Removal of linezolid by conventional intermittent hemodialysis, sustained low-efficiency dialysis, or continuous venovenous hemofiltration in patients with acute renal failure

Fiaccadori, Enrico; Maggiore, Umberto; Rotelli, Carlo; Giacosa, Roberto; Parenti, Elisabetta; Picetti, Edoardo; Sagripanti, Sibilla; Manini, Paola; Andreoli, Roberta; Cabassi, Aderville

doi:10.1097/01.ccm.0000147687.06808.92

Cited by 95 publications

(60 citation statements)

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“…In contrast, two studies revealed either significantly reduced serum linezolid concentrations in critically ill patients on intermittent hemodialysis (IHD) [31] or serum concentrations of linezolid reduced to subtherapeutic values following renal replacement therapy [32]. Fiaccadori studied two patients on ED in which the ED session lasted 8-9 h, whereas the average time of ED in our study was 19.5 h. They also found an important fraction of the administered dose of linezolid was removed, especially in the case of IHD with ED.…”

Section: Discussionmentioning

confidence: 93%

Pharmacokinetics of linezolid in septic patients with and without extended dialysis

Swoboda

Ober

Lichtenstern

et al. 2009

Eur J Clin Pharmacol

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Purpose Linezolid is an option for the treatment of infections caused by multiresistant Gram-positive bacteria. The survival of critically ill patients with acute renal failure (ARF) can be improved by increasing the dose of renal replacement therapy. Extended (daily) dialysis (ED) is a new and important approach to renal replacement therapy in intensive care units. The aim of the study was to evaluate the pharmacokinetics of linezolid in septic patients without ED and on ED, respectively. Methods We studied the pharmacokinetics of linezolid in adult intensive care patients with sepsis (n=5) and anuric septic patients with ARF being treated with ED (n=10). Linezolid 600 mg was administered intravenously twice daily. The pharmacokinetic parameters, their variability, and possible covariates were analyzed using NONMEM. , and peripheral volume of distribution (V 2 )=0.271 L/kg. The clearance in ED patients while on dialysis was increased by 3.5 L/h, and patients with liver transplantation/resection had their clearance reduced by 60%. Intra-individual variability was much smaller than inter-individual variability. Conclusions Our results suggest that linezolid pharmacokinetics in critically ill patients with ARF undergoing ED is not comparable to that in healthy subjects and patients without ARF. The best method of managing linezolid dosage in such a complex group of patients, whose physiology can vary daily, would be to use therapeutic drug monitoring.

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Section: Discussionmentioning

confidence: 93%

Pharmacokinetics of linezolid in septic patients with and without extended dialysis

Swoboda

Ober

Lichtenstern

et al. 2009

Eur J Clin Pharmacol

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“…Consistent with prior reports (4), thrombocytopenia appeared to be duration dependent, occurring more frequently in those treated for greater than 14 days (0/13 versus 13/13, P Ͻ 0.001, Fisher's exact test). Of note, given that renal excretion is the main route of linezolid clearance (5), 6 of the 12 patients receiving hemodialysis developed thrombocytopenia versus 7/32 nonhemodialysis patients (P ϭ 0.07, chi-square test) (Table 2), suggesting that drug or metabolite accumulation may play a role in this AR, despite the fact that linezolid is known to be removed by conventional intermittent hemodialysis (6). Unfortunately, no serum drug or metabolite levels were collected from our patients to assess this issue more closely, but it is the subject of currently ongoing research by our group.…”

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confidence: 99%

Good Clinical Outcomes but High Rates of Adverse Reactions during Linezolid Therapy for Serious Infections: a Proposed Protocol for Monitoring Therapy in Complex Patients

Bishop

Melvani

Howden

et al. 2006

Antimicrob Agents Chemother

131

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We assessed the toxicity and clinical outcomes associated with linezolid therapy (mean duration, 29 ؎ 28 days; range, 8 to 185 days) in 44 patients with serious gram-positive infections. Although a clinical cure was achieved in 73% of the cases, 28/44 (64%) had adverse reactions (thrombocytopenia, n ‫؍‬ 13; anemia, n ‫؍‬ 7; gastrointestinal, n ‫؍‬ 12; peripheral neuropathy, n ‫؍‬ 1; serotonin syndrome, n ‫؍‬ 1), such that a systematic monitoring protocol was developed.

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“…Moreover, in intensive care units (ICUs), extended dialysis (ED), a hybrid of continuous and intermittent renal replacement therapy (RRT), is increasingly used throughout the world (4-7). ED removes various antibiotics more efficiently compared with standard intermittent hemodialysis (IHD) three times a week or continuous RRT (8)(9)(10)(11)(12)(13), as very recently reviewed by Bogard et al (14). A single report from a patient with AKI suggests that higher doses of ampicillin/ sulbactam might also be necessary for critically ill patients treated with ED compared with intermittent hemodialysis (IHD) in the outpatient setting (15).…”

Section: Introductionmentioning

confidence: 97%

Pharmacokinetics of Ampicillin/Sulbactam in Critically Ill Patients with Acute Kidney Injury undergoing Extended Dialysis

Lorenzen

Broll

Kaever

et al. 2012

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives The fixed antibacterial combination of ampicillin and sulbactam is frequently used for various infections. Intact kidneys eliminate approximately 71% of ampicillin and 78% of sulbactam. Patients on thrice-weekly low-flux hemodialysis exhibit an ampicillin t 1/2 of 2.3 hours on and 17.4 hours off dialysis. Despite its frequent use in intensive care units, there are no available dosing recommendations for patients with AKI undergoing renal replacement therapy. The aims of this study were to evaluate the pharmacokinetics of ampicillin/ sulbactam in critically ill patients with AKI undergoing extended dialysis (ED) and to establish a dosing recommendation for this treatment method.Design, setting, participants, & measurements Twelve critically ill patients with anuric AKI being treated with ED were enrolled in a prospective, open-label, observational pharmacokinetic study. Pharmacokinetics after a single dose of ampicillin/sulbactam (2 g/1 g) was obtained in 12 patients. Multiple-dose pharmacokinetics after 4 days of twice-daily ampicillin/sulbactam (2 g/1 g) was obtained in three patients. ResultsThe mean dialyzer clearance for ampicillin/sulbactam was 80.167.7/83.3612.1 ml/min. The t 1/2 of ampicillin and sulbactam in patients with AKI undergoing ED were 2.860.8 hours and 3.561.5 hours, respectively. There was no significant accumulation using a twice-daily dosage of 2 g/1 g ampicillin/sulbactam.Conclusions Our data suggest that in patients treated with ED using a high-flux dialyzer (polysulphone, 1.3 m 2 ; blood and dialysate flow, 160 ml/min; treatment time, 480 minutes), a twice-daily dosing schedule of at least 2 g/1 g ampicillin/sulbactam, with one dose given after ED, should be used to avoid underdosing.

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Removal of linezolid by conventional intermittent hemodialysis, sustained low-efficiency dialysis, or continuous venovenous hemofiltration in patients with acute renal failure

Abstract: In patients with acute renal failure, serum levels of linezolid can be reduced to the subtherapeutic range following renal replacement therapy.

Cited by 95 publications

References 16 publications

Pharmacokinetics of linezolid in septic patients with and without extended dialysis

Pharmacokinetics of linezolid in septic patients with and without extended dialysis

Good Clinical Outcomes but High Rates of Adverse Reactions during Linezolid Therapy for Serious Infections: a Proposed Protocol for Monitoring Therapy in Complex Patients

Pharmacokinetics of Ampicillin/Sulbactam in Critically Ill Patients with Acute Kidney Injury undergoing Extended Dialysis

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