Pharmacokinetics of cefepime in patients with the sepsis syndrome

Kieft, Hans; Hoepelman, Andy I. M.; Knupp, Catherine A.; Dijk, Arie P.J. van; Branger, Judith; Struyvenberg, A; Verhoef, J.

doi:10.1093/jac/32.suppl_b.117

Cited by 37 publications

(16 citation statements)

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“…However, for the treatment of seriously ill patients, cefepime may need to be administered three times dai ly. The concentration of cefepime was above 8 mg/1 during 8 h in patients with the sepsis syndrome [15]. Cefepime is widely distribut ed in biological fluids and tissues.…”

Section: Discussionmentioning

confidence: 99%

In vitro Time-Kill Curves of Cefepime and Cef pirome Combined with Amikacin, Gentamicin or Ciprofloxacin against <i>Klebsiella pneumoniae</i> Producing Extended-Spectrum Beta-Lactamase

Elkhaïli¹,

Linger²,

Levêque³

et al. 1997

Chemotherapy

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Extended-spectrum β-lactamases (ESBLs) are found in numerous Enterobacteriaceae, mainly in Klebsiella pneumoniae. We investigated the pharmacodynamics of two new extended-spectrum cephalosporins, cefepime and cefpirome, alone and combined with either amikacin or gentamicin or ciprofloxacin by means of time-kill curves against ESBL-producing, amino-glycoside-resistant K. pneumoniae. When used alone, cefepime (8 and 16 mg/l) resulted in a 2 and 3 log decrease at 6 h, respectively, but at 24 h regrowth occurred. The combination of cefepime (8 mg/l) with amikacin (4 mg/l) resulted in a 4 log decrease at 6 h, but there were no surviving bacteria at 6 h when combined with amikacin (8 mg/l). The combination of cefepime (16 mg/l) with gentamicin (4 mg/l) resulted in a 4 log decrease in 24 h. The antimicrobial combiantion of cefepime (32 mg/l) with ciprofloxacin (2 mg/l) resulted in a 4 log decrease in 24 h. Cefpirome (8 mg/l) induced a 2 log decrease at 4 h; 32 mg/l cefpirome resulted in a 3 log decrease followed by regrowth at 24 h. The regrowth observed in the late phase with cefpirome alone disappeared when combined with aminoglycoside. When cefpirome (32 mg/l) was used in combination with ciprofloxacin (1 mg/l), it resulted in a 4 log decrease in 24 h.

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Section: Discussionmentioning

confidence: 99%

In vitro Time-Kill Curves of Cefepime and Cef pirome Combined with Amikacin, Gentamicin or Ciprofloxacin against <i>Klebsiella pneumoniae</i> Producing Extended-Spectrum Beta-Lactamase

Elkhaïli¹,

Linger²,

Levêque³

et al. 1997

Chemotherapy

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“…This difference in elimination half-life could be due to difference in age, sex and breed of the animals. The elimination half-life had been reported as 2.38 h in calves (Ismail 2005a), 1.76 h in ewes (Ismail 2005b), 2.1 h in horses (Guglick et al 1998), 2 h in humans (Kieft et al 1993) and 1.65 h in foals and 1.09 h in dogs (Gardner and Papich 2001). While comparing the total body clearance in febrile animals with that of healthy animals, it was found that the value of Cl B (114.2±1.20 ml/kg/h) in febrile animals was significantly (P<0.05) different as compared to healthy animals (104.4± 2.70 ml/kg/h).…”

Section: Discussionmentioning

confidence: 99%

Influence of E. coli lipopolysaccharide induced fever on the plasma kinetics of cefepime in cross-bred calves

Pawar

Sharma

2007

Vet Res Commun

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The pharmacokinetic behavior of cefepime was studied in healthy and febrile cross-bred calves after single intravenous administration (10 mg/kg). The fever was induced with E. coli lipopolysaccharide (1 microg/kg, IV). The drug concentration in plasma was detected by microbiological assay method using E. coli (MTCC 739) test organism. Pharmacokinetic analysis of disposition data indicated that intravenous administration data were best described by 2 compartment open model. At 1 min the concentration of cefepime in healthy and febrile animals were 55.3 +/- 0.54 microg/ml and 50.0 +/- 0.48 microg/ml, respectively and drug was detected up to 12 h. The elimination half-life of cefepime was increased from 1.26 +/- 0.01 h in healthy animals to 1.62 +/- 0.09 h in febrile animals. Drug distribution was altered by fever as febrile animals showed volume of distribution (0.27 +/- 0.02 L/kg) higher than normal animal (0.19 +/- 0.01 L/kg). Total body clearances in healthy and febrile animals were 104.4 +/- 2.70 and 114.2 +/- 1.20 ml/kg/h, respectively. To maintain minimum therapeutic concentration of 1 mug/ml, a satisfactory dosage regimen of cefepime in healthy and febrile cross-bred calves would be 15.5 mg/kg and 8.2 mg/kg body weight, respectively, to be repeated at 8 h intervals. The T>MIC values (8 h) of cefepime suggested that this agent is clinically effective in the treatment of various infections.

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“…A c c e p t e d M a n u s c r i p t 16 Freeze and thaw stability was also assessed using QCs at four concentrations prepared in five aliquots. Analyte stability was determined after three freeze-thaw cycles: Aliquots of the QCs were initially frozen at -80 °C for twenty four hours and then allowed to thaw unassisted at room temperature.…”

Section: Page 16 Of 48mentioning

confidence: 99%

“…The pharmacokinetics of -lactam antibiotics is difficult to predict in the critically ill patient population due to the unpredictable effects of pathophysiologic processes particularly during sever sepsis and malignancy [13,14]. The drug's apparent volume of distribution and clearance may be elevated leading to sub-therapeutic plasma concentrations [4,[15][16][17][18][19][20][21][22][23][24]. On the other hand clearance may be unchanged [17] or decreased [4,18] and in the presence of organ dysfunction such acute kidney injury, diminished clearance may lead to massive accumulation and toxicity [25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Simultaneous determination of seven β-lactam antibiotics in human plasma for therapeutic drug monitoring and pharmacokinetic studies

Sime

Roberts

et al. 2014

Journal of Chromatography B

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractThere is strong evidence in literature supporting the benefit of monitoring plasma concentrations of -lactam antibiotics in the critically ill to ensure appropriateness of dosing.The objective of this work was to develop a method for the simultaneous determination of total concentrations piperacillin, benzylpenicillin, flucloxacillin, meropenem, ertapenem, cephazolin and ceftazidime in human plasma. Sample preparation involved protein precipitation with acetonitrile containing 0.1% formic acid and subsequent dilution of supernatant with 0.1% formic acid in water. Chromatographic separation was achieved on a reversed phase column (C18, 2.6µm, 2.1* 50 mm) via gradient elution using water and acetonitrile, each containing 0.1% formic acid, as mobile phase. Tandem mass spectrometry (MSMS) analysis was performed, after electrospray ionization in the positive mode, with multiple reaction monitoring (MRM). The method is accurate with the inter-day and intra-day accuracies of quality control samples (QCs) ranging from 95%-107% and 95%-108%, respectively. It is also precise with intra-day and inter-day coefficient of variations ranging from 4 to 12 % and 5-14% respectively. The lower limit of quantification was 0.1g/mL for each antibiotic except flucloxacillin (0.25g/mL). Recovery was greater than 96% for all analytes except for ertapenem (78%). Coefficients of variation for the matrix effect were less than 10% over the six batches of plasma. Analytes were stable over three freeze-thaw cycles, and for reasonable hours on the bench top as well as post-preparation. This novel liquid chromatography tandem mass spectrometry method proved accurate, precise and applicable for therapeutic drug monitoring and pharmacokinetic studies of the selected -lactam antibiotics.Page 5 Highlights  We present a method for simultaneous determination of seven beta-lactams in plasma  The selected antibiotics are those commonly used in critically ill patients  The method is accurate, precise and meets validation requirements by guidelines  It proved applicable for therapeutic drug monitoring and pharmacokinetic studies

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Pharmacokinetics of cefepime in patients with the sepsis syndrome

Cited by 37 publications

References 0 publications

In vitro Time-Kill Curves of Cefepime and Cef pirome Combined with Amikacin, Gentamicin or Ciprofloxacin against <i>Klebsiella pneumoniae</i> Producing Extended-Spectrum Beta-Lactamase

In vitro Time-Kill Curves of Cefepime and Cef pirome Combined with Amikacin, Gentamicin or Ciprofloxacin against <i>Klebsiella pneumoniae</i> Producing Extended-Spectrum Beta-Lactamase

Influence of E. coli lipopolysaccharide induced fever on the plasma kinetics of cefepime in cross-bred calves

Simultaneous determination of seven β-lactam antibiotics in human plasma for therapeutic drug monitoring and pharmacokinetic studies

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