Pharmacokinetics of piperacillin–tazobactam: intermittent dosing versus continuous infusion

Buck, C. J.; Bertram, Norbert; Ackermann, T.; Sauerbruch, Tilman; Derendorf, Hartmut; Paar, W. D.

doi:10.1016/j.ijantimicag.2004.08.012

Cited by 78 publications

(88 citation statements)

References 16 publications

(21 reference statements)

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“…The VPC showed an even distribution of the observed data across the percentiles of the simulated data. Table 3 compares the pharmacokinetic parameter estimates observed in our study with other published data from various patient populations (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). The parameter estimates from the present study generally show a lower mean piperacillin CL than data on healthy volunteers and critically patients when CL CR was taken into consideration.…”

Section: Resultssupporting

confidence: 62%

Pharmacokinetics of Piperacillin in Critically Ill Australian Indigenous Patients with Severe Sepsis

Tsai

Stewart

Goud

et al. 2016

Antimicrob Agents Chemother

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iThere are no available pharmacokinetic data to guide piperacillin dosing in critically ill Australian Indigenous patients despite numerous reported physiological differences. This study aimed to describe the population pharmacokinetics of piperacillin in critically ill Australian Indigenous patients with severe sepsis. A population pharmacokinetic study of Indigenous patients with severe sepsis was conducted in a remote hospital intensive care unit. Plasma samples were collected over two dosing intervals and assayed by validated chromatography. Population pharmacokinetic modeling was conducted using Pmetrics. Nine patients were recruited, and a two-compartment model adequately described the data. The piperacillin clearance (CL), volume of distribution of the central compartment (V c ), and distribution rate constants from the central to the peripheral compartment and from the peripheral to the central compartment were 5.6 ؎ 3.2 liters/h, 14.5 ؎ 6.6 liters, 1.5 ؎ 0.4 h ؊1 , and 1.8 ؎ 0.9 h ؊1 , respectively, where CL and V c were found to be described by creatinine clearance (CL CR ) and total body weight, respectively. In this patient population, piperacillin demonstrated high interindividual pharmacokinetic variability. CL CR was found to be the most important determinant of piperacillin pharmacokinetics.

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Section: Resultssupporting

confidence: 62%

Pharmacokinetics of Piperacillin in Critically Ill Australian Indigenous Patients with Severe Sepsis

Tsai

Stewart

Goud

et al. 2016

Antimicrob Agents Chemother

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“…The steady-state blood concentration should be four to five times higher than the MIC (6,27). The breakpoint for P. aeruginosa is used as a sensibility target when the MIC is not available.…”

Section: Discussionmentioning

confidence: 99%

“…Since ceftazidime exhibits time-dependent killing of gram-negative bacteria in vitro or in critically ill patients, studies involving continuous administration of cephalosporin confirm that the steady-state concentration in blood should be four to five times higher than the bacterial MIC (6,27). When the MIC is not available, the European breakpoint is used to calculate the target concentration (8).…”

mentioning

confidence: 99%

Population Pharmacokinetics of Ceftazidime in Intensive Care Unit Patients: Influence of Glomerular Filtration Rate, Mechanical Ventilation, and Reason for Admission

Georges¹,

Conil²,

Seguin³

et al. 2009

Antimicrob Agents Chemother

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The aim of this study was to develop a population-pharmacokinetic model of ceftazidime in intensive care unit patients to include the influence of patients' characteristics on the pharmacokinetics. Forty-nine patients for model building and 23 patients for validation were included in a randomized study. They received ceftazidime at 2 g three times a day or as 6 g per day continuously. A NONMEM pharmacokinetic model was constructed, and the influences of covariates were studied. The model was validated by a comparison of the predicted and observed concentrations. A final model was elaborated from the whole population. Total clearance (CL) was significantly correlated with the glomerular filtration rate (GFR) calculated by modification of the diet in renal disease (MDRD), the central volume of distribution (V1) with intubation, and the peripheral volume of distribution (V2) with the reason for admission. The mean pharmacokinetic parameters were as follows: CL, 5.48 liters/h, 40%; V1, 10.48 liters, 34%; V2, 32.12 liters, 59%; total volume, 42.60 liters, 45%; and intercompartmental clearance, 16.19 liters/h, 42%. In the polytrauma population (mechanically ventilated), the time above the MIC at steady state never corresponds to 100% for discontinuous administration, and the target concentration of five times the MIC was reached with a 6-g/day dose only for patients with an MDRD of <150 ml/min. We showed that the GFR-MDRD, mechanical ventilation, and the reason for admission may influence the achieved concentrations of ceftazidime. Our model allows the a priori dosing to be adjusted to the individual patient.

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“…Over the last decade, new modes of administration have significantly optimised the antimicrobial activity of PIP/TAZ. In several pharmacokinetic studies, continuous infusion of PIP/TAZ was superior to intermittent injection (despite the use of lower doses) [8,9] and also appeared to be a better pharmacoeconomic option [10]. Under these supposedly optimal pharmacokinetic conditions, the objective of this study was to assess the utility of daily serum piperacillin monitoring to achieve pharmacodynamic targets associated with optimal piperacillin activity.…”

Section: Introductionmentioning

confidence: 99%

Daily serum piperacillin monitoring is advisable in critically ill patients

Blondiaux¹,

Wallet²,

Favory³

et al. 2010

International Journal of Antimicrobial Agents

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The aim of the present study was to evaluate the benefit of monitoring serum piperacillin concentrations in critically ill patients. This was an 11-month, prospective, observational study in a 30-bed Intensive Care Unit in a teaching hospital, involving 24 critically ill patients with evidence of bacterial sepsis. All patients received a 66 mg/kg intravenous bolus of piperacillin in combination with tazobactam (ratio 1:0.125) followed by continuous infusion of 200 mg/kg/24 h. The dosage was adjusted when the serum piperacillin concentration either fell below 4 the drug's minimum inhibitory concentration (MIC) for the causative agent or exceeded the toxic threshold of 150 mg/L. With the initial regimen, serum piperacillin concentrations were within the therapeutic target range in only 50.0% of patients (n = 12). This proportion increased to 75.0% (18 patients) (P = 0.006) following dosage adjustment. For patients with low initial serum piperacillin concentrations (n = 8), the percentage of time during which the concentration remained above 4 MIC (%T>4 MIC) was 7.1 ± 5.9% before dosage adjustment and 27.3 ± 8.6%afterwards. In conclusion, in critically ill patients, monitoring and adjustment of serum piperacillin levels is required to prevent overdosing and might also help to correct underdosing, an important cause of antibiotic therapy failure.

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Pharmacokinetics of piperacillin–tazobactam: intermittent dosing versus continuous infusion

Cited by 78 publications

References 16 publications

Pharmacokinetics of Piperacillin in Critically Ill Australian Indigenous Patients with Severe Sepsis

Pharmacokinetics of Piperacillin in Critically Ill Australian Indigenous Patients with Severe Sepsis

Population Pharmacokinetics of Ceftazidime in Intensive Care Unit Patients: Influence of Glomerular Filtration Rate, Mechanical Ventilation, and Reason for Admission

Daily serum piperacillin monitoring is advisable in critically ill patients

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