Pharmacokinetics/pharmacodynamics of antibacterials in the Intensive Care Unit: setting appropriate dosing regimens

Scaglione, Francesco; Paraboni, Luca

doi:10.1016/j.ijantimicag.2008.03.015

Cited by 98 publications

(68 citation statements)

References 250 publications

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“…The 3 most common PK/PD indices (sometimes abbreviated as PD measures) used to predict drug response are: 1) the ratio of the maximal free drug concentration to the MIC (fC max :MIC), 2) the ratio of the free area under the concentration-time curve to the MIC (fAUC:MIC), and 3) the duration of time free drug concentrations remain above the MIC (fT>MIC). [2][3][4]20,21 The PD parameter most predictive of outcomes varies by drug class (Table 1). 20 Certain antibiotics exhibit concentration-dependent bactericidal activity, while others exhibit time-dependent activity ( Table 1).…”

Section: Common Pharmacodynamic Measuresmentioning

confidence: 99%

Use of pharmacodynamic principles to inform β‐lactam dosing: “S” does not always mean success

Lodise¹,

Butterfield²

2011

Journal of Hospital Medicine

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Dose optimization is one of the key strategies for enhancing antimicrobial stewardship. There have been tremendous strides in our understanding of antibiotic exposure-response relationships over the past 25 years. For many antibiotics, the ''pharmacodynamic'' or the exposure variable associated with outcome has been identified. With advances in mathematical modeling, it is possible to apply our understanding of antimicrobial pharmacodynamics (PD) into clinical practice and design empirical regimens that have a high probability of achieving the PD target linked to effect. By optimizing antibiotic doses to achieve PD targets predictive of efficacy, clinicians can improve care and minimize drug toxicity. For b-lactams, the PD parameter most predictive of maximal bactericidal activity is the duration of time free drug concentrations remain above the minimum inhibitory concentration (MIC) during the dosing interval (fT > MIC). Unfortunately, the conventional intermittent b-lactam dosing schemes often used in practice have suboptimal PD profiles. Prolonging the infusion time of b-lactams is one method to maximize the probability of achieving concentrations in excess of the MIC for the majority of the dosing interval, especially against pathogens with elevated MIC values. Prolonged infusions of intravenous b-lactams are not only associated with improved probability of target attainment (PTA) profiles but offer possible cost savings and greater potential for reducing emergence of resistance relative to intermittent infusions. Journal of Hospital Medicine 2011;6:S16-S23. V C

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Section: Common Pharmacodynamic Measuresmentioning

confidence: 99%

Use of pharmacodynamic principles to inform β‐lactam dosing: “S” does not always mean success

Lodise¹,

Butterfield²

2011

Journal of Hospital Medicine

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“…En pacientes con fases tardías de quemaduras, leucemia aguda y la fase hiperdinámica de la sepsis se ha reportado aumento en la depuración de medicamentos. En contraposición, en pacientes con insufi ciencia renal y los mayores de 75 años se ha encontrado disminución de la depuración de medicamentos 10 . Hasta en 54% de los pacientes críticamente enfermos se ha encontrado disfunción hepática, asociada a factores como hipotermia, sepsis e hipotensión, lo cual puede causar disminución de la depuración de los medicamentos eliminados por esta vía, debido a disminución en la actividad enzimática hepatocelular, disminución del fl ujo sanguíneo y/o biliar 26,27 .…”

Section: Cambios Farmacocinéticos En Los Pacientes Críticamente Enfermosunclassified

“…Las nuevas fl uoroquinolonas tienen un elevado volumen de distribución con penetración a casi todos los tejidos. De hecho, 60 a 75% del medicamento en el cuerpo en cualquier momento se puede encontrar a nivel intracelular lo cual contribuye a una menor excreción renal y mayor vida media 10 . El volumen de distribución se afecta mínimamente en los pacientes críticamente enfermos, aunque levofl oxacina requiere aumento de la dosis por disminución de la vida media 57 .…”

Section: Pk/pd Y Quinolonasunclassified

“…En los pacientes críticamente enfermos ocurren variaciones en el volumen extracelular, que pueden causar alteraciones en las concentraciones séricas o tisulares de los medicamentos 10 . Tanto en pacientes neutropénicos, como en modelos animales se ha reportado disminución en las concentraciones séricas, tisulares y en líquidos corporales de los agentes anti-infecciosos, lo cual se puede asociar con inadecuados niveles terapéuticos y estos a su vez pueden causar fracasos y seleccionar cepas resistentes.…”

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Farmacocinética y farmacodinamia de antimicrobianos: a propósito de pacientes con neutropenia y fiebre

Garzón

et al. 2011

Rev. chil. infectol.

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“…However, these studies did not use individually targeted approaches based on the actual serum concentration of beta-lactams and their pharmacokinetics. Although the best clinical practice is to estimate the pharmacokinetic parameters for each patient, the implementation of beta-lactam TDM based on Craig's indices has yet to be investigated in the clinical practice [7]. The aim of this study was to validate the clinical utility of patient-specific beta-lactam TDM in pharmacy clinical practice.…”

Section: Introductionmentioning

confidence: 99%

Application of Beta-lactam Therapeutic Drug Monitoring in Clinical Practice Using HPLC

Aoki¹

2013

JBABM

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In beta-lactam therapy, investigation of the pharmacokinetic-pharmacodynamic (PK-PD) relationship has provided surrogate makers to predict clinical outcome. This study was designed to verify the therapeutic efficacy and clinical utility of beta-lactam therapeutic drug monitoring (TDM) in critically ill patients using high-performance liquid chromatography (HPLC). This cohort study included 13 patients who were intravenously administered ceftazidime (n = 6), cefepime (n = 1), imipenem (n = 1), meropenem (n = 1), or piperacillin (n = 4). Blood samples were collected at 3 time points fitted to a 1-compartment model, and concentrations were determined using HPLC. The PK-PD target was the percentage of the dosing interval during which the antibiotic concentration exceeded the minimum inhibitory concentration for the pathogens (%T > MIC), which is 50% for penicillins (piperacillin), 60% for cephalosporins (ceftazidime and cefepime), and 40% for carbapenems (imipenem and meropenem). Our process using HPLC enables the analytical results of TDM to be available within half a day. The results revealed significant inter-patient pharmacokinetic variability. During the initial regimen, beta-lactam concentrations reached the target %T > MIC in all patients, and dosage reduction was required for 5 patients (38%). Of the 13 evaluable patients, clinical improvement was observed in 11 (85%), and microbiological success was observed in 10 (77%). In summary, beta-lactam TDM achieved the treatment goals and might also allow for the personalization to prevent overdosing for variable pharmacokinetic changes in critically ill patients. These findings indicate that beta-lactam TDM using HPLC can be used in the standard pharmacy clinical practice for critically ill patients.

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Pharmacokinetics/pharmacodynamics of antibacterials in the Intensive Care Unit: setting appropriate dosing regimens

Cited by 98 publications

References 250 publications

Use of pharmacodynamic principles to inform β‐lactam dosing: “S” does not always mean success

Use of pharmacodynamic principles to inform β‐lactam dosing: “S” does not always mean success

Farmacocinética y farmacodinamia de antimicrobianos: a propósito de pacientes con neutropenia y fiebre

Application of Beta-lactam Therapeutic Drug Monitoring in Clinical Practice Using HPLC

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