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#76 Amoxicillin, Still an A-List Antibiotic for Infections of the Airway

When needed, are beta-lactam antibiotics (such as amoxicillin) a reasonable choice in mild-to-moderate bacterial respiratory tract infections in primary care?

In mild-to-moderate respiratory tract infections that require antibiotics, there is little evidence of benefit of broader-spectrum antibiotics over traditional beta-lactam antibiotics like amoxicillin in primary care.  The only exception may be slight benefits for broader-spectrum in COPD patients, but these results are inconsistent.  

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Overall lower-respiratory tract infections: 
  • Cochrane review1 of 16 randomized controlled trials (RCTs) of 2,648 patients with any kind of lower-respiratory tract infection: 
  • No statistically significant difference between azithromycin and amoxicillin with/without clavulanate. 
Community-acquired pneumonia (CAP): 
  • Cochrane review:2 Only one randomized controlled trial (RCT) comparing a beta-lactam antibiotic to another antibiotic in outpatients with CAP 
    • Authors could not extract outcome data for this comparison. 
  • In CAP patients, including those hospitalized: 
    • Cochrane review3 of 28 RCTs (5,939 patients) and 2 subsequent RCTs:4,5 
      • No benefit in mortality or clinical efficacy with broader coverage for atypicals compared to beta-lactam monotherapy. 
  • RCT with 137 mild-to-moderately symptomatic primary care patients with acute exacerbation of COPD.6 
    • No difference in clinical cure between amoxicillin versus amoxicillin/clavulanate (91% versus 93%). 
  • Systematic review7 of 12 RCTs including 2,261 patients with chronic bronchitis (not necessarily COPD) compared “1st-line” antibiotics (like amoxicillin or doxycycline) versus “2nd-line” antibiotics (like macrolides and quinolones) for acute exacerbations: 
    • Symptom resolution/improvement: 85% for 1st-line antibiotics versus 91% for 2nd-line (difference statistically significant). 
      • Studies ranged from 19% worse to 8% better with first-line antibiotics, no heterogeneity testing was reported 
      • No difference in mortality. 
  • Systematic review8 of 8 RCTs including 2,133 patients found no difference in clinical cure between beta-lactams and fluoroquinolones. 
  • Two RCTs (total 359 children) compared amoxicillin to amoxicillin-clavulanate for acute sinusitis and neither found benefit with amoxicillin-clavulanate.9,10 
  • Majority of respiratory tract infections are viral and will not require antibiotics. 
  • Macrolide resistance in Streptococcus pneumoniae is rapidly increasing (2% in 1993 to 24% in 2009), whereas resistance to amoxicillin is just over 3%.11 
  • Limited data report increasing prevalence of Haemophilus influenza among upper respiratory tract infections after the introduction of the conjugated pneumococcal vaccine, although clinical impact has not been demonstrated in well-designed RCTs.12 

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  • Christina Korownyk MD CCFP
  • Sarah Forgie MD FRCPC

1. Laopaiboon M, Panpanich R, Swa Mya K. Cochrane Database Syst Rev 2015;3:CD001954.

2. Pakhale S, Mulpuru S, Verheij TJM, Kochen MM, Rohde GGU, Bjerre JM. Cochrane Database Syst Rev 2014;10:CD002109.

3. Eliakim-Raz N, Robenshtok E, Shefet D, et al. Cochrane Database Syst Rev 2012;9:CD004418.

4. Garin N, Genne D, Carballo S, et al. JAMA Intern Med 2014;174:1894-901.

5. Postma DF, van Wekhoven CH, van Elden LJR, et al. N Engl J Med 2015;372:1312-23.

6. Llor C, Hernández S, Ribas A, et al. Int J Chron Obstruct Pulmon Dis 2009;4:45-53.

7. Dimopoulos G, Siempos II, Korbila IP, et al. Chest 2007;132:447-55.

8. Karageorgopoulos DE, Giannopoulou KP, Grammatikos AP, Dimopoulos G, Falagas ME. CMAJ 2008;178:845-54.

9. Wald ER, Chiponis D, Ledesma-Medina J. Pediatrics 1986;77:795–800.

10. Garbutt JM, Goldstein M, Gellman E, et al. Pediatrics 2001;107:619–25.

11. Canadian Bacterial Surveillance Network [Accessed 2 Aug 2016]

12. Coker TR, Chan LS, Newberry SJ. JAMA 2010;304:2161-9.

Authors do not have any conflicts of interest to declare.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.

Most recent review: 02/08/2016

By: Ricky Turgeon BSc(Pharm) ACPR PharmD


Evidence Updated: New evidence; Bottom Line: No change.

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