Evaluation of in vitro serial antibiotic elution from meropenem-impregnated polymethylmethacrylate beads after ethylene oxide gas and autoclave sterilization

L. A. Báez; C. Langston; S. Givaruangsawat; R. McLaughlin

doi:10.3415/VCOT-10-05-0070

Veterinary and Comparative Orthopaedics and Traumatology, Table of Contents

Vet Comp Orthop Traumatol 2011; 24(01): 39-44
DOI: 10.3415/VCOT-10-05-0070

Original Research

Schattauer GmbH

Evaluation of in vitro serial antibiotic elution from meropenem-impregnated polymethylmethacrylate beads after ethylene oxide gas and autoclave sterilization

L. A. Báez

¹College of Veterinary Medicine, Mississippi State, Mississippi, United States

,

C. Langston

¹College of Veterinary Medicine, Mississippi State, Mississippi, United States

,

S. Givaruangsawat

¹College of Veterinary Medicine, Mississippi State, Mississippi, United States

,

R. McLaughlin

¹College of Veterinary Medicine, Mississippi State, Mississippi, United States

› Author Affiliations

Abstract

Summary

Objectives: To determine the elution properties of meropenem and to compare the elutions of meropenem-impregnated polymethylmethacrylate (PMMA) beads without sterilization (P-M-C) to those sterilized with steam (P-M-A) and ethylene oxide gas (P-M-EO).

Methods: A commercial bead mould was used to produce four groups of beads: one group without antibiotic (negative control), and three groups of meropenem-impregnated beads: P-M-C, P-M-A, and P-M-EO. The beads were placed in a phosphate buffered solution and eluent samples were collected. Concentrations of the antibiotic in eluent samples from the two sterilized groups and the control beads were determined using a microbiological assay at 1, 3, 6 and 12 hours and at 1, 2, 3, 6, 9, 12, 15, 18, 22, 26, and 30 days.

Results: The microbiological assay resulted in no zone of inhibition at all time periods for the P-M-A samples and the samples of PMMA without antimicrobial. The meropenem concentration on the eluent remained above 4 mcg/ml for 15 days in the P-M-C group and until day 18 for P-M-EO group. There was no statistical difference in AUC0-∞ (p <0.318), however significance did occur for MRT (p <0.005) when comparing P-M-C and P-M-EO with the later being higher.

Discussion: The meropenem incorporated in the PMMA beads eluted effectively and gradually decreased after the 24 hour peak, but remained above the concentration level of 4 mcg/ml for 15 days in the P-M-C group and until day 18 for P-M-EO group. Ethylene oxide does not adversely affect meropenem’s elution from PMMA beads.

Keywords

Antibiotic-impregnated polymethylmethacrylate beads - meropenem - PMMA beads - polymethylmethacrylate - sterilization

Full Text

References

References
1 Johnson KA. Osteomyelitis in dogs and cats. J Am Vet Med Assoc 1994; 204: 1882-1887.
2 Muir P, Johnson KA. Anaerobic bacteria isolated from osteomyelitis in dogs and cats. Vet Surg 1992; 21: 463-466.
3 Lee CG, Fu Uin-Chih, Wang Chi-Hwa. Simulation of gentamicin delivery of the local treatment of osteomyelitis. Biotechnology and Bioengineering 2005; 91: 622-635.
4 Budsberg SC, Kemp DT. Antimicrobial distribution and therapeutics in bone. Compend Contin Educ Pract Vet 1990; 12: 1758-1763.
5 Cunningham A, Demarest G, Rosen P. et al. Antibiotic bead production. Iowa Orthop J 2000; 20: 31-35.
6 Phillips H, Boothe DM, Shofer F. et al. In vitro elution studies of amikacin and cefazolin from polymethylmethacrylate. Vet Surg 2007; 36: 272-278.
7 Tobias KM, Schneider RK, Besser TE. Use of anti-microbial-impregnated polymethylmethacrylate. J Am Vet Med Assoc 1996; 208: 841-845.
8 Ramos JR, Howard RD, Pleasant RS. et al. Elution of metronidazole and gentamicin from polymethylmethacrylate beads. Vet Surg 2003; 32: 251-261.
9 Phillips H, Boothe DM, Shofer F. et al. In vitro elution studies of amikacin and cefazolin from polymethylmethacrylate. Vet Surg 2007; 36: 272-278.
10 Seeley SK, Seeley JV, Telehowski P. et al. Volume and surface area study of tobramycin-polymethylmethacrylate beads. Clin Orthop Relat Res 2004; (420) 298-303.
11 Seligson D, Popham GJ, Voos K. et al. Antibiotic-leaching from polymethylmethacrylate beads. J Bone Joint Surg Am 1993; 75: 714-720.
12 Balsamo LH, Whiddon DR, Simpson RB. Does antibiotic elution from PMMA beads deteriorate after 1–year shelf storage?. Clin Orthop Relat Res 2007; 462: 195-199.
13 Ogeer-Gyles JS, Mathews KA, Boerlin P. Nosocomial infections and antimicrobial resistance in critical care medicine. J Vet Emerg Crit Care 2006; 16: 1-18.
14 AstraZeneca Pharmaceuticals LP.. Merrrem^Ò Drug Information Insert. Wilmington, DE 19850
15 Ethell MT, Bennett RA, Brown MP. et al. In vitro elution of gentamicin, amikacin, and ceftiofur from polymethylmethacrylate and hydroxyapatite cement. Vet Surg 2000; 29: 375-382.
16 Ip M, Au C, Cheung SW. et al. A rapid high-performance liquid chromatographic assay for cefepime, cefpirome, and Meropenem. J Antimicrob Chemother 1998; 42: 121-123.
17 Welch AB. Antibiotics in acrylic bone cement, ‘in vitro’ studies. J Biomed Mater Res 1978; 12: 679-700.
18 AOAC, Association of Analytical Chemists In: US FDA Bacteriological Analytical Manual. 8^th edition Gaithersburg, MD; 1995: 20.01-20.04.
19 British Pharmacopoeia Commission Biological assay of antibiotics. In: British Pharmacopoeia, vol. 2, appendix XIV London: The Stationery Office; 1993: A165-A169.
20 Jane STang, Gillevet PM. Reclassification of ATCC 9341 from Micrococcus luteus to Kocuria rhizophila. Int J Syst Evol Microbiol 2003; 53: 995-997.
21 Wichelhaus TA, Dingeldein E, Rauschmann M. et al. Elution characteristics of vancomycin, teicoplanin, gentamicin and clindamycin from calcium sulphate beads. J Antimicrob Chemother 2001; 48: 117-119.
22 Adams K, Couch L, Cierny G. et al. In vitro and in vivo evaluation of antibiotic diffusion from antibiotic-impregnated polymethylmethacrylate beads. Clin Orthop Relat Res 1992; (278) 244-252.
23 Wastney ME, Patterson BH, Linares OA. et al. Investigating biological systems using modeling: Strategies and Software. San Diego, California: Academic Press; 1999
24 Shargel L, Yu ABC. Applied biopharmaceutics and pharmacokinetics: third edition. Norwalk, Connecticut: Appleton & Lange 1993
25 Yamaoka K, Nakagawa T, Uno T. Statistical moments in Pharmacokinetics. J Pharmacokinet and Biopharm 1978; 6: 558-574.
26 Riviere JE. Comparative pharmacokinetics: Principles, techniques and applications. Ames (IA): Iowa State University Press; 1999: 148-167.
27 Picknell B, Mizen L, Sutherland R. et al. Antibacterial activity of antibiotics in acrylic bone cement. J Bone Joint Surg Br 1977; 59: 302-307.
28 Calhoun JH, Mader JT. Antibiotic beads in the management of surgical infections. Am J Surg 1989; 157: 443-449.
29 Marks KE, Nelson CL, Lautenschlager EP. Antibiotic-impregnated acrylic bone cement. J Bone Joint Surg Am 1976; 58: 358-364.
30 Buchholz HW, Elson RA, Heinert K. Antibiotic-loaded acrylic cement: current concepts Clin Orthop Rel Res. 1984; 190: 96-108.
31 Craig WA. Interrelationship between pharmacokinetics and pharmacodynamics in determining dosage regimens for broad-spectrum cephalosporins. Diag Microbiol Infect Dis 1995; 22: 89-96.
32 Walenkamp GHIM. Gentamicin-PMMA beads. A clinical, pharmacokinetic and toxicological study. Darmstadt, Germany: E. Merck; 1983
33 Wahlig H, Dingeldein E. Antibiotics and bone cements: Experimental and clinical long-term observations. Acta Orthop Scand 1980; 51: 49-56.
34 Bowyer GW, Cumberland N. Antibiotic release form impregnated pellets and beads. J Trauma 1994; 36: 331-335.
35 Buchholz HW, Engelbrecht H. Uber die Depotwirkyng einiger Antibiotica bei Vermishchung mit dem Kunstharz Palacos. Chirurg 1970; 41: 511-515.
36 Chapman MW, Hadley WK. The effect of polymethylmethacrylate and antibiotic combinations on bacterial viability. An in vitro and preliminary in vivo study. J Bone Joint Surg Am 1976; 58: 76-81.
37 Hoff SF, Fitzgerald RH, Kelly PH. The depot administration of penicillin-G and gentamicin in acrylic bone cement. J Bone Joint Surg Am 1981; 63: 798-804.
38 Traub WH, Leonhard B. Heat stability of the antimicrobial activity of sixty-two antibacterial agents. J Antimicrob Chemother 1995; 35: 149-154.
39 Singh BK, Parwate DV, Dassarma IB. et al. Radiation sterilization of fluoroquinolones in solid state: Investigation of effect of gamma radiation and electron beam. Appl Radiat Isot 2010; 68: 922-925.