Association between augmented renal clearance and clinical failure of antibiotic treatment in brain-injured patients with ventilator-acquired pneumonia: A preliminary study

Abstract

Objectives: This preliminary study aimed to determine whether augmented renal clearance (ARC) impacts negatively on the clinical outcome in traumatic brain-injured patients (TBI) treated for a first episode of ventilator-acquired pneumonia (VAP).

Methods: During a 5-year period, all TBI patients who had developed VAP were retrospectively reviewed to assess variables associated with clinical failure in multivariate analysis. Clinical failure was defined as an impaired clinical response with a need for escalating antibiotics during treatment and/or within 15 days after the end-of-treatment. Recurrence was considered if at least one of the initial causative bacterial strains was growing at a significant concentration from a second sample. Augmented renal clearance (ARC) was defined by an enhanced creatinine clearance exceeding 130mL/min/1.73m² calculated from a urinary sample during the first three days of antimicrobial therapy.

Main results: During the study period, 223 TBI patients with VAP were included and 59 (26%) presented a clinical failure. Factors statistically associated with clinical failure were GSC≤7 (OR=2.2 [1.1-4.4], P=0.03), early VAP (OR=3.9 [1.9-7.8], P=0.0001), bacteraemia (OR=11 [2.2-54], P=0.003) and antimicrobial therapy≤7 days (OR=3.7 [1.8-7.4], P=0.0003). ARC was statistically associated with recurrent infections with an OR of 4.4 [1.2-16], P=0.03.

Conclusion: ARC was associated with recurrent infection after a first episode of VAP in TBI patients. The optimal administration and dosing of the antimicrobial agents in this context remain to be determined.

Keywords: Augmented renal clearance; Therapeutic failure; Traumatic brain injury; Ventilator-acquired pneumonia; β-lactams.