title: Diffusion of isepamicin into cancellous and cortical bone tissue.
abstract: The degree of penetration of an antibiotic into the infection site is an important factor in its therapeutic efficacy, particularly in bone and joint infections. In the present study, we examined the bone tissue penetration of isepamicin at a dose of 15 mg/Kg, and the results were correlated to microbiologic data to estimate the clinical efficacy of isepamicin in bone infections. In this open-label, single-arm, noncomparative study, subjects of similar age, body weight, height and creatinine clearance who were undergoing elective total hip replacement received a single, parenteral 15 mg/Kg dose of isepamicin. Plasma and bone tissue samples were collected a mean 1.3 hours later and analyzed by a high-pressure liquid chromatography method. Twelve patients (3 men and 9 women; mean age, 73.5 years; mean body weight, 53.5 Kg, mean creatinine clearance, 58.5 mL/min) were enrolled. The mean +/- SD plasma concentration of isepamicin at the time of bone removal was 43.0 +/- 10.4 microg/mL. The mean +/- SD isepamicin concentrations were 11.6 +/- 7.1 microg/mL in cancellous bone tissue and 12.0 +/- 7.3 microg/mL in cortical bone tissue. The mean +/- SD ratios of isepamicin concentration in bone and plasma (bone/plasma) were 0.28 +/- 0.14 for cancellous bone tissue and 0.31 +/- 0.20 for cortical bone tissue. The concentrations achieved in both cancellous and cortical bone tissue were greater than the minimum concentrations required to inhibit the growth of 90% of strains (MIC90) of most of the susceptible pathogens commonly involved in bone infections.
authors.affiliation: Department of Anesthesiology and Intensive Care, Hĵtel-Dieu Hospital, Lyon, France. emmanuel.boselli@chu-lyon.fr
authors.forename: E
authors.initials: E
authors.lastname: Boselli
authors.forename: D
authors.initials: D
authors.lastname: Breilh
authors.forename: J C
authors.initials: JC
authors.lastname: Bel
authors.forename: R
authors.initials: R
authors.lastname: Debon
authors.forename: M C
authors.initials: MC
authors.lastname: Saux
authors.forename: D
authors.initials: D
authors.lastname: Chassard
authors.forename: B
authors.initials: B
authors.lastname: Allaouchiche
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D001682:Biological Availability; D001842:Bone and Bones / Q000378:metabolism*; D005260:Female; D005839:Gentamicins / Q000493:pharmacokinetics*; D006615:Hip / Q000601:surgery; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; C016927:isepamicin