Antibiotic-impregnated Calcium Sulfate Research Articles

Vancomycin-impregnated calcium sulfate beads compared with vancomycin powder in adult spinal deformity patients undergoing thoracolumbar fusion

IntroductionAdult spinal deformity (ASD) surgery patients are at higher risk for surgical site infections (SSIs) due to large incisions, high blood loss, long surgical duration, and extensive instrumentation. The use of vancomycin powder has demonstrated inconsistent results in ASD surgery. Antibiotic-impregnated calcium sulfate beads have been used in arthroplasty and foot and ankle surgery with promising results. The purpose of this study was to provide preliminary data on the use of vancomycin-impregnated calcium sulfate beads in the prevention of SSI following ASD surgery and provide comparisons to the use of vancomycin powder. MethodsA retrospective chart review was performed for 95 consecutive surgical ASD patients at a tertiary care center from January 2017 until March 2020. Patients received either vancomycin powder (powder group) or vancomycin-impregnated calcium sulfate beads (bead group) intrawound prior to closure. Patient demographics, operative course, and incidence of postoperative infections were recorded. A two-tailed chi-squared test was performed to compare infection rates. ResultsNinety-five patients were included for review. Forty-two patients were in the powder group and 53 patients were in the bead group. The bead group was older (59.8 vs 67.8 years, p < 0.01) with similar BMI and rates of diabetes, smoking, and length of surgery. There were four postoperative SSI in the powder group requiring operative irrigation and debridement and one SSI in the bead group (9.5% vs 1.9%, p = 0.09). All infections occurred in the first 90 days of the postoperative period. ConclusionPreliminary examination of the use of vancomycin-impregnated calcium sulfate beads demonstrated a 1.9% surgical site infection rate in adult spinal deformity surgical patients, which was not significantly different compared with the 9.5% infection rate in patients who received vancomycin powder. Prospective study is needed to determine if the differences found are significant in a larger number of patients.

Treatment of Chronic Hematogenous Osteomyelitis in Children With Antibiotic Impregnated Calcium Sulphate.

The purpose of this study was to evaluate the clinical and radiologic outcome of chronic hematogenous osteomyelitis (CHOM) in children, treated with single-stage debridement and dead space management using antibiotic impregnated calcium sulphate pellets. The authors retrospectively evaluated a consecutive series of 34 patients who presented with CHOM from 2011 to 2017. In each case, CHOM was classified according to the Beit CURE classification. Following thorough surgical debridement, the resulting dead space in the bone was filled with the antibiotic impregnated beads before primary closure. Of the 31 patients available for follow up, effective regeneration of bone was confirmed in all cases, with radiographic bone healing typically observed at around 12 weeks. None of the children required reoperation for infection and none had recurrence of infection at the time of final review. The beads were completely absorbed within 3 months. No systemic adverse reactions to the local delivery of antibiotics were observed in this study. The authors found that single-stage debridement in conjunction with antibiotic impregnated calcium sulphate was an effective means of treating CHOM in children, with effective eradication of infection in every case. Level IV-Retrospective case series. See instructions for authors for a complete description of levels of evidence.

Symptomatic Hypercalcaemia Following the Use of Dissolvable Antibiotic Beads in Infected Total Knee Arthroplasty

The gold standard treatment for periprosthetic joint infections is currently a 2-stage revision procedure with the use of antibiotic beads or cement spacer. We report the case of an elderly lady who had an infected total knee replacement and underwent a prosthesis retaining procedure with the use of antibiotic loaded calcium sulphate beads (stimulan in this case). Postoperatively, she became profoundly hypercalcaemic and lethargic. After other causes were excluded, she was taken for surgical washout of the knee joint. This led to prompt normalisation of serum calcium levels and resolution of her symptoms. We recommend the need for routine pre- and postoperative serial calcium measurements when using antibiotic impregnated calcium sulphate beads and that all doctors have an increased awareness of this risk.

Extensive eggshell-like debridement technique plus antibiotic-loaded calcium sulphate for one-stage treatment of chronic calcaneal osteomyelitis

BackgroundManagement of chronic calcaneal osteomyelitis is challenging. At present, there is still no widely accepted, simple, and effective surgical method to eradicate the infection and prevent osteomyelitis recurrence. The objective of this study was to assess the outcomes of one-stage treatment of chronic calcaneal osteomyelitis with a shape-preserving debridement technique combined with antibiotic-loaded calcium sulphate. MethodsBetween 2012 and 2018, 33 patients (33 limbs) with chronic calcaneal osteomyelitis were treated with a novel debridement technique, named “eggshell-like debridement”, plus antibiotic-impregnated calcium sulphate. The infection remission rate, recurrence rate, and amputation rate were analyzed. The American Orthopedic Foot and Ankle Society (AOFAS) ankle and hindfoot score was used to assess postoperative hindfoot function. Results26 patients (81.8%) achieved infection remission without recurrence. In the patients with osteomyelitis remission, pain, limitation of movement, sinus tracts, and typical redness and swelling were generally eliminated. Most of the patients could tolerate full weight-bearing without pain. The average AOFAS ankle and hindfoot score was 88 points (range, 67–100 points), implying the foot function was mostly restored. 6 patients (18.2%) had osteomyelitis recurrence but no amputation was required to elimilate the infection. ConclusionsEggshell-like debridement combined with antibiotic-loaded calcium sulphate is an effective method for one-stage management of chronic calcaneal osteomyelitis. With the application of this technique, secondary autogenous bone or muscle flap grafts are unnecessary. The surgical procedure can be simplified whlie the hindfoot function is well preserved.

Infected bone resection plus adjuvant antibiotic-impregnated calcium sulfate versus infected bone resection alone in the treatment of diabetic forefoot osteomyelitis

BackgroundManaging with diabetic foot osteomyelitis (DFO) is challenging. Even after infective bone resection and thorough debridement, DFO is still difficult to cure and has a high recurrence rate. This retrospective study aims to compare the outcomes of two treatment methods, infected bone resection combined with adjuvant antibiotic-impregnated calcium sulfate and infected bone resection alone, for the treatment of diabetic foot osteomyelitis.MethodsBetween 2015 to 2017, 48 limbs (46 patients) with DFO met the criteria were included for assessment. 20 limbs (18 patients) were included in the calcium sulfate group (the CS group) in which vancomycin and/or gentamicin-impregnated calcium sulfate was used as an adjuvant after infected bone resection while 28 limbs (28 patients) as the control group were undergone infected bone resection only. Systemic antibiotics, postoperative wound care and offloading were continued to be applied following surgery in both groups. The time to healing, healing rate, recurrence rate and amputation rate were compared between the two groups.ResultsIn total, 90% (18/20) limbs in the CS group as compared to 78.6% (22/28) infected limbs in the control group went to heal (P = 0.513). The Mean time to healing was 13.3 weeks in the CS group and 11.2 weeks in control group (P = 0.132). Osteomyelitis recurrence rate was 0% (0/18) in the CS group and 36.4% (8/22) in the control group (P = 0.014). Postoperative leakage in calcium sulfate group was 30.0% (6/20) with a mean duration of 8.5 weeks. Amputation rate in the control group was 7.1% (2/28) compared to 0% (0/20) in the CS group (P = 0.153).ConclusionsAntibiotic-impregnated calcium sulfate as an adjuvant prevents the recurrence of DFO but cannot improve the healing rate, reduce the postoperative amputation rate or shorten the time to healing. Prolonged postoperative leakage as the most common complication can be managed with regular dressing.Level of EvidenceIII, Retrospective Comparative Study.

Local bio-absorbable antibiotic delivery in calcium sulfate beads in hip and knee arthroplasty

Antibiotic-impregnated calcium sulfate (AICS) beads have been used for prevention and treatment of periprosthetic joint infections. We evaluated post-operative complications following the use of AICS beads. 56 patients undergoing complex primary or revision hip or knee arthroplasty received antibiotic calcium sulfate beads. Primary outcomes were wound complication rates. Secondary outcomes included reoperation and reinfection rates. One case (1.7%) of persistent wound drainage occurred requiring surgical irrigation and a poly-exchange. No post-operative infections were seen. Use of 100% pure calcium sulfate AICS beads may help reduce post-operative wound complications. AICS appears to be a safe adjunct tool in local antibiotic delivery.

A novel treatment approach to infected nonunion of long bones without systemic antibiotics

Infected nonunion of long bones may require intravenous antibiotics over a lengthy period which may result in a high rate of complications. This study aims to assess the efficacy of local antibiotics used as a replacement to prolonged intravenous therapy. Thirteen patients with infected nonunion of long bones who failed at least one previous surgery were included. The infection was treated through extensive debridement, application of antibiotic-impregnated calcium sulphate pellets and the bone stabilized with external fixation. These patients were monitored for union and infection by clinical signs, laboratory values, and radiographs over a period of 24 months. The results support an eradication of infection and union in all patients with no antibiotic-associated complications. Local antibiotic delivery using calcium sulphate pellets provides an effective method for treatment of nonunion in long bones and is free of the complications from the intravenous route.

Severe Hypercalcemia Following the Implantation of Antibiotic Impregnated Calcium Sulfate Beads for Prosthetic Joint Infection

Prosthetic joint infections are a significant cause of morbidity and mortality, which affect only a small number of joint replacements annually. Antibiotic impregnated beads are increasingly used to combat these infections. This delivery system is believed to be safe, however, we present a case of a patient who developed severe hypercalcemia several days after implantation of calcium sulfate beads during a revision of an infected total knee athroplasty. A 70-year-old male was admitted to our institution due to infected prosthetic total knee arthroplasty. All of the patient’s pre-operative labs were within normal limits. He was taken for irrigation, debridement and poly exchange of the infected knee by orthopedics. During the procedure, 10 mL of 10 ml of calcium sulfate beads impregnated with Vancomycin and 10 mL of calcium sulfate beads impregnated with Tobramycin was implanted in the knee. Approximately 48-72 hours post-operatively, the patient became more lethargic, confused and had a poor appetite. He was found to be severely hypercalcemic at 14.0 mg/dL An extensive workup for hypercalcemia was unremarkable and the only logical explanation was tbe implanted beads. He was started on aggressive intravenous hydration with IVF and Lasix for volume control with resolution of his symptoms and hypercalcemia. He had no further occurrence of hypercalcemia during follow up period. Hypercalemia is a medical emergency seldomly encountered by internists, but requires acute interventions. This case demonstrates a possible new cause of hypercalcemia in surgical patients, antimicrobial impregnated calcium sulfate beads. Nonetheless, clinicians should be aware of this etiology of hypercalcemia, given the increased utilization of these types of treatments.

Poor Outcomes of Irrigation and Debridement in Acute Periprosthetic Joint Infection With Antibiotic-Impregnated Calcium Sulfate Beads

BackgroundOne proposed strategy to increase the success of irrigation and debridement with implant retention for the treatment of acute periprosthetic joint infection (PJI) is the use of dissolvable antibiotic-impregnated calcium sulfate beads to provide a local depot of antibiotics. The purpose of this study was to evaluate the outcome of such an approach. MethodsThirty-two patients with acute hematogenous (18 patients; 1 bilateral) or acute postoperative (14 patients) PJIs who underwent irrigation and debridement with implant retention and addition of antibiotic-impregnated calcium sulfate beads were retrospectively reviewed. PJI followed 27 total knee arthroplasties and 6 total hip arthroplasties. The most common infecting organisms were methicillin-sensitive Staphylococcus aureus (13 of 33) and Streptococcus (9 of 33). The primary outcome parameter was recurrence of infection according to the Musculoskeletal Infection Society criteria. Patients were followed up for a minimum of 3 months or until failure. ResultsAt a mean of 12.7 months (range, 3-30 months), 16 of the 33 patients failed (48%). Acute hematogenous and acute postoperative PJI had similar failure rates at 47% and 50%, respectively (P = .88). Seven failures required a 2-stage exchange, while 8 patients were treated with chronic antibiotic suppression, being unwilling or unable to undergo further surgical intervention. ConclusionThe addition of antibiotic-impregnated calcium sulfate beads does not appear to improve outcomes of irrigation and debridement with implant retention in the setting of acute hematogenous or acute postoperative PJI. Given the short follow-up in this report, this represents a best-case scenario and the overall failure rate may be higher with further follow-up.

STUDY OF THE DIFFERENT RELEASE CHARACTERISTICS OF ANTIBIOTICS FROM PATIENTS: A DYNAMIC ELUTING SYSTEM TO INVESTIGATE DRUG RELEASE FROM ANTIBIOTIC-IMPREGNATED CALCIUM SULFATE DELIVERY

Background: Antibiotic-impregnated calcium sulfate delivery systems (ACDS) are commonly used to treat chronic osteomyelitis. Our research is to investigate drug release in vitro over a longer period, as a cautious predictor of in vivo release. Methods: The local release behavior of antibiotic in vitro was simulated. The consecutive dynamic eluting experiment was performed based on the pro-operative characteristic of osteomyelitis patients and the determined results of drug concentration in the human drainage tissue fluid (DTF). The concentration of each drug in the receiving solution was detected by ultra-performance liquid chromatography-tandem quadrupole detector mass spectrometry. The ACDS was reviewed by scanning electronic microscopy (SEM) after 48 h, and prepared to be eluted for another examination after 33 days. The mechanism of antibiotic release was analyzed by using the Ritger–Peppas and Weibull equations. Results: The cumulative release rate of vancomycin in a vancomycin-calcium sulfate delivery system (VCDS) was 77.50 % (3.0 mm diameter) and 72.43 % (4.8 mm diameter), while that of the tobramycin in a tobramycin-calcium sulfate delivery system (TCDS) was 88.0 % (3.0 mm diameter) and 84.55 % (4.8 mm diameter). At the 15th day, approximately 27.92% of vancomycin was and 29.35% of tobramycin was released from the local implant in vivo. Using SEM, numerous vancomycin and tobramycin particles were found to be attached to the columnar calcium sulfate crystals at the start of the experiment. The release behavior of the two antibiotics followed a combination of Fickian diffusion and Case II transport mechanisms within the first 48 h, and a Fickian diffusion mechanism during the subsequent time period. The correlation coefficient of tobramycin and vancomycin in vivo and in vitro was 0.9704–0.9949 and 0.9549–0.9782, respectively. Conclusion: A good correlation of the in vivo and in vitro cumulative release rates was observed by comparing the cumulative release rate of drugs in vitro by means of the dynamic eluting model, and in the DTF. Therefore, our study has proved that it is possible to use the dynamic eluting model as a cautious predictor of in vivo release.

Antibiotic-Impregnated Beads for the Treatment of Aortic Graft Infection

Infection of a prosthetic graft after replacement of the ascending aorta is an uncommon but life-threatening complication of surgery. We report the use of antibiotic-impregnated calcium sulfate beads in a patient with ascending aortic graft infection to provide localized, high-dose therapy to the infected region. Perigraft placement of antibiotic beads provides an alternative method for the treatment of aortic graft infection.

Using extended pedicle lateral gastrocnemius muscle flap with antibiotic-impregnated calcium sulfate to salvage distal femur chronic osteomyelitis: a case report

Using extended pedicle lateral gastrocnemius muscle flap with antibiotic-impregnated calcium sulfate to salvage distal femur chronic osteomyelitis: a case report

Treatment of Infected Hip Arthroplasty with Antibiotic-Impregnated Calcium Sulfate Cement

Purpose: To analyze the effectiveness of inserting beads made of calcium sulfate cement that were also impregnated with Vancomycin after debridement of an acute-immediate stage infected hip arthroplasty. Materials and Methods: Between 2002 and 2008, the cases of 13 patients with documented acute-immediate stage infections of hip arthroplasty were reviewed and followed for at least two years postoperatively (average 4.3 years). The preoperative and postoperative clinical and radiologic findings and blood laboratory work of the cases were checked. All cases were performed through retention of the implant and massive debridement and saline irrigation. Next, vancomycin-impregnated calcium sulfate cement beads were inserted. Results: After the first operation, the average interval to wait before performing a second operation was 27.7 days (17~37 days). During the second operation, the erythrocyte sediment rate and C-reactive protein were 150.97 mm/hr (34.6~339.7 mm/hr) and 76.4 mg/L (41~132 mg/L), respectively. Infectious organisms were cultured and isolated. There were 5 cases of Methicillin-resistant Staphylococcus aureus (MRSA). In addition, the results of an antibiotics sensitivity test revealed 8 cases of Vancomycin and 5 cases of 3rd generation Cephalosporin. Radiologic results showed 10 cases with a stable fixation on the last follow-up (femoral stem), and 1 case of hip joint space narrowing, called acetabular erosion. Conclusion: Inserting beads made of calcium sulfate cement that were also impregnated with Vancomycin proved to be a useful treatment for an acute immediate infection of hip arthroplasty.

Antibiotic-impregnated Calcium Sulfate Use in Combat-related Open Fractures

This article presents our experience with the use of antibiotic-impregnated calcium sulfate in the management of comminuted open fractures with a bony defect caused by combat-related blast injuries and high-energy wounds. Calcium sulfate was used 19 times in 15 patients (17 fractures) as a bone graft substitute and a carrier for antibiotics. The anatomic sites of the graft were as follows: 6 calcanei, 1 midfoot, 1 metatarsal, 5 tibiae, 3 femorae, and 1 humerus. The average number of procedures prior to grafting was 6.2 (range, 2-10; median, 6) with grafting performed at an average 28 days after injury (range, 9-194 days; median, 14 days). Average radiographic follow-up of 12 fractures not requiring repeat grafting or amputation was 8.5 months (range 1-19 months; median, 7 months), and all of these fractures demonstrated clinical and radiographic evidence of fracture healing and consolidation. Four patients subsequently underwent 5 transtibial amputations: 2 for persistent infection, 1 when the patient changed his mind against limb salvage acutely, and 2 for severe neurogenic pain. Including the 2 amputations for persistent infection, 4 patients (22.2%) required further surgical management of infection. Three patients (17.6%) subsequently developed heterotopic ossification at the graft site, which required surgical excision. Antibiotic-impregnated calcium sulfate is effective in treating severe, contaminated open fractures by reducing infection and assisting with fracture union.

What is the shelf life of physician-mixed antibiotic-impregnated calcium sulfate pellets?

This pilot study was undertaken to evaluate the short-term in vitro antimicrobial stability of both vancomycin- and tobramycin-impregnated calcium sulfate pellets mixed and stored in a clinical setting. Powdered tobramycin sulfate (500 mg) and vancomycin hydrochloride (500 mg) were blended into separate basins containing 25 g of surgical-grade calcium sulfate powder, then mixed with 8 mL of sterile saline. From this admixture, 6.0-mm pellets were produced. These were removed from the sterile container (stored at room temperature) at 1, 7, 30, 60, 90, and 120 days and tested against a variety of pathogenic bacterial isolates by using a modification of the standardized Kirby-Bauer test. Control pellets containing no antibiotic were also evaluated. There was no inhibition of bacterial growth by the non-antibiotic-impregnated (control) pellets. There was no appreciable difference in the zones of inhibition for any of the organisms with pellets stored for 1, 7, 30, 60, 90, or 120 days. Zones of inhibition for the various antibiotics to the strain of organism tested ranged from 17 mm to 30 mm, depending on the pathogenic isolate and the antibiotic evaluated. The zones of inhibition observed were similar to those designating antibiotic susceptibility in the Kirby-Bauer test. The results of this preliminary study suggest that clinician-mixed calcium sulfate pellets containing either vancomycin or tobramycin, when stored under normal room temperature and ambient humidity, appear to maintain their antimicrobial characteristics for at least 120 days.