Empirical Antibiotic Therapy for Gram-Negative Bacilli Ventilator-Associated Pneumonia: Observational Study and Pharmacodynamic Assessment
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 aime...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/11/11/1664 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Olivier Pajot |
| collection | DOAJ |
| description | 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 <i>P. aeruginosa</i> (40%), <i>Enterobacter</i> spp. (23%), <i>E. coli</i> (20%), and <i>Klebsiella</i> 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</sub>/MIC > 1 and 70% had a C<sub>min</sub>/MIC > 4. In the case of high creatinine clearance (CrCL > 100 mL/min/1.73 m<sup>2</sup>), 70.4% of the patients achieved a C<sub>min</sub>/MIC ratio > 1 versus 91% otherwise (<i>p</i> = 0.041), and 52% achieved a C<sub>min</sub>/MIC ratio > 4 versus 81% (<i>p</i> = 0.018). For aminoglycosides, 94% of the patients had a C<sub>max</sub>/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</sub>/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. |
| first_indexed | 2024-03-09T18:31:43Z |
| format | Article |
| id | doaj.art-e39904bab59d42a99bad9aae2a97f422 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-09T18:31:43Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-e39904bab59d42a99bad9aae2a97f4222023-11-24T07:31:30ZengMDPI AGAntibiotics2079-63822022-11-011111166410.3390/antibiotics11111664Empirical Antibiotic Therapy for Gram-Negative Bacilli Ventilator-Associated Pneumonia: Observational Study and Pharmacodynamic AssessmentOlivier Pajot0Karim Lakhal1Jérome Lambert2Antoine Gros3Cédric Bruel4Thierry Boulain5Denis Garot6Vincent Das7Jean François Timsit8Charles Cerf9Bertrand Souweine10Cendrine Chaffaut11Hervé Mentec12Jean Ralph Zahar13Jean Paul Mira14Vincent Jullien15Victor Dupouy Hospital, Intensive Care Unit, F-95100 Argenteuil, FranceService d’Anesthésie-Réanimation, Hôpital Laënnec, Centre Hospitalier Universitaire, F-44093 Nantes, FranceDepartment of Biostatistics and Medical Information, APHP, Saint-Louis Hospital, F-75010 Paris, FranceMedical-Surgical Intensive Care Unit, André Mignot Hospital, F-78150 Le Chesnay, FranceMedical and Surgical Intensive Care Unit, Paris Saint-Joseph Hospital Network, F-75014 Paris, FranceIntensive Care Unit, Orleans Regional Hospital, 14 Avenue de L’Hôpital CS 86709, CEDEX 02, F-45067 Orléans, FranceService de Médecine Intensive Réanimation, Hôpital Bretonneau, CHU Tours, F-37000 Tours, FranceService de Médecine Intensive Réanimation, Centre Hospitalier Intercommunal André Grégoire, F-93100 Montreuil, FranceAP-HP, Bichat Hospital, Medical and Infectious Diseases Intensive Care Unit (MI2), F-75018 Paris, FranceIntensive Care Unit, Foch Hospital, F-92150 Suresnes, FranceCHU Clermont-Ferrand, Service de Réanimation Médicale, F-63000 Clermont-Ferrand, FranceDepartment of Biostatistics and Medical Information, APHP, Saint-Louis Hospital, F-75010 Paris, FranceVictor Dupouy Hospital, Intensive Care Unit, F-95100 Argenteuil, FranceAP-HP, Hôpital Avicenne, Prévention du Risque Infectieux, GH Paris Seine Saint-Denis, F-93000 Bobigny, FranceDepartment of Medical Intensive Care, Cochin University Hospital, F-75014 Paris, FrancePharmacology Unit, University Sorbonne Paris Nord, Groupe Hospitalier Paris Seine-Saint-Denis, Assistance Publique-Hôpitaux de Paris, Hôpital Jean Verdier, F-93140 Bondy, FranceBackground: 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 <i>P. aeruginosa</i> (40%), <i>Enterobacter</i> spp. (23%), <i>E. coli</i> (20%), and <i>Klebsiella</i> 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</sub>/MIC > 1 and 70% had a C<sub>min</sub>/MIC > 4. In the case of high creatinine clearance (CrCL > 100 mL/min/1.73 m<sup>2</sup>), 70.4% of the patients achieved a C<sub>min</sub>/MIC ratio > 1 versus 91% otherwise (<i>p</i> = 0.041), and 52% achieved a C<sub>min</sub>/MIC ratio > 4 versus 81% (<i>p</i> = 0.018). For aminoglycosides, 94% of the patients had a C<sub>max</sub>/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</sub>/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.https://www.mdpi.com/2079-6382/11/11/1664VAPpharmacokineticspharmacodynamicsintensive care unit |
| spellingShingle | 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 Empirical Antibiotic Therapy for Gram-Negative Bacilli Ventilator-Associated Pneumonia: Observational Study and Pharmacodynamic Assessment Antibiotics VAP pharmacokinetics pharmacodynamics intensive care unit |
| title | Empirical Antibiotic Therapy for Gram-Negative Bacilli Ventilator-Associated Pneumonia: Observational Study and Pharmacodynamic Assessment |
| title_full | Empirical Antibiotic Therapy for Gram-Negative Bacilli Ventilator-Associated Pneumonia: Observational Study and Pharmacodynamic Assessment |
| title_fullStr | Empirical Antibiotic Therapy for Gram-Negative Bacilli Ventilator-Associated Pneumonia: Observational Study and Pharmacodynamic Assessment |
| title_full_unstemmed | Empirical Antibiotic Therapy for Gram-Negative Bacilli Ventilator-Associated Pneumonia: Observational Study and Pharmacodynamic Assessment |
| title_short | Empirical Antibiotic Therapy for Gram-Negative Bacilli Ventilator-Associated Pneumonia: Observational Study and Pharmacodynamic Assessment |
| title_sort | empirical antibiotic therapy for gram negative bacilli ventilator associated pneumonia observational study and pharmacodynamic assessment |
| topic | VAP pharmacokinetics pharmacodynamics intensive care unit |
| url | https://www.mdpi.com/2079-6382/11/11/1664 |
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