Simplifying Piperacillin/Tazobactam Dosing: Pharmacodynamics of Utilizing Only 4.5 or 3.375 g Doses for Patients With Normal and Impaired Renal Function

2016 ◽  
Vol 30 (6) ◽  
pp. 593-599 ◽  
Author(s):  
Abrar K. Thabit ◽  
Mordechai Grupper ◽  
David P. Nicolau ◽  
Joseph L. Kuti
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Renal Function ◽  
Impaired Renal Function ◽  
Inhibitory Concentration ◽  
Prolonged Infusion ◽  
Target Attainment ◽  
Dosing Regimens ◽  
Function Range ◽  
Prescribing Information

Objectives: To evaluate the pharmacodynamic exposure of piperacillin/tazobactam across the renal function range using 4.5 or 3.375 g dosing regimens. Methods: A 5000-patient Monte Carlo simulation was conducted to determine the probability of achieving 50% free time above the minimum inhibitory concentration ( fT > MIC) for piperacillin. Proposed regimens, using solely 4.5 or 3.375 g strengths, were compared with regimens listed in piperacillin/tazobactam prescribing information over creatinine clearance (CrCl) ranges of 120 mL/min to hemodialysis. The probability of target attainment (PTA) at MICs ≤ 16 μg/mL was compared between proposed and standard regimens. Results: At CrCl 41 to 120 mL/min, prolonged infusions of 4.5 g (3 hours) and 3.375 g (4 hours) every 6 hours resulted in ≥95% PTA versus ≥76% for standard regimens (0.5 hour). At CrCl 20 to 40 mL/min, 4.5 and 3.375 g every 8 hours as prolonged infusions achieved slightly higher PTA (≥98%) versus standard regimens (≥93%). Similarly, PTA achieved with prolonged infusions of 4.5 and 3.375 g every 12 hours (≥93%) was comparable with those of standard regimens (≥91%) at CrCl 1 to 19 mL/min. In hemodialysis, 100% PTA was achieved with prolonged infusion regimens. Conclusion: Piperacillin/tazobactam regimens designed around the 4.5 or 3.375 g dose and prolonged infusions provided similar or better PTA at MICs ≤ 16 μg/mL compared with standard regimens. These observations may support the stocking and use of a single piperacillin/tazobactam strength to simplify dosing.

scholarly journals Pharmacodynamic Profiling of Antimicrobials against Gram-negative Respiratory Isolates from Canadian Hospitals

2011 ◽  
Vol 22 (4) ◽  
pp. 132-136 ◽  
Author(s):  
Rebecca A. Keel ◽  
George G. Zhanel ◽  
Sheryl Zelenitsky ◽  
David P. Nicolau
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Enterobacter Cloacae ◽  
The Other ◽  
Prolonged Infusion ◽  
Target Attainment ◽  
Dosing Regimens ◽  
Dose Dependent

The objective of this study was to assess the profile of a variety of dosing regimens for common intravenous antibiotics against contemporaryEnterobacter cloacae,Escherichia coli,Klebsiella pneumoniaeandPseudomonas aeruginosaisolates collected in Canada during 2009, using pharmacodynamic modelling techniques. Monte Carlo simulation was conducted for standard and/or prolonged infusion regimens of cefepime, ceftazidime, ceftriaxone, ciprofloxacin, doripenem, ertapenem, meropenem and piperacillin/tazobactam. The cumulative fraction of response (CFR) was calculated using bactericidal targets for each regimen against each species. All cefepime, doripenem, ertapenem and meropenem regimens achieved optimal exposures against Enterobacteriaceae, whereas target attainment was organism and dose dependent for the other agents. These results support that the currently recommended antimicrobial dosing regimens generally attain acceptable exposures to achieve the requisite pharmacodynamic targets against the Enterobacteriaceae species; however, they fall short of obtaining optimal bactericidal exposures againstP aeruginosa.BACKGROUND: With diminishing antimicrobial potency, the choice of effective empirical therapy has become more challenging. Thus, the pharmacodynamic evaluation of potential therapies is essential to identify optimal agents, doses and administration strategies.METHODS: Monte Carlo simulation was conducted for standard and/or prolonged infusion regimens of cefepime, ceftazidime, ceftriaxone, ciprofloxacin, doripenem, ertapenem, meropenem and piperacillin/tazobactam. Minimum inhibitory concentrations were obtained forEscherichia coli(n=64 respiratory isolates),Enterobacter cloacae(n=53),Klebsiella pneumoniae(n=75) andPseudomonas aeruginosa(n=273) throughout Canada. The cumulative fraction of response (CFR) was calculated using bactericidal targets for each regimen against each species. A CFR ≥90% was defined as optimal.RESULTS: All cefepime, doripenem, ertapenem and meropenem regimens achieved optimal exposures against Enterobacteriaceae, whereas target attainment was organism and dose dependent for the other agents. Prolonged infusion doripenem and meropenem 1 g and 2 g every 8 h, along with standard infusion doripenem and meropenem 2 g every 8 h, were the only regimens to attain optimal exposures againstP aeruginosa. Ciprofloxacin had the lowest CFR againstP aeruginosa,followed by cefepime. Among theP aeruginosaisolates collected in the intensive care unit (ICU) compared with the wards, differences of 0.5% to 10% were noted in favour of non-ICU isolates for all agents; however, marked differences (10% to 15%) in CFR were observed for ciprofloxacin in favour of ICU isolates.CONCLUSION: Standard dosing of cefepime, doripenem, ertapenem and meropenem has a high likelihood of obtaining optimal pharmacodynamic indexes against these Enterobacteriaceae. ForP aeruginosa, aggressive treatment with high-dose and/or prolonged infusion regimens are likely required to address the elevated resistance rates of respiratory isolates from Canada.

Simplified dosing regimens of teicoplanin for patient groups stratified by renal function and weight using Monte Carlo simulation

2012 ◽  
Vol 40 (4) ◽  
pp. 344-348 ◽  
Author(s):  
Takaaki Yamada ◽  
Toshiharu Nonaka ◽  
Takahisa Yano ◽  
Toshio Kubota ◽  
Nobuaki Egashira ◽  
...  
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Renal Function ◽  
Dosing Regimens ◽  
Patient Groups

scholarly journals Evaluation of Intravenous Fosfomycin Disodium Dosing Regimens in Critically Ill Patients for Treatment of Carbapenem-Resistant Enterobacterales Infections Using Monte Carlo Simulation

Antibiotics ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 615
Author(s):  
Pannee Leelawattanachai ◽  
Thitima Wattanavijitkul ◽  
Taniya Paiboonvong ◽  
Rongpong Plongla ◽  
Tanittha Chatsuwan ◽  
...  
Keyword(s):  
Monte Carlo Simulation ◽  
Monte Carlo ◽  
Minimum Inhibitory Concentration ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Inhibitory Concentration ◽  
Clinical Isolates ◽  
Carbapenem Resistant ◽  
Dosing Regimens ◽  
Tract Infections

There are limited intravenous fosfomycin disodium (IVFOS) dosing regimens to treat carbapenem-resistant Enterobacterales (CRE) infections. This study aimed to use Monte Carlo simulation (MCS) for evaluation of IVFOS dosing regimens in critically ill patients with CRE infections. The dosing regimens in critically ill patients with various creatinine clearance were evaluated with MCS using minimum inhibitory concentration (MIC) distributions of fosfomycin against CRE clinical isolates in Thailand and the 24 h area under the plasma drug concentration–time curve over the minimum inhibitory concentration (AUC0-24/MIC) of ≥21.5 to be a target for IVFOS. The achieved goal of the probability of target attainment (PTA) and a cumulative fraction of response (CFR) were ≥90%. A total of 129 non-duplicated CRE clinical isolates had MIC distributions from 0.38 to >1024 mg/L. IVFOS 8 g every 8 h, 1 h, or 4 h infusion, could achieve approximately 90% PTA of AUC0-24/MIC target to treat CRE infections with MICs ≤ 128 mg/L. According to PTA target, an IVFOS daily dose to treat carbapenem-resistant Escherichia coli based on Clinical Laboratory Standards Institute (CLSI) breakpoints for urinary tract infections and one to treatment for CRE infections based on the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints were 16 g/day and 8 g/day, respectively. All dosing regimens of IVFOS against CRE achieved CFR ≤ 70%. This study proposes the IVFOS dosing regimens based on CLSI and EUCAST breakpoints for the treatment of CRE infections. However, further clinical studies are needed to confirm the results of these findings.

scholarly journals Evaluating Ciprofloxacin Dosing for Pseudomonas aeruginosa Infection by Using Clinical Outcome-Based Monte Carlo Simulations

2005 ◽  
Vol 49 (10) ◽  
pp. 4009-4014 ◽  
Author(s):  
Sheryl Zelenitsky ◽  
Robert Ariano ◽  
Godfrey Harding ◽  
Alan Forrest
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Monte Carlo ◽  
Clinical Outcome ◽  
Monte Carlo Simulations ◽  
Standard Dose ◽  
High Dose ◽  
Target Attainment ◽  
Real Patient ◽  
Dosing Regimens ◽  
Cure Rates

ABSTRACT Pseudomonas aeruginosa causes serious infections whose outcome is highly dependent on antimicrobial therapy. The goal of this study was to predict the relative efficacies of three ciprofloxacin dosing regimens for P. aeruginosa infection using clinical outcome-based Monte Carlo simulations (MCS) with “real patient” demographics, pharmacokinetics, MICs, and pharmacodynamics (PDs). Each cohort consisted of 1,000 simulated study subjects. Three ciprofloxacin dosing regimens were studied, including (i) the recommended standard dose of 400 mg given intravenously (i.v.) every 12 h (q12h), (ii) the recommended high dose of 400 mg i.v. q8h, and (iii) a novel, PD-targeted regimen to attain a ƒAUC/MIC value of >86. Probability of target attainment (PTA) and probability of cure (POC) were determined for each regimen. POC with the standard dose was at least 0.90 if pathogen MICs were ≤0.25 μg/ml but only 0.59 or 0.27 if MICs were 0.5 or 1 μg/ml, respectively. Predicted cure rates in these MIC categories were significantly higher at 0.72 and 0.40 with the high dose and 0.91 and 0.72 with the PD-targeted regimen(P < 0.0001). Analyses based on the local susceptibility profile produced PTA and POC estimates of 0.44 and 0.74 with the standard ciprofloxacin dose, 0.58 and 0.81 with the high dose, and 0.84 and 0.93 with the PD-targeted regimen, respectively. In conclusion, as demonstrated by clinical outcome-based MCSs, the highest recommended ciprofloxacin dose of 400 mg i.v. q8h should be used in the treatment of P. aeruginosa infection to improve PD target attainment and clinical cure. However, even this appears ineffective if pathogen MICs are 1 μg/ml, warranting the consideration of a lower MIC breakpoint, ≤0.5 μg/ml.

Sign in / Sign up

Export Citation Format

Share Document