Plasma Trough Concentrations of Beta-Lactam Antibiotics in the Early Phase of Septic Shock

Septic shock necessitates timely antibiotic therapy, often with broad-spectrum beta-lactam antibiotics (ß-LA). To our knowledge, no previous study has examined antibiotic concentrations repeatedly during the initial phase of treatment. This observational study aimed to assess early-phase plasma concentrations of ß-LA in patients with septic shock.

Prospective observational study of patients with septic shock, according to the SEPSIS-3 criteria, who received cefotaxime, piperacillin/tazobactam, or meropenem in accordance with Swedish practice. Demographic and clinical data were recorded for each patient. Consecutive blood samples were obtained during the first 24 h of treatment, and total antibiotic concentrations were measured using liquid chromatography mass spectrometry. Target concentrations were defined as 100% of the time that free (unbound) antibiotic concentrations remained above the minimal inhibitory concentration (fT > MIC).

Twenty-two patients were included, 15 (68%) were male and the median age was 65.5 years (IQR 46.3-65.5). In-hospital mortality was 7/22 (32%). Antibiotic exposure exceeding 100% fT > MIC was achieved in 16 (73%) of the patients. Four patients did not receive the recommended additional dose between the first and second doses of antibiotics; two of them still achieved 100% fT > MIC, whereas the other two attained 66% and 33% fT > MIC, respectively. Among the patients who received the additional dose, four did not achieve 100% fT > MIC. No relationship between mortality and fT > MIC was observed. Significant associations with achieving 100% fT > MIC were observed for older age (p = 0.045) and illness severity (SAPS3, p = 0.025).

Our findings demonstrate considerable variability in antibiotic exposure during the initial 24 h of septic shock treatment, highlighting a critical gap in understanding the clinical relevance of sub-optimal serum antibiotic concentrations and their potential impact on patient outcomes.

Therapeutic drug monitoring of antimicrobials is increasingly being used in research and clinical practice.