Journal of Orthopaedic Surgery 2003: 11(1): 73–79
Use of antibiotic-loaded polymethyl methacrylate beads in the management of musculoskeletal sepsis — a retrospective study
SP Mohanty, MN Kumar, NS Murthy
Department of Orthopaedics, Kasturba Medical College, Manipal 576 119, Karnataka, India
ABSTRACT Purpose. To assess the use of antibiotic-loaded polymethyl methacrylate beads in the management of chronic osteomyelitis of different aetiologies: infected osteosynthesis, infected open fractures, and haematogenous osteomyelitis. Methods. Records of 49 patients with chronic osteomyelitis who were treated at Department of Orthopaedics, Kasturba Medical College, from 1995 to 1999 were studied retrospectively. The diagnosis of chronic osteomyelitis was made on the basis of clinical and radiographic features. Of the 49 patients, 4 had haematogenous osteomyelitis, which later proved to be tuberculosis, and were thus excluded. Antibioticloaded acrylic beads were implanted in the remaining patients after thorough debridement. The implant was removed primarily in 16 patients with infected osteosynthesis, who then underwent decompression and sequestrectomy. All wounds were closed primarily. Peri-operative antibiotics were given for 7
days. Beads were removed at the end of 3 weeks followed by bone grafting in 26 patients. Patients were followed up for an average period of 3.7 years. Results. The infective organisms were sensitive to gentamycin in 26 cases and resistant in 19 cases; 14 cases were sensitive to cefuroxime, 11 to cloxacillin, 8 to ampicillin, and 5 to cotrimoxazole. Seven cases were resistant to all antibiotics tested. Of the 19 patients with gentamycin-resistant infection, only one had a poor result. No adverse systemic side-effects such as ototoxicity or nephrotoxicity were seen. Infection did not recur in 39 patients, but 6 patients had low-grade persistent infection at the last follow-up visit. Conclusion. In chronic infections, especially those following osteosynthesis, antibiotic beads are a valuable adjuvant. The most valuable advantage is that the wound can be closed primarily, thereby reducing the incidence of nosocomial infections and requirement of nursing care.
Key words: antibiotic-loaded polymethyl methacrylate beads; chronic osteomyelitis
Address correspondence and reprint requests to: Dr SP Mohanty, Professor and Head, Department of Orthopaedics, Kasturba Medical College, Manipal 576 119, Karnataka, India. E-mail: firstname.lastname@example.org
All wounds were closed primarily. but the infection was later shown to be tuberculosis.
.0–58. and these patients were thus excluded from the study.74
SP Mohanty et al. The limb was immobilised in plaster of Paris cast or using an external fixator. and were treated in our institution from July 1995 to June 1999 retrospectively. Although such drugs have vastly improved the prognosis of acute osteomyelitis. All osteosynthetic materials when present were removed except for those in 6 patients in whom there was no loosening of the implants and the fractures had not healed well. 18.
Journal of Orthopaedic Surgery
INTRODUCTION Optimal treatment of musculoskeletal infections often requires a combined surgical and antimicrobial approach. 1 proposed the concept of local delivery of antibiotics as a means of preventing infection associated with replacement arthroplasty. Noncommercial fabrication of beads In 14 cases which the commercially prepared PMMA beads (Septopal. The antibiotic bead chain was then implanted. E. who had chronic osteomyelitis of various aetiologies. Germany) were not available. despite intensive treatment with both surgery and prolonged parenteral administration of antimicrobial agents. Osteomyelitis. handmade beads impregnated with cefuroxime were used. If the wound closure was found to be under tension. is not consistently treated with success in this way. Merck. cefuroxime was used in this study:
MATERIALS AND METHODS We studied records of 49 patients.
Radiographic assessment was made to detect the presence of sequestra and implant loosening.8 years (range. All patients had undergone at least one operation before admission.
Figure 1 Prefabricated Septopal bead chain (above) a chain of handmade beads (bottom). despite the extensive array of antibiotics currently available. In the first stage. As gentamycin in powder form was not available in India and liquid gentamycin does not mix uniformly with bone cement. those with infection following open fractures (Group 2).0 years). 37 were men and 8 were women. Preoperative protocol Samples of discharge from all sinuses and wounds were taken for culture and antibiotic sensitivity assays. release incisions were made before the closure. they have not been successful in the management of chronic osteomyelitis or in surgical sepsis following internal fixation. The cavities were decompressed. Of the 45 patients. The median age at presentation was 34. Patients were divided into 3 groups according to the primary cause of infection: patients with infected osteosynthesis (Group 1). The diagnosis of chronic osteomyelitis was made on the basis of clinical and radiographic features of infection that were present for more than 12 weeks. All unhealthy granulation tissue was removed. Four patients had haematogenous osteomyelitis. it was left alone. If the draining sinus tract was found to be away from the previous scar. we assessed the efficacy and difficulties encountered during the use of antibiotic-loaded polymethyl methacrylate (PMMA) beads in different types of chronic osteomyelitis. and those with haematogenous osteomyelitis (Group 3). The implants were not removed with the hope of allowing the fracture to unite. in an attempt to eradicate the infection before implantation of antibiotic-loaded PMMA beads. however. may result in persistence or relapse of the infection and suggests that many fundamental questions remain unanswered. Hamburg. Operative procedure Surgery was performed in 2 stages. Buchholz et al. and thoroughly washed out with copious quantities of normal saline. with an average of 3 operations. the number of beads and the size of the chain were determined by the size of the cavity. The frequent recurrence of sepsis. Klemm2 later extended this concept to the treatment of chronic osteomyelitis. the wound was explored through the pre-existing scar. In this study. Rough and jagged edges of the bone were rounded off so as to prevent entanglement of the bead chain. as in cases of tibial wound closure. curetted.
. (b) after removal of the implant and gentamycin beads. Sutures were removed after 10 days. June 2003
Antibiotic-loaded acrylic beads for musculoskeletal sepsis
8 g of cefuroxime powder was mixed homogenously in a sterile bowl with 40 g of PMMA polymer. 20 ml of PMMA monomer liquid was added. The beads were threaded onto a steel wire and the ends were knotted (Fig. showing healed fracture with no evidence of infection. 2).to 8-mm size were handrolled. to which organisms were sensitive. To this. 1). were given for 7 days. 11 No. In 5 cases of infected gap nonunion. ring fixators were applied and bone transport was performed. When the mixture became doughy and non-sticky. depending on the status of the fracture and the size of the cavity (Fig. then every 3 months for at least 2
Figure 2 Radiographs of a patient with fracture shaft of femur treated by locked intramedullary nail with chronic osteomyelitis: (a) chronic osteomyelitis of the femur with implant in situ. If organisms were found to be resistant to all antibiotics. beads of 5. (c) following the removal of the beads and bone grafting.Vol. the beads were removed and bone grafting was done in 26 cases. After 3 weeks. and (d) at last follow-up. Postoperative protocol Systemic antibiotics. 1. broad-spectrum
antibiotics were administered. Overflow drains were used without suction for the first 24 to 48 hours. Follow-up All patients were followed up at 6-week intervals in the initial 3 months.
the organisms were resistant to all antibiotics tested. ampicillin in 8. and organism responsible for the infection are shown in Tables 1. primary healing of the wound without any recurrence of the discharging sinus. and cotrimoxazole in 5. respectively. Fair: No clinical signs of infection with erythrocyte sedimentation rate returning to normal levels. The results were graded as follows: Good: No clinical features of infection with erythrocyte sedimentation rate returning to normal levels.76
SP Mohanty et al. of patients Group 1 5 8 9 22 Group 2 2 7 4 13 Group 3 0 3 7 10
Table 3 Organisms isolated Organism Staphylococcus aureus Pseudomonas spp Klebsiella spp Haemolytic streptococcus Proteus Mixed infections Total No. The organisms were found to be sensitive to gentamycin in 26 cases and resistant in 19 cases. and 3. At 6 weeks’ follow-up. cloxacillin in 11.
RESULTS Site of infection. in 7 cases. 2. They were sensitive to cefuroxime in 14 cases.7 years (range. The mean follow-up period was 3. all of which belonged to Group 1.
Table 1 Sites and types of osteomyelitis
Group 1 2 3 Total Femur 12 5 6 23 Tibia 5 7 3 15 Site Forearm 2 0 0 2 Humerus 2 1 1 4 Spine 1 0 0 1
Table 2 Duration of infection according to infection type
Duration of infection (months) <3 3–6 >6 Total No. of which 4 healed by epithelisation and 3 required secondary closure.0–5. Poor: Recurrence of the sinus with discharge. whereas 7 healed by secondary intention.
Journal of Orthopaedic Surgery
years. primary healing of the wound. of patients 26 7 2 1 1 8 45
. and complete healing of fracture. duration of infection. and radiographic signs of infected nonunion. 2. 38 wounds healed primarily.0 years). and delayed fracture healing. there was recurrence of drainage in 6 cases.
and long-term systemic antibiotic therapy. primary resistance is uncommon. In contrast. gentamycin is the most suitable: it is thermostable. in addition. Majid et al. and 19%. the most common type of chronic osteomyelitis was due to infected osteosynthesis (49%). 1. In particular.3. saucerization. No adverse systemic side-effects such as ototoxicity or nephrotoxicity were seen.Vol. With the increasing popularity of internal fixation. In addition. the incidence of musculoskeletal infection in our series was higher among relatively young individuals.11 found incidences of 77% postoperative infections. 17% haematogenous osteomyelitis. 30%.5 Of these. the results were good (Fig. respectively. the results were poor. the problem of infected osteosynthesis is increasing. osteomyelitis is more difficult to treat than other infectious disorders because the systemically administered antibiotics fail to reach the site of infection owing to relative avascularity. Furthermore. The principle of depot administration of antibiotic is based on a well-accepted fact that the drug leaches out locally over a period of time. sequestrectomy. Of the 19 cases in which the organism was found to be resistant to gentamycin. and haematogenous osteomyelitis (22%). showing healed fracture with no evidence of infection following removal of the beads and bone grafting. followed by Pseudomonas species. Galey and Uhthoff10 reported an incidence of 51%.3. Infection in the bone can persist despite thorough debridement.
DISCUSSION Musculoskeletal sepsis is a chronic debilitating disease.12 reported that 58% of cases in their series
.9 In this study. followed by Pseudomonas species in 16% of cases.10–12 In 42% of cases in our series. Other authors have also reported Staphylococcus aureus as the most common pathogen. in 6 (13%) cases. Hedstrom et al. Staphylococcus aureus was the most common pathogen (58%). treated by dynamic hip screw with infected nonunion: (a) chronic osteomyelitis with nonunion of the trochanteric fracture with dynamic hip screw in situ. whereas mixed infections were seen in 18% (Table 3). has a broad spectrum of activity.4
Various materials have been tried as a carrier of local antibiotic. June 2003
Antibiotic-loaded acrylic beads for musculoskeletal sepsis
Figure 3 Radiographs of a patient with trochanteric fracture. Majid et al. The resulting bactericidal tissue concentration at the site of infection is therefore higher than the concentration achievable by systemic antibiotic administration. and (c) at last follow-up. 11 No. In 39 (87%) cases.3. 3). 12 identified haematogenous osteomyelitis (51%) as the most common aetiological factor. and 12% infections following open fractures. the organisms were gentamycin resistant. and is bactericidal. 6–8 Of the antibiotics available. followed by open fractures (29%). probably because of their susceptibility to open fractures and subsequent complications.
There was no difference in the clinical outcome between the cases treated with Septopal or those treated with handmade beads. (b) after removal of implant and gentamycin beads. PMMA has the best elution characteristics. only one case had a poor result.
one had poor result. However. Brause BD. antibiotic sensitivity testing is done with a 10. of these. the role of these beads becomes limited. they were found underneath the plates after implant removal. following which there was recurrence of the draining sinus. whereas the antibiotic concentration achieved following the implantation of PMMA beads is more than 50 µg/ml. Callaghan JJ. Clin Orthop 1993. Elson RA.10 This study showed a success rate of 87%.
1. This finding is comparable to the results reported by Galey and Uhthoff10 (67%) and Majid et al. Small RD. Mackowiak et al.207:83–93. The technique also reduces the need for multiple procedures for wound closure as well as the overall cost of treatment. They help to eradiate infection when implanted only after removal of dead and infected material.µ g disc.12 Six out of 45 cases were classified as failures in our series. Clin Orthop 1984. Antibiotic bead chains. which was similar to the observations of Galey and Uhthoff. For chronic infections. especially those following osteosynthesis.78
SP Mohanty et al. In these cases. Clin Orthop 1986. Salvati EA.
CONCLUSION Radical debridement is the cornerstone in the management of musculoskeletal infections. 2 were cases of infected Kuntscher’s nails that were not removed at the time of first-stage surgery.13 were of the opinion that sinus tract cultures may not be representative of the actual pathogen. Klemm KW. There was no difference in the outcome between these 2 groups. Reimplantation in infection.* 1 2 3 4 5 6 Infection (site) Infected Kuntscher's nail (femur) Infected plates and screws (femur) Infected total hip Infected plate and screws (femur) Infected Kuntscher's nail (femur) Infected plate and screws (tibia) Duration (months) 11 9 5 6 9 7 Organism isolated Staphylococcus aureus Mixed infection Mixed infection Staphylococcus aureus Staphylococcus aureus Staphylococcus aureus
Journal of Orthopaedic Surgery
Sensitivity to gentamycin Sensitive Sensitive Resistant Sensitive Resistant Sensitive
* All cases had Group 1 infection and underwent debridement and acrylic bead application without implant removal
were sensitive to gentamycin. they are eradicated. Antibiotic-loaded acrylic cement: current concepts. sequestrectomy. one patient had an infected total hip arthroplasty and the remaining 3 had infected osteosynthesis with plates and screws (Table 4). (78%). because there was not adequate sign of union at the fracture site. Table 4 Details of the patients with poor results Case No. infection could be controlled only for 6 weeks. In addition.295:63–76. 3. Furthermore.14 Of the cases in our series were treated with handmade beads and 31 with Septopal beads. Elution of gentamicin from cement and beads. The handmade beads were slightly more difficult to remove because of their uneven surface and size.3 Usually. This observation could be explained by the fact that when the organisms are exposed to a very high concentration of antibiotics. and debridement.
. The wound and sinus healed after implant removal. This shows that the antibioticloaded PMMA beads are effective even in the presence of resistant organisms. Even though sequestrae were not visible radiologically. The most valuable advantage of this method is that the wound can be closed primarily. Of the 19 patients with infections in which the organism was found to be gentamycin resistant. as postulated by Salvati et al. Heinert K. the use of antibiotic beads is a valuable adjuvant.190:96–108. thereby reducing the incidence of nosocomial infections and the requirement for nursing care. 2. they were less expensive and offered flexibility regarding the choice of antibiotic used. Klein RF. Postoperative cultures were sterile in all patients in our series except in one case of failure. which depended on the sensitivity of the organism. In the presence of infected implants that prevent accessibility to the underlying sequestrae and infected tissues. Buchholz HW. These implants were left in situ with the hope of salvaging the osteosynthesis but with little success.
. Antibiotic containing bone cement beads in the treatment of deep muscle and skeletal infections. Smith JW. 7. 5. Hedstrom SA. Galey JP. Bayston R. The release of gentamicin from polymethylmethacrylate beads. In: Uhthoff HK. Cumberland N. Antibiotic release from impregnated pellets and beads.
Antibiotic-loaded acrylic beads for musculoskeletal sepsis
Wahlig H.61:353–6. Moon MS. Dingeldein E. Mackowiak PA.8:7–10. Berlin: Springer-Verlag. Lindsey RW. Acta Orthop Scand 1980. Torholm C. In vitro pharmacokinetics of antibiotic release from locally implantable materials.Vol. 10. Bowyer GW. 6. Current concepts of infections in orthopaedic surgery. 9. 12. Moon JL.11:627–32. Danhers LE. Lindberg LT.64:460–4. Majid SA.36:331–5. 8. An experimental and pharmacokinetic study. JAMA 1978. Merser S.51:863–9. Siddiki MS. Reuss K. Management of osteomyelitis. Jones SK. Gentamicin-PMMA beads in the treatment of chronic osteomyelitis.239: 2772–5. 13. Lidgren L. editor. Milner RD. J Orthop Surg (Hong Kong) 2000. Acta Orthop Scand 1985. J Bone Joint Surg Br 1978. J Trauma 1994. An appraisal of laboratory investigations and their significance. In vitro comparison with plastic beads. 11. Bergmann R. The use of gentamycin-PMMA beads in chronic osteomyelitis. Diagnostic value of sinus-tract cultures in chronic osteomyelitis. Sorensen TS. Sorensen AI. Rapid release of gentamicin from collagen sponge.56:265–8. Acta Orthop Scand 1990. 1. Miclau T. Gunterberg B.60:270–5. J Orthop Res 1993. June 2003 4. Onnerfalt R. 11 No. The sustained release of antimicrobial drugs from bone cement. 1985. Uhthoff JP. J Bone Joint Surg Br 1982.