Diane M. Citron

Suppression of gastric acid secretion in patients with gastroesophageal reflux disease results in gastric bacterial overgrowth and deconjugation of bile acids

The aim of this study was to test the hypothesis that gastric bacterial overgrowth is a side effect of acid suppression therapy in patients with gastroesophageal reflux disease (GERD) and that the bacteria-contaminated gastric milieu is responsible for an increased amount of deconjugated bile acids. Thirty patients with GERD who were treated with 40 mg of omeprazole for at least 3 months and 10 patients with GERD who were off medication for at least 2 weeks were studied. At the time of upper endoscopy, 10 ml of gastric fluid was aspirated and analyzed for bacterial growth and bile acids. Bacterial over-growth was defined by the presence of more than 1000 bacteria/ml. Bile acids were quantified via high-performance liquid chromatography. Eleven of the 30 patients taking omeprazole had bacterial over-growth compared to one of the 10 control patients. The median pH in the bacteria-positive patients was 5.3 compared to 2.6 in those who were free of bacteria and 3.5 in the control patients who were off medication. Bacterial overgrowth only occurred when the pH was >3.8. The ratio of conjugated to unconjugated bile acids changed from 4:1 in the patients without bacterial overgrowth to 1:3 in those with bacterial growth greater than 1000/ml. Proton pump inhibitor therapy in patients with GERD results in a high prevalence of gastric bacterial overgrowth. The presence of bacterial overgrowth markedly increases the concentration of unconjugated bile acids. These findings may have implications in the pathophysiology of gastroesophageal mucosal injury.

Efficacy of vancomycin and daptomycin against Staphylococcus aureus isolates collected over 29 years

We investigated vancomycin and daptomycin efficacy for Staphylococcus aureus isolates at our institution by testing 221 methicillin-sensitive and 299 methicillin-resistant isolates recovered from serious infections between 1979 and 2007 using a microdilution method. The MIC(90)s for vancomycin remained constant at 2 microg/mL for methicillin-resistant S. aureus (MRSA) and methicillin-sensitive S. aureus (MSSA). For MSSA, the geometric mean vancomycin MICs remained at 1.1 microg/mL but varied from 1.1 to 1.7 for MRSA. Tolerance to vancomycin was seen in 6.5% of MRSA and 10.5% of MSSA. Daptomycin MIC(90)s remained at < or =1 microg/mL, and the daptomycin concentration at which 90% of the strains were killed (MBC(90)) remained at 2 microg/ml. Over 29 years, no trend was detected in vancomycin or daptomycin susceptibilities. Daptomycin had excellent inhibitory and bactericidal activities against all strains throughout the years. Although vancomycins inhibitory activity was consistent over time, vancomycin-tolerant strains whose presence was not predicted by their MIC were found.