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

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.

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

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.

Acute intermittent renal replacement therapy in a rural Scottish intensive care unit – a review of patient and renal outcomes

In this study we report 5-year outcomes for patients who received intermittent haemodiafiltration for Acute Kidney Injury (AKI) between 2010 and 2014 in a small Scottish Intensive Care Unit (ICU). Dialysis independence and mortality at ICU discharge, 30 and 90 days, one and five years were determined. There were 1496 admissions to ICU during the study period. 12% of patient admissions required Renal Replacement Therapy (RRT). 56.3% of patients survived to ICU discharge and all were RRT independent at ICU discharge. 30 day, 90 day, 1 year and 5 year survival was 52.3%, 50.6%, 46.6% and 30.7% respectively. By 5 years, 2 patients had developed end stage kidney disease.

Cardiorenal syndrome in COVID-19

SARS-CoV-2 preferentially targets the human’s lungs, but it can affect multiple organ systems. We report a case of cardiorenal syndrome in a 37-year-old man who had symptoms of fever, myalgia and cough. He tested positive for COVID-19 and presented 5 days later with acute heart failure. Work up was done including echocardiography showing reduced ejection fraction. Later in the hospital course he developed acute renal failure and was treated with intermittent renal replacement therapy. No other definite cause of cardiorenal complications was identified during the course of the disease. A possible link with COVID-19 was considered with underlying mechanisms still needed to be explored. This case highlights the potential of SARS-CoV-2 affecting heart and kidneys. The disease not only involves the organs directly but can exacerbate the underlying comorbid illness.

Association between Prolonged Intermittent Renal Replacement Therapy and All-Cause Mortality in COVID-19 Patients Undergoing Invasive Mechanical Ventilation: A Retrospective Cohort Study

<b><i>Background:</i></b> The mortality rate of critically ill patients with coronavirus disease 2019 (COVID-19) was high. We aimed to assess the association between prolonged intermittent renal replacement therapy (PIRRT) and mortality in patients with COVID-19 undergoing invasive mechanical ventilation. <b><i>Methods:</i></b> This retrospective cohort study included all COVID-19 patients receiving invasive mechanical ventilation between February 12 and March 2, 2020. All patients were followed until death or March 28, and all survivors were followed for at least 30 days. <b><i>Results:</i></b> For 36 hospitalized COVID-19 patients receiving invasive mechanical ventilation, the mean age was 69.4 (±10.8) years, and 30 patients (83.3%) were men. Twenty-two (61.1%) patients received PIRRT (PIRRT group), and 14 cases (38.9%) were managed with conventional strategy (non-PIRRT group). There were no differences in age, sex, comorbidities, complications, treatments, and most of the laboratory findings. During the median follow-up period of 9.5 (interquartile range 4.3–33.5) days, 13 of 22 (59.1%) patients in the PIRRT group and 11 of 14 (78.6%) patients in the non-PIRRT group died. Kaplan-Meier analysis demonstrated prolonged survival in patients in the PIRRT group compared with that in the non-PIRRT group (<i>p</i> = 0.042). The association between PIRRT and a reduced risk of mortality remained significant in 3 different models, with adjusted hazard ratios varying from 0.332 to 0.398. Increased IL-2 receptor, TNF-α, procalcitonin, prothrombin time, and NT-proBNP levels were significantly associated with an increased risk of mortality in patients with PIRRT. <b><i>Conclusion:</i></b> PIRRT may be beneficial for the treatment of COVID-19 patients with invasive mechanical ventilation. Further prospective multicenter studies with larger sample sizes are required.