A Risk Prediction Flowchart of Vancomycin-Induced Acute Kidney Injury to Use When Starting Vancomycin Administration: A Multicenter Retrospective Study.

We previously constructed a risk prediction model of vancomycin (VCM)-associated nephrotoxicity for use when performing initial therapeutic drug monitoring (TDM), using decision tree analysis. However, we could not build a model to be used at the time of initial administration due to insufficient sample size. Therefore, we performed a multicenter study at four hospitals in Japan. We investigated patients who received VCM intravenously at a standard dose from the first day until the initial TDM from November 2011 to March 2019. Acute kidney injury (AKI) was defined according to the criteria established by the "Kidney disease: Improving global outcomes" group. We extracted potential risk factors that could be evaluated on the day of initial administration and constructed a flowchart using a chi-squared automatic interaction detection algorithm. Among 843 patients, 115 (13.6%) developed AKI. The flowchart comprised three splitting variables (concomitant drugs (vasopressor drugs and tazobactam/piperacillin) and body mass index ≥ 30) and four subgroups. The incidence rates of AKI ranged from 9.34 to 36.8%, and they were classified as low-, intermediate-, and high-risk groups. The accuracy of flowchart was judged appropriate (86.4%). We successfully constructed a simple flowchart predicting VCM-induced AKI to be used when starting VCM administration.

Relationship between PK/PD of Cefepime and Clinical Outcome in Febrile Neutropenic Patients with Normal Renal Function.

The efficacy of cefepime (CFPM) is known to depend on the ratio of the time that the serum levels exceed the minimum inhibitory concentration (MIC) to the dosing interval (%T>MIC). The objective of this study was to clarify the relation between %T>MIC and clinical outcome of CFPM, and to identify the optimal dosage regimen. We investigated the outcome of CFPM treatment for febrile neutropenia (FN) patients with normal renal function. Treatment success was defined as the completion of FN therapy with CFPM only. And we calculated %T>MIC for each case based on population pharmacokinetic parameters. The MIC value for simulation was set as 8 µg/mL. In logistic regression analysis, treatment success was significantly associated with the elevation of %T>MIC in the group with persistent neutropenia, yielding a receiver operating characteristic curve with an optimal cutoff value of 73.1%. Next, we simulated %T>MIC for each case under various dosing regimens. For patients whose creatinine clearance (CLcr) exceeded 100 mL/min, it was found to be difficult to attain the objective under the current regimen. In contrast, it was calculated that treatment with 2 g three times a day (t.i.d.) could attain the objective for most of the patients with 3 h of infusion. These results suggest that CFPM treatment under the current regimen is ineffective for FN patients with normal or augmented renal function, and that 2 g t.i.d. is necessary in quite a lot cases, although such use is off-label.

Development of a new measurement method for serum calcium with chlorophosphonazo-III.

BACKGROUND: Although serum calcium has been measured using the o-cresolphthalein complexone (oCPC) method in the clinical laboratory, this method still has some problems regarding linearity and reagent stability. We developed a new measurement procedure using chlorophosphonazo-III (CPZ-III: 2,7-bis (4-chloro-2-phosphonophenylazo) -1,8- dihydroxy-3, 6-naphthalenedisulphonic acid, disodium salt) as a chelator with an acid medium for serum calcium measurement. The present method showed better linearity and reagent stability compared with the oCPC method. METHODS: Characteristics were studied in optimized conditions measuring wavelength by absorption spectra analysis, and interference of protein and metals with Mg(2+), Fe(2+), Cu(2+) and Zn(2+). The method was applied to an automated analyser (7170; Hitachi High Technologies Corp). The measurement performance was evaluated for accuracy, precision, recovery rate, linearity and reagent stability with a comparison study against atomic absorption spectrophotometry (AAS). RESULTS: The within-run and between-run variations (coefficient of variation [CV]) were 0.92-1.01% and 0.75-1.43%, respectively. The linearity was 0-7.0 mmol/L. The comparison study obtained y = 1.002x (AAS) - 0.10, Sy/x = 0.18 mmol/L, n = 50. Reagent stability was at least 20 d at 4 degrees C without daily calibration. CONCLUSION: The new calcium measurement method in serum was demonstrated to have reliable and acceptable performances as a routine test in clinical laboratory.