title: High local concentrations without systemic adverse effects after impaction of netilmicin-impregnated bone.
abstract: BACKGROUND
  When cancellous bone is impregnated with antibiotics the subsequent release of antibiotics from the bone shows a high early release. Hence, impaction of large amounts of netilmicin-impregnated bone may cause toxic netilmicin values in serum.
  
  
  METHODS
  We studied kidney and otovestibular function after impacting 50 g of netilmicin-impregnated cancellous bone during revision hip or knee arthroplasty in 20 patients. The bone was impacted in the acetabulum (n = 8), proximal femur (n = 9) and distal femur/proximal tibia (n = 3). Serum creatinine concentration was measured and audiometry was performed before and after the operation. Netilmicin concentrations in serum, joint fluid, and in urine were recorded postoperatively at regular intervals. We analyzed pharmacokinetics in two study groups receiving bone impregnated with netilmicin (50 mL), at either 50 mg netilmicin/mL (group I) or 100 mg netilmicin/mL (group II).
  
  
  RESULTS
  Neither netilmicin-induced renal toxicity, nor otovestibular toxicity was registered. Peak serum netilmicin values in group I and group II were 0.9 (0.5-1.3) mg/L and 1.8 (0.6-4.0) mg/L, respectively (p = 0.04). Peak netilmicin concentrations in wound drainage fluid in group I and group II were 237 (9-647) mg/L and 561 (196-1132) mg/L, respectively (p = 0.01). In both groups, netilmicin was recovered in urine samples for approximately 4 weeks.
  
  
  CONCLUSIONS
  50 grams of cancellous bone impregnated with 100 mg/mL netilmicin solution was impacted in the hip or knee joint with no adverse effects. Extremely high local concentrations of netilmicin in joint fluid were recorded postoperatively. The use of antibioitic-impregnated cancellous could be an option when performing revision of hip and knee prostheses.
authors.affiliation: Department of Orthopedic Surgery, University Hospital, Trondheim, Norway. eivind.witso@stolav.no
authors.forename: Eivind
authors.initials: E
authors.lastname: Witsø
authors.forename: Leif
authors.initials: L
authors.lastname: Persen
authors.forename: Pål
authors.initials: P
authors.lastname: Benum
authors.forename: Arild
authors.initials: A
authors.lastname: Aamodt
authors.forename: Otto Schnell
authors.initials: OS
authors.lastname: Husby
authors.forename: Kåre
authors.initials: K
authors.lastname: Bergh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001842:Bone and Bones; D004337:Drug Carriers; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009428:Netilmicin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D009428:Netilmicin