Empirical Antibiotic Therapy for Gram-Negative Bacilli Ventilator-Associated Pneumonia: Observational Study and Pharmacodynamic Assessment
Olivier Pajot,
Karim Lakhal,
Jérome Lambert,
Antoine Gros,
Cédric Bruel,
Thierry Boulain,
Denis Garot,
Vincent Das,
Jean François Timsit,
Charles Cerf,
Bertrand Souweine,
Cendrine Chaffaut,
Hervé Mentec,
Jean Ralph Zahar,
Jean Paul Mira,
Vincent Jullien
Affiliations
Olivier Pajot
Victor Dupouy Hospital, Intensive Care Unit, F-95100 Argenteuil, France
Karim Lakhal
Service d’Anesthésie-Réanimation, Hôpital Laënnec, Centre Hospitalier Universitaire, F-44093 Nantes, France
Jérome Lambert
Department of Biostatistics and Medical Information, APHP, Saint-Louis Hospital, F-75010 Paris, France
Antoine Gros
Medical-Surgical Intensive Care Unit, André Mignot Hospital, F-78150 Le Chesnay, France
Cédric Bruel
Medical and Surgical Intensive Care Unit, Paris Saint-Joseph Hospital Network, F-75014 Paris, France
Thierry Boulain
Intensive Care Unit, Orleans Regional Hospital, 14 Avenue de L’Hôpital CS 86709, CEDEX 02, F-45067 Orléans, France
Denis Garot
Service de Médecine Intensive Réanimation, Hôpital Bretonneau, CHU Tours, F-37000 Tours, France
Vincent Das
Service de Médecine Intensive Réanimation, Centre Hospitalier Intercommunal André Grégoire, F-93100 Montreuil, France
Jean François Timsit
AP-HP, Bichat Hospital, Medical and Infectious Diseases Intensive Care Unit (MI2), F-75018 Paris, France
Charles Cerf
Intensive Care Unit, Foch Hospital, F-92150 Suresnes, France
Bertrand Souweine
CHU Clermont-Ferrand, Service de Réanimation Médicale, F-63000 Clermont-Ferrand, France
Cendrine Chaffaut
Department of Biostatistics and Medical Information, APHP, Saint-Louis Hospital, F-75010 Paris, France
Hervé Mentec
Victor Dupouy Hospital, Intensive Care Unit, F-95100 Argenteuil, France
Jean Ralph Zahar
AP-HP, Hôpital Avicenne, Prévention du Risque Infectieux, GH Paris Seine Saint-Denis, F-93000 Bobigny, France
Jean Paul Mira
Department of Medical Intensive Care, Cochin University Hospital, F-75014 Paris, France
Vincent Jullien
Pharmacology Unit, University Sorbonne Paris Nord, Groupe Hospitalier Paris Seine-Saint-Denis, Assistance Publique-Hôpitaux de Paris, Hôpital Jean Verdier, F-93140 Bondy, France
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.
