MRSA Osteomyelitis Research Articles

Efficacy of Novel Antimicrobial Therapies for Treating Staphylococcus Infections in Wistar Rats

The novel semisynthetic lipoglycopeptide dalbavancin has enhanced antibacterial action against a wide range of gram-positive bacteria. This study was conducted to evaluate the efficacy of dalbavancin in treating Staphylococcus Infections in Wistar Rats. Anaesthetized wistar rats had a Kirschner-wire and a clinical MRSA isolate placed into their proximal tibia. Twenty animals were given dalbavancin (20 mg/kg loading dose) throughout the course of four weeks after infection, or they were left untreated. Microbiological analysis was performed on tibial bones and Kirschner-wires twenty-four hours after the last treatment dosage. As opposed to control group, dalbavancin treated group showed improvement in quantitative bacterial cultures of osseous tissue. After four weeks of treatment with dalbavancin, there was no sign of an induced glycopeptide-/lipoglycopeptide-resistant strain. In conclusion, in a rat study, dalbavancin effectively treated experimental implant-related MRSA osteomyelitis. The therapeutic effectiveness of dalbavancin in treating S. aureus infections needs more investigation; ideally, it should be studied in conjunction with biofilm active medicines.

Evidence of bisphosphonate-conjugated sitafloxacin eradication of established methicillin-resistant S. aureus infection with osseointegration in murine models of implant-associated osteomyelitis

Eradication of MRSA osteomyelitis requires elimination of distinct biofilms. To overcome this, we developed bisphosphonate-conjugated sitafloxacin (BCS, BV600072) and hydroxybisphosphonate-conjugate sitafloxacin (HBCS, BV63072), which achieve “target-and-release” drug delivery proximal to the bone infection and have prophylactic efficacy against MRSA static biofilm in vitro and in vivo. Here we evaluated their therapeutic efficacy in a murine 1-stage exchange femoral plate model with bioluminescent MRSA (USA300LAC::lux). Osteomyelitis was confirmed by CFU on the explants and longitudinal bioluminescent imaging (BLI) after debridement and implant exchange surgery on day 7, and mice were randomized into seven groups: 1) Baseline (harvested at day 7, no treatment); 2) HPBP (bisphosphonate control for BCS) + vancomycin; 3) HPHBP (hydroxybisphosphonate control for HBCS) + vancomycin; 4) vancomycin; 5) sitafloxacin; 6) BCS + vancomycin; and 7) HBCS + vancomycin. BLI confirmed infection persisted in all groups except for mice treated with BCS or HBCS + vancomycin. Radiology revealed catastrophic femur fractures in all groups except mice treated with BCS or HBCS + vancomycin, which also displayed decreases in peri-implant bone loss, osteoclast numbers, and biofilm. To confirm this, we assessed the efficacy of vancomycin, sitafloxacin, and HBCS monotherapy in a transtibial implant model. The results showed complete lack of vancomycin efficacy while all mice treated with HBCS had evidence of infection control, and some had evidence of osseous integrated septic implants, suggestive of biofilm eradication. Taken together these studies demonstrate that HBCS adjuvant with standard of care debridement and vancomycin therapy has the potential to eradicate MRSA osteomyelitis.

Vancomycin-Loaded, Nanohydroxyapatite-Based Scaffold for Osteomyelitis Treatment: In Vivo Rabbit Toxicological Tests and In Vivo Efficacy Tests in a Sheep Model

The treatment for osteomyelitis consists of surgical debridement, filling of the dead space, soft tissue coverage, and intravenous administration of antimicrobial (AM) agents for long periods. Biomaterials for local delivery of AM agents, while providing controllable antibiotic release rates and simultaneously acting as a bone scaffold, may be a valuable alternative; thus, avoiding systemic AM side effects. V-HEPHAPC is a heparinized nanohydroxyapatite (nHA)/collagen biocomposite loaded with vancomycin that has been previously studied and tested in vitro. It enables a vancomycin-releasing profile with an intense initial burst, followed by a sustained release with concentrations above the Minimum Inhibitory Concentration (MIC) for MRSA. In vitro results have also shown that cellular viability is not compromised, suggesting that V-HEPHAPC granules may be a promising alternative device for the treatment of osteomyelitis. In the present study, V-HEPHAPC (HEPHAPC with vancomycin) granules were used as a vancomycin carrier to treat MRSA osteomyelitis. First, in vivo Good Laboratory Practice (GLP) toxicological tests were performed in a rabbit model, assuring that HEPHAPC and V-HEPHAPC have no relevant side effects. Second, V-HEPHAPC proved to be an efficient drug carrier and bone substitute to control MRSA infection and simultaneously reconstruct the bone cavity in a sheep model.

Abstract 15603: Simultaneous Suction Debulking of a 3 Cm Lead Vegetation in the Right Ventricle During Extraction

A 49-year-old male with a history of NICM EF 25% with dual-chamber AICD, lupus with nonbacterial endocarditis of aortic valve, IVC filter for recurrent DVT/PE presented with septic shock due to MRSA osteomyelitis and bacteremia. TTE showed 1.8 cm vegetation. The patient had idiopathic thrombocytopenic purpura, for which IVIG was administered. To avoid obligatory systemic exposure to heparin in the setting of ITP with a larger evacuation system and crossing the IVC filter with a large bore cannula, it was decided to proceed with Penumbra evacuation of lead vegetation with simultaneous laser extraction. A short 16F sheath was inserted through the right femoral vein for the procedure. A12F Medtronic Cryo Flex sheath was advanced through the IVC filter under fluoroscopy to provide steerability in the right atrium. TEE-guided Flex sheath positioned abutting the mass/vegetation. Suction only partially retrieved the mass. RA lead was removed using mechanical extraction tools via the left chest pocket. On repeat TEE evaluation, the mass/vegetation was 3 cm on the RV lead. Since we could not aspirate the mass, we used the extraction tools to peel the mass off the lead while providing simultaneous negative suction through the Penumbra cannula. The lead was successfully extracted. TEE showed no residual mass, no significant change in tricuspid regurgitation and no pericardial effusion. Mass biopsy showed calcified blood clots. The patient was discharged on IV antibiotics. Discussion: Most cases to date report using larger systems like AngioVac for extracting larger vegetations/masses with lead extraction. Aspiration tools have been shown to extract malleable masses with lesser procedural-related morbidity. Peeling and aspiration can be used concurrently to remove these masses without significant blood loss, downstream sheading and the need for systemic anticoagulation. Further technique development can benefit in removing under such challenging scenarios.

DAPTOMYCIN-INDUCED EOSINOPHILIC PNEUMONITIS

DAPTOMYCIN-INDUCED EOSINOPHILIC PNEUMONITIS

Thigh Pain In A Football Player

HISTORY: 15 year old football player presenting with left thigh pain for 2 weeks. No acute injury. Pain first noticed with running. Pain is sharp, rated 8/10 at rest. Despite relative rest, no improvement in symptoms; symptoms now present at rest. Does have nighttime pain. Denies radicular symptoms, fever, recent infection, weight loss. PHYSICAL EXAMINATION: MSK: Left Lower Extremity-Inspection: No swelling, deformity, ecchymosis. Antalgic gait. -Palpation: Tenderness over length of rectus femoris. There is no tenderness over the knee, hip, tibia, fibula. -Range of motion: Limited exam due to pain. -Neurovascular: Strength is 4+/5 in flexion. Distally neurovascularly intact with brisk pulses, 2 second capillary refill, and sensation intact to light touch. DIFFERENTIAL DIAGNOSIS: 1. Ewing Sarcoma 2. Osteosarcoma 3. Osteomyelitis 4. Langerhans Cell Histiocytosis TEST AND RESULTS: XR Left Femur:Findings: Focal area of cortical destruction at medial aspect of proximal tibial diaphysis. Adjacent cortex abnormal. Corresponding periosteal reaction, hyperdense soft tissue mass. No pathologic fracture. Impression:Aggressive lesion of proximal femoral diaphysis. Further evaluation with contrast-enhanced MRI recommended. Labs: CRP 2.9- > 8.9-> > 0.1, ESR 117- > 130-> > 2, WBC 8.9, Hgb/Hct 14/41.6, Plt 407CXR: negativeMRI Left Lower Extremity with/without contrast:Impression:1. Aggressive marrow replacing lesion of left femoral diaphysis with anterior projecting soft tissue component. Differential includes Ewing's sarcoma versus osteosarcoma. 2. No additional lower extremity osseous lesion or adenopathy identified. LEFT FEMUR BIOPSY:SPECIMEN: Fragments of reactive bone with mixed inflammation, compatible with osteomyelitis. REPEAT LEFT FEMUR BIOPSY: I&D; obtained additional tissue to r/o malignancy.Specimen: Findings consistent with acute and chronic osteomyelitis. No features of malignancy seen. FINAL/WORKING DIAGNOSIS: Acute on Chronic MRSA Osteomyelitis TREATMENT& OUTCOMES: 1. Admission for IV antibiotics. Febrile on admission; fever curve improved. 2. ID: Oral Antibiotics x 6 weeks. Improving pain, downtrending inflammatory markers until wnl. 3. Ortho: Toe Touch Weightbearing x 6 weeks - > PWB - > WBAT. Completed PT. Cleared for high impact/contact activities.

Reactivation of Dormant Tibial Methicillin- Resistant Staphylococcus aureus Osteomyelitis after 17 Years: A Case Report and Literature Review

Introduction: Staphylococcus aureus is the most common cause of osteomyelitis with significant morbidity and mortality outcomes. Methicillin-susceptible Staphylococcus aureus (MRSA) osteomyelitis reactivation years after the primary episode are a well-known phenomenon. However, there are few case reports documenting dormant MRSA osteomyelitis recurrence years later. Our case report of dormant MRSA tibial osteomyelitis reactivation after 17-years, represents one of the longest documented recurrence intervals from initial bout of MRSA, as well as, the diagnostic and therapeutic challenges involved. Case report: A 55-year-old male reports suffering a Gustilo & Anderson grade 1 open left tibial plafond fracture in 2004 that was managed with wound debridement and Taylor Spatial Frame. Initial management was with debridement and primary closure of the wound and application of a Taylor spatial frame (TSF) as definitive management of the fracture. One month following application of the frame, the patient reports he suffered a pin site infection. This was developed into MRSA osteomyelitis. The wound underwent surgical debridement and once the fracture was consolidated enough at three months, removal of external frame and intramedullary reaming and irrigation was performed. No further soft tissue coverage was required. The patient was treated with a prolonged course of intravenous vancomycin, followed by oral clindamycin. Since this episode, the patient has been asymptomatic and denied any further hospitalisations with return to full function without limitations. The patient does not report any recurrent wounds, discharge, sinus or pain. Seventeen years later, after a closed to the knee, the patient present febrile with knee pain. He was found to have MRSA tibial osteomyelitis, predominantly within the proximal tibia. This was treated with targeted surgical debridement, local antibiotics via an antibiotic impregnated cement nail and prolonged antibiotics. The patient has remained asymptomatic with apparent resolution of infection 6-months post treatment. Conclusion: Our case report represents one of the longest document recurrence intervals of MRSA. Patients with MRSA osteomyelitis should have appropriate treatment and follow-up with orthopaedic surgeons and infectious disease physicians to monitor disease progression and to ensure resolution of the infection.

In vivo evaluation of temperature-responsive antimicrobial-loaded PNIPAAm hydrogels for prevention of surgical site infection.

Surgical site infections (SSIs) are a persistent clinical challenge. Local antimicrobial delivery may reduce the risk of SSI by increasing drug concentrations and distribution in vulnerable surgical sites compared to what is achieved using systemic antimicrobial prophylaxis alone. In this work, we describe a comprehensive in vivo evaluation of the safety and efficacy of poly(N-isopropylacrylamide-co-dimethylbutyrolactone acrylamide-co-Jeffamine M-1000 acrylamide) [PNDJ], an injectable temperature-responsive hydrogel carrier for antimicrobial delivery in surgical sites. Biodistribution data indicate that PNDJ is primarily cleared via the liver and kidneys following drug delivery. Antimicrobial-loaded PNDJ was generally well-tolerated locally and systemically when applied in bone, muscle, articulating joints, and intraperitoneal space, although mild renal toxicity consistent with the released antimicrobials was identified at high doses in rats. Dosing of PNDJ at bone-implant interfaces did not affect normal tissue healing and function of orthopedic implants in a transcortical plug model in rabbits and in canine total hip arthroplasty. Finally, PNDJ was effective at preventing recurrence of implant-associated MSSA and MRSA osteomyelitis in rabbits, showing a trend toward outperforming commercially available antimicrobial-loaded bone cement and systemic antimicrobial administration. These studies indicate that antimicrobial-loaded PNDJ hydrogels are well-tolerated and could reduce incidence of SSI in a variety of surgical procedures.

Humanized Mice Exhibit Exacerbated Abscess Formation and Osteolysis During the Establishment of Implant-Associated Staphylococcus aureus Osteomyelitis.

Staphylococcus aureus is the predominant pathogen causing osteomyelitis. Unfortunately, no immunotherapy exists to treat these very challenging and costly infections despite decades of research, and numerous vaccine failures in clinical trials. This lack of success can partially be attributed to an overreliance on murine models where the immune correlates of protection often diverge from that of humans. Moreover, S. aureus secretes numerous immunotoxins with unique tropism to human leukocytes, which compromises the targeting of immune cells in murine models. To study the response of human immune cells during chronic S. aureus bone infections, we engrafted non-obese diabetic (NOD)–scid IL2Rγnull (NSG) mice with human hematopoietic stem cells (huNSG) and analyzed protection in an established model of implant-associated osteomyelitis. The results showed that huNSG mice have increases in weight loss, osteolysis, bacterial dissemination to internal organs, and numbers of Staphylococcal abscess communities (SACs), during the establishment of implant-associated MRSA osteomyelitis compared to NSG controls (p < 0.05). Flow cytometry and immunohistochemistry demonstrated greater human T cell numbers in infected versus uninfected huNSG mice (p < 0.05), and that T-bet+ human T cells clustered around the SACs, suggesting S. aureus-mediated activation and proliferation of human T cells in the infected bone. Collectively, these proof-of-concept studies underscore the utility of huNSG mice for studying an aggressive form of S. aureus osteomyelitis, which is more akin to that seen in humans. We have also established an experimental system to investigate the contribution of specific human T cells in controlling S. aureus infection and dissemination.

The Antistaphylococcal Activity of Amoxicillin/Clavulanic Acid, Gentamicin, and 1,8-Cineole Alone or in Combination and Their Efficacy through a Rabbit Model of Methicillin-Resistant Staphylococcus aureus Osteomyelitis.

The aim of this research paper is to test the antistaphylococcal effect of 1,8-cineole, amoxicillin/clavulanic acid (AMC), and gentamicin, either separately or in combination against three Staphylococcus aureus strains isolated from patients suffering from osteomyelitis. This activity was tested in vitro by using the microdilution method and the checkerboard assay. The efficacy of these three antibacterial agents was then tested in vivo by using an experimental model of methicillin-resistant S. aureus osteomyelitis in rabbits. This efficacy was assessed after four days of treatment by counting the number of bacteria in the bone marrow. The obtained results in vitro showed that the combination of the AMC with gentamicin did not induce a synergistic effect, whereas the combination of the two antibiotics with 1,8-cineole did. This effect is stronger when AMC is combined with 1,8-cineole as a total synergistic effect was obtained on the three strains used (FIC ≤ 0.5). In vivo, a significant reduction was noted in the number of colonies in the bone marrow when rabbits were treated with AMC associated with either 1,8-cineole or gentamicin compared to rabbits treated with AMC, gentamicin, or 1,8-cineole alone. These results demonstrated that 1,8-cineole showed a synergistic effect in combination with both AMC and gentamicin, which offer possibilities for reducing antibiotic usage. Also, the AMC associated with 1,8-cineole could be used to treat MRSA osteomyelitis.

HISTOPATHOLOGICAL EVALUATION OF EFFECT OF LASER VERSUS FOSFOMYSINE IN TREATMENT OF OSTEOMYELITIS INDUCED BY METHICILLIN-RESISTANT

Introduction: Fosfomycin has been shown highly effective in the treatment of experimental MRSA osteomyelitis. Laser therapy appeared to be a promising alternative technique to pharmacological agents in the treatment of osteomyelitis. Consequently, this study aimed to determine the effects of fosomycin and laser in the treatment of induced osteomylitis by MRSA in rabbits.Material and methods: Localized osteomyelitis was induced in rabbits by percutaneous injection of 0.1 ml of 108 cfu of MRSA clinical isolate into the intramedullary cavity of tibia. After two weeks, tibial osteomyelitis was confirmed radiographically. Rabbits were divided into three groups (each group contained 10 rabbits): untreated controls group, group treated with fosfomycin 75 mg/kg subcutaneously every 24 h and group treated with Diode laser 940 nm, three times weekly. After 14 days of treatment, rabbits were left untreated for 24 hours then euthanized and the tibias harvested. evaluation of treatment was done by measurement of bone density radiologically, Histopathological examination and each tibia were cultured for bacterial counts determinationResults: Bacterial cultures from bones were positive for MRSA in 8 out of 10 (80%) rabbits in the control group, in 9 out of 10 (90%) rabbits in the fosfomycin and laser treated group . Laser group showed the highest bone density among the studied groups. No significant difference was found in the bone cultures and bone density between the three groups; P value 0.302 and 0.157 respectively

A case of using the pedicled gastrocnemius muscle flap for MRSA osteomyelitis

A case of using the pedicled gastrocnemius muscle flap for MRSA osteomyelitis

Local gentamicin administration suppressed MRSA osteomyelitis. The evidence of high dose aminoglycoside is effective for multi-drug resistant bacteria

Local gentamicin administration suppressed MRSA osteomyelitis. The evidence of high dose aminoglycoside is effective for multi-drug resistant bacteria

Delayed Onset Acute Liver Failure in Vancomycin-Induced DRESS Syndrome After Prednisone Taper

A 26-year-old male with bilateral hip MRSA osteomyelitis being treated with Vancomycin was admitted to the hospital for fever and chest pain. He was found to have a troponin I level of 1.0 ng/mL, serum creatinine of 5.9 mg/dL and a random Vancomycin level of 117 mcg/mL. The patient's liver function tests were also elevated with total bilirubin 1.7μmol/L, AST 113 U/L, ALT 142 U/L and alkaline phosphatase 262 U/L. WBC count was 15 K/UL with 11% eosinophils. Urgent hemodialysis for Vancomycin induced acute renal failure was initiated and alternative antibiotics for osteomyelitis were initiated. Transthoracic echocardiogram revealed an ejection fraction of 55%. On day two of hospitalization the patient developed a diffuse maculopapular rash. A 10-day course of oral prednisone for drug-induced rash was initiated with full resolution of symptoms. Liver and renal function tests improved to reference range. Two days following completion of systemic steroid therapy the patient developed acute onset liver failure with studies revealing an AST 3,498 U/L, ALT 1171 U/L and INR 3.6. There was no hemodynamic compromise and abdominal ultrasound was unrevealing. The patient was emergently transferred to a liver transplant center for further management of acute liver failure. Repeat echocardiogram following transfer revealed an ejection fraction of 20%. The patient met clinical criteria for Drug Reaction with Eosinophila and Systemic Symptoms (DRESS) syndrome on the basis of extensive rash, recent peripheral eosinophilia and hepatitis with involvement of the kidneys and heart. Given the time course, prednisone was masking the underlying processes that eventually lead to development of acute liver failure. The patient survived with normalization of liver function tests following continued avoidance of Vancomycin and steroids. In review of literature, DRESS syndrome carries a mortality rate of 10-20%, with most fatalities caused by liver failure. Vancomycin is a frequently utilized antimicrobial that has emerged as increasingly associated with the development of DRESS syndrome and acute liver failure. This case demonstrates a rare presentation where acute liver failure was of delayed onset from recent steroid therapy. In the right clinical setting, a high index of suspicion is necessary for the recognition of this clinical entity as avoidance of inciting medication and steroid therapy can be life saving.

Treatment of tibial nonunion with MRSA osteomyelitis after open fracture

Treatment of tibial nonunion with MRSA osteomyelitis after open fracture

Wound Healing Society 2015 update on guidelines for pressure ulcers.

Wound Healing Society 2015 update on guidelines for pressure ulcers.

Treatment of large bilateral femur and tibial bone defects due to MRSA osteomyelitis using antibiotics impregnated allogenic bone graft; A case report

Treatment of large bilateral femur and tibial bone defects due to MRSA osteomyelitis using antibiotics impregnated allogenic bone graft; A case report

A Case of the MRSA Osteomyelitis of the Olecranon Treated by Calcium Phosphate Cement with Vancomycin

A Case of the MRSA Osteomyelitis of the Olecranon Treated by Calcium Phosphate Cement with Vancomycin

Clinical and haematological predictors of acute hematogenous Methicillin Resistant Staphylococcus aureus (MRSA) osteomyelitis & septic arthritis

IntroductionIn the present study, we observed differences in the clinical and haematological parameters in patients of MRSA and non MRSA acute osteoarticular infection. MethodologyFor the patients of acute haematogenous osteomyelitis/septic arthritis, clinical features, haematological parameters and blood & aspirate cultures were recorded. ResultsOf 81 patients enrolled in the study, 61 were culture positive (22% MRSA). Statistically significant difference was found only in CRP (P < 0.001). ROC curve analysis shows that CRP levels of >13.9 mg/L, MRSA bone and joint infection could be predicted with 92.9% sensitivity and 79.1% specificity (AUC = 89.1). ConclusionEstimation of serum CRP levels at the time of presentation can aid in distinguishing MRSA osteomyelitis from non MRSA one.

High-dose, short-interval daptomycin regimen was safe and well tolerated in three patients with chronic renal failure

BackgroundThe recommended daptomycin dosage is 4 or 6 mg/kg/day for the treatment of complicated skin and soft tissue infections or for Staphylococcus aureus bacteremia, endocarditis, and osteomyelitis. Every other day administration is usually recommended for patients with mild to moderate renal impairment. Higher doses (>6 mg/kg/day) have been explored as a possible alternative. Daptomycin is considered a safe anti-methicillin-resistant S. aureus (MRSA) drug, although renal dysfunction may be worsened. In this paper we report on three patients with chronic renal failure who received a higher dose of daptomycin daily for successful treatment for MRSA bacteremia, MRSA osteomyelitis, and methicillin-resistant S. epidermidis (MRSE) endocarditis.ResultsPrevious administration of other drugs, including vancomycin, teicoplanin, and linezolid, had failed. In spite of daily treatment with daptomycin instead of the recommended alternate day regimen, adverse effects, such as elevation of creatinine and creatine phosphokinase, did not occur.ConclusionThese experiences suggest that administration of high-dose/short-interval daptomycin can be efficient and safe even in the setting of renal dysfunction, and should be considered for the treatment of severe MRSA/MRSE infections in these patients.