Application of Beta-lactam Therapeutic Drug Monitoring in Clinical Practice Using HPLC

Toshiharu Urakami Yosuke Aoki

doi:10.4172/1948-593x.s3-001

Abstract

In beta-lactam therapy, investigation of the pharmacokinetic-pharmacodynamic (PK-PD) relationship has provided surrogate makers to predict clinical outcome. This study was designed to verify the therapeutic efficacy and clinical utility of beta-lactam therapeutic drug monitoring (TDM) in critically ill patients using high-performance liquid chromatography (HPLC). This cohort study included 13 patients who were intravenously administered ceftazidime (n = 6), cefepime (n = 1), imipenem (n = 1), meropenem (n = 1), or piperacillin (n = 4). Blood samples were collected at 3 time points fitted to a 1-compartment model, and concentrations were determined using HPLC. The PK-PD target was the percentage of the dosing interval during which the antibiotic concentration exceeded the minimum inhibitory concentration for the pathogens (%T > MIC), which is 50% for penicillins (piperacillin), 60% for cephalosporins (ceftazidime and cefepime), and 40% for carbapenems (imipenem and meropenem). Our process using HPLC enables the analytical results of TDM to be available within half a day. The results revealed significant inter-patient pharmacokinetic variability. During the initial regimen, beta-lactam concentrations reached the target %T > MIC in all patients, and dosage reduction was required for 5 patients (38%). Of the 13 evaluable patients, clinical improvement was observed in 11 (85%), and microbiological success was observed in 10 (77%). In summary, beta-lactam TDM achieved the treatment goals and might also allow for the personalization to prevent overdosing for variable pharmacokinetic changes in critically ill patients. These findings indicate that beta-lactam TDM using HPLC can be used in the standard pharmacy clinical practice for critically ill patients.

Highlights

Beta-lactams are administered as first-line therapy for the majority of infections
Glycopeptides and aminoglycosides are applied to therapeutic drug monitoring (TDM) to prevent toxicity, this approach has not been widely applied to beta-lactams because of their safety
The use of beta-lactam TDM by high-performance liquid chromatography (HPLC) in the clinical setting. This is the study to describe the use of betalactam TDM in the daily clinical practice for critically ill patients using HPLC

Summary

Introduction

Beta-lactams are administered as first-line therapy for the majority of infections. The pharmacokinetic-pharmacodynamic (PK-PD) theory indicates that the antibacterial activity of these antibiotics is timedependent. To achieve a bactericidal effect, laboratory and clinical evidence indicates that the %T > MIC should be 50% for penicillins, 60% for cephalosporins, and 40% for carbapenems; these appear to be the PK-PD target values for individualized dosage regimens [1,2]. Optimizing the antibiotic regimen should be considered as a critical strategy to maximize therapeutic success while minimizing toxicity and the development of resistance for infectious disease patients [3,4]. In beta-lactam therapy, an understanding of the PKPD relationship has provided surrogate makers to predict the clinical outcome and indicated that it is increasingly necessary to individualize antimicrobial regimen to achieve the optimal antimicrobial treatment rather than to avoid toxicity

Objectives

Methods

Results