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

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.

The stability of carbapenems before and after admixture to PMMA-cement used for replacement surgery caused by Gram-negative bacteria

“…However, only 15 to 30 g cement was tested and higher amounts that are typically used in clinical practice may lead to increased polymerization temperatures. Báez et al reported that meropenem-impregnated PMMA beads were not suitable for applications after autoclave sterilization, since zone growth inhibition was no longer observed after autoclaving [ 23 ]. They conclude that the exothermic reaction combined with the exposure to 121 °C for 15 min during autoclaving rendered meropenem incorporated into the cement bio-actively inert.…”

Nanostructured Platforms for the Sustained and Local Delivery of Antibiotics in the Treatment of Osteomyelitis

“…Another advantage of calcium phosphates is that they could be sterilized by a variety of techniques, including γ-irradiation, gas plasma, supercritical carbon dioxide, or even steam autoclaving (in the case of hydroxyapatite), without causing adverse effects to their structure and properties. By contrast, in general there is currently no established sterilization procedure for polymers that does not modify their structure to some degree, due to (1) physical deformations and chemical changes—scission and cross-linking that occur upon autoclaving, 113 alongside practically inevitable degradation of an encapsulated drug 114 ; (2) surface chemistry modifications that occur upon the application of ethylene oxide, hydrogen peroxide, or ozone 115 ; (3) bulk structural changes and a decrease in the molecular weight that occur during γ-irradiation, 116 while a difficult regulatory path is posed before novel or nontraditional sterilization methods.…”