[Interaction of Phenytoin with Enteral Formulas, Proteins, and Dietary Fiber in Vitro and in Vivo].

Simultaneous administration of enteral formula and phenytoin in the clinical setting is known to reduce the plasma concentration of phenytoin. In this study, we examined the binding of phenytoin with enteral formulas and its components by quantifying the free phenytoin concentration. Furthermore, we investigated the effect of enteral formulas on gastrointestinal absorption of phenytoin in rats. The free phenytoin rate was reduced in vitro when phenytoin and enteral formula or pectin, a dietary fiber in enteral formulas, were co-administered. In vivo, when phenytoin and the enteral formula Mei Balance R® were co-administered, the time to maximum plasma concentration (Tmax) after oral administration was significantly increased. Moreover, the area under the phenytoin concentration-time curve from time zero to 6 h (AUC0-6 h) was significantly increased by co-administration of phenytoin with the enteral formula PG Soft EJ®. These results showed the gastrointestinal absorption of phenytoin differs according to the type of enteral formula. In addition, we found the first time that plasma phenytoin levels increase when combined with enteral formula. Among the components of enteral formulas, in particular, milk protein delayed the absorption of phenytoin. Moreover, milk protein, casein and carrageenan tended to increase AUC0-6 h. These results suggest the change in phenytoin concentration is due not only to the binding of enteral formula but also to the disintegration of components such as protein. Therefore, when co-administrated of phenytoin and enteral formula, phenytoin must be monitored frequently according to the enteral formula interaction.

Does Quinolone- or Macrolide-Resistant Streptococcus agalactiae Bacteremia Affect Patient Outcome? A Multicenter Cohort Study.

The prevalence of quinolone- and macrolide-resistant Group B Streptococcus (GBS) is increasing worldwide, but the relationship between the resistance of GBS to these antibiotics and patient outcome remains unclear. Therefore, we evaluated whether blood stream infection caused by quinolone- or macrolide-resistant GBS is associated with high mortality. Our findings in 77 patients with GBS bacteremia demonstrate that quinolone and macrolide resistance may not be risk factors for 30-day mortality.

Advanced Age is not a Risk Factor for Mortality in Patients with Bacteremia Caused by Extended-Spectrum ß-Lactamase-Producing Organisms: a Multicenter Cohort Study.

A 5-year multicenter retrospective cohort study was conducted across six hospitals in Niigata, Japan. Patients (n = 179) with bacteremia due to extended-spectrum ß-lactamase (ESBL)producing organisms were included in the study. The rates of appropriate carbapenem prescription were 61% (n = 41) in patients aged 65-84 years and 89% (n = 31) in those aged ≥ 85 years. Patients aged ≥ 85 years were significantly more likely to receive carbapenem than their younger counterparts. After propensity score matching, 65 patients were assigned to two groups based on age (65-84 years or ≥ 85 years). Multivariate regression analysis showed that other sites of infection had a positive association with 30-day mortality (odds ratio [OR], 27.50; 95% confidence interval [CI], 2.90-260.00) and biliary tract infection tended to have a positive association with 30-day mortality (OR, 8.90; 95% CI, 0.88- 89.90) compared with urinary tract infection. However, an age ≥ 85 years was not associated with 30-day mortality. Elderly patients aged ≥ 85 years were more likely to be treated with carbapenem; however, old age was not associated with 30-day mortality when bacteremia was caused by ESBLproducing organisms. These results may help clinicians justify withholding carbapenem in patients aged ≥ 85 years.

Impact of alcohol-based hand sanitizers, antibiotic consumption, and other measures on detection rates of antibiotic-resistant bacteria in rural Japanese hospitals.

There are limited data available on the relationship between multidrug-resistant bacteria and infection control activities in small to medium-sized hospitals. Therefore, we collected data on the use of alcohol-based hand sanitizers (ABHSs), personal protective equipment, antibiotics, and the levels of detectable bacteria between April 2014 and March 2015 in 11 Japanese hospitals. Average total antibiotic consumption was 100 defined daily doses per 1000 patient-days (PD), and average use of ABHSs, masks, plastic aprons, and gloves was 5 L per 1000 PD, and 1, 2, and 26 pieces per 1 PD, respectively. Average numbers of isolated (isolation rate) Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase (ESBL)-producing bacteria, and multidrug-resistant Pseudomonas aeruginosa (MDRP) were 107 (8% of total bacterial tests performed), 51 (4%), and 4 (0.3%), respectively. Multivariate analyses of ABHS and tazobactam/piperacillin consumption showed a significant negative association with the MRSA isolation rate (adjusted R2 = 0.87). These findings suggest that hand hygiene is more important than antibiotic consumption in small to medium-sized hospitals.

Does Quick Sepsis-Related Organ Failure Assessment Suggest the Use of Initial Empirical Carbapenem Therapy in Bacteremia Caused by Extended-Spectrum ß-Lactamase-Producing Bacteria? :A Multicenter Case-Control Study.

We hypothesized that quick Sequential Organ Failure Assessment (qSOFA) would be associated with 30-day mortality in bacteremia caused by extended-spectrum ß-lactamase (ESBL)-producing bacteria and might be a selection criterion for the use of carbapenem as initial empirical therapy. A multicenter retrospective study was conducted in six hospitals. All patients who had bacteremia due to ESBL-producing bacteria were included in the study. Multivariable logistic regression analysis was performed to analyze 30-day mortality as the main outcome. A total of 203 adult patients were identified with bacteremia caused by ESBL-producing Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis. In multivariate logistic regression analysis, bacteremia caused by ESBL-producing K. pneumoniae or P. mirabilis (odds ratio [OR] 5.07, 95% confidence interval [CI] 1.64-15.56), underlying liver disease (OR 3.38, 95% CI 1.09-10.00), and underlying solid cancer (OR 3.45, 95% CI 1.27-9.69) were associated with 30-day mortality. In a subgroup analysis, empirical non-carbapenem therapy was associated with 30-day mortality in bacteremia caused by ESBL-producing K. pneumoniae or P. mirabilis. Our results suggest that the qSOFA score is not a selection criterion for the use of carbapenem in initial empirical therapy.