Abstract
BackgroundEffective 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.MethodsBetween 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.ResultsThe 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.ConclusionsECMO 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.
Highlights
Sepsis and septic shock due to pneumonia and infections at other body sites are major life-threatening events, which are frequent causes of admission to intensive care units (ICUs) for specific treatment
Data on antibiotic serum concentrations derived from 112 measurements among Extracorporeal membrane oxygenation (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 minimal inhibitory concentration (MIC) target among ECMO patients, whereas no such difference was observed for ceftazidime and meropenem
Summary
Sepsis and septic shock due to pneumonia and infections at other body sites are major life-threatening events, which are frequent causes of admission to intensive care units (ICUs) for specific treatment. Rapid initiation of an empirical antimicrobial therapy against the most likely pathogens is key to reduce morbidity and mortality in these patients, as delayed treatment was repeatedly demonstrated to be associated with increased mortality [1,2,3]. In 2014, the landmark ‘Defining antibiotic levels in intensive care unit patients’ (DALI) trial demonstrated that serum concentration goals were reached more often when continuous application was performed [8]. Effective antimicrobial treatment is key to reduce mortality associated with bacterial sepsis in patients on intensive care units (ICUs). Extracorporeal membrane oxygenation (ECMO) is increasingly being used for the treatment of respiratory and/or cardiac failure It remains unclear whether dose adjustments are necessary to avoid subtherapeutic drug levels in septic patients on ECMO support.
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