Antimicrobial efficacy of gentamicin‐loaded acrylic bone cements with fusidic acid or clindamycin added

Abstract

The increasing gentamicin resistance among bacteria in septic joint arthroplasty has stimulated interest in adding a second antibiotic into gentamicin-loaded bone cement. A first aim of this in vitro study is to investigate whether addition of fusidic acid or clindamycin to gentamicinloaded bone cement has an additional antimicrobial effect against a collection of 38 clinical isolates, including 16 gentamicin-resistant strains. A modified Kirby-Bauer test, involving measurement of the inhibition zone around antibiotic-loaded bone cement discs on agar plates, was used to investigate whether adding a second antibiotic has an additional antimicrobial effect. Second, a selected number of strains was used to study their survival in an interfacial gap made in the different bone cements to mimic the gap between bone and cement as existing near a prosthesis. Gentamicinloaded bone cement had an antimicrobial activity against 58% of the 38 bacterial strains included in this study, while 68% of the strains were affected by bone cement loaded with a combination of gentamicin and clindamycin. Bone cement loaded with the combination of gentamicin and fusidic acid had antimicrobial activity against 87% of the bacterial strains. In the prosthesis-related gap model, there was a clear trend toward less bacterial survival for gentamicin-loaded bone cement after adding clindamycin or fusidic acid. Addition of clindamycin or fusidic acid into gentamicin-loaded bone cement yields an additional antimicrobial effect. The combination gentamicin and fusidic acid was effective against a higher number of clinical isolates than the combination of gentamicin with clindamycin, including gentamicin-resistant strains. ß

The use of bone cement for the localized, controlled release of the antibiotics vancomycin, linezolid, or fusidic acid: effect of additives on drug release rates and mechanical strength

“…These compounds may dissolve out of the matrix to increase porosity and allow for drug dissolution and release from deeper drug deposits. The encapsulation of fusidic acid in bone cement has been previously reported and demonstrated efficacy against bacteria but in vitro drug release profiles were not investigated [6,13,14,26]. Due to the steady release profiles of the drug from bone cement observed in these studies, this drug appears to be well suited for inclusion in a controlled release system using bone cement.…”

“…Linezolid has been shown to be effective in the treatment of a wide range of drug-resistant infections and to be well suited to encapsulation in bone cement [5,19,34]. Other antibiotics that have been suggested for inclusion in bone cement are fusidic acid [13,14,26] and rifampicin [1,36] as both these drugs have excellent activity against (MRSA) especially when used in combination [1,36].…”

“…However, this drug is not recommended for use in settings where methacillin resistant Staphylococcus aureus (MRSA) bacteria are present due to numerous reports of gentamycin resistance [21,26,36]. Tobramycin or vancomycin have become the drugs of choice for encapsulation in spacers or beads over the last decade [3,21,43].…”

Preparation and characterization of acrylic bone cement with high drug release

“…However, infection often occurs after surgery. Drug-loaded bone cement is used as an application method to prevent and treat prosthesis-related infection [1][2][3][4][5][6][7][8][9][10][11].…”

In-vitro-Untersuchungen zu Elutionskinetiken und antimikrobiellen Wirkungen von Gentamicin- und Clindamycin-haltigen Knochenzementen

“…Aus dem erneuten Erscheinen von vitalen Erregern auf den Gentamicin-beladenen Prüfkörpern nach 72 h muss geschlussfolgert werden, dass die initial hohen Gentamicin-Mengen keine vollständige bakterizide Wirkung aufwiesen und dass die im weiteren Verlauf niedrigen Gentamicin-Mengen eine Vermehrung überlebender Bakterien nicht verhindern konnte. Neut et al [18] konnten in vitro eine höhere antimikrobielle Wirkung von kombinierten Gentamicin-und Clindamycin-beladenen Zementkörpern auf Gentamicin-sensitive Staphylococcusaureus-Stämme im Vergleich zu Prüfkörpern mit alleiniger Gentamicin-Applikation zeigen und begründen den Effekt mit mög-lichen Resistenzbildungen aufgrund der hohen lokalen Gentamicin-Konzentrationen.…”