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The Controversy of Combination vs Monotherapy in the Treatment of Hospitalized Community-Acquired Pneumonia*

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

*From the Department of Microbiology and Infectious Diseases (Dr. Weiss), Maisonneuve-Rosemont Hospital, University of Montreal, Montreal, QC, Canada; and Oscient Pharmaceuticals, Waltham, MA (Mr. Tillotson).

Correspondence to: Karl Weiss, MD, MSc, Department of Microbiology and Infectious Diseases, Maisonneuve-Rosemont Hospital, 5415 L‘Assomption, Montreal, QC, Canada H1T 2M4; e-mail: weisscan@aol.com



Chest. 2005;128(2):940-946. doi:10.1378/chest.128.2.940
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Background: The majority of community-acquired pneumonia (CAP) patients (about 80%) will be treated as outpatients, because therapy with a single agent will work. For the remaining 20% of patients requiring hospitalization, there is some growing debate regarding the efficacy of different management approaches. For hospitalized patients, monotherapy with a respiratory fluoroquinolone agent seems to be gaining popularity, but dual therapy combining a β-lactam and an advanced macrolide still represents a good choice. Indeed, this regimen was recommended for all of the inpatient categories in the latest Infectious Disease Society of America CAP guidelines in 2003.

Aim: The purpose of this review was to examine the current clinical evidence to support one option or the other by gathering all of the available published literature. We will review the existing controversies in terms of microbiology, immunology, and clinical outcomes comparing dual therapy (ie, with any combination of β-lactams, macrolides, or fluoroquinolones) with monotherapy in the treatment of CAP.

Results: For the vast majority of patients with CAP (ie, outpatients and inpatients on medical wards), the type of antibiotic regimen prescribed does not have any significant impact. For patients with severe pneumonia, for which there is no accepted definition so far, the controversy remains alive. Mortality from pneumococcal pneumonia has been reduced over the last decades, but despite improved medical care, bacteremic pneumococcal pneumonia is still as lethal as ever, probably because of the aging population, the greater number of immunocompromised patients, and the number of patients with frequent comorbid conditions. Worldwide, the increasing rates of resistance of Streptococcus pneumoniae to antibiotics are also a serious concern, and the clinical implications are not always obvious. Although limited in number, the four studies showing the importance of adding a macrolide to a β-lactam regimen for the treatment of bacteremic S pneumoniae pneumonia are retrospective and nonblinded, the findings are consistent, and they point to a trend that has to be explored more thoroughly. Studies published in the last few years suggest that combination therapy may be superior for bacteremic S pneumoniae pneumonia.

Conclusion: In the meantime, for practical purposes, patients hospitalized with a diagnosis of severe CAP may benefit from a dual antibiotic therapy combining a third-generation cephalosporin and a macrolide. For the majority of hospitalized patients with CAP who are not severely ill, fluoroquinolone monotherapy remains an approved, tested, and reliable option. Indeed, the time for more aggressive outpatient fluoroquinolone therapy may reduce the number of patients who are hospitalized with CAP. Independent prospective studies comparing combination therapy with standard monotherapy are urgently required for hospitalized patients with severe CAP.


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