Treating acute bacterial exacerbation of chronic bronchitis: how can therapy be optimized?
Resistance Is a Barrier to Successful Treatment
National surveillance studies show that resistance of S. pneumoniae to macrolides, azithromycin in particular, has increased to 27.5% over the past several years (Fig 1). (6,7) More alarmingly, in a recent clinical study of younger, low-risk patients with ABECB, 35% of S. pneumoniae isolates were resistant to azithromycin. (8) This led to significantly more treatment failures (P=0.05). Such treatment failures can result in additional costs due to refills or the prescription of an alternate agent. In fact, in a study of a national managed care organization, 14% of all macrolide prescriptions were refills. (9) Given high resistance rates and corresponding risk of treatment failure, macrolides may no longer be the optimal choice for initial therapy.
Noncompliance Can Result in Suboptimal Outcomes
While amoxicillin/clavulanate exhibits a much lower rate of resistance than azithromycin, it requires a longer course of therapy. Longer therapy is associated with an increase in patient noncompliance. One study showed noncompliance was significantly correlated with treatment that lasted for more than 7 days. (10) If a patient is noncompliant with the prescribed treatment regimen, there may be increased risk for treatment failure.
The Safety of New Agents Is Not Certain
Many adverse drug reactions are uncovered only after the drug has been in use for years. A study published in JAMA demonstrated that of 548 new chemical entities approved between 1975-1999, 10.2% acquired a new black box warning or were withdrawn from the market. (11) Half of these withdrawals occurred within 2 years of the product's introduction. The authors concluded that "the safety of new agents cannot be known with certainty until a drug has been on the market for many years." With unproven safety profiles, are new agents the best choice for ABECB therapy?
How Can We Advance the Therapy of ABECB?
Recently, it has been demonstrated that a higher dose of one respiratory fluoroquinolone can treat exacerbations in as little as 3-5 days. (12) This higher dose provides rapid bactericidal action, fast resolution of symptoms, and fast clinical cures without compromising safety. The higher dose may also prevent the emergence of resistance. (13) In addition, susceptibilities of major respiratory pathogens (S. pneumoniae, H. influenzae) to the fluoroquinolones remain extremely high (>99% in national surveillance studies). (6,7)
For optimal therapy of ABECB, macrolides, amoxicillin/clavulanate, or new agents may not be the best choice. High resistance rates, noncompliance, and unproven safety may be barriers to achieving the best possible outcomes. Taking into account the shorter 3- to 5-day course of therapy, high susceptibilities, and fast clinical cures, it is appropriate to consider respiratory fluoroquinolones your first choice for optimal treatment of ABECB.
Table 1: Criteria for Optimized Therapy of ABECB (6) Evidence based Therapeutic Safe Cost effective Optimal dosage and duration
REFERENCES: 1. Grossman RF. Guidelines for the treatment of acute exacerbations of chronic bronchitis. Chest. 1997;112:310S-313S. 2. American Lung Association. COPD Fact Sheet. Available at: http://www.lungusa.org. Accessed August 31, 2004. 3. Birnbaum HG, Morley M, Greenberg PE, et al. Economic burden of respiratory infections in an employed population. Chest. 2002;122:603-611. 4. Donaldson GC, Seemungal TAR, Bhowmik A, et al. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax. 2002;57:847-852. 5. Seemungal TAR, Donaldson GC, Paul EA, et al. Effect of exacerbation on quality of life in patients with--chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998;157:1418-1422. 6. Data on file. Ortho McNeil Pharmaceutical, Inc. 7. Karlowsky JA, Thornsberry C, Jones ME, et al. Factors associated with relative rates of antimicrobial resistance among Streptococcus pneumoniae in the United States: results from the TRUST Surveillance Program (1998-2002). Clin Infect Dis. 2003;36:963-970. 8. Tennenberg AM, Walker KA, Khashab M, et al. Antimicrobial-resistant Streptococcus pneumoniae isolated from patients with acute bacterial exacerbation of chronic bronchitis. Poster E28. Presented at the 100th International Conference of the American Thoracic Society; May 21-26, 2004:Orlando, Florida. 9. Suda KJ, Garey KW, Bertram CT, et al. Antibiotic failures in an outpatient, national, managed care database. Presented at: 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy; September 14-17, 2003:Chicago, Illinois. 10. Reyes H, Guiscafre H, Munoz O, et al. Antibiotic noncompliance and waste in upper respiratory infections and acute diarrhea. J Clin Epidemiol. 1997;50:1297-1304. 11. Lasser KE, Allen PD, Woolhandler SJ, et al. Timing of new black box warnings and withdrawals for prescription medications. JAMA. 2002;287:2215-2220. 12. Tennenberg A, Walker K, Khashab M, et al. The safety and efficacy of short-course (3-5 day), 750 mg levofloxacin (LVX) for acute bacterial exacerbation of chronic bronchitis (ABECB). Poster 516. Presented at the 100th International Conference of the American Thoracic Society; May 21-26, 2004;Orlando, Florida. 13. Dunbar LM, Wunderink RG, Habib MP, et al. High-dose, short-course levofloxacin for community-acquired pneumonia: a new treatment paradigm. Clin Infect Dis. 2003;37:752-760.
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|Publication:||Internal Medicine News|
|Date:||Dec 1, 2004|
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