Intensive Care Medicine: Published: 01
February 2022
Purpose
Insufficient antimicrobial exposure is associated with worse
outcomes in sepsis. We evaluated whether therapeutic drug monitoring
(TDM)-guided antibiotic therapy improves outcomes.
Methods
Randomized, multicenter, controlled trial from January 2017
to December 2019. Adult patients (n = 254) with sepsis or septic shock were
randomly assigned 1:1 to receive continuous infusion of piperacillin/tazobactam
with dosing guided by daily TDM of piperacillin or continuous infusion with a
fixed dose (13.5 g/24 h if eGFR ≥ 20 mL/min). Target plasma
concentration was four times the minimal inhibitory concentration (range ± 20%)
of the underlying pathogen, respectively, of Pseudomonas aeruginosa in
empiric situation. Primary outcome was the mean of daily total Sequential Organ
Failure Assessment (SOFA) score up to day 10.
Results
Among 249 evaluable patients (66.3 ± 13.7 years;
female, 30.9%), there was no significant difference in mean SOFA score between
patients with TDM (7.9 points; 95% CI 7.1–8.7) and without TDM (8.2 points; 95%
CI 7.5–9.0) (p = 0.39). Patients with TDM-guided therapy showed a lower 28-day
mortality (21.6% vs. 25.8%, RR 0.8, 95% CI 0.5–1.3, p = 0.44) and a higher
rate of clinical (OR 1.9; 95% CI 0.5–6.2, p = 0.30) and microbiological
cure (OR 2.4; 95% CI 0.7–7.4, p = 0.12), but these differences did not
reach statistical significance. Attainment of target concentration was more
common in patients with TDM (37.3% vs. 14.6%, OR 4.5, CI 95%, 2.9–6.9, p < 0.001).
Conclusion
TDM-guided therapy showed no beneficial effect in patients
with sepsis and continuous infusion of piperacillin/tazobactam with regard to
the mean SOFA score. Larger studies with strategies to ensure optimization of
antimicrobial exposure are needed to definitively answer the question.
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