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Three Part Question

In [patients with community acquired pneumonia] are [macrolides combined with beta-lactams better than beta-lactams alone] [in inproving outcome and hastening recovery]

Clinical Scenario

A 65 year old man presents to the A&E department with shortness of breath and cough productive of green sputum. There is radiological evidence of pneumonia on chest x-ray and oral amoxicillin is started. You wonder whether adding in a macrolide would benefit the patient.

Search Strategy

Medline 1966-06/12 using the PubMed interface
The Cochrane Library
[therapy OR therapeutics OR therapeutics OR treatment] AND [residence characteristics OR community] AND [acquired] AND [pneumonia OR pneumonia] AND [beta-lactams OR beta-lactam] AND [macrolide]. LIMIT to English language

Search Outcome

Altogether 97 papers were found in Medline and 0 in The Cochrane Library. A total of 4 papers were relevent to the above clinical question.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Aspa J, Rajas O, Rodriguez de Castro F et al 2006 Spain	638 patients with community-acquired pneumonia due to Streptococcus pneumoniae. Patients were grouped into the following categories: beta-lactam monotherapy (n = 251), macrolide monotherapy (n = 37), beta-lactam plus macrolide (n = 198), levofloxacin alone/combination (n = 48), and other combinations (n = 104). The antibiotic regimen was chosen by the attending physician.	Prospective observational study	30 day mortality	No significant difference	Antibiotic therapy was assigned to patients subjectively by the physician.
Peter M. Houck, Richard F. MacLehose, Michael S. Niederman and Joseph K. Lowery 2001 America	Six antibiotic regimens were initiated during the first 24 h after arrival at hospital were evaluated: monotherapy with a b-lactam; macrolide monotherapy; therapy with a b-lactam plus a macrolide; fluoroquinolone monotherapy; therapy with a b-lactam plus a fluoroquinolone; and any other antibiotics.	Population-based, retrospective study.	30 day mortality rate	1993 Mortality B-lactam monotherapy - 13.9% B-lactam and macrolide combined - 8.3%(CI 0.25-0.69, P0.001) 1995 Mortality B-lactam monotherapy - 11.8% B-lactam and macrolide combined - 8.6%(CI 0.62–1.41, p=0.746) 1997 Mortality B-lactam monotherapy - 13.9% B-lactam and Macrolide combined - 10.2%(CI 0.63–1.19 p=0.375)	39.9% of patients origionally inclused in the study were excluded due to problems with data collection.
Richard B. Brown, MD, FCCP; Paul Ianini, MD; Peter Gross, MD and Mar Kunkel, MD 2003 America	44,814 patients over the age of 18 with a diagnosis of community acquired pneumonia were divided into treatment cohorts based on individual antiobiotic therapy: Monotherapy - (1) ceftriaxone, (2) macroides, (3) other cephalosporins, (4) fluorinated quinolones, (5) penicillins. Dual therapy - the four classes above(except macrolides) plus a macrolide as the second agent.	Retrospective cohort study.	Impact of initial antibiotic choice on 30 day mortality, total hospital costs and hospital length of stay.	Mean length of hospital stay: B-lactam monotherapy 6.09days(4.25SD). B-Lactam and macolide combined 6.08days(3.82SD) Overall p value - 0.0867. Overall mortality: B-lactam monotherapy 8.15%, B-Lactam and macolide combined 2.46% Overall p vaue less than 0.0001	Over 60% of patients had incomplete antibiotic treatment information, and therefore no treatment characterisation was possible.
Garcia Vazquez E, Mensa J, Martinez JA, Marcos MA, Puig J, Ortega M, Torres A. 2005 Spain	A cohort of 1,391 patients with community-acquired pneumonia of unknown etiology, atypical pneumonia, Legionella pneumophila pneumonia, viral pneumonia, or pneumococcal pneumonia was studied according to a standard protocol to analyse whether the addition of a macrolide to beta-lactam empirical treatment decreases mortality rates.	Cohort study	30 day mortality	Mortality rate: B-Lactam monotherapy - 13.3% Mortality rate: B-Lactam and macrolide combined - 6.9% (p=0.001).	An etiological diagnosis was not achieved in 64.2% of patients and therefore it could not be determined if the patients had typical or atypical infection.

Comment(s)

There is good evidence available that combining a B-Lactam antiobiotic with a macrolide improves the clinical outcome of community acquired pneumonia. More research is required into whether the addition of a macroide would continue to be beneficial in patients with suspected uncomplicated, typical infection.

Clinical Bottom Line

In patients who present to hospital with community acquired pneumonia the addition of a macrolide should always be considered. Side effects, complications and cost effectiveness of additional antibiotic therapy must always be taken into consideration.

References

1. Aspa J, Rajas O, Rodriguez de Castro F, Huertas MC, Borderias L, Cabello FJ, Tabara J, Hernandez-Flix S, Martinez-Sanchis A, Torres A; The Pneumococcal Pneumonia in Spain Study Group Impact of initial antibiotic choice on mortality from pneumococcal pneumonia. The European Respiratory Journal 1: Eur Respir J. 2006 May;27(5):1010-9. Epub 2006 Feb 2.
2. Peter M. Houck, Richard F. MacLehose, Michael S. Niederman and Joseph K. Lowery Empiric Antibiotic Therapy and Mortality Among Medicare Pneumonia. Inpatients in 10 Western States : 1993, 1995, and 1997 The cardiopulmonary and Critical Care Journal Chest. 2001 May;119(5):1420-6.
3. Richard B. Brown, Paul Iannini, Peter Gross and Mark Kunkel Impact of Initial Antibiotic Choice on Clinical Outcomes in Community-Acquired Pneumonia: Analysis of a Hospital Claims-Made Database The Cadiopulmonary and Critical Care Journal Chest 2003;123;1503-1511
4. Garcia Vazquez E, Mensa J, Martinez JA, Marcos MA, Puig J, Ortega M, Torres A. Lower mortality among patients with community-acquired pneumonia treated with a macrolide plus a beta-lactam agent versus a beta-lactam agent alone. European Journal of Clinical Microbiology and infectious Diseases. Eur J Clin Microbiol Infect Dis. 2005 Mar;24(3):190-5.