Evaluating Linezolid Dose Based on Renal Function and Body Weight
against Methicillin-Resistant Staphylococcus aureus (MRSA) by Monte
Carlo Simulations
Abstract
Objective: To assess whether dose adjustments of linezolid were needed
based on renal function and body weight against methicillin-resistant
Staphylococcus aureus (MRSA) infections. Methods: Monte Carlo
simulations (MCSs) were conducted to simulate
pharmacokinetic/pharmacodynamic (PKPD) model. Area under the
concentration time curve (AUC)/ minimum inhibitory concentration (MIC)
ratio and percentage of time above the MIC (%T>MIC) were
regarded as PKPD targets. The probability of target attainment (PTA) and
cumulative fractions of response (CFR) were calculated to assess the
efficacy. Regarding safety, trough plasma concentration (Cmin)
> 8 mg/L was used to target for toxicity. Results: Using
AUC /MIC > 100 as the parameter, the CFR of linezolid at
the standard dose [600 mg every 12 h (q12h)] were 57.01%, 93.22%
and 99.93% in patients with normal renal function, patients with renal
dysfunction and low body weight patients with renal dysfunction,
respectively. Using 100%T > MIC as the parameter, all the
CFR of three population groups were more than 90% at the standard dose.
The percentages of Cmin > 8 mg/L at the standard dose of
linezolid were 24.16%, 53.24% and 90.10% in three population groups
on day 7. Conclusions: The risk of thrombocytopenia of linezolid was
extremely high in low body weight patients with renal impairment when
receiving standard linezolid dose. 600 mg q12h might be effective and
safe against MRSA infection in patients with normal renal function,
while 450mg q12h and 300mg q12h in patients with renal dysfunction and
low body weight patients with renal dysfunction, respectively.