Moderators' summary: antibiotics and infection.
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Biomedical subjects
Publications and source records attributed to Jason H Calhoun.
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OBJECTIVES: Staphylococcus aureus is the most common organism isolated in osteomyelitis. Methicillin-resistant S. aureus (MRSA) infections are particularly difficult to treat. We evaluated the efficacy of tigecycline and vancomycin with and without rifampicin in a rabbit model of MRSA osteomyelitis. METHODS: A 28 day antibiotic therapy with a subcutaneous injection of tigecycline (14 mg/kg twice daily), with and without oral rifampicin (40 mg/kg twice daily); or subcutaneous administration of vancomycin (30 mg/kg twice daily), with and without oral rifampicin (40 mg/kg twice daily) were compared. Osteomyelitis was induced with an intramedullary injection of 10(6) colony-forming units of MRSA. Infected rabbits were randomly divided into six groups: tigecycline, tigecycline with oral rifampicin, vancomycin, vancomycin with oral rifampicin, and no treatment control and tigecycline bone penetration groups. Treatment began 2 weeks after infection. After 4 weeks of therapy, the rabbits were left untreated for 2 weeks. Rabbits were then euthanized, and the tibias were harvested. The bones were cultured, and bacterial counts of MRSA were performed. RESULTS: Rabbits that received tigecycline and oral rifampicin therapy (n=14) showed a 100% infection clearance. Rabbits treated with tigecycline (n=10) showed a 90% clearance. Rabbits treated with vancomycin and oral rifampicin (n=10) also showed a 90% clearance. Rabbits treated with vancomycin (n=11) showed an 81.8% clearance. Untreated controls (n=15) demonstrated only a 26% clearance. For the tigecycline bone penetration group, the bone concentrations of tigecycline in the infected tibia were significantly higher than the non-infected ones. CONCLUSIONS: Tigecycline may be an effective alternative to vancomycin in the treatment of MRSA osteomyelitis.
Adult osteomyelitis remains difficult to treat, with considerable morbidity and costs to the health care system. Bacteria reach bone through the bloodstream, from a contiguous focus of infection, from penetrating trauma, or from operative intervention. Bone necrosis begins early, limiting the possibility of eradicating the pathogens, and leading to a chronic condition. Appropriate treatment includes culture-directed antibiotic therapy and operative debridement of all necrotic bone and soft tissue. Treatment often involves a combination of antibiotics. Operative treatment is often staged and includes debridement, dead space management, soft tissue coverage, restoration of blood supply, and stabilization. Clinicians and patients must share a clear understanding of the goals of treatment and the difficulties that may persist after the initial course of therapy or surgical intervention. Chronic pain and recurrence of infection still remain possible even when the acute symptoms of adult osteomyelitis have resolved.
For the staged management of infected total knee arthroplasty (TKA), antibiotic laden polymethylmethacrylate (PMMA) spacers have been recommended. Antibiotic-impregnated PMMA spacers target drug delivery, achieving high local levels while limiting the potential for host toxicity associated with parenteral antimicrobial therapy. This study examined the elution characteristics of an articulating PMMA TKA spacer that has been useful clinically. Tobramycin and vancomycin are both active against many organisms leading to joint infections. We used various combined antibiotic concentrations (maintaining a relative ratio of 55% tobramycin to 45% vancomycin w/w), and then assayed the elution profile of the TKA spacer in vitro. Additionally, the elution qualities of two brands of bone cement, Simplex and Palacos, were compared. Briefly, three groups of PMMA spacers, impregnated with different antibiotic loads, were fashioned from a mold replicating a femoral TKA component. The entire spacer surface area was immersed in sterile phosphate buffered saline (PBS) in a 1:6 ratio of grams of cement to milliliters of PBS and incubated at 37 degrees C for 24 h. After 24 h, aliquot eluates were taken, the PBS discarded, and replaced with fresh, sterile PBS. PBS was changed daily and an aliquot was taken at least weekly for nine weeks. Eluate samples were stored at -70 degrees C until assayed. Each spacer eluate sample's antibiotic concentration was determined by disc diffusion bioassay against Bacillus subtilis. Mean zone inhibition diameters were extrapolated from the standard curve to yield micrograms per milliliter of antibiotic in PBS. In all groups the Palacos spacers demonstrated higher elution levels, above the MIC for the organism used, for a longer period of time than those made with Simplex. Based on the observed elution profiles, antibiotic-impregnated Palacos bone cement may offer a more effective vehicle for local drug delivery during staged treatment of infected TKA.
Osteomyelitis in long bones remains challenging and expensive to treat, despite advances in antibiotics and new operative techniques. Plain radiographs still provide the best screening for acute and chronic osteomyelitis. Other imaging techniques may be used to determine diagnosis and aid in treatment decisions. The decision to use oral or parenteral antibiotics should be based on results regarding microorganism sensitivity, patient compliance, infectious disease consultation, and the surgeon's experience. A suppressive antibiotic regimen should be directed by the results of cultures. Standard operative treatment is not feasible for all patients because of the functional impairment caused by the disease, the reconstructive operations, and the metabolic consequences of an aggressive therapy regimen. Operative treatment includes debridement, obliteration of dead space, restoration of blood supply, adequate soft-tissue coverage, stabilization, and reconstruction.
We present a case of systemic fungal infection caused by Apophysomyces elegans in a 50-year-old patient who developed a progressive skin lesion after a motor vehicle crash. Histopathological and mycological examination of the surgical sample showed non-septated hyphae characteristic of mucoraceous fungi. Despite extensive surgical debridement, and parenteral administration of amphotericin B, the patient died of multi-organ failure. Autopsy findings suggested systemic involvement. The fungi recovered from culture had non-apophyseal and globose sporangi, and branched sporaniophores and was identified as Apophysomyces elegans.
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.
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 effectiveness of oral gatifloxacin was compared to that of standard parenteral antibiotic therapy (nafcillin) for the treatment of experimental methicillin-sensitive Staphylococcus aureus-induced osteomyelitis in a rabbit model. Gatifloxacin was as effective as nafcillin in clearing the infection. Therefore, oral gatifloxacin treatment of osteomyelitis may be an effective alternative to intravenous nafcillin treatment.
The management of musculoskeletal infections is an increasing challenge to clinicians. Bioimplants provide a unique system for skeletal specific drug delivery. Antibiotic-impregnated beads and spacers can be used to treat chronic osteomyelitis and deep soft-tissue infections locally with higher antibiotic concentrations, while avoiding potential systemic side effects.
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The purpose of this study was to determine recurrence rates of pediatric foot and ankle burn deformities treated with the Ilizarov method. A total of 19 patients with 29 foot and ankle deformities were studied. The most common deformity treated was equinus (23). Rocker-bottom and cavus foot deformities were each treated three times. The average age of the patient at the time of the burn injury was 3.2 years, and the average age at the time of fixation was 9.4 years. Equinus contractures averaged -34 degrees (34 degrees of plantarflexion) before surgery and +7 degrees (7 degrees of dorsiflexion) after treatment with the Ilizarov fixator. The recurrence rate for all 29 ankles and feet was 69% (20/29). The recurrence rate for equinus contractures was 74% (17/23). The average time to recurrence was 17.3 months. Only short-term follow-up was available on four of the six feet and ankles that did not recur. Deformity correction in burned feet and ankles is difficult to obtain by any means. The authors recommend using the Ilizarov method to obtain correction of moderate to severe foot and ankle deformities in pediatric burn patients, but the correction obtained is not stable and deformity will likely recur. Parents and patients should anticipate adjunctive nonoperative and operative procedures to keep their feet plantigrade as they grow. In young children, the possibility of having additional surgeries, including repeat Ilizarov procedures, should be discussed. Even older children should expect additional surgeries to prevent recurrent deformities.