Implementation of real-time PCR for the etiological diagnosis of LRTI increased the diagnostic yield considerably, but it did not reduce antibiotic use or costs.

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.

Until recently the concept of immunomodulation in patients with severe sepsis (formerly called sepsis syndrome or septic shock) appeared very promising. Research has focused on the possible therapeutic potential of interfering with cytokine pathways, either by preventing the induction of cytokines, such as TNF-alpha, by neutralization of lipopolysaccharide (LPS), or through the use of agents that attenuate cytokine action. Nowadays research on protein or protein constructs with antibacterial activities such as bacterial/permeability increasing protein (BPI), platelet activating factor receptor antagonists, nitric oxide and cyclo-oxygenase inhibitors, are still being followed. In large clinical trials monoclonal antibodies against core glycolipid (E5, HAIA) were shown to be at best of only marginal benefit, and in some trials results were indecisive. Also, the results with IL-lra, although initially heralded with high expectation, were at the end disappointing and the trials discontinued. Two large trials with monoclonal antibodies against TNF showed some effect in subcategories of patients: a third trial is on its way. Other phase I; II studies include those of soluble TNF receptors and BPI. The area of immunomodulation has now become an area of more realism and the results of early trials has forced investigators to go back the drawing board and to re-investigate the whole concept of immunotherapy and immunoprophylaxis.