, Volume 68, Issue 13, pp 1841–1854 | Cite as

Short- versus Long-Course Antibacterial Therapy for Community-Acquired Pneumonia

A Meta-Analysis
  • George Dimopoulos
  • Dimitrios K. Matthaiou
  • Drosos E. Karageorgopoulos
  • Alexandros P. Grammatikos
  • Zoe Athanassa
  • Matthew E. Falagas
Original Research Article


Background: The evidence for traditionally recommended 7- to 14-day duration of antibacterial therapy for community-acquired pneumonia (CAP) is not well established.

Objectives: We endeavoured to assess the effectiveness and safety of shorter than traditionally recommended antibacterial therapy for CAP.

Methods: We performed a meta-analysis of randomized controlled trials (RCTs) comparing short-(≤7 days) versus long-(≥2 days difference) course therapy for CAP with the same antibacterial regimens, in the same daily dosages.

Results: Five RCTs involving adults (including outpatients and inpatients who did not require intensive care) and two RCTs involving children (aged 2–59 months, residing in developing countries) were included. All RCTs were double-blind and assessed patients with CAP of mild to moderate severity. No differences were found between short- (adults 3–7 days; children 3 days) and long-(adults 7–10 days; children 5 days) course regimens (adults — amoxicillin, cefuroxime, ceftriaxone, telithromycin and gemifloxacin; children — amoxicillin) regarding clinical success at end-of-therapy (six RCTs; 5107 patients [1095 adults, 4012 children]; fixed-effect model [FEM]; odds ratio [OR] = 0.89; 95% CI 0.74, 1.07), clinical success at late follow-up, microbiological success, relapses, mortality (seven RCTs; 5438 patients; FEM; OR = 0.57; 95% CI 0.23, 1.43), adverse events (five RCTs; 3214 patients; FEM; OR = 0. 90; 95% CI 0.72, 1.13) or withdrawals as a result of adverse events. No differences were found in subset analyses of adults or children, and of patients treated with no more than 5-day short-course regimens versus at least 7-day long-course regimens.

Conclusion: No difference was found in the effectiveness and safety of short-versus long-course antimicrobial treatment of adult and paediatric patients with CAP of mild to moderate severity.


  1. 1.
    Jokinen C, Heiskanen L, Juvonen H, et al. Incidence of community-acquired pneumonia in the population of four municipalities in eastern Finland. Am J Epidemiol 1993; 137: 977–88PubMedGoogle Scholar
  2. 2.
    Schappert SM, Burt CW. Ambulatory care visits to physician offices, hospital outpatient departments, and emergency departments: United States, 2001–02. Vital Health Stat 2006; 13: 1–66Google Scholar
  3. 3.
    National Center for Health Statistics. Health, United States, 2006, with chartbook on trends in the health of Americans [online]. Available from URL: http://www.cdc.gov/nchs/data/hus/hus06.pdf [Accessed 2007 Nov 7]
  4. 4.
    Fine MJ, Auble TE, Yealy DM, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med 1997; 336: 243–50PubMedCrossRefGoogle Scholar
  5. 5.
    Lim WS, van der Eerden MM, Laing R, et al. Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study. Thorax 2003; 58: 377–82PubMedCrossRefGoogle Scholar
  6. 6.
    Guest JF, Morris A. Community-acquired pneumonia: the annual cost to the National Health Service in the UK. Eur Respir J 1997; 10: 1530–4PubMedCrossRefGoogle Scholar
  7. 7.
    Niederman MS, Mandell LA, Anzueto A, et al. Guidelines for the management of adults with community-acquired pneumonia: diagnosis, assessment of severity, antimicrobial therapy, and prevention. Am J Respir Crit Care Med 2001; 163: 1730–54PubMedGoogle Scholar
  8. 8.
    Niederman MS, McCombs JS, Unger AN, et al. The cost of treating community-acquired pneumonia. Clin Ther 1998; 20: 820–37PubMedCrossRefGoogle Scholar
  9. 9.
    Oosterheert JJ, Bonten MJ, Schneider MM, et al. Effectiveness of early switch from intravenous to oral antibiotics in severe community acquired pneumonia: multicentre randomised trial. BMJ 2006; 333: 1193–5PubMedCrossRefGoogle Scholar
  10. 10.
    Ramirez JA, Vargas S, Ritter GW, et al. Early switch from intravenous to oral antibiotics and early hospital discharge: a prospective observational study of 200 consecutive patients with community-acquired pneumonia. Arch Intern Med 1999; 159: 2449–54PubMedCrossRefGoogle Scholar
  11. 11.
    Li JZ, Winston LG, Moore DH, et al. Efficacy of short-course antibiotic regimens for community-acquired pneumonia: a meta-analysis. Am J Med 2007; 120: 783–90PubMedCrossRefGoogle Scholar
  12. 12.
    Schentag JJ, Ballow CH. Tissue-directed pharmacokinetics. Am J Med 1991; 91: 5–11SCrossRefGoogle Scholar
  13. 13.
    Dunbar LM, Wunderink RG, Habib MP, et al. High-dose, short-course levofloxacin for community-acquired pneumonia: a new treatment paradigm. Clin Infect Dis 2003; 37: 752–60PubMedCrossRefGoogle Scholar
  14. 14.
    Khan KS, Daya S, Jadad A. The importance of quality of primary studies in producing unbiased systematic reviews. Arch Intern Med 1996; 156: 661–6PubMedCrossRefGoogle Scholar
  15. 15.
    Moher D, Jadad AR, Tugwell P. Assessing the quality of randomized controlled trials: current issues and future directions. Int J Technol Assess Health Care 1996; 12: 195–208PubMedCrossRefGoogle Scholar
  16. 16.
    Higgins JP, Thompson SG. Controlling the risk of spurious findings from meta-regression. Stat Med 2004; 23: 1663–82PubMedCrossRefGoogle Scholar
  17. 17.
    Fletcher J. What is heterogeneity and is it important? BMJ 2007; 334: 94–6PubMedCrossRefGoogle Scholar
  18. 18.
    Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 1959; 22: 719–48PubMedGoogle Scholar
  19. 19.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177–88PubMedCrossRefGoogle Scholar
  20. 20.
    File Jr TM, Mandell LA, Tillotson G, et al. Gemifloxacin once daily for 5 days versus 7 days for the treatment of community-acquired pneumonia: a randomized, multicentre, double-blind study. J Antimicrob Chemother 2007; 60: 112–20PubMedCrossRefGoogle Scholar
  21. 21.
    El Moussaoui R, de Borgie CA, van den Broek P, et al. Effectiveness of discontinuing antibiotic treatment after three days versus eight days in mild to moderate-severe community acquired pneumonia: randomised, double blind study. BMJ 2006; 332: 1355PubMedCrossRefGoogle Scholar
  22. 22.
    Agarwal G, Awasthi S, Kabra SK, et al. Three day versus five day treatment with amoxicillin for non-severe pneumonia in young children: a multicentre randomised controlled trial. BMJ 2004; 328: 791PubMedCrossRefGoogle Scholar
  23. 23.
    Tellier G, Niederman MS, Nusrat R, et al. Clinical and bacteriological efficacy and safety of 5 and 7 day regimens of telithromycin once daily compared with a 10 day regimen of clarithromycin twice daily in patients with mild to moderate community-acquired pneumonia. J Antimicrob Chemother 2004; 54: 515–23PubMedCrossRefGoogle Scholar
  24. 24.
    Leophonte P, Choutet P, Gaillat J, et al. Efficacy of a ten day course of ceftriaxone compared to a shortened five day course in the treatment of community-acquired pneumonia in hospitalized adults with risk factors. Med Mal Infect 2002; 32: 369–81CrossRefGoogle Scholar
  25. 25.
    Pakistan Multicentre Amoxycillin Short Course Therapy (MASCOT) pneumonia study group. Clinical efficacy of 3 days versus 5 days of oral amoxicillin for treatment of childhood pneumonia: a multicentre double-blind trial. Lancet 2002; 360: 835–41CrossRefGoogle Scholar
  26. 26.
    Siegel RE, Alicea M, Lee A, et al. Comparison of 7 versus 10 days of antibiotic therapy for hospitalized patients with uncomplicated community-acquired pneumonia: a prospective, randomized, double-blind study. Am J Ther 1999; 6: 217–22PubMedCrossRefGoogle Scholar
  27. 27.
    Casey JR, Pichichero ME. Metaanalysis of short course antibiotic treatment for group a streptococcal tonsillopharyngitis. Pediatr Infect Dis J 2005; 24: 909–17PubMedCrossRefGoogle Scholar
  28. 28.
    Chastre J, Wolff M, Fagon JY, et al. Comparison of 8 vs 15 days of antibiotic therapy for ventilator-associated pneumonia in adults: a randomized trial. JAMA 2003; 290: 2588–98PubMedCrossRefGoogle Scholar
  29. 29.
    Kozyrskyj AL, Hildes-Ripstein GE, Longstaffe SE, et al. Treatment of acute otitis media with a shortened course of antibiotics: a meta-analysis. JAMA 1998; 279: 1736–42PubMedCrossRefGoogle Scholar
  30. 30.
    Montravers P, Fagon JY, Chastre J, et al. Follow-up protected specimen brushes to assess treatment in nosocomial pneumonia. Am Rev Respir Dis 1993; 147: 38–44PubMedCrossRefGoogle Scholar
  31. 31.
    Awunor-Renner C. Length of antibiotic therapy in in-patients with primary pneumonias. Ann Trop Med Parasitol 1979; 73: 235–40PubMedGoogle Scholar
  32. 32.
    Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007; 44 Suppl. 2: S27–72PubMedCrossRefGoogle Scholar
  33. 33.
    Halm EA, Fine MJ, Marrie TJ, et al. Time to clinical stability in patients hospitalized with community-acquired pneumonia: implications for practice guidelines. JAMA 1998; 279: 1452–7PubMedCrossRefGoogle Scholar
  34. 34.
    Metlay JP, Atlas SJ, Borowsky LH, et al. Time course of symptom resolution in patients with community-acquired pneumonia. Respir Med 1998; 92: 1137–42PubMedCrossRefGoogle Scholar
  35. 35.
    Menendez R, Torres A, Rodriguez de CF, et al. Reaching stability in community-acquired pneumonia: the effects of the severity of disease, treatment, and the characteristics of patients. Clin Infect Dis 2004; 39: 1783–90PubMedCrossRefGoogle Scholar
  36. 36.
    File Jr TM. Clinical efficacy of newer agents in short-duration therapy for community-acquired pneumonia. Clin Infect Dis 2004; 39 Suppl. 3: S159–64PubMedCrossRefGoogle Scholar
  37. 37.
    Fine MJ, Stone RA, Singer DE, et al. Processes and outcomes of care for patients with community-acquired pneumonia: results from the Pneumonia Patient Outcomes Research Team (PORT) cohort study. Arch Intern Med 1999; 159: 970–80PubMedCrossRefGoogle Scholar
  38. 38.
    Branthwaite A, Pechere JC. Pan-European survey of patients’ attitudes to antibiotics and antibiotic use. J Int Med Res 1996; 24: 229–38PubMedGoogle Scholar
  39. 39.
    Hoppe JE, Blumenstock G, Grotz W, et al. Compliance of German pediatric patients with oral antibiotic therapy: results of a nationwide survey. Pediatr Infect Dis J 1999; 18: 1085–91PubMedCrossRefGoogle Scholar
  40. 40.
    Reyes H, Guiscafre H, Munoz O, et al. Antibiotic noncompliance and waste in upper respiratory infections and acute diarrhea. J Clin Epidemiol 1997; 50: 1297–304PubMedCrossRefGoogle Scholar
  41. 41.
    Schrag SJ, Pena C, Fernandez J, et al. Effect of short-course, high-dose amoxicillin therapy on resistant pneumococcal carriage: a randomized trial. JAMA 2001; 286: 49–56PubMedCrossRefGoogle Scholar
  42. 42.
    Guillemot D, Carbon C, Balkau B, et al. Low dosage and long treatment duration of beta-lactam: risk factors for carriage of penicillin-resistant Streptococcus pneumoniae. JAMA 1998; 279: 365–70PubMedCrossRefGoogle Scholar
  43. 43.
    World Health Organization. Acute respiratory infections in children [online]. Available from URL: http://www.who.int/fch/depts/cah/resp_infections/en/ [Accessed 2007 Nov 7]
  44. 44.
    British Thoracic Society Guidelines for the management of community acquired pneumonia in childhood. Thorax 2002; 57 Suppl. 1: il–24Google Scholar
  45. 45.
    McIntosh K. Community-acquired pneumonia in children. N Engl J Med 2002; 346: 429–37PubMedCrossRefGoogle Scholar
  46. 46.
    Shann F. Etiology of severe pneumonia in children in developing countries. Pediatr Infect Dis 1986; 5: 247–52PubMedCrossRefGoogle Scholar
  47. 47.
    Weber MW, Mulholland EK, Greenwood BM. Respiratory syncytial virus infection in tropical and developing countries. Trop Med Int Health 1998; 3: 268–80PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  • George Dimopoulos
    • 1
    • 2
  • Dimitrios K. Matthaiou
    • 1
  • Drosos E. Karageorgopoulos
    • 1
  • Alexandros P. Grammatikos
    • 3
  • Zoe Athanassa
    • 1
  • Matthew E. Falagas
  1. 1.Alfa Institute of Biomedical Sciences (AIBS)AthensGreece
  2. 2.Department of Critical CareAttikon University Hospital, University of AthensAthensGreece
  3. 3.Department of MedicineG. Gennimatas HospitalThessalonikiGreece
  4. 4.Department of MedicineHenry Dunant HospitalAthensGreece
  5. 5.Department of MedicineTufts University School of MedicineBostonUSA

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