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. 2014 Oct 9;2014(10):CD002109.
doi: 10.1002/14651858.CD002109.pub4.

Antibiotics for community-acquired pneumonia in adult outpatients

Smita Pakhale  1 , Sunita Mulpuru, Theo J M Verheij, Michael M Kochen, Gernot G U Rohde, Lise M Bjerre
Affiliations

Antibiotics for community-acquired pneumonia in adult outpatients

Smita Pakhale et al. Cochrane Database Syst Rev. .

Abstract

Background: Lower respiratory tract infection (LRTI) is the third leading cause of death worldwide and the first leading cause of death in low-income countries. Community-acquired pneumonia (CAP) is a common condition that causes a significant disease burden for the community, particularly in children younger than five years, the elderly and immunocompromised people. Antibiotics are the standard treatment for CAP. However, increasing antibiotic use is associated with the development of bacterial resistance and side effects for the patient. Several studies have been published regarding optimal antibiotic treatment for CAP but many of these data address treatments in hospitalised patients. This is an update of our 2009 Cochrane Review and addresses antibiotic therapies for CAP in outpatient settings.

Objectives: To compare the efficacy and safety of different antibiotic treatments for CAP in participants older than 12 years treated in outpatient settings with respect to clinical, radiological and bacteriological outcomes.

Search methods: We searched CENTRAL (2014, Issue 1), MEDLINE (January 1966 to March week 3, 2014), EMBASE (January 1974 to March 2014), CINAHL (2009 to March 2014), Web of Science (2009 to March 2014) and LILACS (2009 to March 2014).

Selection criteria: We looked for randomised controlled trials (RCTs), fully published in peer-reviewed journals, of antibiotics versus placebo as well as antibiotics versus another antibiotic for the treatment of CAP in outpatient settings in participants older than 12 years of age. However, we did not find any studies of antibiotics versus placebo. Therefore, this review includes RCTs of one or more antibiotics, which report the diagnostic criteria and describe the clinical outcomes considered for inclusion in this review.

Data collection and analysis: Two review authors (LMB, TJMV) independently assessed study reports in the first publication. In the 2009 update, LMB performed study selection, which was checked by TJMV and MMK. In this 2014 update, two review authors (SP, SM) independently performed and checked study selection. We contacted trial authors to resolve any ambiguities in the study reports. We compiled and analysed the data. We resolved differences between review authors by discussion and consensus.

Main results: We included 11 RCTs in this review update (3352 participants older than 12 years with a diagnosis of CAP); 10 RCTs assessed nine antibiotic pairs (3321 participants) and one RCT assessed four antibiotics (31 participants) in people with CAP. The study quality was generally good, with some differences in the extent of the reporting. A variety of clinical, bacteriological and adverse events were reported. Overall, there was no significant difference in the efficacy of the various antibiotics. Studies evaluating clarithromycin and amoxicillin provided only descriptive data regarding the primary outcome. Though the majority of adverse events were similar between all antibiotics, nemonoxacin demonstrated higher gastrointestinal and nervous system adverse events when compared to levofloxacin, while cethromycin demonstrated significantly more nervous system side effects, especially dysgeusia, when compared to clarithromycin. Similarly, high-dose amoxicillin (1 g three times a day) was associated with higher incidence of gastritis and diarrhoea compared to clarithromycin, azithromycin and levofloxacin.

Authors' conclusions: Available evidence from recent RCTs is insufficient to make new evidence-based recommendations for the choice of antibiotic to be used for the treatment of CAP in outpatient settings. Pooling of study data was limited by the very low number of studies assessing the same antibiotic pairs. Individual study results do not reveal significant differences in efficacy between various antibiotics and antibiotic groups. However, two studies did find significantly more adverse events with use of cethromycin as compared to clarithromycin and nemonoxacin when compared to levofloxacin. Multi-drug comparisons using similar administration schedules are needed to provide the evidence necessary for practice recommendations. Further studies focusing on diagnosis, management, cost-effectiveness and misuse of antibiotics in CAP and LRTI are warranted in high-, middle- and low-income countries.

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Conflict of interest statement

Smita Pakhale: no potential conflicts of interest to declare. Sunita Mulpuru: no potential conflicts of interest to declare. Theo JM Verheij: I participated in an RCT on the effects of pneumococcal vaccination, funded by Pfizer. Michael M Kochen: no potential conflicts of interest to declare. Gernot GU Rohde: Dr. Rohde received financial benefits for advisory board memberships from Pfizer and consultancy work for Novartis and Takeda as well as payments for lectures from Pfizer, Chiesi, Astra‐Zeneca, GSK, Novartis and Grünenthal. Lise M Bjerre: Dr. Bjerre currently holds operating foundation grants as principal investigator from the Canadian Institutes for Health Research (CIHR) and the Centre for Learning, Research and Innovation in Long‐term care (CLRI) of the Ministry of Health of Ontario; she is also co‐investigator on other CIHR grants. She has never accepted remuneration, gifts or research funds in any form from drug or device manufacturers, or other member of the pharmaceutical industry.

Figures

1
1
Figure1: Antibiotic comparisons in new studies included in this review. The red arrow indicates antibiotic comparisons studied in Udupa 2011.
2
2
Figure 2. Overview of included studies and antibiotic pairs studied in 2009 review. *Indicates studies new to this review; shaded ovals indicate quinolones (gyrase inhibitors), white ovals indicate macrolides
3
3
'Risk of bias' graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
4
4
'Risk of bias' summary: review authors' judgements about each methodological quality item for each included study.
1.1
1.1. Analysis
Comparison 1 Solithromycin versus levofloxacin, Outcome 1 Test‐of‐clinical‐cure.
1.2
1.2. Analysis
Comparison 1 Solithromycin versus levofloxacin, Outcome 2 Bacteriological cure.
1.3
1.3. Analysis
Comparison 1 Solithromycin versus levofloxacin, Outcome 3 Adverse events.
2.1
2.1. Analysis
Comparison 2 Nemonoxacin versus levofloxacin, Outcome 1 Test‐of‐clinical‐cure.
2.2
2.2. Analysis
Comparison 2 Nemonoxacin versus levofloxacin, Outcome 2 Bacteriological cure.
2.3
2.3. Analysis
Comparison 2 Nemonoxacin versus levofloxacin, Outcome 3 Adverse events.
3.1
3.1. Analysis
Comparison 3 Nemonoxacin versus levofloxacin, Outcome 1 Test‐of‐clinical‐cure.
3.2
3.2. Analysis
Comparison 3 Nemonoxacin versus levofloxacin, Outcome 2 Bacteriological cure.
3.3
3.3. Analysis
Comparison 3 Nemonoxacin versus levofloxacin, Outcome 3 Adverse events.
4.1
4.1. Analysis
Comparison 4 Clarithromycin versus amoxicillin, Outcome 1 Test‐of‐clinical‐cure.
6.1
6.1. Analysis
Comparison 6 Cethromycin versus clarithromycin, Outcome 1 Test‐of‐clinical‐cure.
6.2
6.2. Analysis
Comparison 6 Cethromycin versus clarithromycin, Outcome 2 Bacteriological cure.
6.3
6.3. Analysis
Comparison 6 Cethromycin versus clarithromycin, Outcome 3 Adverse events.
7.1
7.1. Analysis
Comparison 7 Clarithromycin versus erythromycin, Outcome 1 Test‐of‐clinical‐cure.
7.2
7.2. Analysis
Comparison 7 Clarithromycin versus erythromycin, Outcome 2 Bacteriological cure.
7.3
7.3. Analysis
Comparison 7 Clarithromycin versus erythromycin, Outcome 3 Radiological cure.
7.4
7.4. Analysis
Comparison 7 Clarithromycin versus erythromycin, Outcome 4 Adverse events.
8.1
8.1. Analysis
Comparison 8 Azithromycin microspheres versus levofloxacin, Outcome 1 Test‐of‐clinical‐cure.
8.2
8.2. Analysis
Comparison 8 Azithromycin microspheres versus levofloxacin, Outcome 2 Bacteriological cure.
8.3
8.3. Analysis
Comparison 8 Azithromycin microspheres versus levofloxacin, Outcome 3 Adverse events.
9.1
9.1. Analysis
Comparison 9 Azithromycin microspheres versus clarithromycin, Outcome 1 Test‐of‐clinical‐cure.
9.2
9.2. Analysis
Comparison 9 Azithromycin microspheres versus clarithromycin, Outcome 2 Bacteriological cure.
9.3
9.3. Analysis
Comparison 9 Azithromycin microspheres versus clarithromycin, Outcome 3 Adverse events.
10.1
10.1. Analysis
Comparison 10 Telithromycin versus clarithromycin, Outcome 1 Test‐of‐clinical‐cure.
10.2
10.2. Analysis
Comparison 10 Telithromycin versus clarithromycin, Outcome 2 Bacteriological cure.
10.3
10.3. Analysis
Comparison 10 Telithromycin versus clarithromycin, Outcome 3 Adverse events.
11.1
11.1. Analysis
Comparison 11 Telithromycin versus levofloxacin, Outcome 1 Test‐of‐clinical‐cure.
11.2
11.2. Analysis
Comparison 11 Telithromycin versus levofloxacin, Outcome 2 Bacteriological cure.
11.3
11.3. Analysis
Comparison 11 Telithromycin versus levofloxacin, Outcome 3 Clinical efficacy against H. influenzae.
11.4
11.4. Analysis
Comparison 11 Telithromycin versus levofloxacin, Outcome 4 Adverse events.
See this image and copyright information in PMC

Update of

References

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