{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T09:28:36Z","timestamp":1762075716411,"version":"build-2065373602"},"reference-count":58,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,19]],"date-time":"2022-11-19T00:00:00Z","timestamp":1668816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Programme Hospitalier de Recherche Clinique National","award":["AOM11259","P110137"],"award-info":[{"award-number":["AOM11259","P110137"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>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 \u03b2-lactams, 65 (58%) aminoglycosides, and two (1.5%) fluoroquinolones. For \u03b2-lactams, 83% of the patients achieved a Cmin\/MIC &gt; 1 and 70% had a Cmin\/MIC &gt; 4. In the case of high creatinine clearance (CrCL &gt; 100 mL\/min\/1.73 m2), 70.4% of the patients achieved a Cmin\/MIC ratio &gt; 1 versus 91% otherwise (p = 0.041), and 52% achieved a Cmin\/MIC ratio &gt; 4 versus 81% (p = 0.018). For aminoglycosides, 94% of the patients had a Cmax\/MIC ratio &gt; 8. Neither \u03b2-lactams nor aminoglycosides PK\/PD parameters were associated clinical outcomes, but our data suggest a correlation between \u03b2-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 \u03b2-lactams. High creatinine clearance should encourage clinicians to focus on PK\/PD issues.<\/jats:p>","DOI":"10.3390\/antibiotics11111664","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T03:07:23Z","timestamp":1669000043000},"page":"1664","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Empirical Antibiotic Therapy for Gram-Negative Bacilli Ventilator-Associated Pneumonia: Observational Study and Pharmacodynamic Assessment"],"prefix":"10.3390","volume":"11","author":[{"given":"Olivier","family":"Pajot","sequence":"first","affiliation":[{"name":"Victor Dupouy Hospital, Intensive Care Unit, F-95100 Argenteuil, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5311-3987","authenticated-orcid":false,"given":"Karim","family":"Lakhal","sequence":"additional","affiliation":[{"name":"Service d\u2019Anesth\u00e9sie-R\u00e9animation, H\u00f4pital La\u00ebnnec, Centre Hospitalier Universitaire, F-44093 Nantes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00e9rome","family":"Lambert","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Medical Information, APHP, Saint-Louis Hospital, F-75010 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antoine","family":"Gros","sequence":"additional","affiliation":[{"name":"Medical-Surgical Intensive Care Unit, Andr\u00e9 Mignot Hospital, F-78150 Le Chesnay, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e9dric","family":"Bruel","sequence":"additional","affiliation":[{"name":"Medical and Surgical Intensive Care Unit, Paris Saint-Joseph Hospital Network, F-75014 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4664-3661","authenticated-orcid":false,"given":"Thierry","family":"Boulain","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, Orleans Regional Hospital, 14 Avenue de L\u2019H\u00f4pital CS 86709, CEDEX 02, F-45067 Orl\u00e9ans, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3556-2364","authenticated-orcid":false,"given":"Denis","family":"Garot","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine Intensive R\u00e9animation, H\u00f4pital Bretonneau, CHU Tours, F-37000 Tours, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Das","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine Intensive R\u00e9animation, Centre Hospitalier Intercommunal Andr\u00e9 Gr\u00e9goire, F-93100 Montreuil, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6063-7383","authenticated-orcid":false,"given":"Jean Fran\u00e7ois","family":"Timsit","sequence":"additional","affiliation":[{"name":"AP-HP, Bichat Hospital, Medical and Infectious Diseases Intensive Care Unit (MI2), F-75018 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles","family":"Cerf","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, Foch Hospital, F-92150 Suresnes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bertrand","family":"Souweine","sequence":"additional","affiliation":[{"name":"CHU Clermont-Ferrand, Service de R\u00e9animation M\u00e9dicale, F-63000 Clermont-Ferrand, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cendrine","family":"Chaffaut","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Medical Information, APHP, Saint-Louis Hospital, F-75010 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herv\u00e9","family":"Mentec","sequence":"additional","affiliation":[{"name":"Victor Dupouy Hospital, Intensive Care Unit, F-95100 Argenteuil, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean Ralph","family":"Zahar","sequence":"additional","affiliation":[{"name":"AP-HP, H\u00f4pital Avicenne, Pr\u00e9vention du Risque Infectieux, GH Paris Seine Saint-Denis, F-93000 Bobigny, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean Paul","family":"Mira","sequence":"additional","affiliation":[{"name":"Department of Medical Intensive Care, Cochin University Hospital, F-75014 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5971-6316","authenticated-orcid":false,"given":"Vincent","family":"Jullien","sequence":"additional","affiliation":[{"name":"Pharmacology Unit, University Sorbonne Paris Nord, Groupe Hospitalier Paris Seine-Saint-Denis, Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Jean Verdier, F-93140 Bondy, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1007\/s00134-020-05980-0","article-title":"Ventilator-Associated Pneumonia in Adults: A Narrative Review","volume":"46","author":"Papazian","year":"2020","journal-title":"Intensive Care Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1086\/516284","article-title":"Pharmacokinetic\/Pharmacodynamic Parameters: Rationale for Antibacterial Dosing of Mice and Men","volume":"26","author":"Craig","year":"1998","journal-title":"Clin. 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