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Communications to the Editor |

Fluoroquinolones for Respiratory Infection : Too Valuable To Overuse (and Too Valuable To Misuse!) FREE TO VIEW

Karl Weiss, MD; Glenn S. Tillotson, MS
Author and Funding Information

Affiliations: Hopital Maisonneuve-Rosemont, Montreal, Quebec, Canada,  Public Health Research Laboratory, New York, NY,  The Ohio State University, Columbus, OH

Correspondence to: Glenn S. Tillotson, MS, Public Health Research Laboratory, 225 Warren St, Newark, NJ 07103



Chest. 2002;122(3):1102-1103. doi:10.1378/chest.122.3.1102
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Published online

To the Editor:

We would like to compliment Drs. Guthrie (December 2001)1and Williams (December 2001)2 on their recent review and editorial, respectively, on community-acquired lower respiratory tract infections. However, we wish to comment on specific aspects of those articles, namely, the current recommendations of recent guidelines in light of changing pathogen susceptibilities. Specifically, we would like to comment on the role of an appropriately chosen fluoroquinolone in providing clinical confidence and in maintaining class activity over time, and also on the relevance of doxycycline as a first-line agent for treating patients with community-acquired pneumonia (CAP).

Since the acceptance of the Guthrie article (in March 2001), the American Thoracic Society guidelines on the management of CAP3 have been published (June 2001). In those recommendations, new respiratory fluoroquinolones play an increasingly prominent role. However, there is a strong caveat in the guidelines about possible lack of response to levofloxacin in those with pneumococcal infections, with advice given on the use of the most potent class member in terms of in vitro and pharmacodynamic properties.,3The growing number of reports about such clinical problems, which parallel the escalating issue of fluoroquinolone resistance in pneumococci in Hong Kong4 and elsewhere, heralds an era of rampant early quinolone use (most notably, levofloxacin).

These clinical failure case reports,59 now numbering at least 18, were not all available to either Guthrie1or Williams2 and now constitute a somber growing warning about impending issues that are likely to become concerns in the United States and Canada. Thus, some of the earlier comments of Guthrie and Williams should now be modified in light of these recent reports. Moreover, these reports probably represent only the tip of the iceberg, as the vast majority of frontline physicians will not report cases of clinical failure in which they have to prescribe a second antibiotic.

One of us (KW) reported on a long-standing outbreak of fluoroquinolone-resistant Streptococcus pneumoniae respiratory infections in a chronic pulmonary disease unit in Montreal, Canada.8The infecting pathogens were not only resistant to ciprofloxacin and levofloxacin but also were less susceptible to the newer class of fluoroquinolones such as gatifloxacin and moxifloxacin. These shifts in minimum inhibitory concentration (MIC) will radically affect the pharmacodynamic (PD) parameters referred to by Doern et al9only last year. Through a surveillance network of respiratory pathogens in Quebec, we noticed for the first time in 2001 an increase of the MIC of levofloxacin for 90% of the strains tested (MIC90) to 2 mg/L compared to that of previous years (MIC90, 1 mg/L). This increase paralleled a sharp jump in levofloxacin consumption in Quebec (1998 [the year levofloxacin was introduced], 0.3 prescriptions per 100 population per year; 2000, 1.28 prescriptions per 100 population).10 Thus, if we are to preserve the fluoroquinolone class as an appropriate agent for specific community respiratory tract infections, it is essential that the American Thoracic Society approach be adopted (ie, use the most [PD] potent class members).,3

Finally, the recommendations of doxycycline use give us some concerns.11First, the resistance to this agent among US isolates of S pneumoniae is > 20%, with some geographic areas approaching 35%.12 It is puzzling to see tetracyclines, as a class, still recommended for treating CAP and acute bacterial exacerbations of chronic bronchitis in an era of increasing resistance, and when almost all the data on tetracyclines were gathered in the 1960s and 1970s when conditions (eg, resistance rates, definition of clinical outcomes, and inclusion criteria) were very different from the present.14

There are numerous in vitro and pharmacodynamic data suggesting that in order to decrease the likelihood of emerging S pneumoniae resistance to fluoroquinolones, the most potent agents should be used initially and not after less active drugs have already been tried and have selected for resistant mutants.15 As clinicians, we were waiting for clinical evidence to support this new approach to antimicrobial use, however, the evidence is now quickly accumulating to turn this hypothesis into reality.

Again, we want to compliment Guthrie1and Williams,2 but, equally, we would like to caution against widespread adoption of less active compounds (not just fluoroquinolones) in the face of a highly labile, infectious entity, the pneumococcus. Evidence is rapidly emerging that we should not dwell on minor successes, because they may soon be memorials in our battle against a fearsome and highly adaptable adversary.

Be not afraid to change for change’s sake, as mutations may be kept at bay.

Drs. Weiss and Tillotson have served as speakers for Bayer and Pharmacia. Dr. Tillotson has served as a consultant for Bayer, Pharmacia, BMS, Johnson & Johnson, and Anbics.

References

Guthrie, R (2001) Community-acquired lower respiratory tract infections: etiology and treatment.Chest120,2021-2034. [PubMed] [CrossRef]
 
Williams, JH, Jr Fluoroquinolones for respiratory infections: too valuable to overuse.Chest2001;120,1771-1775. [PubMed]
 
American Thoracic Society. Guidelines for the management of adults with community-acquired pneumonia: diagnosis, assessment of severity, antimicrobial therapy and prevention.Am J Respir Crit Care Med2001;163,1730-1754. [PubMed]
 
Ho, PL, Yung, RW, Tsang, DN, et al Increasing resistance ofStreptococcus pneumoniaeto fluoroquinolones: results of a Hong Kong multicentre study in 2000.J Antimicrob Chemother2001;48,659-665. [PubMed]
 
Davidson, R, Cavalcanti, R, Brunton, JL, et al Levofloxacin treatment failures of pneumococcal pneumonia in association with resistance.N Engl J Med2002;346,747-750. [PubMed]
 
Empey, PE, Jennings, HR, Thornton, AC, et al Levofloxacin: failure in a patient with pneumococcal pneumonia.Ann Pharmacother2001;35,687-690. [PubMed]
 
Urban, C, Rahman, N, Zhao, X, et al Fluoroquinolone-resistantStreptococcus pneumoniaeassociated with levofloxacin therapy.J Infect Dis2001;184,794-798. [PubMed]
 
Weiss, K, Restieri, C, Gauthier, R, et al A nosocomial outbreak of fluoroquinolone-resistantStreptococcus pneumoniae.Clin Infect Dis2001;33,517-522. [PubMed]
 
Doern, GV, Tillotson, GS, Karcic, AA, et al Fluoroquinolone pharmacodynamics and efficacy.Chest2001;120,319-320. [PubMed]
 
Weiss K, Restieri C, Dolce P, et al. Increasing resistance of.Streptococcus pneumoniae to ciprofloxacin in the province of Quebec, Canada. Paper presented at: 41st ICAAC meeting, American Society for Microbiology, Chicago, IL, December 15–18, 2001, Abstract 707.
 
Heffelfinger, JD, Dowell, SF, Jorgensen, JH, et al Management of community-acquired pneumonia in the era of pneumococcal resistance: a report from the Drug-ResistantStreptococcus pneumoniaeTherapeutic Working Group.Arch Intern Med2000;160,1399-1408. [PubMed]
 
Doern, GV Antimicrobial use and the emergence of antimicrobial resistance withStreptococcus pneumoniaein the United States.Clin Infect Dis2001;33(suppl),S187-S192
 
Grossman, RF, Mukherjee, J, Vaughan, D, et al A 1-year community-based health-economic study of ciprofloxacin vs usual antibiotic treatment in acute exacerbations of chronic bronchitis: the Canadian Ciprofloxacin Health Economic Study Group.Chest1998;113,131-141. [PubMed]
 
Destache, CJ, Dewan, N, O’Donohue, WJ, et al Clinical and economic considerations in the treatment of acute exacerbations of chronic bronchitis.J Antimicrob Chemother1999;43(suppl),107-113
 
Tillotson, G, Zhao, X, Drlica, K Fluoroquinolones as pneumococcal therapy: closing the barn door before the horse escapes.Lancet Infect Dis2001;1,145-146. [PubMed]
 
To the Editor:

I appreciate the recognition by Drs. Weiss and Tillotson that the time between the acceptance of our manuscript and its publication has seen a rapid evolution in our understanding of the proper treatment of Streptococcus pneumoniae lower respiratory tract infections.

I also share their concern as to why the guidelines persist in recommending doxycycline in the face of increasing S pneumoniae resistance to it.

I agree with and support their comments on the proper use of fluoroquinolones in respiratory infections. I have long been concerned, but lacked the evidence to include in the manuscript that the widespread use of older quinolones with marginal MICs for S pneumoniae (specifically levofloxacin) could foster the development of quinolone resistance in this dangerous bacteria. The reports cited by Drs. Weiss and Tillotson support this concern.

Therefore, I think it is important not only that we use quinolones prudently, but that we also use the newer quinolones, specifically gatifloxacin, moxifloxacin, and gemifloxacin if it becomes available, when a quinolone is indicated in respiratory tract infections. I completely support their contention that using the most potent antimicrobial reduces the risk of bacterial survival and mutation. As stated most eloquently by Charles Nightingale of Hartford Hospital (Hartford, CT), “Dead bugs don’t mutate.”

I appreciate them bringing this new, emerging, and critically important data to our attention. I completely support their concerns about the proper choice of quinolones to reduce the development of resistance to these critically valuable antimicrobial agents.


Figures

Tables

References

Guthrie, R (2001) Community-acquired lower respiratory tract infections: etiology and treatment.Chest120,2021-2034. [PubMed] [CrossRef]
 
Williams, JH, Jr Fluoroquinolones for respiratory infections: too valuable to overuse.Chest2001;120,1771-1775. [PubMed]
 
American Thoracic Society. Guidelines for the management of adults with community-acquired pneumonia: diagnosis, assessment of severity, antimicrobial therapy and prevention.Am J Respir Crit Care Med2001;163,1730-1754. [PubMed]
 
Ho, PL, Yung, RW, Tsang, DN, et al Increasing resistance ofStreptococcus pneumoniaeto fluoroquinolones: results of a Hong Kong multicentre study in 2000.J Antimicrob Chemother2001;48,659-665. [PubMed]
 
Davidson, R, Cavalcanti, R, Brunton, JL, et al Levofloxacin treatment failures of pneumococcal pneumonia in association with resistance.N Engl J Med2002;346,747-750. [PubMed]
 
Empey, PE, Jennings, HR, Thornton, AC, et al Levofloxacin: failure in a patient with pneumococcal pneumonia.Ann Pharmacother2001;35,687-690. [PubMed]
 
Urban, C, Rahman, N, Zhao, X, et al Fluoroquinolone-resistantStreptococcus pneumoniaeassociated with levofloxacin therapy.J Infect Dis2001;184,794-798. [PubMed]
 
Weiss, K, Restieri, C, Gauthier, R, et al A nosocomial outbreak of fluoroquinolone-resistantStreptococcus pneumoniae.Clin Infect Dis2001;33,517-522. [PubMed]
 
Doern, GV, Tillotson, GS, Karcic, AA, et al Fluoroquinolone pharmacodynamics and efficacy.Chest2001;120,319-320. [PubMed]
 
Weiss K, Restieri C, Dolce P, et al. Increasing resistance of.Streptococcus pneumoniae to ciprofloxacin in the province of Quebec, Canada. Paper presented at: 41st ICAAC meeting, American Society for Microbiology, Chicago, IL, December 15–18, 2001, Abstract 707.
 
Heffelfinger, JD, Dowell, SF, Jorgensen, JH, et al Management of community-acquired pneumonia in the era of pneumococcal resistance: a report from the Drug-ResistantStreptococcus pneumoniaeTherapeutic Working Group.Arch Intern Med2000;160,1399-1408. [PubMed]
 
Doern, GV Antimicrobial use and the emergence of antimicrobial resistance withStreptococcus pneumoniaein the United States.Clin Infect Dis2001;33(suppl),S187-S192
 
Grossman, RF, Mukherjee, J, Vaughan, D, et al A 1-year community-based health-economic study of ciprofloxacin vs usual antibiotic treatment in acute exacerbations of chronic bronchitis: the Canadian Ciprofloxacin Health Economic Study Group.Chest1998;113,131-141. [PubMed]
 
Destache, CJ, Dewan, N, O’Donohue, WJ, et al Clinical and economic considerations in the treatment of acute exacerbations of chronic bronchitis.J Antimicrob Chemother1999;43(suppl),107-113
 
Tillotson, G, Zhao, X, Drlica, K Fluoroquinolones as pneumococcal therapy: closing the barn door before the horse escapes.Lancet Infect Dis2001;1,145-146. [PubMed]
 
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