Antibiotic concentrations in pus and bone of children with osteomyelitis

Tetzlaff, Thomas R.; Howard, Jorge E.; McCracken, George H.; Calderón, Ernesto; Larrondo, Jose

doi:10.1016/s0022-3476(78)80095-x

Cited by 49 publications

(10 citation statements)

References 12 publications

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“…A study in 8 children with osteomyelitis has reported an elimination half-life of 1.7-1.8 h (5), which is consistent with the values in our patients. Total body clearance and distribution volumes have been reported only in newborn infants; clearance ranged from 0.53-1.1 mlIminlkg and distribution volume from 0.21-0.34 lIkg in these infants (6).…”

Section: Discussionsupporting

confidence: 92%

Pharmacokinetics and tissue concentrations of cefazolin in pediatric patients undergoing gastrointestinal surgery

Nahata

Durrell

Ginn‐Pease

et al. 1991

European Journal of Drug Metabolism and Pharmacokinetics

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Limited information is available on the pharmacokinetics and tissue penetration of cefazolin in pediatric patients. Nine children (age 0.8-10 years) undergoing gastrointestinal operations were studied. A single dose of cefazolin, 15-26 mg/kg was given i.v. over 2-3 min at the time of induction of anaesthesia. Multiple (5-8) blood samples were collected during the operative procedure and in the recovery room. Tissue samples from the rectus abdominis muscle were obtained at the time of incision, during surgery, and at closure. The concentration of cefazolin was measured by a high performance liquid chromatographic method. Peak serum concentrations of cefazolin ranged from 85.8-269.4 mcg/ml. Serum and tissue concentrations at incision were 50.5-169.9 mcg/ml and 1.8-29.7 mcg/g; at closure the serum and tissue concentrations ranged from 17.3-60.9 mcg/ml and 1.19-29.70 mcg/g, respectively. Total clearance, apparent distribution volume, and elimination half-life of cefazolin were 1.43 +/- 0.54 ml/min/kg, 0.08 +/- 0.03 l/kg, and 1.68 +/- 0.55 h respectively. Tissue concentrations of cefazolin were maintained above its minimum inhibitory concentrations against common susceptible pathogens. Hence, the current dosing regimen of cefazolin is adequate to protect against infection in pediatric patients undergoing gastrointestinal surgery.

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Section: Discussionsupporting

confidence: 92%

Pharmacokinetics and tissue concentrations of cefazolin in pediatric patients undergoing gastrointestinal surgery

Nahata

Durrell

Ginn‐Pease

et al. 1991

European Journal of Drug Metabolism and Pharmacokinetics

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“…This is of the same order of magnitude as found by Bryson et al [2], 12-40 pg/ml, who used a bioassay; and Nelson et al [15], 9.2-28.0 pg/ml, who also used a bioassay, but with a different indicator bacterium.…”

Section: Discussionsupporting

confidence: 76%

Dicloxacillin Absorption and Elimination in Children

et al. 1990

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We determined the apparent bioavailability of dicloxacillin in 26 children between the ages of 0.24 and 143 months by comparing the area under the serum concentration versus time curve following intravenous and oral administration of 25 mg/kg. With intravenous infusion the overall mean half-life of elimination was 0.53 ± 0.20 h, the AUC was 70.15 ± 32.18 mg·min/l and the apparent volume of distribution was 0.29 ± 0.09 l/kg. The overall average bioavailability was 59.89%. Children less than 6 months old had a shorter time to peak concentration (1.39 ± 0.49 h) and the lowest oral bioavailability (64.35 ± 13.62%) in comparison to children more than 60 months old. In children older than 60 months the time to peak was 1.79 ± 1.16 h and the average oral bioavailability was 79.38 ± 32.87%. However, children less than 6 months old had the least variability in absorption, the coefficient of variation (CV) of oral bioavailability was 13.62%, while in children between 6 and 40 months old the CV was 60.4%: children older than 60 months had the most variability in absorption, a CV of 32.87%. This variability was not dependent on the formulation administered. After 5 years of age the bioavailability increased with increasing age.

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“…Although previou § investigators have demonstrated differences in the protein binding of antibiotics in interstitial fluid versus serum (12,(36)(37)(38), Rolinson (25) showed that the unbound serum concentration of a drug will equal the unbound concentration of the drug in interstitial fluid regardless of the relative protein binding. Since cefazolin appears to assume equal total concentrations in osseous interstitial fluid and serum, the percentage of protein-bound drug in these two fluid spaces is probably equal.…”

Section: Discussionmentioning

confidence: 99%

Penetration of cefazolin into normal and osteomyelitic canine cortical bone

Daly¹,

Fitzgerald²,

Washington³

1982

Antimicrob Agents Chemother

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The ability of cefazolin to cross the capillary membranes and its concentrations in the interstitial fluid spaces were studied in normal and osteomyelitic canine bone. The maximum extraction after a single capillary passage and the net extraction after 3 min, determined with triple-tracer indicator-dilution techniques, demonstrated that cefazolin readily traversed the capillaries of normal and osteomyelitic bone. These studies suggest that the altered pathophysiology of osteomyelitic tissue and the complex diffusional characteristics of cefazolin enhanced the ability of this agent to cross the endothelial cells lining the capillaries of osteomyelitic bone. Volume of distribution studies demonstrated that cefazolin was distributed in the plasma and interstitial fluid spaces of normal cortical bone.Although these spaces were increased 330 and 941% in osteomyelitic tissue, the distribution of cefazolin increased proportionally. There was a direct correlation between the calculated concentrations of cefazolin in the interstitial fluid spaces of normal and osteomyelitic cortical bone and the simultaneous serum levels in animals in which a steady-state equilibrium had been achieved. These studies suggest that a physiological barrier or concentration gradient for cefazolin does not exist in normal or osteomyelitic bone. Cefazolin can cross the capillary membranes of bone and achieve bactericidal concentrations in the interstitial fluid space of normal and osteomyelitic tissue.

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Antibiotic concentrations in pus and bone of children with osteomyelitis

Cited by 49 publications

References 12 publications

Pharmacokinetics and tissue concentrations of cefazolin in pediatric patients undergoing gastrointestinal surgery

Pharmacokinetics and tissue concentrations of cefazolin in pediatric patients undergoing gastrointestinal surgery

Dicloxacillin Absorption and Elimination in Children

Penetration of cefazolin into normal and osteomyelitic canine cortical bone

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