Fosfomycin single- and multiple-dose pharmacokinetics in patients undergoing prolonged intermittent renal replacement therapy

2021 ◽  
Author(s):  
Lisa K V Gerecke ◽  
Julius J Schmidt ◽  
Carsten Hafer ◽  
Gabriele Eden ◽  
Stefanie M Bode-Böger ◽  
...  
Keyword(s):  
Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Plasma Levels ◽  
Multiple Dose ◽  
Renal Replacement Therapies ◽  
Before And After ◽  
Severe Infections ◽  
Spent Dialysate ◽  
Multiple Dose Pharmacokinetics ◽  
Intermittent Renal Replacement Therapy

Abstract Background Fosfomycin is used increasingly in the treatment of MDR bacteria. It is eliminated by renal excretion, but data regarding dosing recommendations for patients undergoing modern means of renal replacement therapies are scarce. Objectives Evaluation of the pharmacokinetics (PK) of fosfomycin in patients undergoing prolonged intermittent renal replacement therapy (PIRRT) to guide dosing recommendations. Methods Fosfomycin was given in 11 (7 female) patients with severe infections undergoing PIRRT. Plasma levels were measured at several timepoints on the first day of fosfomycin therapy, as well as 5–6 days into therapy, before and after the dialyser, to calculate its clearance. Fosfomycin was measured in the collected spent dialysate. Results The median (IQR) plasma dialyser clearance for fosfomycin was 183.4 (156.9–214.9) mL/min, eliminating a total amount of 8834 (4556–10 440) mg of fosfomycin, i.e. 73.9% (45.3%–93.5%) of the initial dose. During PIRRT, the fosfomycin half-life was 2.5 (2.2–3.4) h. Data from multiple-dose PK showed an increase in fosfomycin Cmax from 266.8 (166.3–438.1) to 926.1 (446.8–1168.0) mg/L and AUC0–14 from 2540.5 (1815.2–3644.3) to 6714 (4060.6–10612.6) mg·h/L. Dialysis intensity during the study was 1.5 L/h. T>MIC was 100% in all patients. Conclusions Patients undergoing PIRRT experience significant fosfomycin elimination, requiring a dose of 5 g/8 h to reach adequate plasma levels. However, drug accumulation may occur, depending on dialysis frequency and intensity.

scholarly journals Intra-dialytic hypotension following the transition from continuous to intermittent renal replacement therapy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
William Beaubien-Souligny ◽  
Yifan Yang ◽  
Karen E. A. Burns ◽  
Jan O. Friedrich ◽  
Alejandro Meraz-Muñoz ◽  
...  
Keyword(s):  
Renal Replacement Therapy ◽  
Hospital Mortality ◽  
Replacement Therapy ◽  
Kidney Injury ◽  
Hemodynamic Instability ◽  
Factors Associated ◽  
Definition Of ◽  
Vasopressor Use ◽  
Cumulative Fluid Balance ◽  
Intermittent Renal Replacement Therapy

Abstract Background Transition from continuous renal replacement therapy (CRRT) to intermittent renal replacement therapy (IRRT) can be associated with intra-dialytic hypotension (IDH) although data to inform the definition of IDH, its incidence and clinical implications, are lacking. We aimed to describe the incidence and factors associated with IDH during the first IRRT session following transition from CRRT and its association with hospital mortality. This was a retrospective single-center cohort study in patients with acute kidney injury for whom at least one CRRT-to-IRRT transition occurred while in intensive care. We assessed associations between multiple candidate definitions of IDH and hospital mortality. We then evaluated the factors associated with IDH. Results We evaluated 231 CRRT-to-IRRT transitions in 213 critically ill patients with AKI. Hospital mortality was 43.7% (n = 93). We defined IDH during the first IRRT session as 1) discontinuation of IRRT for hemodynamic instability; 2) any initiation or increase in vasopressor/inotropic agents or 3) a nadir systolic blood pressure of < 90 mmHg. IDH during the first IRRT session occurred in 50.2% of CRRT-to-IRRT transitions and was independently associated with hospital mortality (adjusted odds ratio [OR]: 2.71; CI 1.51–4.84, p < 0.001). Clinical variables at the time of CRRT discontinuation associated with IDH included vasopressor use, higher cumulative fluid balance, and lower urine output. Conclusions IDH events during CRRT-to-IRRT transition occurred in nearly half of patients and were independently associated with hospital mortality. We identified several characteristics that anticipate the development of IDH following the initiation of IRRT.

Pharmacokinetics of Ceftolozane-Tazobactam during Prolonged Intermittent Renal Replacement Therapy

Chemotherapy ◽  
2018 ◽  
Vol 63 (4) ◽  
pp. 203-206 ◽  
Author(s):  
Matthew Rawlins ◽  
Vesa Cheng ◽  
Edward Raby ◽  
John Dyer ◽  
Adrian Regli ◽  
...  
Keyword(s):  
Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Goodness Of Fit ◽  
Final Model ◽  
Blood Samples ◽  
Compartment Models ◽  
Log Likelihood ◽  
New Antibiotics ◽  
Plasma Pharmacokinetics ◽  
Intermittent Renal Replacement Therapy

Background: Prolonged intermittent renal replacement therapy (PIRRT) eliminates many drugs, and without dosing data, for new antibiotics like ceftolozane/tazobactam, suboptimal concentrations and treatment failure are likely. Objectives: Herein, we describe the effect of PIRRT on the plasma pharmacokinetics of ceftolozane/tazobactam ad­ministered in a critically ill 55-year-old patient with a polymicrobial sternal wound osteomyelitis, including a multiresistant Pseudomonas aeruginosa. Method: Blood samples were taken over 4 days where the patient received a 7.5-h PIRRT treatment. One- and 2-compartment models were tested for ceftolozane and tazobactam separately, and the log-likelihood ratio and goodness-of-fit plots were used to select the final model. Results: Two-compartment models were developed for ceftolozane and tazobactam separately and described significant differences in clearance of ceftolozane and tazobactam with and without PIRRT (8.273 vs. 0.393 and 8.020 vs. 0.767 L/h, respectively). Conclusions: A ceftolozane/tazobactam dose of 500 mg/250 mg appears to be sufficient to attain pharmacokinetic/pharmacodynamic targets during PIRRT while the manufacturer’s recommended dosing of 100 mg/50 mg every 8 h was sufficient during non-PIRRT periods.

Prolonged intermittent renal replacement therapy in children

2017 ◽  
Vol 33 (8) ◽  
pp. 1283-1296 ◽  
Author(s):  
Rajiv Sinha ◽  
Sidharth Kumar Sethi ◽  
Timothy Bunchman ◽  
Valentine Lobo ◽  
Rupesh Raina
Keyword(s):  
Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Intermittent Renal Replacement Therapy

Effect of parameters of renal replacement therapy on platelet aggregation activity

2020 ◽  
Author(s):  
Т.В. Марченко ◽  
А.В. Гончарова ◽  
И.Н. Соловьева ◽  
Е.О. Марченко ◽  
А.М. Исаева
Keyword(s):  
Chronic Kidney Disease ◽  
Platelet Aggregation ◽  
Renal Replacement Therapy ◽  
Kidney Disease ◽  
Replacement Therapy ◽  
Normal Range ◽  
Dialysis Therapy ◽  
Before And After ◽  
Aggregation Activity

Цель исследования: оценить влияние параметров заместительной почечной терапии (ЗПТ) на агрегационную активность тромбоцитов у пациентов с хронической болезнью почек (ХБН). Материалы и методы. Было выполнено 25 процедур гемодиализа (ГД) и 10 процедур гемодиафильтрации (ГДФ) 35 больным с ХБП. Изучали динамику агрегационной активности тромбоцитов до и после экстракорпоральных процедур. Результаты. После процедуры ГД агрегация тромбоцитов снижалась, а после процедуры ГДФ нарастала, не выходя за пределы нормальных значений. Параметры процедур ЗПТ на агрегацию тромбоцитов значимого влияния не оказывали. Заключение. Разовая процедура ЗПТ протяженностью не более 4 ч, проводимая с учетом всех современных требований к диализной терапии, не оказывает негативного влияния на функциональную активность тромбоцитов. Процедура ГДФ приводит к непринципиальному росту агрегационной активности тромбоцитов. Aim: to assess the effect of renal replacement therapy (RRT) parameters on platelet aggregation activity in patients with chronic kidney disease (CKD). Materials and methods. For 35 patients with CKD 25 hemodialysis (HD) procedures and 10 hemodiafiltration (HDF) procedures were performed. We studied the dynamics of platelet aggregation activity before and after extracorporeal procedures. Results. After the HD procedure, platelet aggregation decreased, and after the HDF procedure it increased, without going outside the normal range. Parameters of RRT procedures did not have a significant effect on platelet aggregation. Conclusion. A single RRT procedure not more than 4 hours with all nowadays requirements for dialysis therapy does not adversely affect the functional platelets activity. The HDF procedure leads to an unprincipled increasing of platelet aggregation activity.

Antithrombotic managemement of the blood circuit in intermittent renal replacement therapy

1998 ◽  
pp. 1427-1439
Author(s):  
Philippe Morinière ◽  
Bertrand deCagny ◽  
Najeh El Esper ◽  
Jean M. Achard ◽  
Pierre F. Westeel ◽  
...  
Keyword(s):  
Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Intermittent Renal Replacement Therapy

Biophysics of intermittent renal replacement therapy

1998 ◽  
pp. 1391-1409
Author(s):  
Laurie Garred ◽  
Bernard Canaud ◽  
Martine Leblanc ◽  
Jean-Yves Bosc
Keyword(s):  
Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Intermittent Renal Replacement Therapy
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