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.
Selective digestive decontamination (SDD) is the most extensively studied method for the prevention of infection in patients in intensive care units (ICUs). Despite 27 prospective randomized studies and six meta-analyses, routine use of SDD is still controversial. In this review, we summarize the available scientific information on effectiveness of SDD in ICU patients. The effects of SDD have been studied in different combinations of the concept, using different antibiotics. Comparison of the individual studies, therefore, is difficult. In most studies, SDD resulted in significant reductions in the number of diagnoses of ventilator-associated pneumonia. However, incidences of ventilator-associated pneumonia in control groups ranged from 5% to 85%. Moreover, these reductions in incidences of ventilator-associated pneumonia in individual studies were not associated with improved patient survival, reductions of duration of ventilation or ICU stay, or reductions in antibiotic use. The numbers of patients studied are too small to determine effects on patient survival. Although two meta-analyses suggested a 20% mortality reduction when using the full concept of SDD (topical and systemic prophylaxis) these results should be interpreted with caution. Formal cost-benefit analyses of SDD have not been performed. SDD is associated with the selection of microorganisms that are intrinsically resistant to the antibiotics used. However, the studies are too small and too short to investigate whether SDD will lead to development of antibiotic resistance. As long as the benefits of SDD (better patient survival, reduction in antibiotic use or improved cost-effectiveness) have not been firmly established, the routine use of SDD for mechanically ventilated patients is not advised.
A kinetic turbidimetric Limulus amebocyte lysate (LAL) assay was used to study the effects of gentamicin, amoxycillin and ciprofloxacin (16 x MIC) upon release of lipopolysaccharide at different stages of a growing Escherichia coli 055:B5:H culture in vitro. In this model a linear correlation was present between the logarithms of colony counts and free LAL activities. Untreated E. coli grew from log values of 4.9 +/- 0.15 (low inoculum) and 6.8 +/- 0.08 cfu/ml (high inoculum) at t = 0 to 8.9 +/- 0.05 and 9.1 +/- 0.13 cfu/ml at t = 6 h, respectively. The log values of basal free LAL activities at low and high inoculum sizes were 1.9 +/- 0.07 and 3.3 +/- 0.14 endotoxin units/ml, increasing 2100- and 69-fold, respectively during a 6-h growth. Amoxycillin-induced lysis was not significantly associated with an increase in free LAL activity. Efficacy of bacterial killing by gentamicin was high, but free LAL activity increased only 3.2- and 7.7-fold at the low and high inoculum experiments, respectively. Ciprofloxacin induced cell filamentation during the experiments. At low and high inoculum conditions exposure to ciprofloxacin induced a 43- and 68-fold increase in free LAL activities, respectively. Our data indicate that (a) LPS is released as long as E. coli remain structurally intact; (b) LPS release is enhanced when bacterial biomass increases; and (c) are taken as evidence against the concept of lysis-correlated LPS release.
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