Application of Pharmacodynamic Profiling for the Selection of Optimal β-lactam Regimens in a Large University Hospital

Koomanachai, Pornpan; Yungyuen, Thitiya; Disthaporn, Pensiri; Kiratisin, Pattarachai; Nicolau, David P.

doi:10.1016/j.ijid.2016.03.020

Cited by 8 publications

(3 citation statements)

References 19 publications

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“…The purpose of this mini review was to briefly survey the techniques and decisions researchers made while performing cefepime PTA. Therefore, only the first 20 titles were reviewed, of which 14 met the inclusion criteria of a PTA study, with at least one evaluation of cefepime alone in adult patients ( Table 1 ) [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. A study by Das et al was excluded because cefepime was studied in combination with a novel beta-lactamase inhibitor, changing the risk benefit from cefepime alone [ 28 ].…”

Section: Resultsmentioning

confidence: 99%

“…The MIC of interest was generally set at 8 mg/dL, consistent with the breakpoint defined by the Clinical and Laboratory Standards Institute against pseudomonas aeruginosa [ 35 ]. Success was commonly defined as PTA > 90% against a given MIC; however, some authors defined success as CFR > 90% against an observed MIC distribution [ 18 , 20 , 21 , 26 ].…”

Section: Resultsmentioning

confidence: 99%

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Beta-Lactam Probability of Target Attainment Success: Cefepime as a Case Study

et al. 2023

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Introduction: Probability of target attainment (PTA) analysis using Monte Carlo simulations has become a mainstay of dose optimization. We highlight the technical and clinical factors that may affect PTA for beta-lactams. Methods: We performed a mini review in adults to explore factors relating to cefepime PTA success and how researchers incorporate PTA into dosing decisions. In addition, we investigated, via simulations with a population pharmacokinetic (PK) model, factors that may affect cefepime PTA success. Results: The mini review included 14 articles. PTA results were generally consistent, given the differences in patient populations. However, dosing recommendations were more varied and appeared to depend on the definition of pharmacodynamic (PD) target, definition of PTA success and specific clinical considerations. Only 3 of 14 articles performed formal toxicological analysis. Simulations demonstrated that the largest determinants of cefepime PTA were the choice of PD target, continuous vs. intermittent infusion and creatinine clearance. Assumptions for protein binding, steady state vs. first dose, and simulating different sampling schemes may impact PTA success under certain conditions. The choice of one or two compartments had a minimal effect on PTA. Conclusions: PTA results may be similar with different assumptions and techniques. However, dose recommendation may differ significantly based on the selection of PD target, definition of PTA success and considerations specific to a patient population. Demographics and the PK parameters used to simulate time-concentration profiles should be derived from patient data applicable to the purpose of the PTA. There should be strong clinical rationale for dose selection. When possible, safety and toxicity should be considered in addition to PTA success.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Beta-Lactam Probability of Target Attainment Success: Cefepime as a Case Study

et al. 2023

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“…As two recent studies have suggested, the carbapenem MIC might influence the clinical outcome in patients with Gram-negative bacterial infections (31,32); therefore, optimization of the doripenem dosing regimen according to the MIC for the causative organism is required. In this context, the application of PK profiles to adjust the dosing regimen and the mode of administration is particularly important for infections caused by pathogens with decreased in vitro susceptibility and higher MICs, such as Pseudomonas aeruginosa (33). From our point of view, local susceptibility data could be precious.…”

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetic Analysis of Doripenem after Intravenous Infusion in Korean Patients with Acute Infections

Lee

Kim

Jin

et al. 2017

Antimicrob Agents Chemother

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We investigated the population pharmacokinetics (PK) of doripenem in Korean patients with acute infections and determined an appropriate dosing regimen using a Monte Carlo simulation for predicting pharmacodynamics (PD). Patients (n ϭ 37) with a creatinine clearance (CL CR ) of 20 to 50 ml/min or Ͼ50 ml/min who received a 250-mg or 500-mg dose of doripenem over the course of 1 h every 8 h, respectively, were included in this study. Blood samples were taken predosing and 0 h, 0.5 h, and 4 to 6 h after the fourth infusion. A nonlinear mixed-effect modeling tool was used for the PK analysis and pharmacodynamic simulation; doripenem PK were well described by a one-compartment model. The population mean values of the body weight (WT)-normalized clearance (CL/WT) and the body weight-normalized volume of distribution (V/WT) were 0.109 liter/h/kg of body weight (relative standard error, 9.197%) and 0.280 liter/kg (relative standard error, 9.56%), respectively. Doripenem CL was significantly influenced by CL CR . The proposed equation to estimate doripenem CL in Korean patients was CL/WT ϭ 0.109 ϫ WT ϫ (CL CR /57) 0.688 , where CL/WT is in liters per hour per kilogram. CL in Korean patients was expected to be lower than that in Caucasian patients, regardless of renal function. The Monte Carlo simulation showed that 90% attainment of target PK/PD magnitudes could be achieved with the usual dosing regimens when the MIC was Յ1 mg/liter. However, prolonged infusions (4 h) should be considered, especially when patients have augmented renal function and for patients infected with pathogens with a high MIC. Our results provide an individualized doripenem dosing regimen for patients with various renal functions and for patients infected with bacteria with decreased susceptibility.

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Pharmacodynamic model for β-lactam regimens used in surgical prophylaxis: model-based evaluation of standard dosing regimens

Song

Long

2018

Int J Clin Pharm

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Background Continual evolution of resistance among bacteria against methods of surgical prophylaxis may make currently used beta-lactam regimens inadequate. Objective To re-evaluate beta-lactam regimens in surgical prophylaxis. Setting A pharmacodynamic Monte Carlo simulation (MCS) model based on a number of patients in China. Methods Pharmacodynamic profiling using Monte Carlo simulation up to 4 hours postinfusion was conducted for standard-dose, short-term (0.5 h) and prolonged (2 to 4 h) infusions of ampicillin, cefazolin, cefotaxime, cefoxitin, cefuroxime, ertapenem, and piperacillin/tazobactam in adult patients with normal renal function. Microbiological data were incorporated. Cumulative fraction of response (CFR) was determined for each regimen against populations of S. aureus, coagulase-negative staphylococci and E. coli. The optimal CFR was defined as ≥ 90% response. Main Outcome Measure Cumulative fractions of response of pharmacodynamic target attainment. Results During the first 2 hours postinfusion, piperacillin/tazobactam 3.375 g exhibited consistently optimal cumulative fractions against S. aureus, CoNS and E. coli. Ampicillin 2 g (2 h) also displayed optimal CFRs for S. aureus and E. coli but not for coagulase-negative staphylococci. Cefoxitin 2 g didnot achieve any optimal CFRs, even via 2-h prolonged infusion (maximum 72.8% CFR for S. aureus and 64.5% CFR for E. coli). Cefazolin 2 g (4 h) and cefuroxime 1.5 g (4 h) provided desired CFRs across 4 h postinfusion for S. aureus but provided poor CFRs for coagulase-negative staphylococci and E. coli. Only ertapenem 1 g for E. coli and S. aureus and cefotaxime 1 g for E. coli consistently yielded ≥ 90% CFRs for 4 hour postinfusion. Conclusions Certain dosing regimens may warrant adjustment for improved prevention efficiency and enhanced empirical antibiotic regimens for surgical prophylaxis.

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Application of Pharmacodynamic Profiling for the Selection of Optimal β-lactam Regimens in a Large University Hospital

Cited by 8 publications

References 19 publications

Beta-Lactam Probability of Target Attainment Success: Cefepime as a Case Study

Beta-Lactam Probability of Target Attainment Success: Cefepime as a Case Study

Population Pharmacokinetic Analysis of Doripenem after Intravenous Infusion in Korean Patients with Acute Infections

Pharmacodynamic model for β-lactam regimens used in surgical prophylaxis: model-based evaluation of standard dosing regimens

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