be speculative, it is our belief that the excellent penetration of ciprofloxacin into lung tissue5Bergogne-Berezin E Berthelot G Even P et al.Penetration of ciprofloxacin into bronchial secretions.Eur J Clin Microbiol. 1986; 5: 197-200Crossref PubMed Scopus (32) Google Scholar plays a major role in overcoming the marginal MIC of ciprofloxacin against Streptococcus pneumoniae. Therefore, we agree with Doern and Tillotson that free maximum serum concentration:MIC ratio is probably more accurate than MIC in this respect. To the Editor: Doern and Tillotson correctly state in their letter that the clinical success of fluoroquinolones in treating community-acquired pneumococcal pneumonia should be weighed against the fact that their marginal pharmacodynamic activity may allow resistance emergence. Obviously, the most pharmacodynamic agents should be used. We have reviewed1Karcic AA Khan FA Ciprofloxacin in the treatment of pneumococcal lower respiratory tract infections: does it work?.J Islam Med Assoc North Am. 1998; 30: 83-89Google Scholar eight reports of clinical failures caused by pneumococcus, despite the use of ciprofloxacin. Davies and colleagues2Davies BI Maesen FP Baur C Ciprofloxacin in the treatment of acute exacerbations of chronic bronchitis.Eur J Clin Microbiol. 1986; 5: 226-231Crossref PubMed Scopus (86) Google Scholar reported clinical failure in 17 of 26 patients with pneumococcal chronic bronchitis exacerbations treated with ciprofloxacin. It is possible that this study was flawed, since two lots of medications were used in four different therapeutic regimens. Lee et al3Lee BL Kimbrough RC Jones SR et al.Infectious complications with respiratory pathogens despite ciprofloxacin therapy.N Engl J Med. 1991; 25: 520-521Google Scholar reported three failures of pneumococcal upper respiratory tract infection therapy with ciprofloxacin. One patient with otitis media died. Colville et al4Colville A Knowles M Large D et al.Fluoroquinolones in chronic obstructive pulmonary disease [letter].BMJ. 1994; 308: 1437Crossref PubMed Scopus (6) Google Scholar reported two patients with pneumococcal pneumonia unsuccessfully treated with ciprofloxacin but responding to amoxicillin. During our early clinical trials,1 we were often surprised with the clinical success rate of ciprofloxacin in pneumococcal respiratory tract infections, even in the presence of high minimum inhibitory concentrations (MICs). While the reasons for this may be speculative, it is our belief that the excellent penetration of ciprofloxacin into lung tissue5Bergogne-Berezin E Berthelot G Even P et al.Penetration of ciprofloxacin into bronchial secretions.Eur J Clin Microbiol. 1986; 5: 197-200Crossref PubMed Scopus (32) Google Scholar plays a major role in overcoming the marginal MIC of ciprofloxacin against Streptococcus pneumoniae. Therefore, we agree with Doern and Tillotson that free maximum serum concentration:MIC ratio is probably more accurate than MIC in this respect. Fluoroquinolone Pharmacodynamics and EfficacyCHESTVol. 120Issue 1PreviewTo the Editor: Full-Text PDF