The Pharmacodynamics of Meropenem in Patient With Ventilator-associated Pneumonia
The Pharmacodynamics of Meropenem in Patient With Ventilator-associated Pneumonia
The study was a randomized three-way crossover study. Each subject received meropenem in
 three regimens at room temperature consecutively: (i) bolus injection of 1 g of meropenem
 over 10 min every 8 h for 24 h, (ii) 3-h infusion of 1 g of meropenem via an infusion pump at
 a constant flow rate every 8 h for 24 h, and(iii) 3-h infusion of 2 g of meropenem via an
 infusion pump at a constant flow rate every 8 h for 24 h.

 Clinical and laboratory data such as Age,Sex, Body weight, Electrolyte, Vital signs, APACHE
 II score, BUN, Cr, Blood culture will be collected.

 Nine patients will be enrolled in this study. After completion of the meropenem therapy for 3
 days in this study, all patients will receive other sensitive antibiotics to eradicate their
 bacterial infections.

 Meropenem pharmacokinetic studies were carried out during administration of the third dose of
 each regimen (16 to 24 h after the start of each regimen). Blood samples (approximately 5 ml)
 were obtained by direct venipuncture at the following times: before (time zero) and 10 and 30
 min and

 1, 1.5, 2, 2.5, 3.5, 4, 4.5, 5, 6, and 8 h after the third dose of each regimen.

 The concentrations of meropenem were determined by reverse-phase high-performance liquid
 chromatography.

 Concentration of meropenem in plasma will be simulated in Monte Carlo technique (Computer
 model) to get PK/PD index (40%T>MIC) and reported to % PTA(Probability Target Attainment) and
 %CFR (Cumulative Faction Response)
Introduction:

 Meropenem is a carbapenem antibacterial agent with a broad spectrum of activity against
 several pathogens. In common with other -lactams, the main pharmacokinetic/pharmacodynamic
 parameter that correlates with the therapeutic efficacy is the T>MIC, and administration by
 continuous infusion is the preferred route to maximize this parameter. However, in tropical
 countries the stability of meropenem is an important consideration when continuous infusion
 is to be used.

 Objective:

 The aim of this study was to demonstrate the T>MIC of meropenem when administered by a 3-h
 infusion compared with that when administered by bolus injection.

 Study design:

 The study was conducted with nine patients with ventilator-associated pneumonia. Each subject
 received meropenem in three regimens consecutively: (i) bolus injection of 1 g every 8 h for
 24 h; (ii) 3-h infusion of 1 g every 8 h for 24 h; and (iii) 3-h infusion of 2 g every 8 h
 for 24 h.

 Sample collections:

 Meropenem pharmacokinetic studies were carried out during administration of the third dose of
 each regimen (16 to 24 h after the start of each regimen). Blood samples (approximately 5 ml)
 were obtained by direct venipuncture at the following times: before (time zero) and 10 and 30
 min and 1, 1.5, 2, 2.5, 3.5, 4, 4.5, 5, 6, and 8 h after the third dose of each regimen.

 Meropenem assay:

 The concentrations of meropenem were determined by reverse-phase high-performance liquid
 chromatography. Cefepime (100 mcg/ml) was used as the internal standard, and the samples were
 extracted by the method of Ozkan et al.

 Clinical data and pathogens collection:

 1. Initial patient demographic data (age, sex, weight, diagnosis, APACHE II scores) will be
 collected upon enrollment in the study.

 2. The Gram negative bacilli isolated from sputum in 9 patients will be collected and the
 MIC of the meropenem for pathogens will be determined by E tests upon enrollment in the
 study.

 Duration of study:

 Patients will receive meropenem for 3 days

 Pharmacokinetic and pharmacodynamic analysis:

 Concentration of meropenem in plasma will be simulated in Monte Carlo technique (Computer
 model) to get PK/PD index (40%T>MIC) and reported to % PTA (Probability Target Attainment)
 and %CFR (Cumulative Faction Response) Sample Size: Nine patients with VAP will be enrolled
 in this study.
Inclusion Criteria:

 -  The patients were eligible for the study if they met the following criteria:

 1. older than 18 years

 2. clinical suspicion of VAP, defined by a new and persistent infiltrate on chest
 radiography associated with at least one of the following-purulent tracheal
 secretions, temperature of 38.3 celsius or higher, or a leukocyte count higher
 than 10000.

 Exclusion Criteria:

 -  Patients were excluded from the study if they were pregnant or in circulatory shock
 (which was defined as a systolic blood pressure of 90 mmHg and poor tissue perfusion)
 or had documented hypersensitivity to meropenem or an estimated creatinine
 clearance(determined by the Cockcroft-Gault method) of 60 ml/min.