Case-Control Study of Drug Monitoring of β-Lactams in Obese Critically Ill Patients

Hites, Maya; Taccone, Fabio Silvio; Wolff, Fleur; Cotton, Frédéric; Beumier, Marjorie; Backer, Daniel De; Roisin, Sandrine; Lorent, Sophie; Surin, Rudy; Seyler, Lucie; Vincent, Jean‐Louis; Jacobs, Frédérique

doi:10.1128/aac.01083-12

Cited by 97 publications

(136 citation statements)

References 25 publications

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“…However, individual estimates in our study group ranged from 2.8 to 14.2 liters/h, which is not dissimilar to the range of other published data for critically ill or hospitalized patients (3 to 40 liters/h) (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Regarding piperacillin volume of distribution, the V c in this study was similar to other published data for both healthy volunteers and critically ill patients (13,18,19,21).…”

Section: Discussionsupporting

confidence: 86%

“…We found that piperacillin pharmacokinetics in this population have high interindividual variability compared to those in healthy volunteers (12,13) but are similar to those in other critically ill or hospitalized patients (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Nonetheless, we have also found that renal function, i.e., CL CR , remains the most important determinant of piperacillin dosing requirements.…”

Section: Discussionsupporting

confidence: 69%

“…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%

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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: Discussionsupporting

confidence: 86%

Section: Discussionsupporting

confidence: 69%

Section: Resultssupporting

confidence: 62%

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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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“…However, prescribing physicians should always remember that diffusion of antibiotics in anatomical spaces cannot be easily predicted and is impossible to monitor. These patients are at risk of both under-and over-dosing, as recently reported in a study of serum b-lactam concentrations, where insufficient serum concentrations were observed in 32 % of cases and excessive concentrations in 25 % of cases [14]. In addition, some recent data suggest that in patients undergoing scheduled surgery, tissue distribution is altered, with a 30 % decreased penetration ratio compared to nonobese patients [15].…”

mentioning

confidence: 86%

Continuous administration of linezolid in pneumonia: what is the level of proof?

Mimoz¹,

Montravers²,

Paiva³

2014

Intensive Care Med

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Linezolid, the first available oxazolidinone derivative, has been shown to be an interesting alternative to glycopeptides against resistant gram-positive strains [1]. It distributes well into the lung, with mean percentage penetration in epithelial lining fluid of approximately 100 %, indicating that serum concentrations adequately predict antibiotic concentrations at the target site for extracellular respiratory tract pathogens [1]. Linezolid is a time-dependent antimicrobial agent with a reduced postantibiotic effect. The best pharmacokinetic/pharmacodynamic (PK/PD) parameters to define its activity are time with serum concentrations higher than the minimum inhibitory concentration (T [ MIC) and area under the serum concentration-time curve/minimum inhibitory concentration (AUC/MIC) ratio [1]. Linezolid is mainly a bacteriostatic antimicrobial agent with T [ MIC of at least 40 % being predictive of its efficacy. This objective can be easily achieved for pathogens with MICs of 2-4 mg/l by administration of standard dosing (600 mg intravenously twice a day) in healthy volunteers, suggesting that continuous infusion, the best antimicrobial administration modality for most time-dependent antibiotics as it prolongs effective serum concentrations, may not be essential [1].During the initial phase of septic shock, however, alterations in pharmacokinetic parameters, mostly due to an increase in the volume of drug distribution and/or drug clearance, are frequently observed [2]. These modifications vary from one patient to another and in a single patient from one day to another [2]. They may lead to suboptimal serum and tissue concentrations when drugs are given at the dosage studied in healthy volunteers or in less seriously ill patients. Moreover, critically ill septic patients should be considered as immunosuppressed, and antimicrobials with bactericidal activity may be more effective than those exhibiting only bacteriostatic activity [3]. In an in vivo model of endocarditis, linezolid demonstrated bactericidal activity when T [ MIC was maintained for [75 % of the dosing interval [4]. On the basis of these considerations, achieving T [ MIC close to 100 % is probably the key to obtaining the highest success rate with linezolid in ICU patients.Recently, Zoller et al. [5] showed that there was a high variability of linezolid serum concentrations after standard dosing in 30 critically ill infected patients with a median body mass index of 26 kg/m 2 (range 16-35 kg/ m 2 ), mostly with lung infections. Optimal pharmacodynamic exposure over 24 h, with AUC 0-24h values between 200 and 400 mg h/l and with C min values between 2 and 10 mg/l, could be observed for only 30 and 43 % of the patients, respectively. Regarding these AUC 0-24h and C min values, 63 and 50 % of the patients, respectively, had linezolid concentrations below the lower limit of the corresponding target concentration range and only 7 % Intensive Care Med (2015) 41:157-159

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“…However, recent studies suggest that higher targets are needed in critically ill patients to improve clinical outcome whilst minimizing the development of resistance. Concentrations four to fivefold greater than the MIC are associated with maximum bactericidal activity [3,4]. The PK/PD target was set at 100% fT > 4−5xMIC .…”

mentioning

confidence: 99%

pilot study on pharmacokinetic/pharmacodynamic target attainment in critically ill patients receiving piperacillin/tazobactam

Martı́nková¹,

Malbrain²,

Havel³

et al. 2016

Anaesthesiol Intensive Ther

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Background: In critically ill patients, multi-trauma and intensive therapy can influence the pharmacokinetics (PK) and pharmacodynamics (PD) of antibiotics with time-dependent bacterial killing. Consequently, PK/PD targets (%fT >MIC ) -crucial for antimicrobial effects -may not be attained. Methods: Two patients admitted to the surgical ICU of the University Hospital in Hradec Králove for multiple-trauma were given piperacillin/tazobactam by 1-hour IV infusion 4/0.5 g every 8 h. PK variables: total and renal clearance (CL tot , CL R ), volume of distribution (V d ), and elimination half-life (T 1/2 ) were calculated, followed by glomerular filtration rate (MDRD) and cumulative fluid balance (CFB-total fluid volume based on 24-h registered fluid intake minus output). The PK/PD target attainment (100%fT >MIC ) was defined as free (f) piperacillin plasma concentrations that remain, during the entire dosing interval (T), above the minimum inhibitory concentration (100%fT> MIC ) within days 4-8 (when CFB culminates and disappears). Piperacillin concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and corrected for unbound fraction (22%). Results: CFB culminated over days 2−5 reaching 15−30 L and was associated with a large V d (29−42 L). While MDRD in patient 1 was low (0.3−0.4 mL s -1 1.7 m -2 ), that of patient 2 was increasing (> 3.1 mL s -1 1.7 m -2 ), which was associated with augmented CL R . In patient 2, the fT reached only 62, 52, and 44% on days 4, 6, and 8, respectively. In patient 1, the %fT was much higher, attaining values four to fivefold greater than that targeted. Conclusions: Critically ill patients are at risk of drug under-or overdosing without dose up-titration with regard to covariate effects and individual drug pharmacokinetics.

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Case-Control Study of Drug Monitoring of β-Lactams in Obese Critically Ill Patients

Cited by 97 publications

References 25 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

Continuous administration of linezolid in pneumonia: what is the level of proof?

pilot study on pharmacokinetic/pharmacodynamic target attainment in critically ill patients receiving piperacillin/tazobactam

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