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Objectives: To compare the effectiveness of an early switch to oral antibiotics with the standard 7 day course of intravenous antibiotics in severe community acquired pneumonia., Design: Multicentre randomised controlled trial., Setting: Five teaching hospitals and 2 university medical centres in the Netherlands., Participants: 302 patients in non-intensive care wards with severe community acquired pneumonia. 265 patients fulfilled the study requirements., Intervention: Three days of treatment with intravenous antibiotics followed, when clinically stable, by oral antibiotics or by 7 days of intravenous antibiotics., Main Outcome Measures: Clinical cure and length of hospital stay., Results: 302 patients were randomised (mean age 69.5 (standard deviation 14.0), mean pneumonia severity score 112.7 (26.0)). 37 patients were excluded from analysis because of early dropout before day 3, leaving 265 patients for intention to treat analysis. Mortality at day 28 was 4% in the intervention group and 6% in the control group (mean difference 2%, 95% confidence interval -3% to 8%). Clinical cure was 83% in the intervention group and 85% in the control group (2%, -7% to 10%). Duration of intravenous treatment and length of hospital stay were reduced in the intervention group, with mean differences of 3.4 days (3.6 (1.5) v 7.0 (2.0) days; 2.8 to 3.9) and 1.9 days (9.6 (5.0) v 11.5 (4.9) days; 0.6 to 3.2), respectively., Conclusions: Early switch from intravenous to oral antibiotics in patients with severe community acquired pneumonia is safe and decreases length of hospital stay by 2 days., Trial Registration: Clinical Trials NCT00273676 [ClinicalTrials.gov].

This study evaluated the possible changes in antibiotic use that might follow the implementation of British or North American guidelines for the treatment of community-acquired pneumonia (CAP) in The Netherlands. Patients admitted for mild, moderate and severe CAP were evaluated prospectively. Volume of antibiotic use, based upon guidelines of the British Thoracic Society (BTS), the Infectious Diseases Society of America (IDSA) or the American Thoracic Society (ATS), was estimated and compared to current practice. For 248 patients, current antibiotic use was 3087 defined daily doses. Antibiotic use would increase by 38% if based on ATS guidelines, by 23% if based on IDSA guidelines, and by 21% if based on BTS guidelines. The most significant increase in antibiotic use would occur for cases of moderate CAP, with incremental antibiotic costs of 1 750 000-3 500 000 Euros in The Netherlands.

Background: For years, monotherapy with a beta-lactam antibiotic (penicillin, amoxicillin or second-generation cephalosporin) was recommended as empirical therapy for patients with community-acquired pneumonia (CAP). A combination of a beta-lactam and a macrolide antibiotic was only recommended for patients with severe CAP needing intensive care treatment or when atypical pathogens, i.e. Legionella pneumophila, Mycoplasma pneumoniae and Chlamydia pneumoniae, were strongly suspected. However, new guidelines recommend a combination of a beta-lactam antibiotic plus a macrolide or monotherapy with a fluoroquinolone for all patients hospitalized with CAP. We evaluated whether treatment with a beta-lactam plus macrolide or quinolone monotherapy is truly superior to beta-lactam treatment alone., Methods: We systematically reviewed available studies, retrieved from MEDLINE and by hand-searching reference lists from recent reviews and guidelines on the effectiveness of recommended empirical antimicrobial treatment of patients hospitalized because of CAP., Results: Eight relevant studies were selected. In six studies significant reductions in mortality were found, in one study a reduction in hospital length of stay was found and in one study no beneficial effects could be demonstrated for treatment regimens with fluoroquinolone monotherapy or combinations of beta-lactams and macrolides. The beneficial value of macrolides or fluoroquinolones might be the result of a large and mainly unrecognized role of atypical pathogens in the aetiology of CAP, anti-inflammatory effects of macrolides or resistance to beta-lactams of the most important pathogens. However, the studies supporting the recommended treatment regimen were designed as non-experimental cohort studies. As a consequence, the results may have been influenced by confounding by indication. In addition, the outcomes showed several inconsistencies., Conclusions: A randomized controlled trial is warranted to circumvent the methodological flaws in the designs of the currently available studies. Since the addition of macrolides or treatment with fluoroquinolones may lead to enhanced antibiotic resistance, increased side effects and healthcare-related costs, such a fundamental change in the treatment of CAP should be based on valid data.

A rapid diagnosis of pneumococcal pneumonia may allow the earlier use of narrow-spectrum antimicrobial therapy. It is unknown, however, whether rapid diagnostic testing of patients hospitalized with community-acquired pneumonia (CAP) admitted to hospital lowers costs. Therefore, an algorithm to calculate the costs associated with the diagnosis and treatment of CAP was formulated. Subsequently, the algorithm was applied to clinical data for 122 consecutively admitted patients with CAP whose sputum samples were Gram stained and whose urine was tested for Streptococcus pneumoniae antigen. The costs of initial antimicrobial therapy, personnel, and materials were measured. Compared to the most expensive empirical regimen, rapid diagnostic testing would result in cost savings per patient (PP) of 3.51 Euros for Gram staining and 8.11 Euros for urinary pneumococcal antigen testing (1 Euro is equal to 1.13 US dollars, from 2000 to 2002). Compared to the cheapest regimen, Gram staining would increase the cost by 2.25 Euros PP, and urinary antigen testing would increase the cost by 24.26 Euros PP. In our setting, the use of rapid diagnostic testing would not lower costs. Cost savings depend, however, on the differences in the prices of the different antibiotics chosen and the proportion of evaluable and positive samples.

Purpose of Review: Formerly, patients with community-acquired pneumonia admitted to an intensive care unit were considered as having the severe form of the disease. Recently, guidelines have distinguished severe and non-severe community-acquired pneumonia based on clinical definitions. In this review, we describe the different definitions of severe community-acquired pneumonia, and whether a differentiation based on these definitions reflects variation in etiology, risk factors, diagnostic approaches and treatment., Recent Findings: New definitions do not seem to accurately identify patients with high risks of mortality; patients not admitted to an intensive care unit could also be diagnosed as having severe community-acquired pneumonia. Host-factors, such as genetic factors and underlying diseases, can influence severity of presentation of community-acquired pneumonia. Distribution of pathogens in severe and non-severe disease forms is comparable. Initial antibiotic therapy in patients with severe disease should provide coverage of Streptococcus pneumoniae and Legionella pneumophila, as delay is associated with worse outcomes. However, recent studies also suggested an additional benefit of atypical coverage in non-severe disease. As a result, initial therapy with a beta-lactam plus a macrolide or an anti-pneumococcal fluoroquinolone is recommended for all patients with community-acquired pneumonia. Furthermore, the value of vaccination against pneumococci to prevent episodes of severe disease is yet unknown., Summary: As current guidelines do not adequately identify patients with high risk of mortality and intensive care unit admittance, clinical judgment remains important. Based on distribution of pathogens, investigational procedures and therapy recommended in recent guidelines, differentiation between severe and non-severe community-acquired pneumonia does not seem useful. Whether atypical coverage indeed has additional value in non-severe or pneumococcal CAP, however, remains to be determined. In addition, the preventive benefit of influenza and pneumococcal vaccination for development of SCAP awaits further evidence.

Community-acquired pneumonia is an important cause of hospital admission and mortality in the adult population. The recommended antibiotic for pneumonia caused by Streptococcus pneumoniae is a beta-lactam antibiotic and, for so-called atypical pathogens, a macrolide. In the US and elsewhere, the current recommendation is to start with a beta-lactam antibiotic and a macrolide or with one of the new quinolones. The available literature consists largely of retrospective studies. Because of possible selection bias in these analyses and inconsistencies in reported outcomes, it is not possible to draw any well-founded conclusions from these studies. Reasons for a possible additional benefit of adding a macrolide to the therapy could include: a higher prevalence of undiagnosed atypical pathogens, the anti-inflammatory effects of macrolides, and resistance of the main pathogens against beta-lactam antibiotics. None of these appear to play a significant role. There is no need to revise Dutch guidelines.