학술논문
Empirical Antibiotic Therapy for Gram-Negative Bacilli Ventilator-Associated Pneumonia: Observational Study and Pharmacodynamic Assessment
Document Type
Academic Journal
Author
Source
Antibiotics. November 2022, Vol. 11 Issue 11
Subject
Language
English
ISSN
2079-6382
Abstract
Author(s): Olivier Pajot (corresponding author) [1,*]; Karim Lakhal [2]; Jérome Lambert [3]; Antoine Gros [4]; Cédric Bruel [5]; Thierry Boulain [6]; Denis Garot [7]; Vincent Das [8]; Jean François Timsit [...]
Background: Strong evidence suggests a correlation between pharmacodynamics (PD) index and antibiotic efficacy while dose adjustment should be considered in critically ill patients due to modified pharmacokinetic (PK) parameters and/or higher minimum inhibitory concentrations (MICs). This study aimed to assess pharmacodynamic (PD) target attainment considering both antibiotics serum concentrations and measured MICs in these patients. Method: A multicentric prospective open-label trial conducted in 11 French ICUs involved patients with Gram-negative bacilli (GNB) ventilator-associated pneumonia (VAP) confirmed by quantitative cultures. Results: We included 117 patients. Causative GNBs were P. aeruginosa (40%), Enterobacter spp. (23%), E. coli (20%), and Klebsiella spp. (16%). Hence, 117 (100%) patients received β-lactams, 65 (58%) aminoglycosides, and two (1.5%) fluoroquinolones. For β-lactams, 83% of the patients achieved a C[sub.min]/MIC > 1 and 70% had a C[sub.min]/MIC > 4. In the case of high creatinine clearance (CrCL > 100 mL/min/1.73 m[sup.2]), 70.4% of the patients achieved a C[sub.min]/MIC ratio > 1 versus 91% otherwise (p = 0.041), and 52% achieved a C[sub.min]/MIC ratio > 4 versus 81% (p = 0.018). For aminoglycosides, 94% of the patients had a C[sub.max]/MIC ratio > 8. Neither β-lactams nor aminoglycosides PK/PD parameters were associated clinical outcomes, but our data suggest a correlation between β-lactams C[sub.min]/MIC and microbiological success. Conclusion: In our ICU patients treated for GNB VAP, using recommended antibiotic dosage led in most cases to PK/PD targets attainment for aminoglycosides and β-lactams. High creatinine clearance should encourage clinicians to focus on PK/PD issues.
Background: Strong evidence suggests a correlation between pharmacodynamics (PD) index and antibiotic efficacy while dose adjustment should be considered in critically ill patients due to modified pharmacokinetic (PK) parameters and/or higher minimum inhibitory concentrations (MICs). This study aimed to assess pharmacodynamic (PD) target attainment considering both antibiotics serum concentrations and measured MICs in these patients. Method: A multicentric prospective open-label trial conducted in 11 French ICUs involved patients with Gram-negative bacilli (GNB) ventilator-associated pneumonia (VAP) confirmed by quantitative cultures. Results: We included 117 patients. Causative GNBs were P. aeruginosa (40%), Enterobacter spp. (23%), E. coli (20%), and Klebsiella spp. (16%). Hence, 117 (100%) patients received β-lactams, 65 (58%) aminoglycosides, and two (1.5%) fluoroquinolones. For β-lactams, 83% of the patients achieved a C[sub.min]/MIC > 1 and 70% had a C[sub.min]/MIC > 4. In the case of high creatinine clearance (CrCL > 100 mL/min/1.73 m[sup.2]), 70.4% of the patients achieved a C[sub.min]/MIC ratio > 1 versus 91% otherwise (p = 0.041), and 52% achieved a C[sub.min]/MIC ratio > 4 versus 81% (p = 0.018). For aminoglycosides, 94% of the patients had a C[sub.max]/MIC ratio > 8. Neither β-lactams nor aminoglycosides PK/PD parameters were associated clinical outcomes, but our data suggest a correlation between β-lactams C[sub.min]/MIC and microbiological success. Conclusion: In our ICU patients treated for GNB VAP, using recommended antibiotic dosage led in most cases to PK/PD targets attainment for aminoglycosides and β-lactams. High creatinine clearance should encourage clinicians to focus on PK/PD issues.