Antibiotic therapeutic drug monitoring in intensive care patients treated with different modalities of extracorporeal membrane oxygenation (ECMO) and renal replacement therapy: a prospective, observational single-center study.

BACKGROUND: Effective antimicrobial treatment is key to reduce mortality associated with bacterial sepsis in patients on intensive care units (ICUs). Dose adjustments are often necessary to account for pathophysiological changes or renal replacement therapy. Extracorporeal membrane oxygenation (ECMO) is increasingly being used for the treatment of respiratory and/or cardiac failure. However, it remains unclear whether dose adjustments are necessary to avoid subtherapeutic drug levels in septic patients on ECMO support. Here, we aimed to evaluate and comparatively assess serum concentrations of continuously applied antibiotics in intensive care patients being treated with and without ECMO. METHODS: Between October 2018 and December 2019, we prospectively enrolled patients on a pneumological ICU in southwest Germany who received antibiotic treatment with piperacillin/tazobactam, ceftazidime, meropenem, or linezolid. All antibiotics were applied using continuous infusion, and therapeutic drug monitoring of serum concentrations (expressed as mg/L) was carried out using high-performance liquid chromatography. Target concentrations were defined as fourfold above the minimal inhibitory concentration (MIC) of susceptible bacterial isolates, according to EUCAST breakpoints. RESULTS: The final cohort comprised 105 ICU patients, of whom 30 were treated with ECMO. ECMO patients were significantly younger (mean age: 47.7 vs. 61.2 years; p < 0.001), required renal replacement therapy more frequently (53.3% vs. 32.0%; p = 0.048) and had an elevated ICU mortality (60.0% vs. 22.7%; p < 0.001). Data on antibiotic serum concentrations derived from 112 measurements among ECMO and 186 measurements from non-ECMO patients showed significantly lower median serum concentrations for piperacillin (32.3 vs. 52.9; p = 0.029) and standard-dose meropenem (15.0 vs. 17.8; p = 0.020) in the ECMO group. We found high rates of insufficient antibiotic serum concentrations below the pre-specified MIC target among ECMO patients (piperacillin: 48% vs. 13% in non-ECMO; linezolid: 35% vs. 15% in non-ECMO), whereas no such difference was observed for ceftazidime and meropenem. CONCLUSIONS: ECMO treatment was associated with significantly reduced serum concentrations of specific antibiotics. Future studies are needed to assess the pharmacokinetic characteristics of antibiotics in ICU patients on ECMO support.

Weaning from prolonged veno-venous extracorporeal membrane oxygenation (ECMO) after transfer to a specialized center: a retrospective study.

Veno-venous extracorporeal membrane oxygenation (vvECMO) is increasingly used as rescue therapy in severe respiratory failure. In patients with pre-existent lung diseases or persistent lung injury weaning from vvECMO can be challenging. This study sought to investigate outcomes of patients transferred to a specialized ECMO center after prolonged ECMO therapy. We performed a retrospective analysis of all patients admitted to our medical intensive care unit (ICU) between 01/2013 and 12/2016 who were transferred from an external ICU after > 8 days on vvECMO. 12 patients on ECMO for > 8 days were identified. Prior to transfer, patients underwent ECMO therapy for 18 ± 9.5 days. Total time on ECMO was 60 ± 46.6 days. 11/12 patients could be successfully weaned from ECMO, 7/12 in the first 28 days after transfer (8 ± 8.8 ECMO-free days at day 28). In 7 patients, ECMO could be terminated after at least partial lung recovery, in 4 patients after salvage lung transplant. No patient died or needed re-initiation of ECMO therapy at day 28. In summary, weaning from vvECMO was feasible even after prolonged ECMO courses and salvage lung transplant could be avoided in most cases. Patients may benefit from transfer to a specialized ECMO center.