Hidetoshi Ishii1,2, Keita Hirai1,3, Kyohei Sugiyama2, Eiji Nakatani4,5, Midori Kimura2, Kunihiko Itoh1,3. 1. Department of Clinical Pharmacology & Genetics, School of Pharmaceutical Sciences, University of Shizuoka. 2. Department of Pharmacy, Shizuoka General Hospital. 3. Laboratory of Clinical Pharmacogenomics, Shizuoka General Hospital. 4. Clinical Research Center, Shizuoka General Hospital, Shizuoka. 5. Department of Biostatistics and Data Science, Osaka University Graduate School of Medicine, Osaka, Japan.
Abstract
BACKGROUND: Adjustment of initial vancomycin (VCM) dosage has been recommended on the basis of the renal function nomogram in therapeutic drug monitoring guidelines in Japan. However, this nomogram has not been clinically validated, and few studies have focused on its usefulness in patients with risk of augmented renal function. Therefore, this study aimed to evaluate the validity of the VCM nomogram and the association between patient conditions related to augmented renal function and its accuracy. METHODS: In this retrospective study, we screened data of 398 patients who received VCM and had estimated glomerular filtration rates ≥30 mL·min·1.73 m. Patients who met nomogram dosing criteria were categorized into a nomogram group, and the associations of age, renal function, and individual conditions such as febrile neutropenia, solid tumor, blood cancer, and brain injury with subtherapeutic concentrations (<10.0 mcg/mL) of VCM were evaluated. RESULTS: In total, 177 patients were categorized into the nomogram group, and 83 (47%), 81 (46%), and 13 patients (7%) had VCM trough concentrations of 10-20, <10, and >20 mcg/mL, respectively. Age <50 years was only significantly associated with subtherapeutic trough concentrations. Specific conditions of patients such as febrile neutropenia, solid tumor, and blood cancer were associated with elevated VCM clearance; however, there was no decline in trough VCM concentrations regardless of the presence of the specific conditions. CONCLUSIONS: The Japanese VCM dosing nomogram was effective in minimizing the number of instances of supratherapeutic VCM serum concentrations; however, it lacked accuracy in achieving target trough concentrations. The accuracy of the nomogram could be enhanced by categorizing patients according to age. Nevertheless, this study provides novel evidence of the usefulness of this nomogram in avoiding subtherapeutic concentrations of VCM in patients with risk factors for augmented renal clearance.
BACKGROUND: Adjustment of initial vancomycin (VCM) dosage has been recommended on the basis of the renal function nomogram in therapeutic drug monitoring guidelines in Japan. However, this nomogram has not been clinically validated, and few studies have focused on its usefulness in patients with risk of augmented renal function. Therefore, this study aimed to evaluate the validity of the VCM nomogram and the association between patient conditions related to augmented renal function and its accuracy. METHODS: In this retrospective study, we screened data of 398 patients who received VCM and had estimated glomerular filtration rates ≥30 mL·min·1.73 m. Patients who met nomogram dosing criteria were categorized into a nomogram group, and the associations of age, renal function, and individual conditions such as febrile neutropenia, solid tumor, blood cancer, and brain injury with subtherapeutic concentrations (<10.0 mcg/mL) of VCM were evaluated. RESULTS: In total, 177 patients were categorized into the nomogram group, and 83 (47%), 81 (46%), and 13 patients (7%) had VCM trough concentrations of 10-20, <10, and >20 mcg/mL, respectively. Age <50 years was only significantly associated with subtherapeutic trough concentrations. Specific conditions of patients such as febrile neutropenia, solid tumor, and blood cancer were associated with elevated VCM clearance; however, there was no decline in trough VCM concentrations regardless of the presence of the specific conditions. CONCLUSIONS: The Japanese VCM dosing nomogram was effective in minimizing the number of instances of supratherapeutic VCM serum concentrations; however, it lacked accuracy in achieving target trough concentrations. The accuracy of the nomogram could be enhanced by categorizing patients according to age. Nevertheless, this study provides novel evidence of the usefulness of this nomogram in avoiding subtherapeutic concentrations of VCM in patients with risk factors for augmented renal clearance.