DALI: Defining Antibiotic Levels in Intensive Care Unit Patients: Are Current  -Lactam Antibiotic Doses Sufficient for Critically Ill Patients?

Roberts, Jason A.; Paul, Sanjoy K.; Akova, Murat; Bassetti, Matteo; Waele, Jan J. De; Dimοpoulos, George; Kaukonen, Kirsi‐Maija; Koulenti, Despoina; Martin, Claude; Montravers, Philippe; Rello, Jordi; Rhodes, Andrew; Starr, Therese; Wallis, Steven C.; Lipman, Jeffrey; Study, Dali

doi:10.1093/cid/ciu027

Cited by 893 publications

(782 citation statements)

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“…These would be clinical messages that would further enhance our understanding of this area, although de Montmollin and colleagues have provided important data to help direct further research in this area. In the context of similar recent data from other antibiotics [5,6], this problem should not be considered restricted to aminoglycosides. Indeed, quantification of the clinical advantages of an individualized approach to dosing is urgently required.…”

Section: Why Is This Study Important Controversial and Thought-provomentioning

confidence: 99%

Amikacin dosing in the ICU: we now know more, but still not enough…

Rosa

Roberts

2014

Intensive Care Med

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Section: Why Is This Study Important Controversial and Thought-provomentioning

confidence: 99%

Amikacin dosing in the ICU: we now know more, but still not enough…

Rosa

Roberts

2014

Intensive Care Med

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“…fT>MIC) associated with positive clinical outcomes for β-lactams in critically ill patients is a fT>MIC between 50% to 100% of the dosing interval. 3 Recent studies reported the PK/PD efficacy index for the β-lactamase inhibitor (BLI) tazobactam to be the percentage of time during which the unbound concentration remains above a threshold concentration (fT>CT). 4,5 fT>CT targets ranged from 35 to 85% of the dosing interval, depending on the antibiotic-BLI combination and stability of the β-lactamase.…”

Section: Introductionmentioning

confidence: 99%

Dose optimization of piperacillin/tazobactam in critically ill children

Cock¹,

Dijkman

Jaeger

et al. 2017

Journal of Antimicrobial Chemotherapy

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Running title: Paediatric piperacillin/tazobactam dose rationale SynopsisObjectives. The aim of this study was to characterize the population pharmacokinetics of piperacillin and tazobactam in critically ill infants and children, in order to develop an evidence-based dosing regimen.Patients and Methods. This pharmacokinetic study enrolled patients admitted to the paediatric ICU for whom intravenous piperacillin/tazobactam (8:1 ratio) was indicated (75 mg/kg q6h based on piperacillin). Piperacillin/tazobactam concentrations were measured by a liquid chromatography-tandem mass spectrometry method. Pharmacokinetic data was analysed using nonlinear mixed effects modelling.Results. Piperacillin and tazobactam blood samples were collected from 47 patients (median age: 2.83 years; range: 2 months -15 years). Piperacillin and tazobactam disposition was best described by a two-compartment model which included allometric scaling and a maturation function to account for the effect of growth and age. Mean clearance estimates for piperacillin and tazobactam were 4.00 L/h and 3.01 L/h for a child of 14 kg. Monte Carlo simulations showed that an intermittent infusion of 75 mg/kg (based on piperacillin) q4h over 2 hours, 100 mg/kg q4h given over 1 hour or a loading dose of 75 mg/kg followed by a continuous infusion of 300 mg/kg/24h were minimally required to achieve the therapeutic targets for piperacillin (60 % fT>MIC>16 mg/L). Conclusion. Standard intermittent dosing regimens do not ensure optimalpiperacillin/tazobactam exposure in critically ill patients, thereby risking treatment failure. The use of a loading dose followed by a continuous infusion is recommended for treatment of severe infections in children >2 months of age.

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“…In selected cases, generally in immunocompromised patients or patients with previous exposure to oseltamivir, there is a higher risk for antiviral resistance; in case of refractory influenza A infection which persists despite neuraminidase inhibitors treatment, a study to assess virus resistance for oseltamivir should be performed and zanamivir should be initiated. It was observed that ICU patient might need an adjustment of the dose of antibiotic because of a different pharmacokinetic and pharmacodynamics; despite that, it seems not to be the case when enteral oseltamivir treatment is initiated [20]; in a study performed in ICU patients with pH1N1 infection, enteral absorption and plasmatic levels of Oseltamivir were therapeutic when a dose of 75 mg twice daily was delivered [21].…”

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confidence: 99%