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 [ClinicalTrials.gov].

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.