Linezolid pharmacokinetic/pharmacodynamic profile in critically ill septic patients: intermittent versus continuous infusion

Adembri, Chiara; Fallani, Stefania; Cassetta, Maria Iris; Arrigucci, Silvia; Ottaviano, A; Pecile, Patrizia; Mazzei, Teresita; Gaudio, Raffaele De; Novelli, Andréa

doi:10.1016/j.ijantimicag.2007.09.009

Cited by 149 publications

(90 citation statements)

References 32 publications

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“…Therefore, there was a high variability of linezolid AUC 0-24h and C min values, with C min values differing more than 100-fold between the different patients and more than 30-fold within single patients. These data are in line with other studies observing very low, usually insufficient AUC 0-24h or C min linezolid values [6][7][8] and also in line with papers showing C min values differing more than 50-fold between different patients [8,9].…”

supporting

confidence: 93%

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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supporting

confidence: 93%

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

Mimoz¹,

Montravers²,

Paiva³

2014

Intensive Care Med

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“…The authors recommend a loading dose of 600 mg three times daily for the first 24 h, or the administration of the total daily dose by CI. Indeed, linezolid is stable and recent data demonstrated that 1200 mg/24 h by CI maintained concentrations between 7 and 10 mg/L and was associated with better pharmacodynamic parameters than intermittent administration of the same daily dose [73].…”

Section: Critically Ill Patientsmentioning

confidence: 99%

Treatment options for methicillin-resistant Staphylococcus aureus (MRSA) infection: Where are we now?

Edwards

Andini

Esposito

et al. 2014

Journal of Global Antimicrobial Resistance

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“…It is a valid therapeutic alternative to glycopeptides against multiresistant Gram-positive strains such as staphylococci, streptococci and enterococci, which are particularly frequent in the ICU [37]. Linezolid is a time-dependent antimicrobial agent with a persistent antibiotic effect and the PK/PD indices T >MIC and AUC/MIC are important determinants of its efficacy in vitro and in vivo [38,39].…”

Section: Linezolidmentioning

confidence: 99%

“…In an in vivo model of endocarditis, Jacqueline et al showed not only that continuous infusion was more effective than intermittent doses, but also that switching from intermittent dosing to continuous infusion (at the same daily dose) led to in vivo bactericidal activity [43]. Moreover, a recent trial A c c e p t e d M a n u s c r i p t administered by intermittent or continuous infusion in 16 critically ill septic patients [37].…”

Section: Buerger Et Al Have Recently Demonstrated a High Inter-indivmentioning

confidence: 99%

Pharmacokinetic/pharmacodynamic (PK/PD) considerations in the management of Gram-positive bacteraemia

Scaglione

2010

International Journal of Antimicrobial Agents

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Linezolid pharmacokinetic/pharmacodynamic profile in critically ill septic patients: intermittent versus continuous infusion

Cited by 149 publications

References 32 publications

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

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

Treatment options for methicillin-resistant Staphylococcus aureus (MRSA) infection: Where are we now?

Pharmacokinetic/pharmacodynamic (PK/PD) considerations in the management of Gram-positive bacteraemia

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