Increased β-Lactams dosing regimens improve clinical outcome in critically ill patients with augmented renal clearance treated for a first episode of hospital or ventilator-acquired pneumonia: a before and after study

• Published in: Critical care (London, England) Vol. 23; no. 1; p. 379
• Main Authors: Carrié, Cédric, Chadefaux, Grégoire, Sauvage, Noémie, de Courson, Hugues, Petit, Laurent, Nouette-Gaulain, Karine, Pereira, Bruno, Biais, Matthieu
• Format: Journal Article
• Language: English
• Published: England BioMed Central 27-11-2019; BMC
• Subjects: Adult; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - therapeutic use; Antibiotics; Antimicrobial agents; Augmented renal clearance; beta-Lactams - administration & dosage; beta-Lactams - therapeutic use; Clinical outcomes; Critical care; Critical illness; Critical Illness - therapy; Dose-Response Relationship, Drug; Drug dosages; Drug resistance; Female; Healthcare-Associated Pneumonia - drug therapy; Healthcare-Associated Pneumonia - epidemiology; Hospital-acquired pneumonia; Humans; Intensive care; Laboratories; Licenses; Male; Middle Aged; Pathogens; Patients; Pneumonia; Pneumonia - drug therapy; Pneumonia - epidemiology; Pneumonia, Ventilator-Associated - drug therapy; Pneumonia, Ventilator-Associated - epidemiology; Retrospective Studies; Treatment Outcome; Ventilator-acquired pneumonia; Ventilators; β-Lactams; Hospital-acquired pneumonia; Critical illness; Ventilator-acquired pneumonia; β-Lactams; Augmented renal clearance
• ISSN: 1364-8535; 1466-609X; 1364-8535; 1366-609X
• DOI: 10.1186/s13054-019-2621-4

Augmented renal clearance (ARC) is recognized as a leading cause of β-lactam subexposure when conventional dosing regimens are used. The main objective was to compare the clinical outcome of ARC patients treated by conventional or increased β-lactam dosing regimens for a first episode of hospital or ventilator-acquired pneumonia (HAP-VAP).
In this single-center, retrospective study, every ARC patient treated by β-lactam for a first episode of HAP-VAP was included during two 15-month periods, before (Control period) and after (Treatment period) the modification of a local antibiotic therapy protocol. ARC was defined by a 24-h measured creatinine clearance ≥ 150 ml/min. The primary endpoint was defined as a therapeutic failure of the antimicrobial therapy or a HAP-VAP relapse within 28 days. Inverse probability of treatment weight (IPTW) was derived from a propensity score model. Cox proportional hazard models were used to evaluate the association between treatment period and clinical outcome.
During the study period, 177 patients were included (control period, N = 88; treatment period, N = 89). Therapeutic failure or HAP-VAP relapse was significantly lower in the treatment period (10 vs. 23%, p = 0.019). The IPTW-adjusted hazard ratio of poor clinical outcome in the treatment period was 0.35 (95% CI 0.15-0.81), p = 0.014. No antibiotic side effect was reported during the treatment period.
Higher than licensed dosing regimens of β-lactams may be safe and effective in reducing the rate of therapeutic failure and HAP-VAP recurrence in critically ill augmented renal clearance (ARC) patients.