In vitro pharmacokinetics of antibiotic release from locally implantable materials

Abstract

Local deposition of antibiotics has became increasingly popular in the management of open fractures or osteomyelitis, and several substances have been employed as the vehicle for delivery. Although the elution characteristics of some substances have been documented, a comparative study of the characteristics of the commonly used substances could establish the clinical indications for particular vehicles. Cylindrical pellets of uniform size (6 x 4 mm) were prepared from bone graft (BG), demineralized bone matrix (DBM), plaster of Paris (POP), or polymethylmethacrylate (PMMA), with 25 mg of tobramycin/g of substance in each pellet. The pellets were suspended in phosphate buffered saline, and the antibiotic concentration in the buffer was determined at various time intervals by an enzyme immunoassay. BG and DBM eluted 70 and 45% of their antibiotic load by 24 h, and negligible amounts were detected at 1 week; POP released 17% of its load by 24 h, with trace amounts detected at 3 weeks; and PMMA eluted 7% at 24 h, with trace amounts detected for as long as 14 days. These findings suggest that the optimal vehicle for local deposition of antibiotic depends on the clinical setting. BG and DBM may be best employed when brief antibiotic coverage is required (as for acute contaminated open fractures), whereas POP and PMMA may be better suited for long-term coverage (such as for established osteomyelitis).

Comparing PMMA and calcium sulfate as carriers for the local delivery of antibiotics to infected surgical sites

“…Miclau et al tested the elution characteristics of bone graft (BG) demineralized bone matrix (DBM), PMMA, and calcium sulfate (plaster of Paris, POP), using pellets containing 25 mg of tobramycin. 20 BG and DBM rapidly eluted their antibiotic load in the first 24 h, and only trace amounts were detectable at one week. PMMA released only 7% of its load at 24 h, and trace amounts were detectable at two weeks.…”

The Treatment of Chronic Osteomyelitis with a Biodegradable Antibiotic-Impregnated Implant

“…One of the most well known materials studied is calcium sulfate. 3,4,7,8,11 Calcium sulfate is a bioceramic that occurs naturally. Surgical-grade calcium sulfate is a relatively pure alpha hemihydrate crystal, which can be hydrated producing solid implants.…”

Elution of Metronidazole and Gentamicin from Polymethylmethacrylate Beads

“…The procedures used for the elution studies were similar to those previously reported (Picknell 1977;Miclau 1993;Bowyer 1994;Ethell 2000). The PMMA- …”

“…The amount and duration of the antibiotic release in vitro cannot be directly applied to an in vivo setting (Miclau 1993). The elution of the antibiotic from the bone cement may be affected by both the volume of the washings and the frequency with which the beads are bathed.…”

“…The elution of the antibiotic from the bone cement may be affected by both the volume of the washings and the frequency with which the beads are bathed. If the volume of the washings is smaller in vitro than in vivo, then the antibiotic concentrations attained in vitro may be greater than in vivo (Miclau 1993). In vivo tissue concentrations may also vary, depending on the vascularity of the tissues, which will affect the rate of antibiotic absorption and clearance (Miclau 1993).…”