Abstract
Introduction
In the northern hemisphere about 12/1000 people a year (on average) contract pneumonia while living in the community, with most cases caused by Streptococcus pneumoniae. Mortality ranges from about 5% to 35% depending on severity of disease, with a worse prognosis in older people, men, and people with chronic diseases.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions to prevent community-acquired pneumonia? What are the effects of treatments for community-acquired pneumonia in outpatient settings, in people admitted to hospital, and in people receiving intensive care? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 15 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics (oral, intravenous), different combinations, and prompt administration of antibiotics in intensive-care settings, early mobilisation, influenza vaccine, and pneumococcal vaccine.
Key Points
In the northern hemisphere about 12/1000 people a year (on average) contract pneumonia while living in the community, with most cases caused by Streptococcus pneumoniae.
People at greatest risk include those at the extremes of age, smokers, alcohol-dependent people, and people with lung or heart disease or immunosuppression.
Mortality ranges from about 5% to 35% depending on severity of disease, with a worse prognosis in older people, men, and people with chronic diseases.
Deaths from influenza are usually caused by pneumonia. Influenza vaccine reduces the risk of clinical influenza, and may reduce the risk of pneumonia and mortality in older people.
Pneumococcal vaccine is unlikely to reduce all-cause pneumonia or mortality in immunocompetent adults, but may reduce pneumococcal pneumonia in this group.
Antibiotics lead to clinical cure in at least 80% of people with pneumonia being treated in the community or in hospital, although no one regimen has been shown to be superior to the others in either setting.
Early mobilisation may reduce hospital stay compared with usual care in people being treated with antibiotics.
Intravenous antibiotics have not been shown to improve clinical cure rates or survival compared with oral antibiotics in people treated in hospital for non-severe community-acquired pneumonia.
Prompt administration of antibiotics may improve survival compared with delayed treatment in people receiving intensive care for community-acquired pneumonia, although we found few studies.
We don't know which is the optimum antibiotic regimen to use in these people.
About this condition
Definition
Community-acquired pneumonia is pneumonia contracted in the community rather than in hospital. It is defined by clinical symptoms (such as cough, sputum production, and pleuritic chest pain) and signs (such as fever, tachypnoea, and rales), with radiological confirmation.
Incidence/ Prevalence
In the northern hemisphere, community-acquired pneumonia affects about 12/1000 people a year, particularly during winter, and in people at the extremes of age (annual incidence in people aged <1 year old: 30–50/1000; 15–45 years old: 1–5/1000; 60–70 years old: 10–20/1000; 71–85 years old: 50/1000).
Aetiology/ Risk factors
More than 100 micro-organisms have been implicated in community-acquired pneumonia, but most cases are caused by Streptococcus pneumoniae (see table 1 ). Case-control study data suggest that smoking is probably an important risk factor. One large cohort study conducted in Finland (4175 people aged at least 60 years) suggested that risk factors for pneumonia in older people included alcoholism (RR 9.0, 95% CI 5.1 to 16.2), bronchial asthma (RR 4.2, 95% CI 3.3 to 5.4), immunosuppression (RR 3.1, 95% CI 1.9 to 5.1), lung disease (RR 3.0, 95% CI 2.3 to 3.9), heart disease (RR 1.9, 95% CI 1.7 to 2.3), institutionalisation (RR 1.8, 95% CI 1.4 to 2.4), and increasing age (age at least 70 years v 60–69 years; RR 1.5, 95% CI 1.3 to 1.7).
Table 1.
Causes of community-acquired pneumonia (see text).
| USA (% of participants)* | UK (% of participants)† | Susceptibility (laboratory results)‡ | |
| Streptococcus pneumoniae | 20–60 | 60–75 | 25% penicillin resistant, sensitive to quinolones |
| Haemophilus influenzae | 3–10 | 4–5 | 30% ampicillin resistant, sensitive to cephalosporins or amoxicillin–clavulanic acid (co-amoxiclav) |
| Staphylococcus aureus | 3–5 | 1–5 | Methicillin-resistant S aureus rare as cause of community-acquired pneumonia |
| Chlamydia pneumoniae | 4–6 | ND | Sensitive to macrolides, tetracyclines, quinolones |
| Mycoplasma pneumoniae | 1–6 | 5–18 | Sensitive to macrolides, tetracyclines, quinolones |
| Legionella pneumophilia | 2–8 | 2–5 | Sensitive to macrolides, tetracyclines, quinolones |
| Gram-negative bacilli | 3–10 | Rare | |
| Aspiration | 6–10 | ND | |
| Viruses | 2–15 | 8–16 | |
*Pooled data from 15 published reports from North America; †data from British Thoracic Society; ‡susceptibility data from recent studies. ND, no data.
Prognosis
Severity varies from mild to life-threatening illness within days of the onset of symptoms. A prospective cohort study (>14,000 people) found that old age was an extremely important factor in determining prognosis. One systematic review of prognosis studies for community-acquired pneumonia (search date 1995, 33,148 people) found overall mortality to be 13.7%, ranging from 5.1% for ambulant people to 36.5% for people who required intensive care. Prognostic factors significantly associated with mortality were: male sex (OR 1.3, 95% CI 1.2 to 1.4), absence of pleuritic chest pain (OR 2.00, 95% CI 1.25 to 3.30), hypothermia (OR 5.0, 95% CI 2.4 to 10.4), systolic hypotension (OR 4.8, 95% CI 2.8 to 8.3), tachypnoea (OR 2.9, 95% CI 1.7 to 4.9), diabetes mellitus (OR 1.3, 95% CI 1.1 to 1.5), neoplastic disease (OR 2.8, 95% CI 2.4 to 3.1), neurological disease (OR 4.6, 95% CI 2.3 to 8.9), bacteraemia (OR 2.8, 95% CI 2.3 to 3.6), leukopenia (OR 2.5, 95% CI 1.6 to 3.7), and multilobar radiographic pulmonary infiltrates (OR 3.1, 95% CI 1.9 to 5.1).
Aims of intervention
Prevention: to prevent onset of pneumonia. Treatment: to cure infection clinically, to reduce mortality, to alleviate symptoms, to enable return to normal activities, and to prevent recurrence, while minimising adverse effects of treatments.
Outcomes
For the question on prevention: mortality; incidence of pneumonia; admission to hospital or intensive care, including duration of hospital stay; adverse effects of vaccination. For the questions on treatment: mortality; clinical cure, variably defined but usually defined as return to premorbid health status or complete absence of symptoms or signs, such as fever, chills, cough, dyspnoea, or sputum production, improvement (relief of symptoms), treatment failure; admission to hospital or intensive care, including duration of hospital stay (for treatment in people admitted to hospital); complications (empyema, endocarditis, lung abscess); quality of life; adverse effects of treatments.
Methods
Clinical Evidence search and appraisal January 2010. The following databases were used to identify studies for this systematic review: Medline 1966 to January 2010, Embase 1980 to January 2010, and The Cochrane Database of Systematic Reviews 2009, Issue 4 (1966 to date of issue). An additional search within The Cochrane Library was carried out for the Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA). We also searched for retractions of studies included in the review. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the contributor for additional assessment, using predetermined criteria to identify relevant studies. Study design criteria for inclusion in this review were: published systematic reviews of RCTs and RCTs in any language, at least single blinded, and containing >20 individuals of whom >80% were followed up. There was no minimum length of follow-up required to include studies. We excluded all studies described as "open", "open label", or not blinded unless blinding was impossible. We included systematic reviews of RCTs and RCTs where harms of an included intervention were studied applying the same study design criteria for inclusion as we did for benefits. In addition we did an observational search for the prompt versus delayed antibiotics option. We searched for prospective and retrospective cohort studies with or without a control group with a minimum size of 50 people. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the MHRA, which are added to the reviews as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).
Table.
GRADE Evaluation of interventions for Community-acquired pneumonia.
| Important outcomes | Clinical cure, Hospital admission, Incidence of pneumonia, Mortality | ||||||||
| Studies (Participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
| What are the effects of interventions to prevent community-acquired pneumonia? | |||||||||
| 8 (405,064) | Mortality | Influenza vaccine versus no vaccine | 2 | 0 | 0 | 0 | 0 | Low | Note: cohort studies |
| at least 10 (at least 23,386) | Incidence of pneumonia | Influenza vaccine versus no vaccine | 2 | 0 | 0 | 0 | 0 | Low | Note: cohort studies |
| 14 (729,803) | Hospital admission | Influenza vaccine versus no vaccine | 2 | 0 | 0 | –1 | 0 | Very low | Note: cohort studies. Directness point deducted for combined admissions for influenza and pneumonia |
| 11 (45,609) | Mortality | Pneumococcal vaccination versus no vaccination | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for weak methods in some RCTs (Jadad scores). Consistency point deducted for statistical heterogeneity among RCTs |
| 13 (45,783) | Incidence of pneumonia | Pneumococcal vaccination versus no vaccination | 4 | –1 | –1 | 0 | 0 | Low | Quality point deducted for weak methods in some RCTs (Jadad scores). Consistency point deducted for statistical heterogeneity among RCTs |
| What are the effects of treatments for community-acquired pneumonia in outpatient settings? | |||||||||
| 2 (280) | Clinical cure | Clarithromycin versus erythromycin | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for weak methods (randomisation, allocation concealment, outcome definition). Directness point deducted for possibility of publication bias |
| 1 (318) | Clinical cure | Telithromycin versus clarithromycin | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for no intention-to-treat analysis (65% of those randomised reported). Directness point deducted for possibility of publication bias |
| 1 (363) | Clinical cure | Azithromycin versus levofloxacin | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for weak methods (randomisation, allocation concealment). Directness point deducted for possibility of publication bias |
| 1 (411) | Clinical cure | Azithromycin versus clarithromycin | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for clinical per-protocol analysis (82% of those randomised reported). Directness point deducted for possibility of publication bias |
| 1 (123) | Clinical cure | Telithromycin versus levofloxacin | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for sparse data. Directness point deducted for possibility of publication bias |
| What are the effects of treatments for community-acquired pneumonia in people admitted to hospital? | |||||||||
| 1 (119) | Clinical cure | Intravenous amoxicillin plus oral amoxicillin versus intravenous amoxicillin plus placebo | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for sparse data. Directness point deducted for restricted population (mild to moderate disease, had responded to intravenous amoxicillin) |
| 24 (5244) | Mortality | Atypical coverage regimens versus non-atypical coverage regimens | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for weak methods (allocation concealment, blinding). Directness point deducted as low mortality in studies (3.2%) as compared with normally seen in this group (10%), which may affect generalisability |
| 25 (5053) | Clinical cure | Atypical coverage regimens versus non-atypical coverage regimens | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for weak methods (allocation concealment, blinding). Directness point deducted as low mortality in studies (3.2%) as compared with normally seen in this group (10%), which may affect generalisability |
| 1 (378) | Clinical cure | Penicillin versus cephalosporins | 4 | 0 | 0 | –2 | 0 | Low | Directness points deducted for inclusion of co-intervention (erythromycin) and unclear follow-up |
| 1 (480) | Clinical cure | Quinolones versus co-amoxiclav (amoxicillin–clavulanic acid) | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for no intention-to-treat analysis. Directness point deducted for inclusion of co-intervention |
| 2 (834) | Clinical cure | Daptomycin versus ceftriaxone | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for no intention-to-treat analysis |
| 1 (459) | Hospital admission | Early mobilisation versus usual care | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for group randomisation. Directness point deducted for small number of comparators |
| 1 (145) | Clinical cure | Different early-mobilisation regimens versus each other | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for sparse data. Directness point deducted for proxy outcome (duration of fever) |
| 1 (<145) | Hospital admission | Different early-mobilisation regimens versus each other | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| 4 (591) | Mortality | Oral versus intravenous antibiotics | 4 | 0 | 0 | –1 | 0 | Moderate | Directness point deducted for restricted population (non life-threatening illness) |
| at least 1 (545) | Clinical cure | Oral versus intravenous antibiotics | 4 | 0 | 0 | –1 | 0 | Moderate | Directness point deducted for restricted population (non life-threatening illness) |
| at least 1 (unclear) | Hospital admission | Oral versus intravenous antibiotics | 4 | –1 | 0 | –2 | 0 | Very low | Quality point deducted for incomplete reporting of results. Directness points deducted for restricted population (non life-threatening illness) and no direct statistical comparison between groups |
| What are the effects of treatments in people with community-acquired pneumonia receiving intensive care? | |||||||||
| 3 (988) | Mortality | Prompt versus delayed antibiotic treatment | 2 | –1 | 0 | 0 | 0 | Very low | Note: cohort studies. Quality point deducted for incomplete reporting of results |
We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.
Glossary
- Bottle blowing
aims to help push air into the lungs to open up inflamed alveoli so that oxygen can pass into the bloodstream. Bottle blowing requires a person to sit up in bed and take deep breaths, which assist the lungs, and may encourage the person to cough and bring up sputum, thereby helping the lungs to recover.
- Low-quality evidence
Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
- Moderate-quality evidence
Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
- Vaccine efficiency (VE)
VE = 1 minus the relative risk (RR), that is, the relative risk reduction (RRR) expressed as a percentage. For example, if RR = 0.4, VE = 60%, that is (1 – 0.4 = 0.6) × 100.
- Very low-quality evidence
Any estimate of effect is very uncertain.
Antivirals for influenza, in review on influenza
Vaccines to prevent influenza in older people, in review on influenza
Disclaimer
The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.
References
- 1.Foy HM, Cooney MK, Allan I, et al. Rates of pneumonia during influenza epidemics in Seattle, 1964–1975. JAMA 1979;241:253–258. [PubMed] [Google Scholar]
- 2.Murphy TF, Henderson FW, Clyde WA, et al. Pneumonia: an 11 year study in a pediatric practice. Am J Epidemiol 1981;113:12–21. [DOI] [PubMed] [Google Scholar]
- 3.McConnochie KM, Hall CB, Barker WH. Lower respiratory tract illness in the first two years of life: epidemiologic patterns and costs in a suburban pediatric practice. Am J Public Health 1988;78:34–39. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Porath A, Schlaeffer F, Lieberman D. The epidemiology of community-acquired pneumonia among hospitalized adults. J Infect 1997;34:41–48. [DOI] [PubMed] [Google Scholar]
- 5.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;137:977–988. [DOI] [PubMed] [Google Scholar]
- 6.Houston MS, Silverstein MD, Suman VJ. Risk factors for 30-day mortality in elderly patients with lower respiratory tract infection. Arch Intern Med 1997;157:2190–2195. [PubMed] [Google Scholar]
- 7.Bartlett JG, Mundy LM. Community-acquired pneumonia. N Engl J Med 1995;333:1618–1624. [DOI] [PubMed] [Google Scholar]
- 8.Almirall J, Gonzalez CA, Balanco X, et al. Proportion of community-acquired pneumonia attributable to tobacco smoking. Chest 1999;116:375–379. [DOI] [PubMed] [Google Scholar]
- 9.Koivula I, Sten M, Makela PH. Risk factors for pneumonia in the elderly. Am J Med 1994;96:313–320. [DOI] [PubMed] [Google Scholar]
- 10.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;336:243–250. [DOI] [PubMed] [Google Scholar]
- 11.Fine MJ, Smith MA, Carson CA, et al. Prognosis and outcomes of patients with community-acquired pneumonia: a meta-analysis. JAMA 1996;275:134–141. Search date 1995. [PubMed] [Google Scholar]
- 12.Rivetti D, Jefferson T, Thomas R, et al. Vaccines for preventing influenza in the elderly. In: The Cochrane Library Issue 4, 2009. Chichester, UK: John Wiley & Sons Ltd. Search date 2006. [Google Scholar]
- 13.Moberley S, Holden J, Tatham DP, et al. Vaccines for preventing pneumococcal infection in adults. In: The Cochrane Library, Issue 4, 2009. Chichester, UK: John Wiley & Sons, Ltd. Search date 2007. [Google Scholar]
- 14.Bjerre LM, Verheij TJ, Kochen MM. Antibiotics for community acquired pneumonia in adult outpatients. In: The Cochrane Library, Issue 4, 2009. Chichester, UK: John Wiley & Sons, Ltd. Search date 2009. [Google Scholar]
- 15.Food and Drug Administration. Ketek (telithromycin) Tablets. January 2006. Available online at: http://www.accessdata.fda.gov/psn/printer-full.cfm?id=54 (last accessed 2 July 2010). [Google Scholar]
- 16.el Moussaoui R, De Borgie CAJM, 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;332:1355–1358. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Robenshtok E, Shefet D, Gafter-Gvili A, et al. Empiric antibiotic coverage of atypical pathogens for community acquired pneumonia in hospitalized adults. In: The Cochrane Library, Issue 4, 2009. Chichester, UK: John Wiley & Sons, Ltd. Search date 2007. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Roson B, Carratala J, Tubau F, et al. Usefulness of betalactam therapy for community-acquired pneumonia in the era of drug-resistant Streptococcus pneumoniae: a randomized study of amoxicillin–clavulanate and ceftriaxone. Microb Drug Resist 2001;7:85–96. [DOI] [PubMed] [Google Scholar]
- 19.Finch R, Schurmann D, Collins O, et al. Randomized controlled trial of sequential intravenous (i.v.) and oral moxifloxacin compared with sequential i.v. and oral co-amoxiclav with or without clarithromycin in patients with community-acquired pneumonia requiring initial parenteral treatment. Antimicrob Agents Chemother 2002;46:1746–1754. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Pertel PE, Bernardo P, Fogarty C, et al. Effects of prior effective therapy on the efficacy of daptomycin and ceftriaxone for the treatment of community-acquired pneumonia. Clin Infect Dis 2008;46:1142–1151. [DOI] [PubMed] [Google Scholar]
- 21.Iezzoni LI, Moskowitz MA. A clinical assessment of MedisGroups. JAMA 1988;260:3159–3163. [DOI] [PubMed] [Google Scholar]
- 22.Mundy L, Leet TL, Darst K, et al. Early mobilization of patients hospitalized with community-acquired pneumonia. Chest 2003;124:883–889. [DOI] [PubMed] [Google Scholar]
- 23.Bjorkqvist M, Wiberg B, Bodin L, et al. Bottle-blowing in hospital-treated patients with community-acquired pneumonia. Scand J Infect Dis 1997;29:77–82. [DOI] [PubMed] [Google Scholar]
- 24.Marras TK, Nopmaneejumruslers C, Chan CK. Efficacy of exclusively oral antibiotic therapy in patients hospitalized with nonsevere community-acquired pneumonia: a retrospective study and meta-analysis. Am J Med 2004;116:385–393. Search date 2003. [DOI] [PubMed] [Google Scholar]
- 25.Yu KT, Wyer PC, Yu Kenneth T, et al. Evidence-based emergency medicine/critically appraised topic. Evidence behind the 4-hour rule for initiation of antibiotic therapy in community-acquired pneumonia. Ann Emerg Med 2008;51:651–662. [DOI] [PubMed] [Google Scholar]
- 26.Berjohn CM, Fishman NO, Joffe MM, et al. Treatment and outcomes for patients with bacteremic pneumococcal pneumonia. Medicine (Baltimore) 2008;87:160–166. [DOI] [PubMed] [Google Scholar]