© 2007 American Thoracic Society
Atypical Coverage for Community-acquired PneumoniaFrom the Authors:
We appreciate the interest of Dr. Robenshtok and colleagues regarding our article (1). They expressed concern that our conclusions are not consistent with two meta-analyses of randomized controlled trials, which found that atypical coverage is not necessary for patients with community-acquired pneumonia (CAP) (2, 3). There were limited patients with severe CAP in both meta-analyses. It should be emphasized that the studies reviewed were industry sponsored, had limited tests performed for atypical pathogens, and were powered to show noninferiority. The overall mortality in each meta-analysis was 1.9 and 3.7%, respectively, because patients with severe pneumonia were excluded. In this regard, the mortality rate in our study (11.4%) more closely reflected the mortality due to CAP in the real-world population ( We mentioned in discussing the limitations of our study that the potential for bias was present, and Robenshtok and colleagues agreed. They also noted that classical multivariable techniques might not be suitable to adjust for differences between the two groups of patients. While it is true that multivariable analyses cannot correct serious baseline imbalances, our two study populations were remarkably similar on several key variables. Where imbalances did exist, multivariable analyses, such as the Cox proportional hazards regression, were sufficient to adjust for them (5). Furthermore, our multivariate analyses were unique because we adjusted not only for factors related to disease severity but also for processes of care due to the likely differences in management of CAP throughout the world. The use of propensity score matching, which would be effective for matching on one or two variables, would not strengthen or weaken our conclusions, and would make it more difficult for readers to interpret and use our results. Robenshtok and colleagues requested a propensity-matched analysis addressing outcomes of patients in whom atypical pathogens were actually found. Although this is a pertinent inquiry, we had two separate databases (a clinical database and a microbiological database) preventing us from performing the matched analysis of interest. Finally, we appreciate the intention of a randomized trial comparing a β-lactam drug alone to a regimen covering atypical pathogens, because the indication is based on the presence of several retrospective studies, including ours (see References 17–22 in our article). However, we do not feel it would be ethical to design a study that includes an arm to receive treatment that is not recommended in United States guidelines for CAP (6), which are supported by a number of retrospective studies that found an increased mortality among patients prescribed a β-lactam alone. Nor would we expect any review board in the United States to approve such a study.
University of Louisville
University of Alberta Hospital
S. Maria della Misericordia Hospital
University of Milan
Instituto Nacional del Torax
Summa Health System
Joan XXIII University Hospital
Hospital Universitario La Fe
Hospital de Clinicas
University of Louisville FOOTNOTES Conflict of Interest Statement: F.W.A. has received funding from Pfizer ($500) and Ortho-McNeil ($750) for speaking within the last 3 years. J.T.S. has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. A.S.L. has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. P.P. has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. T.J.M. has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. P.R. has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. F.B. reports having received consulting fees from Pfizer, Sanofi-Aventis, Altana, Wyeth, Schering-Plough, and GlaxoSmithKline (GSK); lecture fees from Bayer, Sanofi-Aventis, Pfizer, Abbott, Altana, and GSK; and grant support from Pfizer, Altana, and Abbott. P.F. has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. T.M.F. has received funding from the following companies for the following relationships in the preceding 3 years: Ortho-McNeil, Oscient, Pfizer, and Sanofi-Aventis for recent research funding; Bayer, GSK, Merck, Ortho-McNeil, Oscient, Pfizer, Sanofi-Aventis, Schering-Plough, and Wyeth for consulting; Abbott, GSK, Merck, Ortho-McNeil, Oscient, Pfizer, Sanofi-Aventis, Schering-Plough, and Wyeth for speakers' bureaus; the aggregate amount received for the preceding 3 years exceeds $10,000 for each of the pharmaceutical manufacturers listed. J.R. has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. R.M. has received $2,000 for speaking in a conference sponsored by Pfizer. C.M.L. has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. J.A.R. has received a grant from Bayer/Schering-Plough in the amount of $355,000 for a clinical trial (10/2004 through 4/2006); he also received a grant from Pfizer Pharmaceuticals in the amount of $250,000 for a clinical trial that is currently in progress. REFERENCES
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