Patient: Male, 79Final Diagnosis: DRESSSymptoms: Eosinophilia • fever • interstitial pneumonitis • skin rashMedication: Teicoplanin • vancomycinClinical Procedure: —Specialty: Infectious DiseasesObjective:Adverse events of drug therapyBackground:Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a potentially life-threatening syndrome comprising severe skin eruption, fever, eosinophilia, lymphadenopathy, and involvement of internal organs. Here, we describe a case of DRESS syndrome caused by cross-reactivity between vancomycin and subsequent teicoplanin administration.Case Report:A 79-year-old male was admitted to our hospital for the treatment of injuries incurred in a traffic accident. Eosinophilia and lung dysfunction appeared after vancomycin administration. These symptoms were improved temporarily by withdrawal of vancomycin and administration of corticosteroid, but exacerbated by subsequent teicoplanin administration. These symptoms disappeared after discontinuation of teicoplanin. Based on comprehensive assessment of the overall clinical course, we judged that DRESS syndrome was induced by cross-reactivity between vancomycin and subsequent teicoplanin administration. Using the European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) scoring system, we categorized DRESS syndrome related to vancomycin and teicoplanin as “probable.” We describe, for the first time, DRESS syndrome (defined using the RegiSCAR scoring system) caused by cross-reactivity between vancomycin and subsequent teicoplanin administration.Conclusions:Clinicians should be aware that DRESS syndrome can be induced by cross-reactivity between vancomycin and teicoplanin.

Background Bucolome is a non-steroidal anti-inflammatory drug and uricosuric agent, currently used only in Japan. It is known to induce drug interactions by inhibiting cytochrome P450 (CYP) 2C9. It is often used to enhance the anticoagulant effect of warfarin by utilizing its drug interactions. There are only a few reports on drug interactions of bucolome and the mechanism remain poorly understood. Case presentation An 81-year-old woman with a history of type 2 diabetes mellitus was taking glimepiride 2 mg/day and voglibose 0.6 mg/day. After hospitalization, the patient underwent surgical aortic valve replacement surgery (day 0). Glimepiride and voglibose were resumed on the second postoperative day (day 2), and warfarin was started to prevent thromboembolism. Since the prothrombin time-international normalized ratio on day 9 was low at 1.24, 300 mg/day of bucolome was added to enhance the effect of warfarin. A gradual decrease in blood glucose levels was observed from the day after bucolome administration was initiated. Hypoglycemia in the 56–57 mg/dL range occurred before lunch and dinner on the 6th day (day 14) of bucolome administration, due to which voglibose was discontinued. Hypoglycemia below 70 mg/dL was not observed thereafter, and the general condition of the patient was stable. Conclusions Based on the clinical course and literature review, we believe that hypoglycemia in the present case was due to a drug interaction, caused by inhibition of CYP2C9 by bucolome and competitive inhibition of CYP2C9 by warfarin, which affected the pharmacokinetics of glimepiride. The possibility of hypoglycemia due to drug interactions should be considered by physicians, when bucolome is included to enhance the effect of warfarin, in patients taking glimepiride.

Hypertensive emergency is a situation in which uncontrolled hypertension is associated with acute end-organ damage. Nicardipine hydrochloride is a calcium channel blocker indicated for the treatment of hypertensive emergencies. However, nicardipine infusion-related phlebitis is a common and significant problem in clinical practice. The aim of this study was to survey the incidence of nicardipine infusion-related phlebitis and to identify associated risk factors for phlebitis. We conducted a retrospective observational study at Fukuoka Tokushukai medical center. A total of 79 patients who received precision continuous infusion of nicardipine were enrolled in this study. Nicardipine infusion-related phlebitis occurred in 34 (25.7％) of 132 peripheral intravenous catheters. On multivariate logistic analysis, "the dosing period over 24 hours" and "no co-infusion of saline" were significantly associated with an increased risk of nicardipine infusionrelated phlebitis. The odds ratio (OR) and 95％ confidence interval (95％ CI) for the occurrence of phlebitis with respect to "the dosing period over 24 hours" and "no co-infusion of saline" were 5.04 (2.012 -12.657) and 3.36 (1.190 -9.514), respectively. In addition, the optimal cut-off level of the dilution rate of saline was determined to be 4.23 times (sensitivity 73.5％, specificity 58.8％) based on receiver operating characteristic (ROC) analysis for predicting the occurrence of phlebitis. To minimize the risk of peripheral phlebitis, we propose that medical professionals should consider changing the infusion site every 24 hours at least and co-infusing saline diluted more than 4-5 times.Key words --hypertensive emergency, nicardipine, precision continuous drip infusion, phlebitis, risk factor, intensive care unit

Fosphenytoin (FOS) is a phosphate ester prodrug developed as an alternative to intravenous phenytoin for acute treatment of seizures. Although both FOS and phenobarbital (PB) are used for status epilepticus as second-line drugs, there is no data on their comparative efficacy and safety. We retrospectively analyzed data from children treated with FOS or PB for convulsive status epilepticus and acute exacerbation of seizures. Our aim was to compare the efficacy and safety of intravenous FOS with those of intravenous PB for convulsive status epilepticus and acute exacerbation of seizures. Seventy-seven children were included in the study: 54 received FOS, and 23 received PB. The primary end point was recurrence of seizures and drug-related adverse events. The response rate, defined as no recurrence of seizures within 24 hours after termination of seizure, was 92％ (50/54) and 95％ (22/23) in FOS group and in PB group, respectively. Adverse events occurred in 27％ (15/54) of patients in FOS group and in 95％ (22/23) of patients in PB group (P < 0.01). Although no serious adverse events occurred in patients in both FOS group and PB group, the incidence of both sedation and disturbance of consciousness were significantly higher in PB group than FOS group. From these results, FOS is recommended as second-line drugs for status epilepticus and acute exacerbation of seizures. However, the optimal serum concentration achievement rate was significantly lower in FOS group than PB group. To maintain optimal serum phenytoin levels (10 -20 µg/mL), higher doses of FOS might be required.