Background and importance With the increase of multidrug-resistant Gram-negative bacteria, aminoglycoside therapy is frequently essential, and its management is especially problematic in dialysis patients.
Aim and objectives The aim was to calculate the mean dose of gentamicin required to optimise pharmacokinetic/pharmacodynamics (PK/PD) parameters in intermittent haemodialysis patients to determine an initial dosing protocol.
Material and methods We performed a retrospective observational study including patients treated with gentamicin from January 2009 to April 2020, who were on a 4-hour haemodialysis programme three times per week. Gentamicin was administered 1 hour pre-dialysis and monitoring was performed by drawing a trough level (pre-dose) and a peak level (30 min after the infusion ended) at each administration. Gentamicin concentration was analysed by chemiluminescent microparticle immunoassay (CMIA).The estimation of kinetic parameters was performed by Bayesian methods with a single-compartment population model implemented in the Abbottbase-Pharmacokinetic System. Dialysis was introduced into the model as a disposition factor that increases drug clearance only during the 4 hours of dialysis. Data were evaluated using chi-square test. Significance was designated at p<0.05.
Results We identified 19 dialysis patients on gentamicin treatment. Gentamicin was used in 7 cases to treat infections caused by carbapenemase-producing Klebsiella pneumoniae, 8 skin-and-soft tissue infections, 5 urinary tract infections, 3 bacteraemias, 2 pneumonias and 1 endocarditis. Mean and range of age was 66 (45–80) years, weight 67.89 (44–88) kg and haematocrit 29.6% (22%–38%).The ratio of ABW/IBD was 1.04. Nine patients used the FX80 dialyser, 7 used the FX10 and 3 other dialysers, with a mean filtration rate of 2200 mL. In all patients residual diuresis was nil.Treatment duration was variable, 17 (4–47) days. Gentamicin was initiated at a mean dose (±SD) of 2.35±0.52 mg/kg (80–240 mg). After monitoring, 76.5% of patients achieved optimal levels of both Cmax (>8 µg/mL) and Cmin (<2 µg/mL), compared to 26.7% at baseline (p<0.001). The mean dose to maintain target values was 2.56±0.53 mg/kg, being the mean kinetic parameters: Vd=0.33±0.1 L/kg; inter-dialysis CL=0.46±0.16 L/hour and half-life=33.65±17.29 hours.
Conclusion and relevance To optimise the PK/PD parameters of gentamicin in patients undergoing haemodialysis, an initial dose of 2.5 mg/kg 1 hour pre-dialysis is proposed, without the need for loading doses. However, due to its complex management and high pharmacokinetic variability, strict monitoring from the first dose is essential.
Conflict of interest No conflict of interest
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