Tolerability, Safety, and Efficacy of Tedizolid as Oral Treatment for Bone and Joint Infections

The problem of interest is that doctors are looking for new antibiotic treatments for bone
and joint infections. Treatment for bone and joint infection is not standardized, which
allows a wide range of antibiotic therapy to potentially be given. A type of bacteria called
S. aureus is the most common cause of bone and joint infection. Methicillin resistant S.
aureus (MRSA) is a type of bacteria that is not killed by some antibiotics, and it is
increasingly common in U.S. and non-U.S. medical centers. Trauma-associated bone and joint
infection is also a common problem. Victims of major trauma often suffer bone fractures,
which require temporary or permanent use of metal or other synthetic devices such as
external-fixation pins, plates, and screws. These synthetic devices can also get infected and
cause bone and joint infections.

This problem will be studied by investigating whether an antibiotic called tedizolid is
tolerable, safe and effective to treat bone and joint infections. Tedizolid is a new
FDA-approved antibiotic, and can be given through the bloodstream via an IV or orally in the
form of a pill. Tedizolid has less side effects compared to linezolid and is effective
against types of bacteria like S. aureus. Other research also suggests that the side effects
associated with long-term therapy of older types of antibiotics may not be found with
tedizolid.

This study will advance scientific knowledge of antibiotic treatments for bone and joint
infections. Given the large and increasing burden of disease of bone and joint infection and
the increasing acceptability of oral antibiotics for its management, tedizolid holds promise
as a good option for patients with bone and joint infection. Harbor-UCLA Medical Center is a
large medical center in the County of Los Angeles, the most populous County in the United
States. The Infectious Disease consult service sees many bone and joint infections. Use of
prolonged antibiotics is common in this setting. The investigators believe tedizolid
addresses the unmet need for an oral antibiotic that is well-tolerated and efficacious for
use as a prolonged therapy for bone and joint infection.

Inclusion Criteria:

- Treatment of bone and joint infection in which therapy for Gram positive organisms is
documented or suspected, as determined by the treating physician and treatment of at
least 4 weeks is planned. Bone and joint infection and trauma-associated bone and
joint infection will defined clinically using radiologic (e.g., MRI) and/or surgical
(e.g., intra-operative findings)

- Aged between 18 years and 85 years.

- Plans to treat bone and joint infection in outpatient setting.

- No limited planned course of antibiotics (i.e., no indefinite treatment plans for
chronic suppression). Co-administration of other antibiotics that target other
causative or potentially causative organisms (e.g., fluoroquinolones) is acceptable.

- Able to come to the research clinic for study follow-up visits for the study period.

Exclusion Criteria:

- Planned prolonged hospitalization (> 1 week).

- Pregnancy (all female subjects of childbearing age will be given a pregnancy test
prior to enrollment) or breast feeding. If a women is of childbearing potential, she
must consistently use an acceptable method of contraception (IUD, injectable
contraceptive, birth control patch, OCP, barrier method, abstinence) from baseline
through the course of antibiotics (4-12 weeks). If a male patient's sexual partner is
of childbearing potential, the male patient must acknowledge that they will
consistently use an acceptable method of contraception as defined above from baseline
through the course of antibiotics (4-12 weeks).

- Comorbidities that, in the opinion of the investigator, are uncontrolled (e.g.,
diabetes, hypertension, psychiatric disease).

- Peripheral or optic neuropathy.

- Underlying hematologic cytopenias (e.g., baseline thrombocytopenia, or severe anemia,
or leukopenia) as determined by the following limits from a baseline CBC/CMP obtained
within the past 14 days. Note that if a CBC has not been performed within the past 14
days, a CBC will be performed on the day of enrollment prior to any study drug being
administered to ensure the patient does not meet exclusion criteria. Cytopenias are
defined as:

1. Hemoglobin (Hgb) < 8.0g/dL

2. WBC < 4,000 k/cumm

3. Platelets < 150,000 k/cumm

- Severe hepatic dysfunction as defined by liver function tests (ALT, ALP, AST, total
bilirubin) > 3.0 times the upper limit of normal. as determined by the following
limits from a baseline CMP obtained within the past 7 days. If a CMP has not been
performed within the past 7 days, baseline levels may be used from a CMP performed
within the past 2 months as long as another CMP is performed on the day of enrollment
and the subject's levels are within the following limits.

- Hypersensitivity to tedizolid or other oxazolidinone-class antibiotics or similar
compounds.

- Ongoing antibiotic-associated colitis.

- A diet high in tyramine-containing foods such as pickled or fermented meats and
cheeses, wine, or avocados per investigator discretion.

- Concurrent use of sodium picosulfate (brand names: Sodipic Picofast, Laxoberal,
Laxoberon, Purg-Odan, Picolax, Guttalax, Namilax, Pico-Salax and Prepopik).

- Previous participation in the study.

- Use of tedizolid for any condition in the past 3 months.

- Any other medical, psychological, or social condition that, in the opinion of the
Investigator, would prevent the patient from fully participating in the study or would
represent a concern for study compliance or constitute a safety concern to the
patient.