Evaluation of Clinical Efficacy of Maeda’s Nomogram for Vancomycin Dosage Adjustment in Adult Japanese MRSA Pneumonia Patients

Abstract

The clinical efficacy of Maeda's nomogram for vancomycin dosage adjustment was evaluated by comparison with a standard dosage regimen (package insert information: vancomycin dose reduced in elderly patients and patients with renal dysfunction, with Moellering's nomogram used for renal-dysfunction patients) in adult Japanese MRSA pneumonia patients. Using Maeda's nomogram, the vancomycin dose is fixed at 1,000 mg while the dosing interval is varied in accordance with individual creatinine clearance. Using a standard dosage regimen, 5 patients out of 27 (18.5%) achieved target plasma levels of vancomycin (25-40 microg/mL for peak and 5-15 microg/mL for trough) within 2-6 days. Using Maeda's nomogram, 38 patients out of 53 (71.7%) achieved target levels in that time. A higher clinical response (complete resolution of all signs and symptoms of MRSA infection) to vancomycin therapy was also obtained with Maeda's nomogram when evaluated approximately 2-weeks after discontinuation of vancomycin therapy (43.4% versus 18.5% for the standard regimen). In conclusion, the Maeda's nomogram regimen with a 1,000 mg vancomycin dose was shown to achieve target plasma levels of vancomycin at a higher rate and provide higher clinical efficacy in vancomycin therapy of MRSA pneumonia patients, as compared with the currently available standard dosage regimen.

Population pharmacokinetics of vancomycin in adult Chinese patients with post-craniotomy meningitis and its application in individualised dosage regimens

“…Several studies [43][44][45][46] report VCM dose nomograms, based on pre-defined TTCRs and patient characteristics. The dose is directly selected from the nomogram, and patients tend to have VCM trough concentrations within the target range, as compared to traditional methods [45,52].…”

“…Additionally, most reports only contain one VCM nomogram, which corresponds to one TTCR using only one PK model. However, there are many recommended TTCRs that vary between reports [12,[44][45][46]53]. One nomogram from one PK model could not be applied to all TTCRs, which may be inconvenient, since the TTCR may vary between patients.…”

“…In NONMEM, patient demographic and medication data are imported to estimate the steady trough concentrations of commonly used serial dosing regimens, using the maximum a posteriori Bayesian method (MAPB), based on established PPK models [42]. This allows for the estimation of the trough concentration when administering intravenous VCM (500, 750, 1000, 1250, or 1500 mg) twice a day [43][44][45][46]. Finally, the appropriate dosing regimen is determined according to the pre-defined target trough concentration range (TTCR) and the predicted concentrations of various regimens.…”

Evaluation of a protocol for vancomycin administration in critically patients with and without kidney dysfunction

“…Throughout the period considered by our study, the protocol set a weight-based loading dose of 1000 mg for patients with a body weight <65 Kg, and 1500 mg for patients with a body weight >65 Kg [ 5 ], diluted in a 100 ml of saline solution and administered over 60 minutes when the loading dose was 1000 mg; and over 90 min when the loading dose was 1500 mg. The loading dose was followed by the infusion of a dose of vancomycin calculated according to the CrCl [ 17 ]: specifically, 2000 mg/day if creatinine clearance was >50 ml/min/1,73 m 2 , 1500 mg/day if creatinine clearance was between 20–50 ml/min/1,73 m 2 , 1000 mg/day if creatinine clearance was between 10–20 ml/min/1,73 m 2 and 500 mg/day if creatinine clearance was < 10 ml/min/1,73 m 2 . Consecutive infusion rate was adjusted according to VSC: the daily dose was increased by 500 mg when VSC was <15 mg/L, left unchanged when VSC was between 15–25 mg/L, and was decreased by 500 mg when VSC was >25 mg/L and the infusion was interrupted for 6 hours when VSC exceeded 30 mg/L [ 5 , 7 ] (Table 1 ).…”

Observational clinical study on the effects of different dosing regimens on vancomycin target levels in critically ill patients: Continuous versus intermittent application

“…In contrast, nomograms have been analyzed with the intention to improve dosing patterns, but they failed to help in achieving sufficient vancomycin serum levels [6]. Similarly, using dosing recommendations provided by the current vancomycin product information has been demonstrated to be even worse for obtaining target serum levels [7]. Consequently, TDM is recommended to guide vancomycin therapy [3], and data from a recent clinical trial showed that repeated measurements increase the safety of target serum levels in a subset of medical ICU patients [8].…”