Repeated Piperacillin-Tazobactam Plasma Concentration Measurements in Severely Obese Versus Nonobese Critically Ill Septic Patients and the Risk of Under– and Overdosing
| Autor: | Nicolas Molinari, Jeremy Signe, Samir Jaber, Boris Jung, Anne-Catrin Uhlemann, Martin Mahul, Hélène Jean-Pierre, Dominique Breilh, Rachel Legeron |
|---|---|
| Přispěvatelé: | Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Hydrosciences Montpellier (HSM), Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Herrada, Anthony |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty medicine.drug_class Critical Illness 030106 microbiology Antibiotics Penicillanic Acid Microbial Sensitivity Tests Critical Care and Intensive Care Medicine Body Mass Index 03 medical and health sciences 0302 clinical medicine Pharmacokinetics polycyclic compounds medicine Article CLINIQUE Humans Obesity Prospective Studies 030212 general & internal medicine Infusions Intravenous Intensive care medicine Prospective cohort study Aged Aged 80 and over Piperacillin 2. Zero hunger [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology Dose-Response Relationship Drug business.industry Middle Aged medicine.disease Shock Septic Anti-Bacterial Agents 3. Good health Piperacillin Tazobactam Drug Combination Shock (circulatory) Anesthesia Piperacillin/tazobactam Female medicine.symptom business Monte Carlo Method Body mass index [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology medicine.drug |
| Zdroj: | Critical Care Medicine Critical Care Medicine, Lippincott, Williams & Wilkins, 2017, 45 (5), pp.e470-e478. ⟨10.1097/CCM.0000000000002287⟩ Critical Care Medicine, 2017, 45 (5), pp.e470-e478. ⟨10.1097/CCM.0000000000002287⟩ |
| ISSN: | 0090-3493 1530-0293 |
| DOI: | 10.1097/CCM.0000000000002287⟩ |
| Popis: | International audience; Obesity and critical illness modify pharmacokinetics of antibiotics, but piperacillin-tazobactam continuous IV infusion pharmacokinetics has been poorly studied in obese critically ill patients. We aimed to compare pharmacokinetics of piperacillin in severely obese and nonobese patients with severe sepsis or septic shock. We hypothesized that plasma concentration variability would expose the critically ill to both piperacillin under and overdosing.METHODS:Prospective comparative study. Consecutive critically ill severely obese (body mass index, > 35 kg/m) and nonobese patients (body mass index, < 30 kg/m) were treated with 16 g/2 g/24 hr continuous piperacillin-tazobactam infusion. Piperacillin plasma concentration was measured every 12 hours over a 7-day period by high-pressure liquid chromatography. Unbound piperacillin plasma concentration and fractional time of plasma concentration spent over 64 mg/L (4-fold the minimal inhibitory concentration for Pseudomonas aeruginosa) were compared between the two groups. We performed 5,000 Monte Carlo simulations for various dosing regimens and minimal inhibitory concentration and calculated the probability to spend 100% of the time over 64 mg/L.RESULTS:We enrolled 11 severely obese and 12 nonobese patients and obtained 294 blood samples. We did not observe a statistically significant difference in piperacillin plasma concentrations over time between groups. The fractional time over 64 mg/L was 64% (43-82%) and 93% (85-100%) in obese and nonobese patients, respectively, p = 0.027 with intra- and intergroup variability. Five nonobese and two obese patients experienced potentially toxic piperacillin plasma concentrations. When 64 mg/L was targeted, Monte Carlo simulations showed that 12 g/1.5 g/24 hr was inadequate in both groups and 16 g/2 g/24 hr was adequate only in nonobese patients.CONCLUSION:Using a conventional dosing of 16 g/2 g/24 hr continuous infusion, obese patients were more likely than nonobese patients to experience piperacillin underdosing when facing high minimal inhibitory concentration pathogens. The present study suggests that piperacillin drug monitoring might be necessary in the sickest patients who are at the highest risk of unpredictable plasma concentration exposing them to overdose, toxicity, underdosing, and treatment failure. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|