ABSTRACT
To assess fosfomycin (FOS) elimination in patients with sepsis and acute kidney injury (AKI) undergoing slow-extended daily dialysis (SLEDD) with the Genius system in a prospective observational study. After ethics committee approval ten patients with sepsis and AKI stage 3 underwent daily SLEDD sessions of eight hours. FOS was applied i.v. at doses of 3 × 5 g per day. FOS serum levels were measured pre- and post hemofilter before, during, and after SLEDD sessions, and instantaneous clearance was calculated. In five of the patients, we analyzed FOS levels after the first dose, in the other five patients serum levels were measured during ongoing therapy. FOS was eliminated rapidly via the hemofilter. FOS clearance decreased from 152 ± 10 mL/min (start of SLEED session) to 43 ± 38 mL/min (end of SLEDD session). In 3/5 first-dose patients after 4-6 h of SLEDD the FOS serum level fell below the EUCAST breakpoint of 32 mg/L for Enterobacterales and Staphylococcus species. In all patients with ongoing fosfomycin therapy serum levels were high and above the breakpoint at all times. FOS toxicity or adverse effects were not observed. FOS serum concentrations exhibit wide variability in critically ill patients with sepsis and AKI. FOS is eliminated rapidly during SLEDD. A loading dose of 5 g is not sufficient to achieve serum levels above the EUCAST breakpoint for common bacteria in all patients, considering that T > MIC > 70% of the dosing interval indicates sufficient plasma levels. We thus recommend a loading dose of 8 g followed by a maintenance dose of 5 g after a SLEDD session in anuric patients. We strongly recommend therapeutic drug monitoring of FOS levels in critically ill patients with AKI and dialysis therapy.
Subject(s)
Acute Kidney Injury/therapy , Fosfomycin/administration & dosage , Fosfomycin/adverse effects , Sepsis/therapy , Acute Kidney Injury/complications , Aged , Critical Illness , Dose-Response Relationship, Drug , Drug Monitoring , Enterobacter , Female , Hemodynamics , Hemofiltration , Humans , Male , Middle Aged , Prospective Studies , Renal Dialysis , Sepsis/complicationsABSTRACT
Non-01 cholera vibrios for the first time has been isolated from freshwater in Poland. In October 1994 during bacteriological examination of Bug water by a two-step enrichment method in alkaline peptone water at pH 8.6 and TCBS. Repeated examination in November, December and January in the same and other locations among the polish-ukrainian borderline revealed persistence of V. cholerae in the river; 22 strains were isolated. All 22 strains were identical to V. cholerae E1 Tor 01 Ogawa reference strain except to antigens 0. The strains isolated from water were no agglutinable by standard 01 serum neither by 0139 serum. Determination of their antigens 0 is under investigations. They might be pathogenic for people as it could be judged by their high resistance to bile, proteolytic and haemolytic activity. No cholera-like cases were notified on the polish side of the river.
