Risk factors for cefmetazole-non-susceptible bacteremia in acute cholangitis.

INTRODUCTION: Cefmetazole (CMZ), an antibiotic with limited international distribution, is recommended by the Tokyo Guidelines 2018 (TG18) for non-severe cases of acute cholangitis (AC). However, the risk factors for CMZ-non-susceptible (CMZ-NS) bacteremia in AC remain unclear. Here, we aimed to investigate the risk factors for CMZ-NS bacteremia and evaluate mortality in patients with AC. METHODS: This single-center, retrospective, observational study included all patients diagnosed with definite bacteremic AC, based on TG18, from April 2019 to March 2023. Risk factors for CMZ-NS bacteremia were analyzed by univariate, and age- and sex-adjusted, logistic regression analyses. Mortality was compared by cause of obstruction, CMZ-susceptible/CMZ-NS bacteremia, and initial treatment. RESULTS: In total, 165 patients were enrolled. CMZ-NS bacteremia was diagnosed in 46 (27.9 %) patients. Histories of diabetes mellitus, hepato-biliary-pancreatic cancer, malignant biliary obstruction, and endoscopic sphincterotomy were identified as significant factors associated with the risk of CMZ-NS bacteremia. Thirteen patients died within 30 days of hospital admission. The mortality of patients with AC and malignant biliary obstruction was statistically higher than that of patients with bile duct stones. No patients with AC and bile duct stones died in the group with CMZ-NS bacteremia and inappropriate initial antibiotics. CONCLUSIONS: In AC, a history of diabetes mellitus, hepato-biliary-pancreatic cancer, malignant biliary obstruction, and endoscopic sphincterotomy are associated with an increased risk of CMZ-NS bacteremia. Therefore, the choice of empiric therapy for AC should be based on the etiology and patient background, rather than on the severity.

Current Status of Outpatient Oral Antimicrobial Prescription and the Influence of Antimicrobial Stewardship for Inpatients: A Repeated Cross-Sectional Study at a Japanese Community Hospital.

This study aimed to clarify the details of outpatient oral antimicrobial use (AMU) at a Japanese community hospital and investigate the influence of the current inpatient-based antimicrobial stewardship (AS) on outpatients. A repeated cross-sectional study was conducted in Komaki City Hospital. Data on patients, physicians, and oral antibiotics were collected in October 2013, 2016, and 2019, and appropriateness of treatment and surgical antimicrobial prophylaxis (SAP) was evaluated. The percentage of patients receiving oral antibiotics increased significantly from 4.7% in 2013 (345/7338) to 5.9% in 2019 (365/6146), and the overall number of antimicrobial prescriptions per 1000 outpatients increased from 51.8 in 2013 to 68.0 in 2019. Prescriptions for third-generation cephalosporins per 1000 outpatients decreased (from 21.4 to 6.3), whereas the number of prescriptions for penicillin (from 3.8 to 15.3), fluoroquinolones (from 7.0 to 13.2), and co-trimoxazole (from 5.0 to 15.8) increased from 2013 to 2019. The appropriate AMU for overall infections significantly increased (from 68.4% in 2013 to 83.7% in 2019). The choice and duration of AMU significantly improved for SAP. However, even in 2019, only 29.3% of patients received antibiotics before surgery. The improved selection of antibiotics on outpatient prescription may be due to the influence of AS-which is focused on inpatients-while prescriptions for fluoroquinolones and prophylactics also increased. The challenges of antimicrobial administration after surgeries were also highlighted.

[Preparation of dealcholized onetaxotere®, docetaxel injection formulation and its pharmacokinetics in rats].

Onetaxotere®(OTAX)injection, which is a docetaxel(DOC)injection formulation, cannot be administered to those patients with alcohol intolerance or hypersensitivity, because it contains ethanol as a dissolving agent. To broaden treatment options for those patients, we tried to eliminate ethanol from OTAX injection. Under sterile conditions, dealcoholization was carried out using nitrogen gas in a hot water bath at 50°C. By this method, the ethanol included in OTAX injection was almost completely removed and DOC in the formulation was stable for 28 days. When the dealcoholized or untreated OTAX injection was intravenously injected in rats, no significant differences in the pharmacokinetic parameters of DOC were observed between those with dealcoholized and untreated OTAX injections. It is expected that dealcoholized OTAX may be useful in patients with alcohol-related difficulties.

[Effect of tacrolimus on the pharmacokinetics and glucuronidation of SN-38, an active metabolite of irinotecan].

The present study has investigated the effect of tacrolimus on the pharmacokinetics of an active metabolite of irinotecan (CPT-11), 7-ethyl-10-hydroxy-camptothecin (SN-38) and SN-38 glucuronide (SN-38G) in rats. The effect of tacrolimus on SN-38 glucuronidation was also investigated in human and rat liver microsomes. When tacrolimus (0.5 mg/kg) was intravenously injected in rats 15 min before intravenous injection of CPT-11 (5 mg/kg), tacrolimus decreased the plasma concentration of SN-38G. Tacrolimus significantly decreased the area under plasma concentration-time curve (AUC) of SN-38G without change in the mean residence time. On the contrary, significant changes in the pharmacokinetic parameters of SN-38 were not observed. SN-38 glucuronidation in human and rat liver microsomes was inhibited dose-dependently by the presence of tacrolimus and the 50% inhibition concentration (IC50) values of tacrolimus in rat and human liver microsomes were 10.33 µM and 3.58 µM, respectively. When the inhibition type was determined by Lineweaver-Burk and Dixon plots, the inhibition was noncompetitive and the calculated inhibition constant (Ki) values for rat and human liver microsomes were 12.57 µM and 3.88 µM, respectively. These findings suggest that tacrolimus inhibits UGT1A1-mediated SN-38 glucuronidation. Considering the IC50 and Ki values for tacrolimus, it is likely that tacrolimus does not alter the pharmacokinetics of SN-38 and SN-38G at the clinically used dosages, suggesting the possibility that tacrolimus can use safely for cancer patients with irinotecan chemotherapy.

[A very elderly case of advanced gastric cancer with disseminated carcinomatosis of bone marrow and multiple bone metastasis, diagnosed by extremely elevated serum alkaline phosphatase levels, and treated with low-dose S-1 to avoid disseminated intravascular coagulation].

We report an 87-year-old woman who was admitted to our hospital due to anemia and extremely elevated serum alkaline phosphatase (ALP) levels. We diagnosed advanced gastric cancer with disseminated carcinomatosis of the bone marrow and multiple bone metastasis. She was immediately treated with low-dose S-1 (50mg/body, p.o., days 1-14) and zoledronic acid hydrate (4mg/body, i.v., day 1) to avoid disseminated intravascular coagulation (DIC). After 1 course of the treatment, she could completely avoid DIC and we found the primary lesion and the metastasis had decreased. Now she is an outpatient and continues treatment without relapse for about 6 months. We consider low-dose S-1 and zoledronic acid hydrate combination therapy to be an effective strategy against advanced gastric cancer with disseminated carcinomatosis of the bone marrow and multiple bone metastasis in very elderly cases.