Ceftaroline in the Treatment of Bone and Joint Infections

Study Overview
=================
Brief Summary
-----------------
This is a study to evaluate the efficacy of Ceftaroline in the treatment of bone and joint infections.

Detailed Description
-----------------
Study evaluates the efficacy of Ceftaroline 600mg IV every 8 hours for the treatment of acute osteomyelitis and/or infected joints.

Official Title
-----------------
Ceftaroline in the Treatment of Bone and Joint Infections

Conditions
-----------------
Osteomyelitis, Joint Infections

Intervention / Treatment
-----------------
* Drug: Ceftaroline


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults > 18 years of age with the following osteoarticular infections: Infected prosthetic knee or hip (first or second episode) with 2 stage procedure planned. Criteria for infected joint: Sinus tract which communicates with the joint Preoperative diagnosis by diagnostic, culture positive arthrocentesis Intraoperative diagnosis-evidence of purulence/inflammation is seen by the surgeon and/or the pathologist, and at least 2 intraoperative samples grow the same organism (only 1 needed if S. aureus) OR Acute osteomyelitis of an extremity Criteria for acute osteomyelitis (all 4 needed) Onset less than 4 weeks prior to evaluation Radiographic (plain, MRI, TC) evidence of osteomyelitis Positive culture from bone or blood culture with organism known to cause osteomyelitis Orthopedic consultant must concur with diagnosis. PLUS: Positive bone/joint or blood culture for an organism known to cause osteomyelitis which is Ceftaroline susceptible Exclusion criteria: Immunocompromised hosts: AIDS/HIV patients Cancer requiring ongoing chemotherapy or radiation therapy steroid on an ongoing basis. Any condition requiring > 20 mg prednisone or equivalent TNF (tumor necrosing factor) inhibitor use (ongoing) Organ transplant list Diabetic foot infections Osteomyelitis in association with decubitus ulcers Vertebral osteomyelitis/spinal epidural abscess Septic bursitis Gonococcal arthritis Ceftaroline nonsusceptible organisms isolated from bone, joint or blood. Infected external fixation devices Calculated creatinine clearance < 50 mL/min at baseline History of severe penicillin/B lactam allergy (ID to evaluate) Intravenous drug use - lifetime exclusion Patients with a nail puncture wound to foot Patients at high risk for MDR (multidrug resistant) Gram negative organisms Please note the use of antibiotic containing cement is not exclusion, as it represents standard of care in some of the infections to be studied

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acute Osteomyelitis - Non MRSA<br>For treatment of Acute osteomyelitis (< 6 months duration) Non MRSA isolate- Ceftaroline 600 MG (milligram) IV (intra-venous) every 8 hours for 6 weeks. | Drug: Ceftaroline<br>* The duration of treatment will vary based on type of infection (acute osteomyelitis or joint infection) and if MRSA positive or negative.<br>* Other names: azabicyclo[4.2.0]oct-2-ene-2-carboxylate;|
| Experimental: Acute osteomyelitis MRSA isolate<br>For treatment of Acute osteomyelitis (< 6 months duration) MRSA isolate- Ceftaroline 600 MG IV every 8 hours for 8 weeks. | Drug: Ceftaroline<br>* The duration of treatment will vary based on type of infection (acute osteomyelitis or joint infection) and if MRSA positive or negative.<br>* Other names: azabicyclo[4.2.0]oct-2-ene-2-carboxylate;|
| Experimental: Prosthetic joint infection<br>For treatment of prosthetic joint infection Ceftaroline 600 mg IV every 8 hours for 6 weeks. | Drug: Ceftaroline<br>* The duration of treatment will vary based on type of infection (acute osteomyelitis or joint infection) and if MRSA positive or negative.<br>* Other names: azabicyclo[4.2.0]oct-2-ene-2-carboxylate;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained clinical remission from the treated osteoarticular infection | Sustained clinical remission is defined by the absence of either clinical or microbiological evidence of failure at 1 year after study drug completion, in patients who complete the protocol's antibiotic regimen(s) and did not require subsequent antibiotics for their osteoarticular infection beyond the protocol prescribed regimen. | 1 year after study drug completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Initial clinical success from the treated osteoarticular infection | Initial clinical success will be measured by the agreement of the Infectious disease consultant and Orthopedic surgeon that the patient has had a positive response to therapy. Success will be measured by decrease of CRP (C reactive protein) by 50% from baseline if initially elevated, no evidence of drainage, sinus tract formation or infection related bone instability. Follow up cultures, if available are negative for originally isolated organism. In patients with prothetic joints no new warmth, tenderness or inflammation. | 30 days after conclusion of study antibiotic | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Osteoarticular infections, Osteomyelitis, Joint infections, MRSA (Methicillin- Resistant Staphylococcus Aureus), MSSA (Methicillin- Susceptible Staphylococcus Aureus)