Biomaterial-associated infection of gentamicin-loaded PMMA beads in orthopaedic revision surgery.

In two-stage orthopaedic revision surgery, high local levels of antibiotics are achieved after removal of an infected prosthesis through temporary implantation of gentamicin-loaded beads. However, despite their antibiotic release, these beads act as a biomaterial surface to which bacteria preferentially adhere, grow and potentially develop antibiotic resistance. Gentamicin-loaded beads were retrieved from 20 patients with prosthesis-related infections. Excised tissue samples were taken for routine culture, while beads were analysed in an extensive laboratory procedure. Extensive culture procedures indicated the presence of bacteria on gentamicin-loaded beads in 18 of the 20 patients involved, while 12 of these 18 patients were considered free of infection by routine culture. Nineteen of 28 bacterial strains isolated were gentamicin resistant and cultures from three patients yielded highly gentamicin-resistant sub-populations. It is concluded that routine culture of excised tissues in orthopaedic revision surgery is inadequate to ascertain full eradication of infection, especially as infecting, antibiotic-resistant bacteria preferentially adhere to and grow on gentamicin-loaded beads. Extensive examination of the bead surfaces is proposed as a more reliable indication that infection has been eradicated.

Staphylococcus aureus biofilm formation on different gentamicin-loaded polymethylmethacrylate bone cements.

In this in vitro study, the formation of a Staphylococcus aureus biofilm on six gentamicin-loaded bone cements (CMW1, CMW3, CMW Endurance, CMW2000, Palacos, and Palamed) was determined in a modified Robbins device over a 3 days time span and related with previously (Van de Belt et al., Biomaterials 21 (2000) 1981) measured kinetics of antibiotic release by these cement brands. The influence of gentamicin release on biofilm formation was quantified by expressing the number of colony-forming units on gentamicin-loaded cement relative to the number of viable organisms on unloaded cement of the same brand. Biofilms formed on all gentamicin-loaded cements, despite the release of antibiotics, followed a consistent pattern in time with a maximum number of colony-forming units per unit cement area found between 24 and 30 h after inoculation. None of the gentamicin-loaded cements showed a reduction in biofilm formation relative to unloaded cements within 6 h after inoculation, whereas only gentamicin-loaded CMW1 and Palacos reduced biofilm formation 24 h after inoculation. Alternatively, CMW Endurance, CMW2000, and Palamed did not exhibit any initial reductions in biofilm formation, but effects started after 72, 48, and 72 h, respectively. Biofilm reduction by gentamicin-loaded CMW3 lasted the longest from 24 to 72 h. Interestingly, each cement seemed to have a different "window-of-effectiveness" with regard to reduction in biofilm formation that did not relate with the gentamicin-release kinetics. Summarising, this study demonstrates that although gentamicin loading of bone cements yields reductions in biofilm formation, S. aureus is able to grow on gentamicin-loaded bone cements.

Infection of orthopedic implants and the use of antibiotic-loaded bone cements. A review.

Infections by bacteria are a serious complication following orthopedic implant surgery, that can usually only be cured by removing the implant, since the biofilm mode of growth of infecting bacteria on an implant surface protects the organisms from the host immune system and antibiotic therapy. Over the past few decades, attempts have been made to prevent and cure orthopedic implant infections by incorporating antibiotics in polymethylmethacrylate bone cements, in primary and revision surgery. However, the clinical efficacy of antibiotic-releasing bone cements is not accepted by all and the long-term exposure to low doses from antibiotic-releasing bone cements in patients is strongly related to the emerging threat of antibiotic resistance in medicine today. In this article, we start by reviewing the mechanisms governing the formation of an infectious biofilm on orthopedic implant materials, the release mechanisms and properties of clinically-used, antibiotic-loaded bone cements. The clinical efficacy of antibiotic-loaded bone cements is evaluated analyzing separatedly the prophylactic and therapeutic uses of these products.

Surface roughness, porosity and wettability of gentamicin-loaded bone cements and their antibiotic release.

In this study, the release of gentamicin as a function of time was measured for six different gentamicin-loaded bone cements and related with the surface roughness, porosity and wettability of the cements. Initial release rates varied little between the six bone cements (CMW1, CMW3, CMW Endurance, CMW 2000, Palacos, and Palamed) and ranged from 8.6 to 14.1 microg/cm2/h. The total amounts of gentamicin released after 1 week varied between 4.0 and 5.3% of the total amount of antibiotic incorporated for the CMW cements and was 8.4% for Palacos. Palamed released after 1 week significantly more of the gentamicin incorporated (17.0%). The wettability of all cements was similar (water contact angles between 70 and 80 degrees), but the surface roughness and the porosity of the cements varied markedly. Initial release rates increased with surface roughness, although the correlation coefficient was low (0.64), while total amounts released increased linearly (correlation coefficient 0.97) with the bulk porosity of the cements. Consequently, it can be concluded that the release kinetics of gentamicin from bone cements is controlled by a combination of surface roughness and porosity.

Gentamicin release from polymethylmethacrylate bone cements and Staphylococcus aureus biofilm formation.

We measured the formation of a Staphylococcus aureus biofilm in vitro on unloaded and gentamicin-loaded bone cements (CMW3 and Palacos R) and related the formation to antibiotic release rates. All experiments were done in triplicate. Microbial growth on gentamicin-loaded cements occurred despite the release of antibiotic. Biofilm formation on gentamicin loaded CMW3 bone cement was one fourth to one fifth less than on the unloaded bone cement, while biofilm formation on Palacos R bone cement was not significantly affected by antibiotic loading. More gentamicin was released from CMW3 (79 mg) than from Palacos R (70 mg), but the percentage gentamicin released after one week relative to the total amount incorporated was significantly lower for CMW3 (4.7%) than for Palacos R (8.4%). After one day, subinhibitory concentrations of antibiotics were eluted from the cements. We concluded that antibiotic-loaded bone cement does not necessarily inhibit the formation of an infectious biofilm in vitro.

Repeat chemonucleolysis is safe and effective.

A review was made of 85 patients who received a second injection of chymopapain because of a recurrent disc herniation between 1980 and 1996. All patients were pretreated for 3 days with H1 and H2 receptor blockers. Immediate sensitivity reactions were not seen. Four Type 1 and one Type 2 reactions were seen after the the second injection. No other complications were seen. In this group of 85 patients, 66 patients received a second injection at the same level as primary treatment after a period of 57.1 months (range, 2-143 months). Two patients were lost to followup. Four patients had surgery, three with good results. Good results and no complications were seen in three patients who had a third chemonucleolysis because of another recurrence after 15, 40, and 56 months, respectively. The remaining 57 patients were interviewed after 64 months (range, 3-143 months). Using the Prolo scale, 51 patients were rated as having excellent or good results, and six patients were rated as having fair or poor results.