Study | Endpoints | Antibiotic | Design | Results | Conclusions |
---|---|---|---|---|---|
Donadello et al. [100] | To investigate whether ECMO could alter the pharmacokinetics of meropenem and piperacillin/tazobactam in ICU patients | Meropenem Piperacilin/tazobactam | Retrospective, case-control study in 67 ICU patients Antibiotics daily dosing was done according to renal dosing Beta-lactam plasma concentrations were measured T2 and just before administration of the subsequent dose T0 TDM results in ECMO patients (VV or VA) were matched (1:1) to TDM results of non-ECMO patients (total 41 TDM matches) according to the following criteria: drug regimen; renal function (same ClCr or, if on CRRT, same CRRT intensity with an acceptable difference of 10%); total body weight; SOFA score at the time of treatment initiation; age | For both antibiotics, there were numerical differences but with no statistical significance in Vd, t1/2 and CL between ECMO patients and controls The proportions of insufficient (13/41 vs12/41), adequate (15/41 vs 19/41), and excessive (13/41 vs 10/41) drug concentrations were similar in ECMO and control patients | PK parameters and TDM results were not significantly altered in ECMO patients compared with control ICU patients Almost 30% of the overall TDM results were associated with insufficient antibiotic concentrations to optimally treat P. aeruginosa |
Shekar et al. [101] | To describe single-dose meropenem PK during ECMO using critically ill patients with sepsis and not receiving ECMO as controls | Meropenem | Open-label, descriptive, matched-cohort PK study Adult ICU patients on ECMO (no RRT n = 6; on RRT n = 5) and controls (no renal dysfunction n = 5; on RRT n = 5) Meropenem doses in ECMO: 1 g 8/8 h (n = 8); 1.5 g 8/8 h (n = 2) and 2 g bolus; and 1 g 8/8 h (n = 1) Controls: 1.5 g bolus and 1 g 8/8 h (no renal dysfunction); 1 g 8/8 h | Controls vs ECMO Cmax: 65.4 (58.7–74.4) vs 55.3 (37.8–60.4) mg/L Cmin: 4.2 (0.0–5.7) vs 7.2 (4.0–17.2) mg/L Vd: 0.45 ± 0.17 vs 0.41 ± 0.13 L/kg, P = 0.21 Clearance: 7.9 ± 5.9 vs 11.7 ± 6.5 L/h, P = 0.18 ECMO patients, trough concentrations > 2 mg/L were achieved in all patients. Through concentrations > 8 mg/L (targeting less susceptible microorganisms) were achieved in only 8 out of 11 patients, 5 of them being on RRT | Standard meropenem dosing (1 g IV 8-hourly) as an intermittent bolus infusion in ECMO patients is likely to result in drug concentrations sufficient to treat highly susceptible Gram-negative pathogens However, when treating less susceptible P. aeruginosa (MIC90 8 mg/L) and Acinetobacter species (MIC90 16 mg/L) higher meropenem doses may have to be considered |
Welsch et al. [102] | To report the cases of two patients on VV ECMO for refractory ARDS following lung transplantation and treated empirically with imipenem | Imipenem | Case report Imipenem 1 g every 6 h Serum and mini-BAL samples (native and transplant lung) collected at steady state after 2 days of therapy immediately before the fifth drug dose Enterobacter cloacae was isolated from the respiratory sample of patient 1 and Klebsiella pneumoniae was isolated from the respiratory sample of patient 2 MIC of the two isolated strains were 0.125 and 0.25 mg/L, respectively | BAL concentrations were undetectable (< 0.5 mg/L) Serum T > MIC of both microorganisms was 100% Considering more resistant microorganisms, such as P. aeruginosa with MIC > 2 mg/L, the probability of achieving a fractional time above MIC > 50% or 100% was also high There was great variability in the residual serum concentration of imipenem between the two patients | An elevated dosing regimen (4 g/24 h) is more likely to optimize drug exposure, and therapeutic drug monitoring is recommended |