CMAJ • March 31, 2009; 180 (7). doi:10.1503/cmaj.1080133.
© 2009 Canadian Medical Association or its licensors
All editorial matter in CMAJ represents the opinions of the authors and not necessarily those of the Canadian Medical Association.
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Letters

Study conclusions should reflect results

Konstantinos Z. Vardakas, MD*, Ilias I. Siempos, MD* and Matthew E. Falagas, MD MSc{dagger}

*Alfa Institute of Biomedical Sciences, Athens, Greece; {dagger}Department of Medicine, Tufts University School of Medicine, Boston, Mass.

Three of the authors respond:

We thank Andrew Morris for his interest in our meta-analysis.1 We chose mortality as our primary outcome because of the considerable mortality rate attributed to community-acquired pneumonia in several previous studies. However, the mortality rate for patients with pneumonia in several of the randomized controlled trials included in our meta-analysis was extremely low, and the mortality rate for patients in the subgroups with severe or bacteremic pneumonia was not reported. Therefore, we believe that the available data were too limited to reach a strong conclusion on this important outcome.

On the other hand, secondary outcomes such as treatment success may provide significant evidence regarding the effectiveness of antibiotic regimens. We stated in our article that macrolides and β-lactams (the comparators of fluoroquinolones in the randomized controlled trials included in the meta-analysis) are also effective for the treatment of community-acquired pneumonia. However, we believe that more data on the comparative effectiveness of various antibiotics are needed for patients with severe community-acquired pneumonia. Unfortunately, the available relevant blinded and high-quality randomized controlled trials enrolled only patients with mild or moderately severe pneumonia, a group in which the anticipated success rate would be higher for all antibiotics (compared with that in patients with severe community-acquired pneumonia). Thus, we elected to include all randomized controlled trials in our meta-analysis, an approach that is not unique in the literature; for example, the Cochrane Collaboration suggests including all the available evidence in the primary analysis and proceeding to sensitivity or subgroup analyses to refine the outcomes.2 Finally, we cannot overemphasize that physicians should also be aware of the problems related to the use of the various antimicrobial agents, including fluoroquinol ones: they may be associated with ad verse events such as arrhythmias,3 Clostridium difficile–associated diarrhea4,5 and the emergence of antimicrobial resistance.6,7

Footnotes

Competing interests: None declared.


REFERENCES

  1. Vardakas KZ, Siempos II, Grammatikos A, et al. Respiratory fluoroquinolones for the treatment of community-acquired pneumonia: a meta-analysis of randomized controlled trials. CMAJ 2008;179:1269-77.[Abstract/Free Full Text]
  2. Higgins J, Green S, editors. Cochrane handbook for systematic reviews of interventions; version 4.2.6. Oxford (UK): The Cochrane Collaboration; 2008. Available: www.cochrane.org/resources/handbook/Handbook4.2.6Sep2006.pdf (accessed 2009 Feb. 27).
  3. Falagas ME, Rafailidis PI, Rosmarakis ES. Arrhythmias associated with fluoroquinolone therapy. Int J Antimicrob Agents 2007;29:374-9.[CrossRef][Medline]
  4. Pépin J, Saheb N, Coulombe MA, et al. Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile–associated diarrhea: a cohort study during an epidemic in Quebec. Clin Infect Dis 2005;41:1254-60.[CrossRef][Medline]
  5. Kazakova SV, Ware K, Baughman B, et al. A hospital outbreak of diarrhea due to an emerging epidemic strain of Clostridium difficile. Arch Intern Med 2006;166:2518-24.[Abstract/Free Full Text]
  6. Kopterides P, Koletsi PK, Michalopoulos A, et al. Exposure to quinolones is associated with carbapenem resistance among colistin-susceptible Acinetobacter baumannii blood isolates. Int J Antimicrob Agents 2007;30:409-14.[CrossRef][Medline]
  7. Falagas ME, Rafailidis PI, Kofteridis D, et al. Risk factors of carbapenem-resistant Klebsiella pneumoniae infections: a matched case control study. J Antimicrob Chemother 2007;60:1124-30.[Abstract/Free Full Text]




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