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. 2022 Nov 19;11(11):1664.
doi: 10.3390/antibiotics11111664.

Empirical Antibiotic Therapy for Gram-Negative Bacilli Ventilator-Associated Pneumonia: Observational Study and Pharmacodynamic Assessment

Olivier Pajot  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  9 , Charles Cerf  10 , Bertrand Souweine  11 , Cendrine Chaffaut  3 , Hervé Mentec  1 , Jean Ralph Zahar  12 , Jean Paul Mira  13 , Vincent Jullien  14
Affiliations

Empirical Antibiotic Therapy for Gram-Negative Bacilli Ventilator-Associated Pneumonia: Observational Study and Pharmacodynamic Assessment

Olivier Pajot et al. Antibiotics (Basel). .

Abstract

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 Cmin/MIC > 1 and 70% had a Cmin/MIC > 4. In the case of high creatinine clearance (CrCL > 100 mL/min/1.73 m2), 70.4% of the patients achieved a Cmin/MIC ratio > 1 versus 91% otherwise (p = 0.041), and 52% achieved a Cmin/MIC ratio > 4 versus 81% (p = 0.018). For aminoglycosides, 94% of the patients had a Cmax/MIC ratio > 8. Neither β-lactams nor aminoglycosides PK/PD parameters were associated clinical outcomes, but our data suggest a correlation between β-lactams Cmin/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.

Keywords: VAP; intensive care unit; pharmacodynamics; pharmacokinetics.

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Conflict of interest statement

Pajot reports personal fees from MSD unrelated to the submitted work. No other disclosures were reported.

Figures

Figure 1
Figure 1
Flowchart.
Figure 2
Figure 2
Proportion of patients achieving PK/PD targets for β-lactams, i.e., Cmin/MIC > 1 (A) or Cmin/MIC > 4 (B), according to CrCL.
See this image and copyright information in PMC

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