Elution of metronidazole and gentamicin from polymethylmethacrylate beads.
OBJECTIVE
To characterize the elution and bioactivity of metronidazole and gentamicin sulfate polymerized, individually and in combination, with polymethylmethacrylate (PMMA).


METHODS
In vitro experimental study.


METHODS
PMMA beads containing metronidazole (3 concentrations), gentamicin sulfate, or metronidazole and gentamicin sulfate were immersed in 5 mL of phosphate-buffered saline in triplicate. Eluent was replaced at specified time intervals for 1 or 21 days, and antibiotic concentrations were measured by high-performance liquid chromatography. Changes in antibiotic bioactivity attributable to polymerization or copolymerization of the antibiotics with PMMA, ethylene oxide sterilization, and storage of AIPMMA beads containing metronidazole were evaluated.


RESULTS
Antibiotic elution patterns were similar for all groups. Day 1 elution for groups containing metronidazole or gentamicin individually represented a mean 63%-66% and 79%, respectively, of the 21-day total. Approximately 50% of the day 1 elution occurred during the first hour. The elution of metronidazole was dose dependent. The elution of metronidazole (day 3-21) and gentamicin (all days) was significantly greater when metronidazole and gentamicin were combined (P <.05). The addition of metronidazole delayed polymerization of PMMA. Neither polymerization nor copolymerization of metronidazole and gentamicin with PMMA, gas sterilization, or 2-month storage of beads containing metronidazole significantly affected antimicrobial bioactivity.


CONCLUSIONS
Metronidazole elution from PMMA was dose dependent. Copolymerization of metronidazole and gentamicin sulfate in PMMA resulted in increased rates of elution. Intraoperative preparation of metronidazole-impregnated PMMA beads is not practical, but sterilization and storage for 2 months should not affect efficacy.


CONCLUSIONS
The local delivery of biologically active metronidazole and gentamicin by elution from PMMA is feasible.
Ramos
Jose R
JR
Department of Large Animal Clinical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061, USA.
Howard
Rick D
RD
Pleasant
R Scott
RS
Moll
H David
HD
Blodgett
Dennis J
DJ
Magnin
Geraldine
G
Inzana
Thomas J
TJ
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D001441:Bacteroides fragilis / Q000187:drug effects*; D001843:Bone Cements / Q000737:chemistry; D001850:Bone Diseases, Infectious / Q000517:prevention & control / Q000662:veterinary*; D003692:Delayed-Action Preparations; D004356:Drug Storage; D004926:Escherichia coli / Q000187:drug effects*; D005839:Gentamicins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D008795:Metronidazole / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D019904:Polymethyl Methacrylate / Q000737:chemistry
D000900:Anti-Bacterial Agents; D001843:Bone Cements; D003692:Delayed-Action Preparations; D005839:Gentamicins; D008795:Metronidazole; D019904:Polymethyl Methacrylate