Antibiotic Beads Research Articles

In vitro elution of vancomycin from biodegradable beads

The current antibiotics delivery system for orthopedic infection treatment uses polymethylmethacrylate (PMMA) beads as a drug release. However the nonbiodegradable nature of the PMMA necessitates a second operation to remove the beads. This article explores the alternative of using biodegradable polymers as antibiotic beads for a long-term drug release. The effect of different processing factors on the release rate of the beads was investigated. To manufacture an antibiotic bead, polylactide-polyglycolide copolymers were mixed with vancomycin. The mixture was compressed and sintered at 55 degrees C to form beads of different sizes. An elution method was employed to characterize the release rate of antibiotic over a 35-day period at 37 degrees C. Biodegradable beads released high concentrations of antibiotic (well above the breakpoint sensitivity concentration) in vitro for the period of time needed to treat bone infection; i.e., 4-6 weeks. A bacterial inhibition test was carried out to determine the relative activity of the released antibiotics. The diameter of the sample inhibition zone ranged from 6.5-10 mm, which is equivalent to 12.5-100% of relative activity. By changing the processing parameters, we were able to control the release rate of the beads. This provides advantages of meeting the specific antibiotics requirement for patients with various surgical infections.

In vitro elution of vancomycin from biodegradable beads.

The current antibiotics delivery system for orthopedic infection treatment uses polymethylmethacrylate (PMMA) beads as a drug release. However the nonbiodegradable nature of the PMMA necessitates a second operation to remove the beads. This article explores the alternative of using biodegradable polymers as antibiotic beads for a long-term drug release. The effect of different processing factors on the release rate of the beads was investigated. To manufacture an antibiotic bead, polylactide-polyglycolide copolymers were mixed with vancomycin. The mixture was compressed and sintered at 55 degrees C to form beads of different sizes. An elution method was employed to characterize the release rate of antibiotic over a 35-day period at 37 degrees C. Biodegradable beads released high concentrations of antibiotic (well above the breakpoint sensitivity concentration) in vitro for the period of time needed to treat bone infection; i.e., 4-6 weeks. A bacterial inhibition test was carried out to determine the relative activity of the released antibiotics. The diameter of the sample inhibition zone ranged from 6.5-10 mm, which is equivalent to 12.5-100% of relative activity. By changing the processing parameters, we were able to control the release rate of the beads. This provides advantages of meeting the specific antibiotics requirement for patients with various surgical infections.

Management of femoral diaphyseal infected nonunion with antibiotic beads local therapy, external skeletal fixation, and staged bone grafting.

Fifteen patients with femoral shaft fractures complicated by infected nonunions were treated with a two-stage protocol. In the first stage, radical debridement was performed along with antibiotic bead chains local therapy and external skeletal fixation. In the second stage, the debrided nonunion site was repaired with bone grafting and the external skeletal fixator was used until bony union was achieved. The time between the first and second stages of treatment was 2 to 6 weeks. The debrided bone defects ranged from 0.5 to 15 cm. Autogenous iliac cancellous bone grafting was performed in 11 patients, and microvascularized osteoseptocutaneous fibular transfer was performed in 4 patients. Wound healing and bone union were achieved in all 15 cases. The duration of external fixation of these patients ranged from 7 to 15 months, with an average of 9 months. Minor pin-track infection was seen in seven patients. Postoperative infection after the second-stage bone grafting occurred in three patients. These three infections were arrested by limited debridement along with 2 to 4 weeks of parenteral antibiotic therapy. In one case, stress fracture occurred at 11 months after microvascularized fibular transfer; this was managed with another 5 months of external skeletal fixation. With an aggressive physical therapy program, 10 patients achieved nearly full range of knee motion and 5 patients had relevant knee flexion deficits. The follow-up averaged 58 months (range, 40-76 months); no recurrence of osteomyelitis was observed even at 76 months. We have found that our two-stage treatment with antibiotic beads local therapy, definitive external skeletal fixation, and staged bone grafting is an acceptable treatment protocol for the management of femoral diaphyseal infected nonunion. It results in rapid recovery from osteomyelitis and a predictable recovery from nonunion.

Implantation of antibiotic impregnated PMMA beads for infection after implantation of endoprosthesis

Implantation of antibiotic impregnated PMMA beads for infection after implantation of endoprosthesis

Management for Postoperative Infection of Fractures

It is often difficult to eradicate infection and achieve bony union in postoperative infection after fracture fixation. Authors treated 14 such cases from February 1992 to February 1998, and followed up for 6 to 35 months. The purpose of this study is to review the clinical features of the postoperative infection and assess the treatment modality which influence the time required for attaining bony union and healing of infection. The results were as follows : 1. Primary fixation were left in place in 5 cases of stable fixation, and new external fixation and/or another fixations were required in 8 cases of unstable fixation. 2. Time required for achieving union was 4.7 months for stable primary fixation and 12.8 months for unstable primary fixation. 3. Time required for healing in infection was 3.5 months for stable primary fixation and 14.4 months for unstable primary fixation. 4. Bony union was delayed as the number of surgical procedures were increased. 5. Antibiotic cement beads were inserted for 5 cases into bony defect and dead space after curettage and sequestrectomy, and pus discharge was stopped after 8.8 weeks in average.

The use of antibiotic-impregnated cement in infected reconstructions after resection for bone tumours.

We have studied 35 patients with infected reconstructions after segmental resection for bone tumours. Two different regimes of treatment were employed both of which entailed debridement and the use of cement impregnated with antibiotic. In 25 patients gentamicin-PMMA beads were used and in ten an antibiotic-impregnated cement spacer. Better results were achieved with the second procedure in terms of cases healed, the number of operations, time of healing, time of recovery and the functional score. The use of vancomycin in the cement spacer gave better local control.

Clinical Response to Antibiotic Impregnated Polymethyl Methacrylate Bead Implantation of Dogs with Severe Infections after Limb Sparing and Allograft Replacement -18 Cases (1994-1996)

SummarySuccessful treatment of severe orthopaedic infections in people and animals has been augmented by the use of antibiotic impregnated polymethyl methacrylate (PMMA) bead implantation at the site of infection. High local wound concentrations of antimicrobials can be achieved without resulting in toxic levels systemically. Clinical, radiographic and pathological response was evaluated following PMMA beads impregnated with vancomycin and tobramycin implanted in 18 dogs with severe infections following “limb sparing” operation with allograft replacement for osteosarcoma. A variety of aerobic and anaerobic bacterial organisms were cultured from the sites of infection and numerous systemic antimicrobial drug combinations were used in an attempt to control the infections prior to the implantation of the beads. In 12 of 18 (67%) dogs implanted, clinical signs of infection resolved within a median of four weeks post implantation. Three of 12 (25%) had recurrence of signs at a median of 17 weeks post implantation. This was not a randomized, prospective controlled trial and limitations to the study exist, the most notable being the variability in individual patient treatment. However, antibiotic impregnated PMMA bead implantation may play a role in the treatment of severe infections in dogs.Eighteen dogs with severe infections were implanted with polymethyl methacrylate beads impregnated with tobramycin and vancomycin. In 67% of dogs implanted, clinical signs of infection resolved within a median of four weeks. Antibiotic impregnated PMMA bead implantation may play a role in the treatment of severe orthopedic infections in dogs.This study was supported in part by grant number 2 PO1 CA 29582 from the National Cancer Institute. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute, USA.

Staged management of infected humeral nonunion.

Fourteen patients with infected humeral nonunion complicated by sinus discharge were treated with a staged protocol consisting of (1) radical debridement with local antibiotic beads implantation, and (2) external skeletal fixation with autologous bone grafting. In the first stage, a thorough debridement and sequestrectomy were done. Antibiotic beads were used to obliterate the bone defect, and the wound was then directly closed. In the second stage, the bead chains were replaced with autogenous cancellous bone graft. Unilateral Hoffman external skeletal fixators were applied simultaneously. The mean follow-up period was 73.6 months (range, 29 months to 9 years). The length of time to achieve bony union ranged from 3.5 to 8 months (average, 4.3 months). Hoffman pin complication was found in two cases, which were then shifted to plate internal fixation. All the infections were eradicated, and the wounds healed without further skin graft or flap coverage. All the fractures achieved bony union except for one in a patient who died. Most patients acquired satisfactory function of elbow motion after removal of external fixation and physical therapy. The method of two-stage management was effective for infected humeral nonunion. Not only was the infection eradicated and osseous union achieved, but also the limb function and joint motion were preserved.

Treatment of Osteomyelitis With a Biodegradable Antibiotic Implant

A biodegradable antibiotic implant was developed and evaluated in a localized osteomyelitic rabbit model. The biodegradable antibiotic implant was made of polylactic acid and poly(DL-lactide):co-glycolide combined with vancomycin. Localized rabbit tibial osteomyelitis was developed with Staphylococcus aureus. Infected rabbits were divided into eight groups, depending on treatment with or without debridement, systemic antibiotics, or biodegradable beads. After 4 weeks of therapy, the radiographs were obtained of the involved bones, which also were cultured for concentrations of Staphylococcus aureus per gram of bone. Treatment with antibiotic containing polylactic acid and poly(DL-lactide):co-glycolide beads, with and without systemic vancomycin, resulted in bone colony forming unit levels of 10(2.93) and 10(2.84) colony forming units per gram bone, respectively. These bacterial concentrations were approximately 100 times lower than those observed for all other treatment groups. A biodegradable antibiotic bead may provide extended bactericidal concentrations of antibiotics for the time needed to completely treat the particular orthopaedic infection and does not require the surgery needed to remove the polymethylmethacrylate beads.

Management of large infected tibial defects with antibiotic beads local therapy and staged fibular osteoseptocutaneous free transfer.

Fifteen patients with tibial fractures complicated by large infected tibial defects were treated with a two-stage protocol. In the first stage, antibiotic-impregnated polymethylmethacrylate bead chains were used to obliterate the debrided osseous defect, and a meshed porcine skin was used for temporary wound coverage. In the second stage, the bead chains were removed, and the defects were reconstructed with a microvascularized fibular osteoseptocutaneous free transfer. The time between the first and second stages of treatment was 2 to 6 weeks. The bone defects ranged from 6 to 16 cm, and the skin defect areas ranged from 10 to 82 cm2. Wound healing and bony union were achieved in all 15 cases. An additional muscle flap or skin graft was required for only three patients with a large skin defect. Minor pin tract infections were seen in two patients. Stress fractures in three cases were successfully managed with bracing, external skeletal fixation or plating, and cancellous bone grafting. All of the most recent roentgenograms showed good consolidation and hypertrophy of grafted fibular bones. No recurrence of osteomyelitis was observed during an average follow-up period of 50 months (range, 36-86 months). We therefore conclude that this treatment protocol provides rapid recovery from osteomyelitis. The fibular osteoseptocutaneous graft is a useful method for the reconstruction of a large tibial defect, and it also offers the unique advantage of simultaneously reconstructing a moderate skin defect.

Antibiotic Bead Pouch Dressing

The antibiotic bead pouch is a dressing consisting of antibiotic laden polymethylmethacrylate (PMMA) beads placed in a wound, which is covered by a porous membrane (Opsite). This paper outlines the method, rationale and results of the use of this dressing technique for extensive wounds before definitive wound closure. A case series review of 15 consecutive patients with a variety of soft tissue wounds that were managed with an antibiotic bead pouch dressing is presented. The method of dressing has been a useful and successful adjunct to the management of extensive infected and contaminated wounds.

Reamed nailing of open tibial fractures: does the antibiotic bead pouch reduce the deep infection rate?

Eighty-one open tibial fractures were treated by reamed intramedullary nailing. There were 38 type II, 23 type IIIa and 20 type IIIb injuries. At the end of the nailing procedure the first 26 fractures (15 type II, five type IIIa, and six type IIIb) had antibiotic prophylaxis and delayed closure of the open wound. The subsequent 55 fractures (23 type II, 18 type IIIa, and 14 type IIIb) had identical management but in addition had an antibiotic bead pouch inserted into the open wound following debridement. Three amputations were performed: one (3.8%) in the group treated without a bead pouch and two (3.6%) in the bead pouch group in patients with grade IIIb fractures and severe crushing injuries. Of the remainder, there were four deep infections (16%) in the 25 fractures treated prior to the use of the bead pouch and two (4%) deep infections in the 53 fractures following introduction of the bead pouch. Addition of the bead pouch to the wound management protocol was associated with a worthwhile reduction of deep infection.

骨関節感染症の治療経験 抗生剤含有骨セメント使用例

Regardless of advances in antibiotics and surgical treatment, bone and joint infections remain refractory diseases. We report on 5 patients treated with antibiotic impregnated PMMC beads. Subjects included 3 men and 2 women with a mean age of 49.4 years (range: 4-74 years) with an average follow-up of 4 years 1 month (range: 1 year 3 months to 7 years 4 months). We treated 3 cases of osteomyelitis and 2 cases of postoperative infections by mixing antibiotics at 3 times the maximum dose with PMMC beads, and inserted them for 3 to 11 weeks (mean 5.8 weeks). We measured the serum concentration of antibiotics after inserting the antibiotic-PMMC beads, and investigated the amount of antibiotic leaching into the surrounding tissue. All cases improved on clinical examination, and made satisfactory progress. We confirmed that the treatment of bone and joint infection by antibiotic-PMMC beads was safe ad effective.

Hematogenous osteomyelitis of the calcaneus in children: Surgical treatment and use of implanted antibiotic beads

Hematogenous osteomyelitis is a relatively uncommon disorder that may prove elusive to early diagnosis and treatment. Metaphyseal long bones are commonly involved and the calcaneus is rarely affected. A high index of suspicion should be maintained regarding the pediatric patient with pain out of proportion to a minor injury. Delay in the diagnosis of hematogenous osteomyelitis in the pediatric patient can result in irreversible growth disturbances and devastating sequelae. The authors present a typical case history with an unusual postoperative course and a review of the clinical aspects and surgical treatment of hematogenous calcaneal osteomyelitis in a child.

Local application of antibiotics in orthopaedic infections.

Local administration of high doses of antibiotics may be done with the use of antibiotic beads. The advantages of this treatment modality would seem to outweigh the disadvantages.

人工骨ｈｙｄｒｏｘｙａｐａｔｉｔｅからの抗生物質放出制御と抗菌活性

人工骨ｈｙｄｒｏｘｙａｐａｔｉｔｅからの抗生物質放出制御と抗菌活性

The management of open fractures associated with arterial injury requiring vascular repair.

Seventy-two open fractures associated with arterial injury requiring vascular repair (Gustilo type IIIC injuries) were treated at the University of Louisville from May 1983 and through 1992. The involved anatomic areas were the humerus (four), forearm (ten), femur (eight), tibia (31), ankle (ten), and foot (nine). Fracture management consisted of careful débridement, wound irrigation, fasciotomy, and fracture stabilization. Additionally, 40 wounds (55.6%) were treated with the supplemental use of local antibiotics (tobramycin-PMMA bead chains). Twenty-three patients (32.1%) underwent primary amputation, and 49 (67.99%) of the injured vessels were repaired. There were seven secondary amputations because of infection or poor revascularization, resulting in an overall amputation rate of 41.6%. The wound infection rate was 13.9% (10 of 72) and the rate for osteomyelitis was 4.2% (3 of 72). The local use of the antibiotic bead chains was of significant benefit in lowering infectious complications. Primary coverage of soft-tissue defects with free tissue transfer had an infection rate of 66%; temporary wound coverage with the "antibiotic bead pouch" technique until wound closure can be obtained in a sterile and viable environment appears to be a better option.

TIMING OF WOUND CLOSURE IN SEVERE COMPOUND FRACTURES

In a consecutive series of 1085 open fractures treated from May 1983 to July 1992, 381 severe compound fractures in 335 patients were managed with the antibiotic bead pouch technique. There were 27 grade I (marked swelling, compartment syndrome), 115 grade II, and 239 grade III open fractures (94 type IIIA, 114 type IIIB, and 31 type IIIC). These fractures were managed with early administration of broad spectrum antibiotics, copious wound irrigation, serial debridements, and external skeletal stabilization. Tobramycin-PMMA beads were placed in the wound, and porous plastic film (Opsite, Smith and Nephew Medical, Limited, Hall, England) covered the soft tissue defect. This dressing was changed every 48 to 72 hours until wound coverage/closure could be obtained. Infection rate, either on an acute or chronic basis, was 2.6% in grade II open fractures and 8.4% in grade III compound fractures. There was no infected wound or bone in the grade I category. Those fractures that did not develop an infection were closed at a mean time of 7.6 days; those that developed an infection were closed at a mean time of 17.9 days. The difference was statistically significant (P < 0.001). When severe open fractures are managed with the antibiotic bead pouch technique, wound closure should be obtained within 1 week to prevent infectious complications.

Optimal timing of wound closure in severe open fractures with temporary coverage by skin substitute

In a consecutive series of 1085 open fractures treated at the University of Louisville Level I Trauma Center from May 1983 to July 1992, 381 severe compound fractures in 335 patients were managed with the antibiotic bead pouch technique. There were 27 grade I (marked swelling, compartment syndrome), 115 grade II and 239 grade III open fractures (94 type IIIA, 114 type IIIB and 31 type IIIC). These fractures were managed with early administration of broad spectrum antibiotics, copious wound irrigation, serial debridements and external skeletal stabilization. Tobramycin-PMMA-beads were placed in the wound and porous plastic film (Opsite) covered the soft tissue defect. This dressing was changed every 48 to 72 hours until wound coverage/closure could be obtained. Infection rate either on an acute or chronic basis was 2.6% in grade II open fractures and 8.4% in grade III compound fractures. There was no infected wound or bone in the grade I category. Those fractures which did not develop an infection were closed at a mean time of 7.6 days; those which developed an infection were closed at a mean time of 17.9 days. The difference was statistically highly significant (p < 0.001). When severe open fractures are managed with the antibiotic bead pouch technique, wound closure should be obtained within one week to prevent infectious complications.

Ｂｒｏｄｉｅ骨膿ようの治療経験

We observed 4 cases of so-called Brodie's abscess. All patients were male, and two were adults. Diagnosis was made by blood examination, roentgenogram, tomogram, CT, scintiphotograph, bactenological culture, and clinical symptoms.Patients were treated by surgical evacuation of the abscess and with antibiotics.In the 2 adult cases, the focus was relatively large, therefore we initially evacuated the abscess surgically and inserted antibiotic mixed cement beads. Secondly we performed a bone graft.No recurrences were seen.We believe that surgical evacuation of the lesion, followed by antibiotics, is an appropriate treatment, and that use of antibiotic mixed cement beads would decrease recurrence of this abscess.