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Alobaid A.S.,University of Queensland | Brinkmann A.,General Hospital of Heidenheim | Frey O.R.,General Hospital of Heidenheim | Roehr A.C.,General Hospital of Heidenheim | And 10 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2016

Objectives: The objectives of this study were to determine the effects of obesity on unbound trough concentrations and on the achievement of pharmacokinetic (PK)/pharmacodynamic (PD) targets of piperacillin and meropenem in critically ill patients. Methods: This study retrospectively analysed therapeutic-drug-monitoring data from ICU databases in Australia, Germany and Spain, as well as from a large PK study. The presence of obesity was defined as a BMI ≥ 30 kg/m2, and patients were also categorized based on level of renal function. The presence of obesity was compared with unbound piperacillin and meropenem trough concentrations. We also used logistic regression to describe factors associated with the achievement of the PK/PD targets, an unbound concentration maintained above the MIC breakpoint (100% fT>MIC and 100% fT>4×MIC) of Pseudomonas aeruginosa. Results: In all, 1400 patients were eligible for inclusion in the study. The median age and weight were 67 years (IQR 52-76 years) and 79 kg (69-90 kg), respectively, and 65% of participants were male. Significantly lower median piperacillin trough concentrations [29.4 mg/L (IQR 17.0-58.0 mg/L)] were found in obese patients compared with non-obese patients [42.0 mg/L (21.5-73.5 mg/L)] (P = 0.001). There was no difference for meropenem trough concentrations [obese 10.3 mg/L (IQR 4.8-16.0 mg/L) versus non-obese 11.0 mg/L (4.3-18.5 mg/L); P = 0.296]. Using logistic regression, we found that the presence of obesity was not associated with achievement of 100% fT>MIC, but the use of prolonged infusion, a creatinine clearance ≤ 100 mL/min, increasing age and female gender were for various PK/PD targets for both piperacillin and meropenem (P < 0.05). Conclusions: This large dataset has shown that the presence of obesity in critically ill patients may affect piperacillin, but not meropenem, unbound trough concentrations. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. Source

Wong G.,University of Queensland | Sime F.B.,University of South Australia | Sime F.B.,Basil Hetzel Institute for Translational Health Research | Lipman J.,University of Queensland | And 2 more authors.
BMC Infectious Diseases | Year: 2015

High mortality and morbidity rates associated with severe infections in the critically ill continue to be a significant issue for the healthcare system. In view of the diverse and unique pharmacokinetic profile of drugs in this patient population, there is increasing use of therapeutic drug monitoring (TDM) in attempt to optimize the exposure of antibiotics, improve clinical outcome and minimize the emergence of antibiotic resistance. Despite this, a beneficial clinical outcome for TDM of antibiotics has only been demonstrated for aminoglycosides in a general hospital patient population. Clinical outcome studies for other antibiotics remain elusive. Further, there is significant variability among institutions with respect to the practice of TDM including the selection of patients, sampling time for concentration monitoring, methodologies of antibiotic assay, selection of PK/PD targets as well as dose optimisation strategies. The aim of this paper is to review the available evidence relating to practices of antibiotic TDM, and describe how TDM can be applied to potentially improve outcomes from severe infections in the critically ill. © 2014 Wong et al.; licensee BioMed Central Ltd. Source

Elgar N.J.,4A Respiratory Medicine | Esterman A.J.,University of South Australia | Antic N.A.,Adelaide Institute for Sleep Health | Smith B.J.,4A Respiratory Medicine | Smith B.J.,Basil Hetzel Institute for Translational Health Research
Journal of Clinical Sleep Medicine | Year: 2016

Study Objectives: Health professionals are frequently required to report to relevant authorities all drivers who are potentially unsafe due to medical conditions. We aimed to assess both the effect of mandatory reporting (MR) on patient self-predicted behavior and what factors might encourage unsafe drivers to self-report to these authorities. Methods: We included 5 questions in the South Australian Health Omnibus Survey, an annual, community based, face-to-face survey. We asked (1) how subjects would behave towards their doctor in light of MR if they believed their licences were at risk due to a medical condition; and (2) which factor(s) would cause them to self-report to the same authorities. Results: Responses to 3,007 surveys (response rate 68.5%, age 15-98) showed that 9.0% would avoid diagnosis, lie to their doctor, or doctor shop in order to keep their licence; 30.8% were unaware of the legislated requirement to self-report; and 37.9% were unaware of potentially jeopardizing insurance support if they failed to comply. If educated in these 2 areas, warned about the dangers of driving against medical advice and instructed to do so by their doctor, then 95.8% of people would self-report to the authorities, a number significantly higher than could be reported by their doctors (91.0%). Conclusions: MR causes 9.0% of people to predict to behave towards their doctor in a manner that reduces road safety. With education and encouragement to do so, more people will self-report to the authorities than could be reported by their doctors via the MR pathway. Source

Sinnollareddy M.G.,University of Queensland | Sinnollareddy M.G.,University of South Australia | Sinnollareddy M.G.,Basil Hetzel Institute for Translational Health Research | Roberts J.A.,University of Queensland | And 15 more authors.
Critical Care | Year: 2015

Introduction: The objective of the study was to describe the pharmacokinetics (PK) of fluconazole, anidulafungin, and caspofungin in critically ill patients and to compare with previously published data. We also sought to determine whether contemporary fluconazole doses achieved PK/pharmacodynamic (PD; PK/PD) targets in this cohort of intensive care unit patients. Methods: The Defining Antibiotic Levels in Intensive care unit patients (DALI) study was a prospective, multicenter point-prevalence PK study. Sixty-eight intensive care units across Europe participated. Inclusion criteria were met by critically ill patients administered fluconazole (n = 15), anidulafungin (n = 9), and caspofungin (n = 7). Three blood samples (peak, mid-dose, and trough) were collected for PK/PD analysis. PK analysis was performed by using a noncompartmental approach. Results: The mean age, weight, and Acute Physiology and Chronic Health Evaluation (APACHE) II scores of the included patients were 58 years, 84 kg, and 22, respectively. Fluconazole, caspofungin, and anidulafungin showed large interindividual variability in this study. In patients receiving fluconazole, 33% did not attain the PK/PD target, ratio of free drug area under the concentration-time curve from 0 to 24 hours to minimum inhibitory concentration (fAUC0-24/MIC) ≥100. The fluconazole dose, described in milligrams per kilogram, was found to be significantly associated with achievement of fAUC0-24/MIC ≥100 (P = 0.0003). Conclusions: Considerable interindividual variability was observed for fluconazole, anidulafungin, and caspofungin. A large proportion of the patients (33%) receiving fluconazole did not attain the PK/PD target, which might be related to inadequate dosing. For anidulafungin and caspofungin, dose optimization also appears necessary to minimize variability. © 2015 Sinnollareddy et al. Source

Sime F.B.,University of South Australia | Sime F.B.,Basil Hetzel Institute for Translational Health Research | Roberts M.S.,University of South Australia | Roberts M.S.,Basil Hetzel Institute for Translational Health Research | And 5 more authors.
Annals of Intensive Care | Year: 2012

The pharmacokinetics of beta-lactam antibiotics in intensive care patients may be profoundly altered due to the dynamic, unpredictable pathophysiological changes that occur in critical illness. For many drugs, significant increases in the volume of distribution and/or variability in drug clearance are common. When "standard" beta-lactam doses are used, such pharmacokinetic changes can result in subtherapeutic plasma concentrations, treatment failure, and the development of antibiotic resistance. Emerging data support the use of betalactam therapeutic drug monitoring (TDM) and individualized dosing to ensure the achievement of pharmacodynamic targets associated with rapid bacterial killing and optimal clinical outcomes. The purpose of this work was to describe the pharmacokinetic variability of beta-lactams in the critically ill and to discuss the potential utility of TDM to optimize antibiotic therapy through a structured literature review of all relevant publications between 1946 and October 2011. Only a few studies have reported the utility of TDM as a tool to improve beta-lactam dosing in critically ill patients. Moreover, there is little agreement between studies on the pharmacodynamic targets required to optimize antibiotic therapy. The impact of TDM on important clinical outcomes also remains to be established. Whereas TDM may be theoretically rational, clinical studies to assess utility in the clinical setting are urgently required. © 2012 Sime et al.; licensee Springer. Source

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