a Bayer AG, Wuppertal, Germany; b Department of Pathology and Medicine, Northwestern University Medical School, Chicago, IL 60611, USA
Sir,
The recent leading article by Legg & Bint,1 addressing quinolones and pneumococci, raised several key points and ended on a crucial hypothesis for the future treatment of respiratory tract infections (RTIs). The role of fluoroquinolones in RTI therapy has been, at times, an emotionally charged one, perhaps because of the widespread, successful use of these compounds. A major reason for the remarkable chemical evolution of the quinolone molecule has been the inexorable rise in overall microbial resistance to antimicrobial agents. The hypothesis posed by Legg & Bint was that we should not use these newer quinolone agents as empirical first-line therapy for lower respiratory tract infections. However, historical examples from other antimicrobial agent classes may exist to teach us that the real issue is to choose the best agent(s) to use within a specific class.
Ciprofloxacin was pilloried by the infectious disease community and became the subject of many anecdotal case-reports of clinical failure for pneumococcal infections. Ironically, as noted by the authors, analysis of the literature and various databases showed ciprofloxacin to yield high clinical response rates (8590%). Admittedly, none of these strains was penicillin resistant, but, as Legg & Bint point out, this status has little bearing on in vitro ciprofloxacin activity, with an MIC90 of 12 mg/L being typical at the time of ciprofloxacin's introduction into clinical use.1 Confidence was gained when additional investigation showed 100% bacterial eradication and clinical success for hospitalized patients with severe pneumonia caused by Streptococcus pneumoniae and Haemophilus influenzae given ciprofloxacin monotherapy at the appropriate dose of 400 mg iv every 8 h.2
The discussion of emerging resistance in pneumococci to the older agents (ciprofloxacin, levofloxacin and ofloxacin) is of concern, and must be addressed. We believe the new quinolones bring something genuinely innovative to the clinical setting, as they were designed to tackle the growing pneumococcal resistance problem. The latest report with moxifloxacin bears out the enhanced outcome from one of these new compounds, with clinical and bacteriological response rates 95% against S. pneumoniae, for both the fluoroquinolone and clarithromycin treatment arms.3 New laboratory research also indicates that the structural modifications made in this new agent reduce the propensity to select for quinolone-resistant mutants.4
The historical perspective shows us that all agents in a given class are not equal in their design and therapeutic outcome. Early after the release of the extended-spectrum cephalosporins all, including ceftazidime, were considered very active for the potential treatment of pneumococcal meningitis, and they were even recommended as a major component of the therapy of acute bacterial meningitis.5 We now realize that only one or two of these agents had the pharmacodynamic properties to stay the course in treatment of severe pneumococcal disease, thus suggesting that not only does the appropriate class of agent need to be chosen for optimizing outcome, but that selecting the right drug within the class is essential.
Finally, a recent report by Gleason et al.6 demonstrates that specific initial therapy for primarily community-acquired serious RTI can lower mortality rates for people aged over 65 years. Those researchers found that beginning treatment with either a second- or third-generation cephalosporin combined with a macrolide, or a fluoroquinolone alone, reduced mortality by as much as 30%. They concluded that use of one of these three regimens provides potential opportunities to reduce the mortality and thereby improve the quality of care for elderly patients with pneumonia.6
Perhaps the issue for debate posed by Legg & Bint would best be reworded to decide whether it is now time to use a new fluoroquinolone as an empirical first choice therapy for community-acquired lower respiratory tract infections, so that we endeavour to maximize efficacy while minimizing resistance. The alternative approach is to reserve these new agents until widespread resistance develops in pneumococci secondary to the continued prescribing of older quinolones such as ciprofloxacin and levofloxacinand let the bugs' solve the question of antimicrobial agent choice for us.
Notes
J Antimicrobial Chemother 2000; 45: 709710
* Corresponding author. Tel: +1-312-926-3205; Fax: +1-312-908-4137; E-mail: lancer{at}nwu.edu
References
1
.
Legg, J. M. & Bint, A. J. (1999). Will pneumococci put quinolones in their place? Journal of Antimicrobial Chemotherapy 44, 4257.
2 . Fink, M. P., Snydman, D. R., Niederman, M. S., Leeper, K. V., Johnson, R. H., Heard, S. O. et al. (1994). Treatment of severe pneumonia in hospitalized patients: results of a multicenter, randomized, double-blind trial comparing ciprofloxacin with imipenem cilastatin. Antimicrobial Agents and Chemotherapy 38, 54757.[Abstract]
3 . Fogarty, C., Grossman, C., Williams, J., Haverstock, D., Church, D. et al. (1999). Efficacy and safety of moxifloxacin vs clarithromycin for community-acquired pneumonia. Infections in Medicine 16, 74863.[ISI]
4 . Pestova, E., Millichap, J. J., Noskin, G. A. & Peterson, L. R. (2000). Intracellular targets of moxifloxacin: a comparison with other fluoroquinolones. Journal of Antimicrobial Chemotherapy 45, 583 590.
5 . Neu, H. (1987). Cephalosporins in the treatment of meningitis. Drugs 34, Suppl. 2, 13553.[ISI][Medline]
6
.
Gleason, P. P., Meehan, T. P., Fine, J. M., Galusha, D. H. & Fine, M. J. (1999). Associations between initial antimicrobial therapy and medical outcomes for hospitalized elderly patients with pneumonia. Archives of Internal Medicine 159, 256272.