Pharmacokinetics and Pharmacodynamics of Intravenous Levofloxacin in Patients with Early-Onset Ventilator-Associated Pneumonia

Pea, Federico; Qual, Elena Di; Cusenza, Aldo; Brollo, Loris; Baldassarre, Marco; Furlanut, Mario

doi:10.2165/00003088-200342060-00008

Cited by 54 publications

(41 citation statements)

References 33 publications

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“…The pharmacokinetics of levofloxacin in plasma confirmed our previous findings for patients with early-onset ventilatorassociated pneumonia (28), suggesting that high b.i.d. dosages (500 mg b.i.d.)…”

Section: Discussionsupporting

confidence: 88%

“…dosages (500 mg b.i.d.) are needed to ensure optimal drug exposure in ICU patients, mainly because the renal clearance of levofloxacin, which is the most predictive parameter of its interindividual pharmacokinetic variability (28,30), may be increased due either to the frequent hyperdynamic conditions or to cotreatment with hemodynamically active drugs.…”

Section: Discussionmentioning

confidence: 99%

“…Plasma and CSF levofloxacin concentrations were analyzed by a high-pressure liquid chromatography method validated in our laboratory, as described previously (28,32). The analytical method chosen was not stereospecific, since levofloxacin has been shown to be stereochemically stable in body fluids without any metabolic inversion to dofloxacin (10,34).…”

Section: Methodsmentioning

confidence: 99%

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Levofloxacin Disposition in Cerebrospinal Fluid in Patients with External Ventriculostomy

Pea

Pavan

Nascimben³

et al. 2003

Antimicrob Agents Chemother

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In vitro levofloxacin exhibits both potent or intermediate activity against most of the pathogens frequently responsible for acute bacterial meningitis and synergistic activity with some beta-lactams. Since levofloxacin was shown to penetrate the cerebrospinal fluid (CSF) during meningeal inflammation both in animals and in humans, the disposition of levofloxacin in CSF was studied in 10 inpatients with external ventriculostomy because of communicating hydrocephalus related to subarachnoid occlusion due to cerebral accidents who were treated with 500 mg of levofloxacin intravenously twice a day because of extracerebral infections. Plasma and CSF concentration-time profiles and pharmacokinetics were assessed at steady state. Plasma and CSF levofloxacin concentrations were analyzed by high-pressure liquid chromatography. The peak concentration of levofloxacin at steady state (C max ss )was 10.45 mg/liter in plasma and 4.06 mg/liter in CSF, respectively, with the ratio of the C max ss in CSF to the C max ss in plasma being 0.47. The areas under the concentration-time curves during the 12-h dosing interval (AUC 0-s) were 47.69 mg ⅐ h/liter for plasma and 33.42 mg ⅐ h/liter for CSF, with the ratio of the AUC 0-for CSF to the AUC 0-for plasma being 0.71. The terminal-phase half-life of levofloxacin in CSF was longer than that in plasma (7.02 ؎ 1.57 and 5.51 ؎ 1.36 h, respectively; P ‫؍‬ 0.034). The ratio of the levofloxacin concentration in CSF to the concentration in plasma progressively increased with time, from 0.30 immediately after dosing to 0.99 at the end of the dosing interval. In the ventricular CSF of patients with uninflamed meninges, levofloxacin was shown to provide optimal exposure, which approximately corresponded to the level of exposure of the unbound drug in plasma. The findings provide support for trials of levofloxacin with twice-daily dosing in combination with a reference beta-lactam for the treatment of bacterial meningitis in adults. This cotreatment could be useful both for overcoming Streptococcus pneumoniae resistance and for enabling optimal exposure of the CSF to at least one antibacterial agent for the overall treatment period.Levofloxacin is a fluoroquinolone antibiotic characterized by a broad antimicrobial spectrum that covers, among other organisms, the pathogens most frequently responsible for acute bacterial meningitis (Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, and Escherichia coli) and also other sporadic agents of central nervous system (CNS) infections, such as Streptococcus agalactiae (13).In in vitro studies based on the time-kill curve method, levofloxacin was recently shown to exhibit synergistic (or at least additive) activity with some beta-lactam antibiotics against both gram-positive and gram-negative microorganisms (11,27,33,35). The degree of this synergy was sometimes of the same extent as that which occurs between beta-lactams and aminoglycosides (4).Previous pharmacokinetic studies documented that levofloxacin could adequately penetrat...

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Levofloxacin Disposition in Cerebrospinal Fluid in Patients with External Ventriculostomy

Pea

Pavan

Nascimben³

et al. 2003

Antimicrob Agents Chemother

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“…Ambulatory volunteers exhibited exceptionally elevated levofloxacin clearance, likely due to their significantly higher creatinine clearance (as measured by the 24-h urine creatinine). This resulted in a much lower AUC than would be expected in normal-weight individuals (12). Conversely, the acutely ill patients receiving levofloxacin had an AUC similar to those for normal-weight individuals (although there was also significant variability within this acutely ill population).…”

Section: Discussionmentioning

confidence: 84%

“…Serum concentrations were sequentially obtained 1. 5 (C max ), 3,4,5,8,12, and 24 (trough) hours after the beginning of the intravenous infusion. Serum samples were collected after the first dose only.…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics of Intravenous Levofloxacin Administered at 750 Milligrams in Obese Adults

Cook

Martin

Adams

et al. 2011

Antimicrob Agents Chemother

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The physiochemical properties of levofloxacin suggest that it is an agent which may exhibit altered pharmacokinetics in obese individuals. The purpose of this study was to describe the pharmacokinetics of a single 750-mg intravenous dose of levofloxacin in both hospitalized and ambulatory obese individuals. The hypothesis was that a standard dose of levofloxacin in obese individuals would achieve serum concentrations likely to be therapeutic. A single levofloxacin dose of 750 mg was infused over 90 min, and seven serial serum samples were subsequently obtained to evaluate the pharmacokinetics after the first dose. The peak concentrations of levofloxacin were comparable to those seen with normal-weight individuals. However, the area under the concentration-time curve and clearance were quite variable. Accelerated clearance was evident in the ambulatory obese individuals. Further investigation of the effects of obesity on the pharmacokinetics of levofloxacin is necessary to ensure optimal dosing.

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Review of Clinical Pharmacokinetics of Levofloxacin with Special Emphasis in Burn Wound Patients

Dash

Rais

Srinivas

2018

Recent Clinical Techniques, Results, and Research in Wounds

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Pharmacokinetics and Pharmacodynamics of Intravenous Levofloxacin in Patients with Early-Onset Ventilator-Associated Pneumonia

Cited by 54 publications

References 33 publications

Levofloxacin Disposition in Cerebrospinal Fluid in Patients with External Ventriculostomy

Levofloxacin Disposition in Cerebrospinal Fluid in Patients with External Ventriculostomy

Pharmacokinetics of Intravenous Levofloxacin Administered at 750 Milligrams in Obese Adults

Review of Clinical Pharmacokinetics of Levofloxacin with Special Emphasis in Burn Wound Patients

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