Multiple Blood Culture Sampling, Proper Antimicrobial Choice, and Adequate Dose in Definitive Therapy Supported by the Antimicrobial Stewardship Team Could Decrease 30-Day Sepsis Mortality Rates.

Objective: This study aimed to identify factors that should be focused on by the antimicrobial stewardship team for treating patients with sepsis, by investigating the mortality of patients with sepsis within 30 days and the mortality-related factors in our hospital over a 10-year period from the perspective of appropriate antimicrobial use. Methods: Factors associated with 30-day mortality were investigated using hierarchical multiple logistic regression in 1406 patients with pathogen-identified sepsis in Hirosaki University Hospital. These factors were clinical data, microbiological data, antimicrobials used in empiric and definitive therapies, presence/absence of ineffective use, underdosing as evaluated using Monte Carlo simulation, and practice of de-escalation. Results: The ineffective use of antimicrobials in empiric therapy and the underdosing and ineffective use in definitive therapy were significantly associated with 30-day mortality (odds ratio [OR] = 2.70, 3.72, and 3.65, respectively). Multiple blood culture sampling was inversely associated with these inappropriate antimicrobial uses. Every year, the 30-day mortality rate has been decreasing, in line with the increase in multiple blood culture sampling and de-escalation; the inappropriate use of antimicrobials has also decreased. Conclusion: Multiple blood culture sampling, proper choice of antimicrobial, and using an adequate dose in definitive therapy could decrease the 30-day mortality rate in patients with sepsis and these factors could be supported by the antimicrobial stewardship team.

Relationship Between Change Rate of Tacrolimus Clearance During Continuous Intravenous Infusion and Recipient Recovery at an Early Stage After Living Donor Liver Transplantation.

BACKGROUND AND OBJECTIVE: Tacrolimus clearance (CL) is significantly altered according to recovery of liver function at an early stage after living donor liver transplantation (LDLT). In this study, we aimed to examine the impact of the change rate from postoperative day (POD) 1 in CL (ΔCL) of tacrolimus during continuous intravenous infusion (CIVI) on recipient recovery. METHODS: A tacrolimus population pharmacokinetic model on POD1 after LDLT was developed using Phoenix NLME 1.3. The CLPOD1 was calculated using the final model. The CLPOD4-7 was calculated by dividing total daily tacrolimus dose by the area under the concentration-time curve from 0 to 24 h. RESULTS: Data were obtained from 57 LDLT recipients, along with 540 points (177 points on POD1, 363 points on POD4-7) of tacrolimus whole blood concentrations at CIVI. The median tacrolimus CL decreased from POD1 to POD4 (from 2.73 to 1.40 L/h) and was then stable until POD7. Stepwise Cox proportional hazards regression analyses showed that the graft volume (GV)/standard liver volume (SLV) ratio (GV/SLV) and the tacrolimus ΔCLPOD6 were independent factors predicting early discharge (within 64 days median value) of recipients after LDLT [hazard ratio (HR) = 1.041, P = 0.001 and HR = 1.023, P = 0.004]. CONCLUSIONS: The tacrolimus ΔCL during CIVI immediately after LDLT in each recipient was a useful indicator for evaluation of recovery at an early stage after LDLT.

Influence of Media on Seasonal Influenza Epidemic Curves.

BACK GROUND: Theoretical investigations predicting the epidemic curves of seasonal influenza have been demonstrated so far; however, there is little empirical research using ever accumulated epidemic curves. The effects of vaccine coverage and information distribution on influenza epidemics were evaluated. MATERIALS AND METHODS: Four indices for epidemics (i.e., onset-peak duration, onset-end duration, ratio of the onset-peak duration to onset-end duration and steepness of epidemic curves) were defined, and the correlations between these indices and anti-flu drug prescription dose, vaccine coverage, the volume of media and search trend on influenza through internet were analyzed. Epidemiological data on seasonal influenza epidemics from 2002/2003 to 2013/2014 excluding 2009/2010 season were collected from National Institute of Infectious Diseases of Japan. RESULTS: The onset-peak duration and its ratio to onset-end duration correlated inversely with the volume of anti-flu drug prescription. Onset-peak duration correlated positively with media information volume on influenza. The steepness of the epidemic curve, and anti-flu drug prescription dose inversely correlated with the volume of media information. Pre-epidemic search trend and media volume on influenza correlated with the vaccine coverage in the season. Vaccine coverage had no strong effect on epidemic curve. CONCLUSION: Education through media has an effect on the epidemic curve of seasonal influenza.

[Role of university hospitals in regional infection control network].

Activities and the understanding of infection control in healthcare facilities have improved in the past decade since a certification system for medical personnel, such as infection control nurse and infection control doctor, were introduced in Japan. These specialists are distributed among tertiary general hospitals, while many small and mid-scale hospitals have no infection control specialists. In 2012, the Japanese Ministry of Health, Labour and Welfare launched a new strategy for further improvement of infection control by supporting a regional network of infection control activities. Through the infection control network, small or mid-scaled hospitals can utilize infection control specialists in tertiary general hospitals, enter educational programs on infection control and consult in cases of nosocomial infection outbreaks. As part of the regional infection control network, we established an information network system, named ReNICS, to share the bacteriological test results of the hospitals in Akita prefecture. ReNICS offers epidemiological data on bacteria identified in the region. We can identify the spread of multi-drug resistant bacteria and can roughly estimate the quality of infection control activities in each facility. As a similar information network is being prepared in Hirosaki University Hospital Infection Control Center in Aomori, a prefecture neighboring Akita, we discussed the roles of university hospitals for a regional infection control network.

Blockade of inflammatory responses by a small-molecule inhibitor of the Rac activator DOCK2.

Tissue infiltration of activated lymphocytes is a hallmark of transplant rejection and organ-specific autoimmune diseases. Migration and activation of lymphocytes depend on DOCK2, an atypical Rac activator predominantly expressed in hematopoietic cells. Although DOCK2 does not contain Dbl homology domain typically found in guanine nucleotide exchange factors, DOCK2 mediates the GTP-GDP exchange reaction for Rac through its DHR-2 domain. Here, we have identified 4-[3'-(2″-chlorophenyl)-2'-propen-1'-ylidene]-1-phenyl-3,5-pyrazolidinedione (CPYPP) as a small-molecule inhibitor of DOCK2. CPYPP bound to DOCK2 DHR-2 domain in a reversible manner and inhibited its catalytic activity in vitro. When lymphocytes were treated with CPYPP, both chemokine receptor- and antigen receptor-mediated Rac activation were blocked, resulting in marked reduction of chemotactic response and T cell activation. These results provide a rational of and a chemical scaffold for development of the DOCK2-targeting immunosuppressant.