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Repeated Piperacillin-Tazobactam Plasma Concentration Measurements in Severely Obese Versus Nonobese Critically Ill Septic Patients and The Risk of Under and Overdosing.

dc.rights.licenseauthentificationen_US
dc.contributor.authorJUNG, B.
dc.contributor.authorMAHUL, M.
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorBREILH, Dominique
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorLEGERON, Rachel
dc.contributor.authorSIGNE, J.
dc.contributor.authorJEAN-PIERRE, H.
dc.contributor.authorUHLEMANN, A. C.
dc.contributor.authorMOLINARI, N.
dc.contributor.authorJABER, S.
dc.date.accessioned2020-11-26T15:21:00Z
dc.date.available2020-11-26T15:21:00Z
dc.date.issued2017-02
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/21224
dc.description.abstractEnOBJECTIVE: 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, \textgreater 35 kg/m) and nonobese patients (body mass index, \textless 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.
dc.language.isoENen_US
dc.subject*Article CLINIQUE
dc.title.enRepeated Piperacillin-Tazobactam Plasma Concentration Measurements in Severely Obese Versus Nonobese Critically Ill Septic Patients and The Risk of Under and Overdosing.
dc.title.alternativeCrit Care Meden_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1097/CCM.0000000000002287en_US
dc.subject.halSciences du Vivant [q-bio]/Médecine humaine et pathologieen_US
bordeaux.journalCrit Care Meden_US
bordeaux.pagee–470–e478en_US
bordeaux.volume45en_US
bordeaux.hal.laboratoriesBiologie des maladies cardiovasculaires - U1034en_US
bordeaux.issue5en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.exportfalse
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