Colistin pharmacokinetics in intensive care unit patients on continuous venovenous haemodiafiltration: an observational study

Μάρκου, Νικόλαος; Fousteri, Marizoza; Markantonis, Sophia L.; Zidianakis, Basilios; Hroni, D; Boutzouka, Eleni; Baltopoulos, George

doi:10.1093/jac/dks257

Cited by 60 publications

(50 citation statements)

References 9 publications

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“…In conclusion, both CMS and colistin are cleared by CVVHDF, although the clearance of CMS is not restored to the values found in related studies (9,13), and the data from this study corroborate findings in previous studies (4)(5)(6)(7). The dosage regimen of 160 mg CMS q8h that was used has been motivated by the risk of accumulation of drug and concomitantly increased risk of toxicity.…”

supporting

confidence: 79%

“…The dialyzer clearance was similar to that determined for the four patients on continuous renal replacement therapy reported by Garonzik et al (4), whereas Marchand et al (6) presented similar dialyzer extraction ratios. Unfortunately, colistin is notorious for its ability to be adsorbed to many different materials, such as laboratory utensils (11) as well as HDF filters (7). Therefore, we were not able to reliably measure the concentrations of CMS and colistin in the combined dialysate/ultrafiltrate, and thus sieving was not possible to calculate.…”

mentioning

confidence: 98%

See 1 more Smart Citation

Colistin Methanesulfonate and Colistin Pharmacokinetics in Critically Ill Patients Receiving Continuous Venovenous Hemodiafiltration

Karvanen

Plachouras

Friberg

et al. 2013

Antimicrob Agents Chemother

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dThis report describes the pharmacokinetics of colistin methanesulfonate (CMS) and colistin in five intensive care unit patients receiving continuous venovenous hemodiafiltration. For CMS, the mean maximum concentration of drug in plasma (C max ) after the fourth dose was 6.92 mg/liter and total clearance (CL) 8.23 liters/h. For colistin, the mean concentration was 0.92 mg/ liter and CL/metabolized fraction (f m ) 18.91 liters/h. Colistin concentrations were below the current MIC breakpoints, and the area under the concentration-time curve for the free, unbound fraction of the drug over 24 h in the steady state divided by the MIC (fAUC/MIC) was lower than recommended, suggesting that a dosage regimen of 160 mg CMS every 8 h (q8h) is inadequate.T he use of colistin, an old antibiotic, has recently reemerged due to the increased prevalence of infections caused by multidrugresistant Gram-negative bacteria (MDR-GNB), especially in critically ill patients (1, 2). Such patients often suffer from acute renal impairment necessitating renal replacement therapy (3). However, there are only scarce data on the effect of renal replacement methods on the pharmacokinetics of colistin (4-7). The present study was undertaken to study the elimination of colistin methanesulfonate (CMS) and colistin in patients undergoing continuous venovenous hemodiafiltration (CVVHDF) to contribute to the knowledge regarding the pharmacokinetics of colistin in this population.Patients admitted to the Critical Care Unit of University General Hospital Attikon in Athens, Greece, were eligible for the study if they fulfilled the following inclusion criteria: (i) they were 18 years of age or older; (ii) they were receiving colistin treatment as part of their standard care due to probable or documented infection by MDR-GNB; and (iii) they were receiving CVVHDF treatment as renal replacement therapy. For each patient, the following were recorded: age, body weight, serum creatinine (s-Cr), creatine clearance (CrCL), serum albumin (s-Alb), hemoglobin (Hb), hematocrit (Hct), and Acute Physiology and Chronic Health Evaluation II (APACHE II) score on the first day of colistin administration.The study was approved by the Ethics Committee of the Hospital (registration no. 3/30-3-07). Informed consent was provided by the patients or nearest relatives.CMS (colistin methanesulfonate [Colistin/Norma]; Norma Hellas, Athens, Greece) was administered every 8 h (q8h) by intravenous infusion over 15 min according to local practice at a dose of 2 million units (MU), equivalent to 160 mg CMS, dissolved in 100 ml of normal saline solution.Vascular access was obtained by insertion of a double lumen dialysis catheter. Each patient was dialyzed using the Prisma system (Hospal-Gambro). Continuous venovenous hemodiafiltration (CVVHDF) was performed using an acrylonitrile and sodium methallyl sulfonate copolymer hollow-fiber high-flux hemofilter (AN69 HF) with a membrane surface area of 0.9 m 2 (M100 predilution filter set; Hospal). Hemosol B0 solution (Gambro) was infused as a...

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supporting

confidence: 79%

mentioning

confidence: 98%

Colistin Methanesulfonate and Colistin Pharmacokinetics in Critically Ill Patients Receiving Continuous Venovenous Hemodiafiltration

Karvanen

Plachouras

Friberg

et al. 2013

Antimicrob Agents Chemother

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“…Recent data shows that colistin is efficiently removed by CRRT and that doses similar to those used in normal renal function are likely necessary. 24,46,47 A dose recommendation of 192 mg of CBA daily for each 1 mg/L of desired C ss,avg was recommended by Garonzik and colleagues in their extensive study of colistin PK-PD, but it was based on 4 patients. 24 Another study of 3 patients receiving CRRT reported substantial clearance of colistin by CRRT, though total clearance was somewhat reduced.…”

Section: Polymyxinsmentioning

confidence: 99%

“…24 Another study of 3 patients receiving CRRT reported substantial clearance of colistin by CRRT, though total clearance was somewhat reduced. 47 A report of polymyxin B in 2 patients receiving CRRT showed that it was minimally removed and suggested that it should probably not be adjusted for extracorporeal elimination, though data is not definitive. 48 Both polymyxins exhibit concentration-dependent killing and that the pharmacodynamic parameter that is most closely associated with efficacy is the free areaunder-the-curve (AUC) to MIC ratio (fAUC/MIC).…”

Section: Polymyxinsmentioning

confidence: 99%

Pharmacodynamic and pharmacokinetic considerations in the treatment of critically Ill patients infected with carbapenem-resistant Enterobacteriaceae

Neuner

Gallagher

2016

Virulence

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Carbapenem-Resistant Enterobacteriaceae (CRE) are an emerging healthcare crisis. Infections due to CRE are associated with high morbidity and mortality, especially in critically ill patients. Due to the multi-drug resistant nature of these infections only limited treatment options are available. Antimicrobials that have been described for the treatment of CRE infections include carbapenems, polymyxins, fosfomycin, tigecycline, aminoglycosides, and ceftazidime-avibactam. Given the limited treatment options it is imperative the pharmacokinetic and pharmacodynamics (PK-PD) characteristics of these agents are considered to optimize treatment regimens. This review will focus on the PK-PD challenges of the current treatment options for CRE infections.

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“…Investigators may also consider calculating the fraction of the administered dose that is recovered in the effluent in order to assess the need to administer supplemental drug doses to CRRT patients. Finally, determination of the contribution of adsorption to CL EC may be important for select drugs and hemofilters (6,35).…”

Section: Estimation Of Pharmacokinetic Parametersmentioning

confidence: 99%

Pharmacokinetic Assessment in Patients Receiving Continuous RRT

Nolin¹,

Aronoff²,

Fissell³

et al. 2015

Clinical Journal of the American Society of Nephrology

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The effect of AKI and modern continuous RRT (CRRT) methods on drug disposition (pharmacokinetics) and response has been poorly studied. Pharmaceutical manufacturers have little incentive to perform pharmacokinetic studies in patients undergoing CRRT because such studies are neither recommended in existing US Food and Drug Administration (FDA) guidance documents nor required for new drug approval. Action is urgently needed to address the knowledge deficit. The Kidney Health Initiative has assembled a work group composed of clinicians and scientists representing academia, the FDA, and the pharmaceutical and dialysis industries with expertise related to pharmacokinetics, AKI, and/or CRRT. The work group critically evaluated key considerations in the assessment of pharmacokinetics and drug dosing in CRRT, practical constraints related to conducting pharmacokinetic studies in critically ill patients, and the generalizability of observations made in the context of specific CRRT prescriptions and specific patient populations in order to identify efficient study designs capable of addressing the knowledge deficit without impeding drug development. Considerations for the standardized assessment of pharmacokinetics and development of corresponding drug dosing recommendations in critically ill patients with AKI receiving CRRT are proposed.

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Colistin pharmacokinetics in intensive care unit patients on continuous venovenous haemodiafiltration: an observational study

Cited by 60 publications

References 9 publications

Colistin Methanesulfonate and Colistin Pharmacokinetics in Critically Ill Patients Receiving Continuous Venovenous Hemodiafiltration

Colistin Methanesulfonate and Colistin Pharmacokinetics in Critically Ill Patients Receiving Continuous Venovenous Hemodiafiltration

Pharmacodynamic and pharmacokinetic considerations in the treatment of critically Ill patients infected with carbapenem-resistant Enterobacteriaceae

Pharmacokinetic Assessment in Patients Receiving Continuous RRT

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