Background Vancomycin is commonly used to treat Enterococcus faecium ( E. faecium ) bacteremia. However, there are very few studies on the association between the trough concentration, area under the curve from 0 to 24 h /minimum inhibitory concentration (AUC 24 /MIC) ratio, and the therapeutic effect of vancomycin on E. faecium bacteremia. This study aimed to investigate the associations between vancomycin pharmacokinetic/pharmacodynamic parameters, patient characteristics, and mortality in patients with E. faecium bacteremia . Methods This retrospective study included patients with E. faecium bacteremia who received vancomycin between April 2012 and February 2018 at a single acute care hospital in Japan. Patients who received renal replacement therapy (hemodialysis or continuous hemodiafiltration), had an unmeasured serum vancomycin concentration, with unmeasured laboratory values, or received other antibiotics for treating E. faecium bacteremia were excluded from the study. The bivariate associations between 30-day all-cause mortality and patient characteristics were assessed. Results Among 87 patients diagnosed with E. faecium bacteremia, 45 were included in the final analysis. Of these, 12 (26.7%) died within 30 days of the diagnosis. The vancomycin trough concentration was higher in the 30-day all-cause mortality patients than in the survival patients (20.5 vs. 14.6 μg/mL; P = 0.022). There was no significant difference in the proportion of patients with a vancomycin AUC 24 /MIC ≤389 between the groups. The 30-day all-cause mortality patients showed a higher Charlson Comorbidity Index (CCI) and Sequential Organ Failure Assessment score at the first measurement of the vancomycin trough concentration than the survival patients. The same finding was observed among patients with a high CCI score (≥5 points). Conclusions Whereas the vancomycin trough concentration and AUC 24 /MIC ratio were not associated with mortality in patients with E. faecium bacteremia, disease severity was associated with mortality in these patients.

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This study was designed to clarify the influence of long-term enteral nutrition (EN) on the pharmacokinetics of digoxin. Rats were fed EN diets (semi-digested, digested, and elemental) for 4 weeks, then digoxin (0.05 mg/kg) was administered orally. The AUC(0-∞) and k(a) of digoxin were significantly reduced in the semi-digested diet group versus the control, while the AUC(0-∞) was significantly increased in the digested and elemental diet groups. The mRNA level of Slco1a4 was significantly reduced at the upper small intestine in all EN groups. Further, the expression levels of P-glycoprotein (P-gp) protein and Abcb1a mRNA were increased at the same site in all EN groups, and the increases were significant in the elemental diet group. Cyp3a2 protein and mRNA expressions were significantly reduced in the liver in the digested and elemental diet groups. Abcb1a mRNA was also significantly reduced in the kidney in these groups. These results indicate that the absorption kinetics at the small intestine is influenced by semi-digested diet, and the elimination kinetics in the liver and kidney are influenced by digested and elemental diet. Semi-digested diet also altered digoxin pharmacokinetics in humans. Thus, the effect of long-term EN on digoxin pharmacokinetics depended on the dietary components.

The aim of this report was to evaluate whether days of therapy (DOT), antimicrobial use density (AUD), and the rate of resistance of Pseudomonas aeruginosa to meropenem (the rate of resistance) change after stepwise execution of antimicrobial stewardship for carbapenems. Since April 2012, antimicrobial stewardship for carbapenems has been performed by an infection control team comprising physicians and pharmacists specializing in infectious diseases. The stewardship included surveillance of all cases of carbapenem use since April 2012, intervention and feedback for cases of inappropriate carbapenem use since April 2013, and unification of carbapenems since November 2014. Surveillance implementation alone led to an increase in the rate of resistance, DOT, and AUD. However, the rate of resistance, DOT, and AUD decreased when surveillance implementation was combined with intervention and feedback. On the other hand, DOT and AUD decreased and the rate of resistance was unchanged upon combining these approaches and unification of carbapenems. These results suggest that focus on implementation of surveillance would not be sufficient to ensure the appropriate use of carbapenems and that interventions and feedback regarding inappropriate carbapenem use would be important for promoting appropriate carbapenems use. Furthermore, these results suggest that unification of carbapenems does not negatively affect the rate of resistance.

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