Effectiveness of early switch from intravenous to oral antibiotics in severe community acquired pneumonia: multicentre randomised trial

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

Impact of rapid detection of viral and atypical bacterial pathogens by real-time polymerase chain reaction for patients with lower respiratory tract infection

BACKGROUND: Rapid diagnostic tests with a high sensitivity for lower respiratory tract infection (LRTI) could lead to improved patient care and reduce unnecessary antibiotic use and associated costs. Diagnostic yields, feasibility, and costs of real-time polymerase chain reaction (PCR) of nasopharyngeal and oropharyngeal swab specimens in the routine diagnostic work-up for LRTI were determined. METHODS: In a randomized controlled trial, nasopharyngeal and oropharyngeal swab specimens from patients admitted for antibiotic treatment of LRTI were evaluated by means of real-time PCR for respiratory viruses and atypical pathogens, as well as by conventional diagnostic procedures. Real-time PCR results for patients in the intervention group were reported to the treating physician; results for patients in the control group were not made available. RESULTS: A total of 107 patients (mean age [+/- standard deviation], 63.6+/-16.3 years) were included, of whom 55 were allocated to the intervention group. The pathogens detected most frequently were influenza virus (14 patients), Streptococcus pneumoniae (8), coronavirus (6), Staphylococcus aureus (5), and rhinoviruses (5). Real-time PCR increased the diagnostic yield from 23 cases (21% of patients) to 47 cases (43% of patients), compared with conventional diagnostic tests. The detection of viral pathogens by PCR was associated with the winter season, less infiltrates on chest radiographs, lower C-reactive protein levels, and shorter duration of symptoms. Use of real-time PCR results resulted in partial or total cessation of antibiotic treatment for 6 patients (11%; 95% confidence interval, 2-19), but overall antibiotic use was comparable in the intervention group and the control group (median duration of treatment, 10.0 vs. 9.0 days; P=not significant). Use of real-time PCR increased treatment and diagnostic costs with 318.17 per patient. CONCLUSIONS: 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

Effectiveness of discontinuing antibiotic treatment after three days versus eight days in mild to moderate-severe community acquired pneumonia: randomised, double blind study

Objective To compare the effectiveness of discontinuing treatment with amoxicillin after three days or eight days in adults admitted to hospital with mild to moderate-severe community acquired pneumonia who substantially improved after an initial three days' treatment. Design Randomised, double blind, placebo controlled non-inferiority trial. Setting Nine secondary and tertiary care hospitals in the Netherlands. Participants Adults with mild to moderate-severe community acquired pneumonia (pneumonia severity index score ≤ 110). Interventions Patients who had substantially improved after three days' treatment with intravenous amoxicillin were randomly assigned to oral amoxicillin (n = 63) or placebo (n = 56) three times daily for five days. Main outcome measures The primary outcome measure was the clinical success rate at day 10. Secondary outcome measures were the clinical success rate at day 28, symptom resolution, radiological success rates at days 10 and 28, and adverse events. Results Baseline characteristics were comparable, with the exception of symptom severity, which was worse in the three day treatment group. In the three day and eight day treatment groups the clinical success rate at day 10 was 93% for both (difference 0.1%, 95% confidence interval - 9% to 10%) and at day 28 was 90% compared with 88% (difference 2.0%, - 9% to 15%). Both groups had similar resolution of symptoms. Radiological success rates were 86% compared with 83% at day 10 (difference 3%, - 10% to 16%) and 86% compared with 79% at day 28 (difference 6%, - 7% to 20%). Six patients (11%) in the placebo group and 13 patients (21%) in the active treatment group reported adverse events (P = 0.1). Conclusions Discontinuing amoxicillin treatment after three days is not inferior to discontinuing it after eight days in adults admitted to hospital with mild to moderate-severe community acquired pneumonia who substantially improved after an initial three days' treatment