Use of antibiotic-loaded polymethylmethacrylate beads for the treatment of extracavitary prosthetic vascular graft infections

PURPOSE: This study was conducted to assess the efficacy of antibiotic-loaded polymethylmethacrylate (PMMA) beads in the management of lower extremity extracavitary prosthetic arterial graft infection. METHODS: This was a retrospective review of 34 patients treated for vascular surgical site (VSS) infections involving 36 prosthetic lower extremity arterial bypasses using antibiotic-loaded PMMA beads and culture-specific parenteral antibiotics for 4 to 6 weeks. Sites of graft infection were explored, debrided, and cultured. As determined from the results of Gram's stains of VSS purulence, PMMA powder was polymerized with an antibiotic (vancomycin, daptomycin, or tobramycin/gentamicin, or a combination), molded into a chain of beads, and implanted adjacent to the infected graft after debridement and pulsed-spray antibacterial lavage. All wounds were closed primarily with planned exploration to verify sterilization before a graft preservation or in situ replacement procedure. Treatment outcomes, including wound sterilization, were analyzed based on tissue culture isolates, procedures for persistent infection, and freedom from graft infection. RESULTS: Cultures isolated 42 pathogens, (32 gram-positive, 9 gram-negative, 1 Candida albicans) with methicillin-resistant Staphylococcus aureus (MRSA) cultured from 16 (44%) of 36 surgical site infections. As determined from the initial operative Gram's stain or a prior culture result, vancomycin PMMA beads were implanted in 29 of 36 VSS infections at the first procedure; daptomycin (n = 4) or tobramycin (n = 3) beads were implanted in the rest. Repeat VSS exploration and culture results led to an average of 2.5 antibiotic bead replacements before definitive treatment. A sterile (no growth on tissue culture) VSS was achieved in 87% of cases before a graft preservation (n = 16) or in-situ replacement of an infected graft (n = 20) procedure. No patient deaths occurred. Early and late limb salvage was 100%. Infection recurred in 4 (11%) VSSs during a mean 23-month follow-up period, one within 3 months owing to unrecognized bowel injury associated with in situ replacement of an aortofemoral graft limb. CONCLUSION: Antibiotic-loaded PMMA beads may be a useful adjunct in the contemporary surgical management of VSS infection involving a prosthetic graft. Wound sterilization was achieved in most VSSs before graft preservation or an in-situ replacement procedure, including infections caused by MRSA, a pathogen isolated in half of the extracavitary prosthetic graft infections. This preliminary trial shows the potential benefit of this new technique, but further study is required to prove efficacy.     

The treatment of experimental osteomyelitis by surgical debridement and the implantation of calcium sulfate tobramycin pellets.

Calcium sulfate was used as a biodegradable delivery system for the administration of antibiotics in musculoskeletal infection. New Zealand white rabbits were infected with Staplylococcus aureus, debrided, and randomized to one of four treatment groups: calcium sulfate pellets with 10% tobramycin sulfate, placebo calcium sulfate pellets and IM tobramycin, placebo calcium sulfate pellets, or debridement. Serum and wound exudate tobramycin concentrations and serum calcium levels were measured. Radiographs, cultures, and histology were analyzed for efficacy and treatment. Rabbits treated with 10% tobramycin sulfate pellets showed a significantly higher eradication of infection (11/13) than rabbits treated with debridement only (5/12), placebo pellets and IM tobramycin (5/14). or placebo pellets (3/13). In the group receiving 10% tobramycin sulfate pellets, serum tobramycin concentrations peaked 3 h post-operatively at 5.87 microg/ml and were non-detectable after day 1. In the group receiving placebo pellets and IM tobramycin, serum concentrations peaked at 7.82 microg/ml 1 h post-operatively, fell to 6.12 microg/ml on day 2, and averaged 4.18 microg/ ml for the remainder of the treatment period. The wound exudate tobramycin concentrations in the animals treated with tobramycin sulfate pellets peaked at 11.9 mg/ml on day 1 and dropped to 2.5 microg/ml on day 7. There was no significant difference in the serum calcium levels in any of the treatment groups. Calcium sulfate containing tobramycin sulfate has potential utility as a biodegradable local antibiotic delivery system in the treatment of musculoskeletal infections.     

Wound and serum levels of tobramycin with the prophylactic use of tobramycin-impregnated polymethylmethacrylate beads in compound fractures

Antibiotic-impregnated polymethylmethacrylate (PMMA) beads have been useful in treating orthopedic infections. Local delivery has been reported to establish wound antibiotic levels well above the therapeutic range while avoiding serum levels associated with increased incidence of side effects. After operative debridement, 70 patients with compound fractures were treated prophylactically with tobramycin-impregnated PMMA beads. Observations of antibiotic levels in 27 patients demonstrated antibiotic levels in the wound drainage and clot that were significantly in excess of the usual therapeutic range for tobramycin and simultaneous nontoxic serum levels. Significant levels of tobramycin can be achieved in the extracellular fluid at the fracture site when tobramycin-impregnated PMMA beads are placed in the wound after irrigation and debridement.     

Effective treatment of osteomyelitis with biodegradable microspheres in a rabbit model

Biodegradable microspheres were manufactured from a high molecular weight copolymer of 50% lactic and 50% glycolic acid and the antibiotic tobramycin. It was hypothesized that the microspheres would be more effective than polymethylmethacrylate beads in the local delivery of tobramycin and that the microspheres would not inhibit bone healing. Osteomyelitis was established in 40 New Zealand White rabbits using Staphylococcus aureus. All animals had irrigation and debridement of the infected radii four weeks after inoculation and were divided into five treatment groups: debridement alone, microspheres alone, microspheres containing tobramycin plus parenteral treatment with cefazolin, polymethylmethacrylate beads containing tobramycin plus parenteral cefazolin, and parenteral cefazolin. All animals were sacrificed after 4 weeks of treatment. The group treated with microspheres plus parenteral antibiotics was the only group to have a significantly higher percentage of animals without bacteria after 4 weeks of treatment when compared with the control group. Additionally, the animals treated with microspheres had a higher degree of bone healing in the defect than the animals treated with bone cement. The most effective treatment was biodegradable microspheres combined with parenteral antibiotic in this rabbit osteomyelitis model.     

Comparative evaluation of the diffusion of tobramycin and cefotaxime out of antibiotic-impregnated polymethylmethacrylate beads

Both tobramycin and cefotaxime diffuse from antibiotic-impregnated polymethylmethacrylate (PMMA) beads in quantities sufficient to inhibit the growth of bacteria on agar lawns or in broth cultures over a 28-day period. Extraction of antibiotic from tobramycin or cefotaxime-impregnated PMMA beads revealed that substantial amounts of both antibiotics remained within the beads despite 28 days of diffusion. Diffusion of antibiotic from the PMMA beads during the initial 3-5 days is much greater than occurs for the remainder of the 4-week period. The results of the study suggest that perhaps tobramycin of cefotaxime-impregnated PMMA beads would produce local levels of antibiotic high enough to sterilize a given dead space for a period of 28 days.     

In vitro and in vivo evaluation of antibiotic diffusion from antibiotic-impregnated polymethylmethacrylate beads.

The elution of antibiotics from antibiotic-impregnated polymethylmethacrylate (PMMA) beads was measured in mongrel dogs. The antibiotics, used in mixture with Simplex cement, included cefazolin (Ancef; 4.5 g/40 g cement powder), ciprofloxacin (Cipro; 6 g/40 g powder), clindamycin (Cleocin; 6 g/40 g powder), ticarcillin (Ticar; 12 g/40 g powder), tobramycin (Nebcin; 9.8 g/40 g powder), and vancomycin (Vancocin; 4 g/40 g powder). After a pneumatic drill was used to dredge a trough in the tibia, five beads were implanted. During the next 28 days, seroma samples and serum samples were taken for antibiotic measurements. On Day 28, the dogs were killed, beads removed, and the seroma, serum, bone, and granulation tissue sampled. The results of the study showed that clindamycin, vancomycin, and tobramycin exhibited good elution characteristics and had consistently high levels in bone and granulation tissue.     

In vitro elution of tobramycin from bioabsorbable polycaprolactone beads

OBJECTIVES: To compare the in vitro elution characteristics of tobramycin impregnated beads made of polycaprolactone (PCL) and polymethylmethacrylate (PMMA). DESIGN: Six-millimeter PCL and PMMA beads with 6% tobramycin were formed and placed in phosphate-buffered saline or newborn calf serum and incubated at room temperature or 37 degrees C. Aliquots were taken at intervals for eight weeks. Tobramycin levels were determined by fluorescent assay and antibacterial efficacy was assessed by measuring the zones of inhibition against Staphylococcus aureus and Pseudomonas aeruginosa on agar diffusion plates. RESULTS: Tobramycin elution rates at room temperature were similar up to three weeks. At three weeks, elution rates from PCL beads were twice those from PMMA beads, and at eight weeks, elution from PCL was quadruple that from PMMA. At 37 degrees C, tobramycin elution rates from PCL were eight times greater than those from PMMA by eight weeks. Total tobramycin eluted from PCL beads was 38.9% and 20% in PMMA beads. All samples showed bacteriostatic activity against S. aureus and P. aeruginosa at eight weeks. CONCLUSIONS: These in vitro results show that PCL has superior antibiotic elution characteristics compared with PMMA, and this may translate into a more effective antibiotic delivery vehicle. In addition, PCL is a bioabsorbable polymer, which may decrease the need for a second surgical procedure to remove retained beads.     

Treatment of experimental osteomyelitis with a fibrin sealant antibiotic implant

Two methods currently are available for the delivery of antibiotics: intravenous injection with a long-term indwelling catheter and local implant of antibiotic-containing polymethylmethacrylate beads. Both of these methods have significant disadvantages. A fibrin sealant implant, impregnated with tobramycin, was evaluated in a rabbit model of osteomyelitis to determine whether it has the potential of supplying a basis for bone reconstruction and providing an improved treatment method for the delivery of antibiotics to orthopaedic infections. Localized tibial osteomyelitis, with methicillin-sensitive Staphylococcus aureus, was developed surgically in female New Zealand White rabbits. After 2 weeks, rabbits with evidence of osteomyelitis were treated with debridement alone, debridement plus systemic tobramycin, debridement plus fibrin sealant, debridement plus fibrin sealant loaded with tobramycin, polymethylmethacrylate beads loaded with tobramycin, or not treated at all (control). After 4 weeks of therapy, the rabbits were sacrificed and the involved bones were cultured for concentrations of methicillin-sensitive Staphylococcus aureus per gram of bone and marrow. Preliminary data (N = 14) indicate fibrin sealant plus tobramycin may be as effective as polymethylmethacrylate beads plus tobramycin against methicillin-sensitive Staphylococcus aureus osteomyelitis in a rabbit model.     

The prophylactic use of antibiotic impregnated beads in open fractures

Four hundred four compound fractures were reviewed in 339 patients treated between August 1983 and November 1987. The 252 males and 87 females had a mean age of 33 years (range, 14-86). One hundred twenty-seven (31.4%) fractures were classified as Grade I, 153 (38.9%) as Grade II, and 124 (30.7%) as Grade III by Gustilo's classification. The mean Injury Severity Score was 15 (range, 9-57). Three hundred thirty-four of the open fractures (82.7%) were managed with antibiotic-impregnated bead chains (tobramycin) and systemic antibiotic prophylaxis (cefazolin, tobramycin, and penicillin). Seventy open fractures (17.3%) received systemic antibiotic prophylaxis (cefazolin, tobramycin, and penicillin) without supplemental use of the antibiotic beads. All open fractures underwent acute irrigation and debridement. In the 404 fractures 46.5% of wounds were closed primarily, 12.9% underwent delayed primary closure, 7.9% were left open, and 32.7% were temporized by the antibiotic bead pouch technique until definitive flap coverage and skin grafting were performed. Of the 404 fractures evaluated, 17 (4.2%) developed an acute wound infection. Of these wound infections, eight (11.4%) were in the group managed with systemic antibiotics alone. By comparison, nine (2.7%) of open fractures treated with combined systemic antibiotics and antibiotic-impregnated beads developed an infection. Chronic osteomyelitis developed in 18 of 404 open fractures (4.5%). Ten (14.3%) open fractures which developed osteomyelitis were managed with systemic antibiotics whereas eight (2.4%) fractures managed with systemic antibiotics and antibiotic-impregnated beads developed a chronic infection.(ABSTRACT TRUNCATED AT 250 WORDS)     

Local administration of antibiotics with an implantable osmotic pump

A totally implantable drug pump was evaluated as a delivery system in the treatment of osteomyelitis. Gentamicin levels in rabbit serum and bone obtained by systemic administration are compared with levels in rabbit serum and bone obtained by local administration via an implantable drug pump. Systemic administration gave mean gentamicin bone levels ranging from less than 1 microgram/gm to 3.6 micrograms/gm, while drug pump administration gave bone levels ranging from 10.8 micrograms/gm to 64.0 micrograms/gm (micrograms = microgram, or 10(-6) gram). To evaluate the drug pump as a mode of therapy, acute staphylococcal osteomyelitis was induced in ten rabbits. Drug pumps filled with amikacin were inserted in five of the infected animals. Three of these were culture-negative at one week. One had a scant growth of Staphylococcus from the pump, and one had scant growth from the pump and the wound. Clinically, none of these five rabbits appeared infected at seven days. The remaining five rabbits were all culture-positive, with heavy growths of staphylococci from their wounds, and clinically, all appeared grossly infected at seven days. These data demonstrate that high local and low systemic levels of antibiotics can be achieved with an implantable drug pump and that this method can sterilize an infected musculoskeletal wound. Therefore, antibiotic administration via an implantable drug pump is an important potential mode of therapy in the treatment of osteomyelitis.     

In vitro characteristics of tobramycin-PMMA beads: compressive strength and leaching

Antibiotic-impregnated polymethylmethacrylate (PMMA) bone cement beads have been used as a local drug delivery system for the treatment of bone and soft tissue infections. The beads deliver a high local level of antibiotic with a decreased risk of toxic systemic levels. This study was undertaken to determine the antibiotic release characteristics of tobramycin-impregnated beads over time and to determine the compressive strength of these beads. Acrylic resin (PMMA) bone cement beads were prepared with three different concentrations of tobramycin. The beads were tested for compressive strength, and their antibiotic release characteristics were determined over a 21 day period by radioimmunoassay and by biological testing against a variety of bacteria. The compressive strength of the beads was found to be adequate to avoid fragmentation during their clinical use. There was gradual release of tobramycin from the beads over the entire 21 days, but the release was most marked during the first 48 hours. There was antibiotic activity against both gram-negative and gram-positive organisms, except Enterococcus, for the entire 21 day period. The release of tobramycin followed a curvilinear relationship and was directly related to the initial antibiotic concentration of the bead. Tobramycin-impregnated polymethylmethacrylate beads may represent a reliable method of local antibiotic delivery with sustained activity against a broad spectrum of organisms.     

Perioperative prophylaxis with sulbactam and ampicillin compared with metronidazole and cefotaxime in the prevention of wound infection in children undergoing appendectomy

Sulbactam is a beta-lactamase inhibitor, which when administered with ampicillin, increases the latter agents antibacterial activity against beta-lactamase producing organisms. One hundred children between the ages of 5 and 14 undergoing emergency appendectomy were entered into a prospective randomized trial comparing sulbactam and ampicillin (SA) with metronidazole and cefotaxime (MC) as prophylaxis against postoperative wound infection. Patients in whom the appendix was perforated or gangrenous received a 72-hour course of antibiotics, others received a single dose only. The overall wound infection rate was 8% (14% in patients with perforation or gangrene and 4% in those without). There was no difference in infection rate between the two antibiotic groups; there were three wound infections and one subphrenic abscess in patients receiving SA and four wound infections in patients receiving MC. SA, therefore, appears to be a suitable antibiotic combination for use as prophylaxis in appendicitis in children.     

MRSA-Infektionen des Bewegungsapparats

INTRODUCTION: We present gentamicin-vancomycin-impregnated beads that can be produced intraoperatively in moulds and demonstrated their successful use in ten cases of problematic Methicillin-resistant Staphylococcus aureus (MRSA) infection. METHODS: To produce the antibiotically loaded PMMA beads, a two-part mould of polyoxymethylene was used. The mixture of PMMA and antibiotic is poured into the mould halves, and during polymerisation the halves bond together. The in vivo antibiotic concentrations of wound secretion from the redon drainage were measured by fluorescence-polarisation immunoassay, and a concentration/time function was determined. The PMMA beads (2 g of vancomycin plus 0.5 g of gentamicin plus 40 g of PMMA) were implanted in ten patients aged 41-76 years. RESULTS: In all ten patients, the infection was cured (follow-up 15 months). CONCLUSION: The combination of gentamicin and vancomycin in the PMMA of standardised beads represents a good alternative in the treatment of MRSA infections. Understanding of the mechanism of antibiotic release from PMMA allows differentiated dosing during systemic application.     

Comparative studies of antibiotic therapy after penetrating abdominal trauma

Two prospective, randomized trials of the efficacy of antibiotic regimens after penetrating abdominal trauma demonstrated that a combination of clindamycin and tobramycin was superior to cefamandole or cefoxitin in preventing postinjury wound infection but that no difference could be demonstrated between combination therapy (clindamycin plus tobramycin) and moxalactam. Infection was more likely to occur after a gunshot wound or with a high injury severity score and occurred after the 10th postinjury day only in those patients who received cefamandole or cefoxitin. There was a higher incidence of culture of B. fragilis in the latter groups as well as infections due to resistant organisms. Short-term antibiotic therapy for 72 hours with either tobramycin plus clindamycin or moxalactam appears adequate for the majority of patients after gunshot or knife wounds. The costs of these regimens to the patient were similar in our hospital. The most important single factor, however, in maintaining low infection rates after penetrating injury to the abdominal cavity is appropriate and timely surgical management.     

Experimental osteomyelitis treatment with antibiotic-impregnated hydroxyapatite

A calcium hydroxyapatite antibiotic implant was evaluated to determine its efficacy as an antibiotic delivery system in a localized osteomyelitis rabbit model. Localized rabbit tibial osteomyelitis was developed with an intramedullary injection of methicillin resistant Staphylococcus aureus. Infected rabbits were randomized and divided into eight groups depending on treatment with or without debridement, systemic antibiotics, antibiotic-impregnated polymethylmethacrylate beads, or calcium hydroxyapatite implants with and without antibiotic impregnation. All treatments began 2 weeks after infection. After 4 weeks of therapy, the involved bones were cultured for concentrations of Staphylococcus aureus per gram of bone. Rabbits (n = 11) that had calcium hydroxyapatite (impregnated with vancomycin) implanted into the dead space after the debridement surgery had an 81.8% infection clearance after treatment. Rabbits (n = 10) that had polymethylmethacrylate beads (impregnated with vancomycin) implanted into the dead space after debridement surgery had a 70% clearance rate. All other treatment modalities resulted in less than 50% clearance rates. Calcium hydroxyapatite may be an effective alternative to polymethylmethacrylate for providing local antibiotic therapy in cases of methicillin resistant Staphylococcus aureus osteomyelitis.     

Determining potential of PMMA as a depot for rifampin to treat recalcitrant orthopaedic infections

BackgroundOpen fractures are often complicated by infection. In cases of severe soft tissue and vascular injury, systemic antibiotics may be ineffective due to their inability to reach and provide direct antimicrobial activity to the zone of injury. High antibiotic concentrations within the wound can be achieved with reduced systemic toxicity by using local antibiotic delivery. As bacteria associated with musculoskeletal injuries frequently form biofilms, antibiotic selection is important. Herein, the use of rifampin, an antibiotic with activity against biofilms, delivered via polymethylmethacrylate (PMMA) beads is evaluated for use in a traumatic musculoskeletal wound model.MethodsPMMA beads loaded with rifampin, or combinations of rifampin and vancomycin, were prepared and evaluated for time to curing, drug release kinetics in vitro, and infection prevention in vivo using a well-established rat model of musculoskeletal infection. A segmental bone defect was created and contaminated with methicillin susceptible Staphylococcus aureus (UAMS-1). Wounds were debrided, irrigated, and treated with PMMA beads, containing rifampin or combinations of rifampin plus vancomycin, following a 6-h (early) or 24-h (delayed) treatment. After 14 days, tissue, implants, and beads were removed for bacterial quantification and assessed for rifampin resistance.ResultsThere was a direct association between loaded concentration and release kinetics of the rifampin and vancomycin from PMMA beads. Higher rifampin concentrations delayed PMMA curing times. The addition of vancomycin to PMMA resulted in more rapid release of rifampin from beads. However, the highest concentration of rifampin loaded PMMA beads (10% wt/wt) was the only treatment to significantly reduce bacterial counts. No rifampin resistance was observed.ConclusionAlthough higher concentrations of rifampin resulted in significant reductions of bacteria, these levels extended PMMA curing times and transformed PMMA material characteristics. While these characteristics make the material unsuitable for weight-bearing applications, such as total joint arthroplasty, the use of rifampin-loaded PMMA beads may be an effective intervention in a contaminated traumatic extremity wound due to its ability to eradicate biofilms.     

Delayed infections after posterior TSRH spinal instrumentation for idiopathic scoliosis: revisited

OBJECTIVE: To determine the incidence of delayed infections in idiopathic scoliosis treated with TSRH instrumentation, proper wound management after instrumentation removal, and whether the previously identified bacterial trend remains consistent. METHODS: All patients with idiopathic scoliosis > or =2 years after surgery with posterior TSRH instrumentation were included. Those cases with delayed infections were retrospectively reviewed. Time of presentation (infection) from index operation, clinical picture, sedimentation rate, presence of pseudarthrosis, organisms grown on culture, type of wound closure, and duration of antibiotics were examined. RESULTS: A total of 489 patients were identified > or =2 years postoperation; 23 had delayed infections (4.7%). Time of presentation averaged 27 months after initial surgery. Spontaneous drainage occurred in 15 patients, fluctuance in 6, and neither in the remaining 2 (pain and fever). Sedimentation rate averaged 48 mm/hr. All patients had instrumentation removed. Primary closure (1 stage) was performed in 14 patients, and delayed primary closure (> or =2 stages) was performed in nine patients. All wounds healed uneventfully. Cultures at the time of instrumentation removal grew Propionibacterium acnes in 12 patients, Staphylococcus epidermidis (or Staphylococcus coagulase-negative) in 4, Micrococcus varians in 1, and Staphylococcus aureus in 1. Five patients had negative cultures. After removal, patients received parenteral antibiotics; in 21 of these patients this was followed by oral antibiotics. CONCLUSIONS: Low-virulent skin organisms are primarily responsible for delayed infections. Intraoperative seeding followed by subclinical quiescent periods appears to be the method by which infection occurs. The increased bulk and modularity of modern instrumentation systems can lead to inflammation and bursa formation, thus contributing significantly to the activation of these infections. Primary wound closure results in successful wound healing. Delayed closure after 48 hours is unnecessary. Short-term postoperative parenteral antibiotics (2-5 days) followed by short-term oral antibiotics (7-14 days) is recommended.     

Treatment of experimental osteomyelitis by surgical debridement and the implantation of bioerodable,polyanhydride-gentamicin beads

Osteomyelitis was induced in the radius in 77 rabbits and confirmed by histological examination and culture. At 4 weeks, the wounds were debrided and the animals were treated with (a) fatty acid dimersebacic acid beads (a bioerodable composite) impregnated with 20% or (b) 10% gentamicin sulfate, (c) placebo beads and intramuscular gentamicin sulfate. (d) placebo beads alone, or (e) debridement only. After 4 weeks, eradication of infection was determined by histological examination and culture. Osteomyelitis was eradicated in 93% of the animals treated with the beads and 20% gentamicin, in 67% of those treated with the beads arid 10% gentamicin, in 25% of those treated with placebo beads and intramuscular gentamicin, in 7% of those treated with placebo beads alone, and in 12.5% of those treated with debridement only (p values from <0.001 to 0.02). Fatty acid dimer-sehacie acid beads with gentamicin were then implanted in noninfected rabbits, and gentamicin sulfate concentrations in bone, serum, urine, and wound exudate were measured. Gentamicin sulfate was detectable in bone for as long as 8 weeks after implantation. Levels as high as 4,746 g/ml were present in the wound exudate for the first 7 days. Levels in the serum peaked at 1.03 μg/ml. Urine levels peaked at 135 μg/ml.     

Bacterial adherence to plain and tobramycin-laden polymethylmethacrylate beads.

Antibiotic-impregnated polymethylmethacrylate (PMMA) bead chains are in current clinical use for prophylaxis and management of osteomyelitis. The in vivo interaction between PMMA beads and an experimentally infected wound is examined. Two modes of bacterial adherence to plain PMMA beads are demonstrated. In this report, tobramycin-sensitive bacteria did not attach to tobramycin-laden beads. Therefore, implanted PMMA beads should contain an antibiotic to which the infecting bacteria is sensitive.     

Treatment of experimental osteomyelitis by methicillin resistant Staphylococcus aureus with bone cement system releasing grepafloxacin

The authors examined the effectiveness of the local anti-microbial treatment on methicillin resistant Staphylococcus aureus (MRSA) experimental osteomyelitis. Thirty-six rabbits with chronic MRSA osteomyelitis of the right femur were treated with local grepafloxacin delivery system prepared by a mixture of acrylic bone cement (polymethyl methacrylate, PMMA) plus 4% grepafloxacin. Osteomyelitis was induced by inoculating MRSA (100 μl of cultured bacteria; 10⁷) and the local insertion of a needle, serving as a foreign body, at the upper third of the femur. The course of the infection was followed by clinical, radiographic and microbiological examination. In the third week, all animals were re-operated, needles were removed, and antibiotic containing acrylic cement was implanted. Thereafter, one control and five treated animals were sacrificed per week, within 6 weeks. Osteomyelitis was found in all rabbits. In vitro grepafloxacin levels remained high throughout the 6 weeks of the experiment. Histologically tissue reaction against the cement was not observed. Osteomyelitis lesions and bone structure were progressively repaired after cement implantation. Biomechanical analysis showed no significant influence on the mechanical properties of acrylic cement due to grepafloxacin. The above mixture could prove to be an important supplementary method for the treatment of bone infections. Such a system could replace the use of gentamycin PMMA beads in the treatment of patients with chronic osteomyelitis due to MRSA. Furthermore, the proposed method could be used as a spacer after removal septic loosened prostheses in combination with systemic administration of antibiotics.