Reply

Despina G. Contopoulos-Ioannidis1,2, John P. A. Ioannidis1,3 and Joseph Lau3,*

1 Clinical Trials and Evidence-Based Medicine Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina 45110, Greece; 2 Department of Pediatrics, George Washington University School of Medicine, Washington, DC 20010; 3 Division of Clinical Care Research, New England Medical Center, Department of Medicine, Tufts University School of Medicine, Boston, MA 02111, USA

Sir,

Dr Kopjar1 alludes to a sensitivity analysis that we had already performed as part of the meta-analysis on acute exacerbations of chronic bronchitis.2 Sensitivity analyses involving the exclusion of outliers are unavoidably determined post-hoc,3 and therefore they should be interpreted very cautiously. The main conclusions should be based on the analysis of the entire set of available data. Small studies may reach unusual results due to an imbalance in the number of high-risk, failure-prone patients in the compared arms4 or due to other technical and design reasons. However, it is difficult to base a broad clinical recommendation upon a post-hoc analysis that excludes specific outliers. Moreover, we used the DerSimonian and Laird random effects model to estimate the summary effect for the relative efficacy of azithromycin versus other antibiotics in acute exacerbations of chronic bronchitis. This model does not ignore heterogeneity as Dr Kopjar believes; conversely, it incorporates the between study heterogeneity in the calculations, so it is perfectly appropriate in this setting.3

While it is possible that azithromycin may be superior to traditional courses of other antibiotics, the currently available data are not totally conclusive. Moreover, there is accumulating evidence that even short courses of short-acting antibiotics may be efficient in the treatment of acute exacerbation of chronic bronchitis.57 Thus in such settings it might be difficult to prove a definitive azithromycin superiority, when the cost benefit is also taken into account. Ultra-short courses of azithromycin may need to be considered in future clinical trials for the treatment of this condition.

Footnotes

* Corresponding author. Tel: +1-617-636-7670; Fax: +1-617-636-8023; E-mail: JLau1{at}lifespan.org Back

References

1 . Kopjar, B. (2002). Azithromycin is effective in patients with chronic bronchitis. Journal of Antimicrobial Chemotherapy 50, 433–434.[Free Full Text]

2 . Contopoulos-Ioannidis, D. G., Ioannidis, J. P., Chew, P. & Lau, J. (2001). Meta-analysis of randomized controlled trials on the comparative efficacy and safety of azithromycin against other antibiotics for lower respiratory tract infections. Journal of Antimicrobial Chemotherapy 48, 691–703.[Abstract/Free Full Text]

3 . Lau, J., Ioannidis, J. P. A. & Schmid, C. H. (1997). Quantitative synthesis in systematic reviews. Annals of Internal Medicine 127, 820–6.[Abstract/Free Full Text]

4 . Ioannidis, J. P. A. & Lau, J. (1997). The impact of high risk patients on the results of clinical trials. Journal of Clinical Epidemiology 50, 1089–98.[ISI][Medline]

5 . Schaberg, T., Ballin, I., Huchon, G., Bassaris, H., Hampel, B. & Reimnitz, P. (2001). A multinational, multicentre, non-blinded, randomized study of moxifloxacin oral tablets compared with co-amoxiclav oral tablets in the treatment of acute exacerbation of chronic bronchitis. Journal of International Medical Research 29, 314–28.[ISI][Medline]

6 . Chodosh, S., DeAbate C. A., Haverstock, D., Aneiro, L. & Church, D. (2000). Short-course moxifloxacin therapy for treatment of acute bacterial exacerbation of chronic bronchitis. The Bronchitis Study Group. Respiratory Medicine 94, 18–27.[ISI][Medline]

7 . Gotfried, M. H., DeAbate, C. A., Fogarty, C., Mathew, C. P. & Sokol, W. N. (2001). Comparison of 5-day, short-course gatifloxacin therapy with 7-day gatifloxacin therapy and 10-day clarithromycin therapy for acute exacerbation of chronic bronchitis. Clinical Therapeutics 23, 97–107.[ISI][Medline]





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