scholarly journals Population Pharmacokinetics of Colistin Methanesulfonate and Formed Colistin in Critically Ill Patients from a Multicenter Study Provide Dosing Suggestions for Various Categories of Patients

2011 ◽  
Vol 55 (7) ◽  
pp. 3284-3294 ◽  
Author(s):  
S. M. Garonzik ◽  
J. Li ◽  
V. Thamlikitkul ◽  
D. L. Paterson ◽  
S. Shoham ◽  
...  
Keyword(s):  
Renal Replacement Therapy ◽  
Creatinine Clearance ◽  
Replacement Therapy ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Multidrug Resistant ◽  
Parameter Estimates ◽  
Highly Active ◽  
Dosing Regimens ◽  
Colistin Methanesulfonate

ABSTRACTWith increasing clinical emergence of multidrug-resistant Gram-negative pathogens and the paucity of new agents to combat these infections, colistin (administered as its inactive prodrug colistin methanesulfonate [CMS]) has reemerged as a treatment option, especially for critically ill patients. There has been a dearth of pharmacokinetic (PK) data available to guide dosing in critically ill patients, including those on renal replacement therapy. In an ongoing study to develop a population PK model for CMS and colistin, 105 patients have been studied to date; these included 12 patients on hemodialysis and 4 on continuous renal replacement therapy. For patients not on renal replacement, there was a wide variance in creatinine clearance, ranging from 3 to 169 ml/min/1.73 m2. Each patient was treated with a physician-selected CMS dosage regimen, and 8 blood samples for PK analysis were collected across a dosage interval on day 3 or 4 of therapy. A linear PK model with two compartments for CMS and one compartment for formed colistin best described the data. Covariates included creatinine clearance on the total clearance of CMS and colistin, as well as body weight on the central volume of CMS. Model-fitted parameter estimates were used to derive suggested loading and maintenance dosing regimens for various categories of patients, including those on hemodialysis and continuous renal replacement. Based on our current understanding of colistin PK and pharmacodynamic relationships, colistin may best be used as part of a highly active combination, especially for patients with moderate to good renal function and/or for organisms with MICs of ≥1.0 mg/liter.

scholarly journals Population Pharmacokinetics of Unbound Ceftolozane and Tazobactam in Critically Ill Patients without Renal Dysfunction

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Fekade B. Sime ◽  
Melissa Lassig-Smith ◽  
Therese Starr ◽  
Janine Stuart ◽  
Saurabh Pandey ◽  
...  
Keyword(s):  
Creatinine Clearance ◽  
Population Pharmacokinetics ◽  
Critically Ill ◽  
Rate Constant ◽  
Critically Ill Patients ◽  
Plasma Concentrations ◽  
Peripheral Compartment ◽  
Parameter Estimates ◽  
Pharmacokinetic Data ◽  
Dosing Regimens

ABSTRACT Evaluation of dosing regimens for critically ill patients requires pharmacokinetic data in this population. This prospective observational study aimed to describe the population pharmacokinetics of unbound ceftolozane and tazobactam in critically ill patients without renal impairment and to assess the adequacy of recommended dosing regimens for treatment of systemic infections. Patients received 1.5 or 3.0 g ceftolozane-tazobactam according to clinician recommendation. Unbound ceftolozane and tazobactam plasma concentrations were assayed, and data were analyzed with Pmetrics with subsequent Monte Carlo simulations. A two-compartment model adequately described the data from twelve patients. Urinary creatinine clearance (CLCR) and body weight described between-patient variability in clearance and central volume of distribution (V), respectively. Mean ± standard deviation (SD) parameter estimates for unbound ceftolozane and tazobactam, respectively, were CL of 7.2 ± 3.2 and 25.4 ± 9.4 liters/h, V of 20.4 ± 3.7 and 32.4 ± 10 liters, rate constant for distribution of unbound ceftolozane or tazobactam from central to peripheral compartment (Kcp) of 0.46 ± 0.74 and 2.96 ± 8.6 h−1, and rate constant for distribution of unbound ceftolozane or tazobactam from peripheral to central compartment (Kpc) of 0.39 ± 0.37 and 26.5 ± 8.4 h−1. With dosing at 1.5 g and 3.0 g every 8 h (q8h), the fractional target attainment (FTA) against Pseudomonas aeruginosa was ≥85% for directed therapy (MIC ≤ 4 mg/liter). However, for empirical coverage (MIC up to 64 mg/liter), the FTA was 84% with the 1.5-g q8h regimen when creatinine clearance is 180 ml/min/1.73 m2, whereas the 3.0-g q8h regimen consistently achieved an FTA of ≥85%. For a target of 40% of time the free drug concentration is above the MIC (40% fT>MIC), 3g q8h by intermittent infusion is suggested unless a highly susceptible pathogen is present, in which case 1.5-g dosing could be used. If a higher target of 100% fT>MIC is required, a 1.5-g loading dose plus a 4.5-g continuous infusion may be adequate.

Doripenem dosing regimens in Asian critically ill patients with continuous renal replacement therapy

2019 ◽  
Vol 52 ◽  
pp. 233-236 ◽  
Author(s):  
Weerachai Chaijamorn ◽  
Punyawee Puchsaka ◽  
Sutthiporn Pattharachayakul ◽  
Taniya Charoensareerat ◽  
Nattachai Srisawat ◽  
...  
Keyword(s):  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Dosing Regimens

scholarly journals Dosing of antibiotics in patients with sepsis, including those undergoing renal replacement therapy

2019 ◽  
Vol 1 (16) ◽  
pp. 47-57
Author(s):  
A. O. Shalginskikh ◽  
S. V. Yakovlev ◽  
D. N. Protsenko ◽  
I. N. Sychev ◽  
M. P. Suvorova ◽  
...  
Keyword(s):  
Renal Replacement Therapy ◽  
Antibiotic Therapy ◽  
Replacement Therapy ◽  
Critically Ill ◽  
Antimicrobial Therapy ◽  
Critically Ill Patients ◽  
Antibacterial Drugs ◽  
Dosing Regimens ◽  
Determining Factor ◽  
Selection Of

In critically ill patients the adequacy of starting empirical antimicrobial therapy is a determining factor of the survival of patients with sepsis This article describes the main aspects of the empirical prescription of antibiotics in patients with sepsis who are on renal replacement therapy. Changes in the pharmacokinetic and pharmacodynamic mechanisms that lead to the selection of specific dosing regimens for antibiotics are described. Information on dosing changes for current groups of antibacterial drugs is presented. The purpose of this article is to rationalize antibiotic therapy in a selected group of patients.

Antibiotic Dosing in Critically Ill Patients Undergoing Renal Replacement Therapy

2015 ◽  
Vol 26 (3) ◽  
pp. 244-251 ◽  
Author(s):  
Gregory M. Susla
Keyword(s):  
Renal Failure ◽  
Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Residual Renal Function ◽  
Underlying Condition ◽  
Antibiotic Drugs ◽  
Dosing Regimens ◽  
Antibiotic Dosing

Continuous renal replacement therapy is frequently used to manage acute renal failure in critically ill patients. Antibiotic drugs used to treat infections in critically ill patients need to be dosed on the basis of the method of renal replacement therapy to be used, degree of residual renal function, and the sensitivity of the organism to be treated. Antibiotic dosing regimens must then be continuously monitored and adjusted according to modifications made to the renal replacement circuit and the patient’s underlying condition.

The Effect of Renal Replacement Therapy and Antibiotic Dose on Antibiotic Concentrations in Critically Ill Patients: Data From the Multinational Sampling Antibiotics in Renal Replacement Therapy Study

2020 ◽  
Author(s):  
Jason A Roberts ◽  
Gavin M Joynt ◽  
Anna Lee ◽  
Gordon Choi ◽  
Rinaldo Bellomo ◽  
...  
Keyword(s):  
Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Optimal Dosing ◽  
Wide Variability ◽  
Dosing Regimens ◽  
Trough Concentrations ◽  
Lower Limits ◽  
Antibiotic Dosing

Abstract Background The optimal dosing of antibiotics in critically ill patients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically ill patients receiving RRT and relate observed trough antibiotic concentrations to optimal targets. Methods We performed a prospective, observational, multinational, pharmacokinetic study in 29 intensive care units from 14 countries. We collected demographic, clinical, and RRT data. We measured trough antibiotic concentrations of meropenem, piperacillin-tazobactam, and vancomycin and related them to high- and low-target trough concentrations. Results We studied 381 patients and obtained 508 trough antibiotic concentrations. There was wide variability (4–8-fold) in antibiotic dosing regimens, RRT prescription, and estimated endogenous renal function. The overall median estimated total renal clearance (eTRCL) was 50 mL/minute (interquartile range [IQR], 35–65) and higher eTRCL was associated with lower trough concentrations for all antibiotics (P < .05). The median (IQR) trough concentration for meropenem was 12.1 mg/L (7.9–18.8), piperacillin was 78.6 mg/L (49.5–127.3), tazobactam was 9.5 mg/L (6.3–14.2), and vancomycin was 14.3 mg/L (11.6–21.8). Trough concentrations failed to meet optimal higher limits in 26%, 36%, and 72% and optimal lower limits in 4%, 4%, and 55% of patients for meropenem, piperacillin, and vancomycin, respectively. Conclusions In critically ill patients treated with RRT, antibiotic dosing regimens, RRT prescription, and eTRCL varied markedly and resulted in highly variable antibiotic concentrations that failed to meet therapeutic targets in many patients.

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