Clinical Review & Education
JAMA Clinical Evidence Synopsis
Antibiotics for Acute Bronchitis Susan M. Smith, MD; John Smucny, MD; Tom Fahey, MD
CLINICAL QUESTION Are antibiotics associated with improved outcomes in patients with
acute bronchitis? BOTTOM LINE Prescribing antibiotics for acute bronchitis was associated with reduced overall and nighttime cough and with an approximately half-day reduction in duration of cough, in days feeling ill, and in days with impaired activities. However, at follow-up, there were no significant differences in patients receiving antibiotics compared with those receiving placebo in overall clinical improvements or limitations in work or other activities. There was a significant increase in adverse effects in the antibiotic group, particularly gastrointestinal symptoms.
Acute bronchitis is common and is characterized by a cough that may be productive and associated with wheezing, fever, or both when pneumonia is not suspected.1 Although most cases of acute bronchitis are caused by viral infections, antibiotics are still commonly prescribed.2,3 This JAMA Clinical Evidence Synopsis summarizes a Cochrane review1 to assess the association of antibiotics with clinical outcomes and adverse events for patients with acute bronchitis.
Summary of Findings At follow-up, there was no difference in patients described as being clinically improved between antibiotic and placebo groups (11 studies with 3841 patients; risk ratio [RR], 1.07 [95% CI, 0.99 to 1.15]). At follow-up, antibiotics were associated with a lower prevalence of cough (4 studies with 275 patients; RR, 0.64 [95% CI, 0.49 to 0.85]; number needed to treat [NNT] to benefit, 6); and a lower prevalence of night cough (4 studies with 538 patients; RR, 0.67 [95% CI, 0.54 to 0.83]; NNT to benefit, 7). Antibiotics were associated with a shorter mean cough duration (7 studies with 2776 patients; mean
Evidence Profile No. of randomized trials: 17 Study years: Conducted, 1969-2010; published, 1970-2013 No. of patients: 5099, presenting with acute cough and no background history of chronic respiratory disease Sex: Not reported
difference, −0.46 days [95% CI, −0.87 to −0.04]) (Table). There were no differences in the prevalence of a productive cough at follow-up or in mean duration of productive cough. Antibiotics were associated with a reduction in days feeling ill (5 studies with 809 patients; mean difference, −0.64 days [95% CI, −1.16 to −0.13]) and a reduction in days with limited activity (6 studies with 767 patients; mean difference, −0.49 days [95% CI, −0.94 to −0.04]). Antibiotic therapy was not associated with differences in reported activity limitations at follow-up compared with the control group. Antibiotic therapy was associated with an increased rate of adverse effects (12 studies with 3496 patients; RR, 1.20 [95% CI, 1.05 to 1.36]; NNT to harm for an additional adverse effect, 24).
Discussion In these studies, an antibiotic prescription for acute bronchitis was associated with a half day shorter duration of cough. This improvement should be viewed in the context of an average cough duration of 8 to 9 days in the 7 studies reporting this outcome. This average cough duration is shorter than that reported in observational studies and could be explained by several factors including shorter follow-up periods in most of the studies included in this review or differences in patient selection between studies. This finding needs to be balanced against an association of antibiotics with an increased rate of adverse effects. Patients often underestimate the typical cough duration and when cough does not resolve within their expected time frame may request antibiotic therapy, thereby encouraging antibiotic therapy for this common self-limited condition.4
Race/ethnicity: Not reported Age: 3 years or older; 9 trials included children and adults, 8 trials included adults only Settings: All studies were conducted in ambulatory settings, in either primary care or outpatient clinics depending on the country Countries: 14 countries; Belgium, England, France, Germany, Italy, Kenya, the Netherlands, Poland, Slovakia, Slovenia, Spain, Sweden, Wales, and United States Comparison: 16 studies used placebo as a comparison; 1 study compared antibiotic with no treatment Primary outcomes: Cough-related outcomes, clinical improvement, adverse effects
2678
Limitations
Although duration of illness and associated symptoms varied between studies, they were broadly consistent with definitions used by primary care physicians. Thus, our results may be generalizable to the management of acute bronchitis in primary care practices. However, it is possible that, even with broad inclusion criteria, older patients and those with complex comorbid diseases may not be enrolled in trials, limiting generalizability to these groups.5 In addition, this review does not address the management of bronchitis in patients with chronic respiratory disease and we were unable to specifically look at the effectiveness of antibiotics for acute bronchitis in children compared with adults.
JAMA December 24/31, 2014 Volume 312, Number 24 (Reprinted)
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a New York University User on 05/21/2015
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JAMA Clinical Evidence Synopsis Clinical Review & Education
Table. Associations of Antibiotics With Patient Outcomes in Acute Bronchitis Antibiotic
Placebo
No. of Studies
No. of Patients
Cough
4
143
47
132
Night cough
4
271
80
267
Productive cough
7
366
135
347
129
RR, 0.97 (0.82 to 1.16)
Days of cough, mean (SD)
7
1402
Days of productive cough, mean (SD)
6
357
Outcome
Events, No.
No. of Patients
Point Estimate (95% CI)
NNT to Benefit or to Harm
67
RR, 0.64 (0.49 to 0.85)
6
119
RR, 0.67 (0.54 to 0.83)
7
Events, No.
Cough-related outcomes At follow-up
8.2 (5.4)
1374
9.1 (5.9)
AMD, −0.46 (−0.87 to −0.04)
342
5.8 (4.1)
AMD, −0.43 (−0.93 to 0.07)
5.5 (4)
Other clinical outcomes At follow-up Clinically improved
11
1922
1407
1919
1277
RR, 1.07 (0.99 to 1.15)
Limitations in work or activities
5
239
23
239
34
RR, 0.75 (0.46 to 1.22)
Abnormal lung examination
5
314
58
299
104
RR, 0.54 (0.41 to 0.70)
Days of feeling ill, mean (SD)
5
411
8 (5.2)
398
8.1 (5.9)
AMD, −0.64 (−1.16 to −0.13)
Days of impaired activities, mean (SD)
6
397
3.6 (2.7)
370
4.2 (3.2)
AMD, −0.49 (−0.94 to −0.04)
12
1773
323
RR, 1.20 (1.05 to 1.36)
Adverse effectsa
401
1723
6
24
Abbreviations: AMD, adjusted mean difference; NNT, number needed to treat; RR, risk ratio. a
Antibiotic adverse effects including nausea, vomiting, diarrhea, headaches, and rash.
Comparison of Findings With Current Practice Guidelines
Areas in Need of Future Study
The National Institute for Care Excellence in the United Kingdom states that antibiotics should not be used for acute cough when pneumonia is not suspected in otherwise healthy adults and children.6 The US Centers for Disease Control and Prevention, the American Academy of Family Physicians, the American College of Physicians/ American Society of Internal Medicine, and the Infectious Diseases Society of America all recommend not prescribing antibiotics for acute bronchitis.7
Some antibiotic prescribing may result from uncertainty about the potential benefit in more vulnerable patients such as those 75 years and older and those with multiple comorbidities.4 However, these groups may be more susceptible to adverse effects of antibiotics due to interactions with other medications. Future research should focus on these groups of patients and on physician and patient education to optimize antibiotic prescribing in primary care settings.
ARTICLE INFORMATION Author Affiliations: HRB Centre for Primary Care Research, Department of General Practice, Royal College of Surgeons in Ireland Medical School, Dublin (Smith, Fahey); Palo Alto Medical Foundation, Dublin Center, Dublin, California (Smucny). Corresponding Author: Susan M. Smith, MD, HRB Centre for Primary Care Research, Department of General Practice, Royal College of Surgeons in Ireland Medical School, 123 St Stephen’s Green, Dublin 2, Ireland ([email protected]). Section Editor: Mary McGrae McDermott, MD, Senior Editor. Author Contributions: Dr Smith had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for
jama.com
Disclosure of Potential Conflicts of Interest and none were reported. Submissions: We encourage authors to submit papers for consideration as a JAMA Clinical Evidence Synopsis. Please contact Dr McDermott at [email protected]. Correction: This article was corrected on February 17, 2015, to change the number needed to treat for adverse effects to 24 in the text and Table. REFERENCES 1. Smith SM, Fahey T, Smucny J, Becker LA. Antibiotics for acute bronchitis. Cochrane Database Syst Rev. 2014;3(3):CD000245. 2. European Centre for Disease Control. Trend of antimicrobial consumption by country. http://www .ecdc.europa.eu/en/healthtopics/antimicrobial _resistance/esac-net-database/Pages/overview -country-consumption.aspx. Accessed October 1, 2014.
Antibiotic prescribing for adults with acute bronchitis in the United States, 1996-2010. JAMA. 2014;311(19):2020-2022. 4. Little P, Stuart B, Moore M, et al; GRACE consortium. Amoxicillin for acute lower respiratory tract infection in primary care when pneumonia is not suspected. Lancet Infect Dis. 2013;13(2):123-129. 5. Moore M, Little P, Rumsby K, et al. Predicting the duration of symptoms in lower respiratory tract infection. Br J Gen Pract. 2008;58(547):88-92. 6. National Institute for Health and Care Excellence. Cough: clinical knowledge summaries. http://cks.nice.org.uk/cough. Accessed April 22, 2014. 7. Snow V, Mottur-Pilson C, Gonzales R; American Academy of Family Physicians; American College of Physicians-American Society of Internal Medicine; Centers for Disease Control; Infectious Diseases Society of America. Principles of appropriate antibiotic use for treatment of acute bronchitis in adults. Ann Intern Med. 2001;134(6):518-520.
3. Barnett ML, Linder JA; Antibiotic Prescribing for Adults with Acute Bronchitis in the United States.
(Reprinted) JAMA December 24/31, 2014 Volume 312, Number 24
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a New York University User on 05/21/2015
2679
JAMA Clinical Evidence Synopsis
Antibiotics for Acute Bronchitis Susan M. Smith, MD; John Smucny, MD; Tom Fahey, MD
CLINICAL QUESTION Are antibiotics associated with improved outcomes in patients with
acute bronchitis? BOTTOM LINE Prescribing antibiotics for acute bronchitis was associated with reduced overall and nighttime cough and with an approximately half-day reduction in duration of cough, in days feeling ill, and in days with impaired activities. However, at follow-up, there were no significant differences in patients receiving antibiotics compared with those receiving placebo in overall clinical improvements or limitations in work or other activities. There was a significant increase in adverse effects in the antibiotic group, particularly gastrointestinal symptoms.
Acute bronchitis is common and is characterized by a cough that may be productive and associated with wheezing, fever, or both when pneumonia is not suspected.1 Although most cases of acute bronchitis are caused by viral infections, antibiotics are still commonly prescribed.2,3 This JAMA Clinical Evidence Synopsis summarizes a Cochrane review1 to assess the association of antibiotics with clinical outcomes and adverse events for patients with acute bronchitis.
Summary of Findings At follow-up, there was no difference in patients described as being clinically improved between antibiotic and placebo groups (11 studies with 3841 patients; risk ratio [RR], 1.07 [95% CI, 0.99 to 1.15]). At follow-up, antibiotics were associated with a lower prevalence of cough (4 studies with 275 patients; RR, 0.64 [95% CI, 0.49 to 0.85]; number needed to treat [NNT] to benefit, 6); and a lower prevalence of night cough (4 studies with 538 patients; RR, 0.67 [95% CI, 0.54 to 0.83]; NNT to benefit, 7). Antibiotics were associated with a shorter mean cough duration (7 studies with 2776 patients; mean
Evidence Profile No. of randomized trials: 17 Study years: Conducted, 1969-2010; published, 1970-2013 No. of patients: 5099, presenting with acute cough and no background history of chronic respiratory disease Sex: Not reported
difference, −0.46 days [95% CI, −0.87 to −0.04]) (Table). There were no differences in the prevalence of a productive cough at follow-up or in mean duration of productive cough. Antibiotics were associated with a reduction in days feeling ill (5 studies with 809 patients; mean difference, −0.64 days [95% CI, −1.16 to −0.13]) and a reduction in days with limited activity (6 studies with 767 patients; mean difference, −0.49 days [95% CI, −0.94 to −0.04]). Antibiotic therapy was not associated with differences in reported activity limitations at follow-up compared with the control group. Antibiotic therapy was associated with an increased rate of adverse effects (12 studies with 3496 patients; RR, 1.20 [95% CI, 1.05 to 1.36]; NNT to harm for an additional adverse effect, 24).
Discussion In these studies, an antibiotic prescription for acute bronchitis was associated with a half day shorter duration of cough. This improvement should be viewed in the context of an average cough duration of 8 to 9 days in the 7 studies reporting this outcome. This average cough duration is shorter than that reported in observational studies and could be explained by several factors including shorter follow-up periods in most of the studies included in this review or differences in patient selection between studies. This finding needs to be balanced against an association of antibiotics with an increased rate of adverse effects. Patients often underestimate the typical cough duration and when cough does not resolve within their expected time frame may request antibiotic therapy, thereby encouraging antibiotic therapy for this common self-limited condition.4
Race/ethnicity: Not reported Age: 3 years or older; 9 trials included children and adults, 8 trials included adults only Settings: All studies were conducted in ambulatory settings, in either primary care or outpatient clinics depending on the country Countries: 14 countries; Belgium, England, France, Germany, Italy, Kenya, the Netherlands, Poland, Slovakia, Slovenia, Spain, Sweden, Wales, and United States Comparison: 16 studies used placebo as a comparison; 1 study compared antibiotic with no treatment Primary outcomes: Cough-related outcomes, clinical improvement, adverse effects
2678
Limitations
Although duration of illness and associated symptoms varied between studies, they were broadly consistent with definitions used by primary care physicians. Thus, our results may be generalizable to the management of acute bronchitis in primary care practices. However, it is possible that, even with broad inclusion criteria, older patients and those with complex comorbid diseases may not be enrolled in trials, limiting generalizability to these groups.5 In addition, this review does not address the management of bronchitis in patients with chronic respiratory disease and we were unable to specifically look at the effectiveness of antibiotics for acute bronchitis in children compared with adults.
JAMA December 24/31, 2014 Volume 312, Number 24 (Reprinted)
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a New York University User on 05/21/2015
jama.com
JAMA Clinical Evidence Synopsis Clinical Review & Education
Table. Associations of Antibiotics With Patient Outcomes in Acute Bronchitis Antibiotic
Placebo
No. of Studies
No. of Patients
Cough
4
143
47
132
Night cough
4
271
80
267
Productive cough
7
366
135
347
129
RR, 0.97 (0.82 to 1.16)
Days of cough, mean (SD)
7
1402
Days of productive cough, mean (SD)
6
357
Outcome
Events, No.
No. of Patients
Point Estimate (95% CI)
NNT to Benefit or to Harm
67
RR, 0.64 (0.49 to 0.85)
6
119
RR, 0.67 (0.54 to 0.83)
7
Events, No.
Cough-related outcomes At follow-up
8.2 (5.4)
1374
9.1 (5.9)
AMD, −0.46 (−0.87 to −0.04)
342
5.8 (4.1)
AMD, −0.43 (−0.93 to 0.07)
5.5 (4)
Other clinical outcomes At follow-up Clinically improved
11
1922
1407
1919
1277
RR, 1.07 (0.99 to 1.15)
Limitations in work or activities
5
239
23
239
34
RR, 0.75 (0.46 to 1.22)
Abnormal lung examination
5
314
58
299
104
RR, 0.54 (0.41 to 0.70)
Days of feeling ill, mean (SD)
5
411
8 (5.2)
398
8.1 (5.9)
AMD, −0.64 (−1.16 to −0.13)
Days of impaired activities, mean (SD)
6
397
3.6 (2.7)
370
4.2 (3.2)
AMD, −0.49 (−0.94 to −0.04)
12
1773
323
RR, 1.20 (1.05 to 1.36)
Adverse effectsa
401
1723
6
24
Abbreviations: AMD, adjusted mean difference; NNT, number needed to treat; RR, risk ratio. a
Antibiotic adverse effects including nausea, vomiting, diarrhea, headaches, and rash.
Comparison of Findings With Current Practice Guidelines
Areas in Need of Future Study
The National Institute for Care Excellence in the United Kingdom states that antibiotics should not be used for acute cough when pneumonia is not suspected in otherwise healthy adults and children.6 The US Centers for Disease Control and Prevention, the American Academy of Family Physicians, the American College of Physicians/ American Society of Internal Medicine, and the Infectious Diseases Society of America all recommend not prescribing antibiotics for acute bronchitis.7
Some antibiotic prescribing may result from uncertainty about the potential benefit in more vulnerable patients such as those 75 years and older and those with multiple comorbidities.4 However, these groups may be more susceptible to adverse effects of antibiotics due to interactions with other medications. Future research should focus on these groups of patients and on physician and patient education to optimize antibiotic prescribing in primary care settings.
ARTICLE INFORMATION Author Affiliations: HRB Centre for Primary Care Research, Department of General Practice, Royal College of Surgeons in Ireland Medical School, Dublin (Smith, Fahey); Palo Alto Medical Foundation, Dublin Center, Dublin, California (Smucny). Corresponding Author: Susan M. Smith, MD, HRB Centre for Primary Care Research, Department of General Practice, Royal College of Surgeons in Ireland Medical School, 123 St Stephen’s Green, Dublin 2, Ireland ([email protected]). Section Editor: Mary McGrae McDermott, MD, Senior Editor. Author Contributions: Dr Smith had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for
jama.com
Disclosure of Potential Conflicts of Interest and none were reported. Submissions: We encourage authors to submit papers for consideration as a JAMA Clinical Evidence Synopsis. Please contact Dr McDermott at [email protected]. Correction: This article was corrected on February 17, 2015, to change the number needed to treat for adverse effects to 24 in the text and Table. REFERENCES 1. Smith SM, Fahey T, Smucny J, Becker LA. Antibiotics for acute bronchitis. Cochrane Database Syst Rev. 2014;3(3):CD000245. 2. European Centre for Disease Control. Trend of antimicrobial consumption by country. http://www .ecdc.europa.eu/en/healthtopics/antimicrobial _resistance/esac-net-database/Pages/overview -country-consumption.aspx. Accessed October 1, 2014.
Antibiotic prescribing for adults with acute bronchitis in the United States, 1996-2010. JAMA. 2014;311(19):2020-2022. 4. Little P, Stuart B, Moore M, et al; GRACE consortium. Amoxicillin for acute lower respiratory tract infection in primary care when pneumonia is not suspected. Lancet Infect Dis. 2013;13(2):123-129. 5. Moore M, Little P, Rumsby K, et al. Predicting the duration of symptoms in lower respiratory tract infection. Br J Gen Pract. 2008;58(547):88-92. 6. National Institute for Health and Care Excellence. Cough: clinical knowledge summaries. http://cks.nice.org.uk/cough. Accessed April 22, 2014. 7. Snow V, Mottur-Pilson C, Gonzales R; American Academy of Family Physicians; American College of Physicians-American Society of Internal Medicine; Centers for Disease Control; Infectious Diseases Society of America. Principles of appropriate antibiotic use for treatment of acute bronchitis in adults. Ann Intern Med. 2001;134(6):518-520.
3. Barnett ML, Linder JA; Antibiotic Prescribing for Adults with Acute Bronchitis in the United States.
(Reprinted) JAMA December 24/31, 2014 Volume 312, Number 24
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a New York University User on 05/21/2015
2679
