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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.

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.

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.

Two hundred and forty-six patients infected with human immunodeficiency virus (HIV) who also had disseminated Mycobacterium avium complex received either azithromycin 250 mg every day, azithromycin 600 mg every day, or clarithromycin 500 mg twice a day, each combined with ethambutol, for 24 weeks. Samples drawn from patients were cultured and clinically assessed every 3 weeks up to week 12, then monthly thereafter through week 24 of double-blind therapy and every 3 months while on open-label therapy through the conclusion of the trial. The azithromycin 250 mg arm of the study was dropped after an interim analysis showed a lower rate of clearance of bacteremia. At 24 weeks of therapy, the likelihood of patients' developing 2 consecutive negative cultures (46% vs. 56%, P=.24) or 1 negative culture (59% vs. 61%, P=.80) was similar for azithromycin 600 mg (n=68) and clarithromycin (n=57), respectively. The likelihood of relapse was 39% versus 27% (P=.21) on azithromycin compared with clarithromycin, respectively. Of the 6 patients who experienced relapse, none of those randomized to receive azithromycin developed isolates resistant to macrolides, compared with 2 of 3 patients randomized to receive clarithromycin [corrected]. Mortality was similar in patients comprising each arm of the study (69% vs. 63%; hazard, 95.1% confidence interval, 1.1 [0.7, 1.7]). Azithromycin 600 mg, when given in combination with ethambutol, is an effective agent for the treatment of disseminated M. avium disease in patients infected with HIV.