Abstract: 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. 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.

Plain-language summary: We identified 11 trials (with 3352 participants older than 12 years with a diagnosis of community-acquired pneumonia), fully published in peer-reviewed journals, focused on treatment of pneumonia in adolescents and adults treated in the community in outpatient settings. This included five new trials included since our last review published in 2009. None of the trials included antibiotics versus placebo; all trials included one or more antibiotics. All participants were diagnosed with pneumonia based upon clinical diagnosis by the physician and chest X-ray. All included trials were well conducted; nine of the 11 trials were sponsored by bio-pharmaceutical companies manufacturing the antibiotics used in the study, or their authors were closely linked with the company. Nine of the included trials compared different antibiotics and, hence, we could not combine the results of the individual trials to present our overall conclusion. There were some notable adverse events in seven studies: 1) erythromycin demonstrated significant gastrointestinal side effects compared to clarithromycin in two studies; 2) nemonoxacin demonstrated higher gastrointestinal (nausea, diarrhoea) and nervous system (dizziness, headache) adverse events compared to levofloxacin; 3) cethromycin demonstrated more side effects, especially a distortion of the sense of taste, than clarithromycin; 4) gastritis and diarrhoea were more common in the high-dose amoxicillin group (1 g three times a day) compared to the other three antibiotic groups (clarithromycin, azithromycin and levofloxacin). Unfortunately, there were not enough trials to compare the effects of different antibiotics for pneumonia acquired and treated in the community.