Efficacy of Oral Antibiotic Therapy Compared to Intravenous Antibiotic Therapy for Osteomyelitis

Phase 2

Terminated

Conditions: Osteomyelitis

Interventions: Drug: Intravenous Antibacterial Agent
Drug: Oral Antibacterial Agent

Registration Number: NCT02168816

Lead Sponsor: Loyola University

Brief Summary: The Infectious Diseases Society of America (IDSA) 2012 guidelines for the diagnosis and treatment of diabetic foot infections state that for the treatment of diabetic foot osteomyelitis "No data support the superiority of any specific antibiotic agent or treatment strategy, route, or duration of therapy." Traditionally, osteomyelitis has been treated with a long course of intravenous antibiotics, generally six weeks. Oral antibiotics with high bioavailability and adequate bone penetration have been shown in published studies to be effective for the treatment of osteomyelitis.

The investigators propose to conduct a prospective, single-center, randomized, open trial at Loyola University Medical Center (LUMC) comparing the efficacy of oral antibiotic therapy to intravenous (IV) antibiotic therapy for the treatment of diabetic foot osteomyelitis. The investigators hypothesize that oral antibiotic therapy is equivalent to IV antibiotic therapy. Bone/tissue cultures are obtained for all patients for clinical purposes and are sent to pathology for histologic examination and to the clinical microbiology laboratory for culture and susceptibility. Patients will receive six weeks of IV or oral antibiotic therapy depending upon their randomization group. Primary outcomes at six months clinical follow-up will include: (i) no evidence of bone infection and (ii) resolution of ulcer.

Detailed Description: Currently, available literature is not adequate to determine the best agent, route, or duration of antibiotic therapy for the treatment of chronic osteomyelitis. The standard of therapy has been to treat patients with a parenteral antibiotic for four to six weeks. In a recent literature review by Spellberg et al. it was concluded that oral and parenteral antibiotic therapy have similar cure rates for the treatment of chronic osteomyelitis. Oral antibiotic therapy is associated with a lower risk to the patient due to avoiding the need of a central IV line. Additionally, oral therapy costs less than a course of IV antibiotics. Oral antibiotics with high bioavailability and good bone penetration include, fluoroquinolones, linezolid, trimethoprim/sulfamethoxazole (2 tabs bid), clindamycin and metronidazole. These antibiotics have been shown in recent studies to obtain levels in the bone that exceed the minimum inhibitory concentration (MIC) levels of the targeted organisms. According to the IDSA 2012 guidelines for the treatment of diabetic foot infections, the diagnosis of osteomyelitis can be made via plain radiographs or MRI imaging (more sensitive). A bone scan can be considered if an MRI cannot be done. The preferred method of diagnosis is by bone culture and histology. The guidelines also recommend surgical debridement to healthy tissue for diabetic foot infections followed by antibiotic therapy.

The Purpose of this study is to compare the efficacy of oral antibiotic therapy with intravenous antibiotic therapy for the treatment of diabetic foot osteomyelitis following surgical debridement. They hypothesis is that oral antibiotic therapy is equivalent to intravenous antibiotic therapy for the treatment of diabetic foot osteomyelitis.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 30

Inclusion Criteria

18 years of age and older
Diagnosis of Diabetes Mellitus (per past medical history documented in the patient medical record)
Foot osteomyelitis (distal to ankle)
Surgical debridement (in operating room)

Exclusion Criteria

Absolute neutrophil count (ANC) < 500
Pregnant or lactating patients
Patients with organisms resistant to oral therapy
Internal hardware
Definitive amputations (BKA)
Limb ischemia [absent pedal pulses or ankle-brachial index (ABI) < 0.5]

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Midfoot	Intravenous Antibacterial Agent	Individuals with an infection on the midfoot are randomized to an intravenous antibacterial agent or an oral antibacterial agent.
Midfoot	Oral Antibacterial Agent	Individuals with an infection on the midfoot are randomized to an intravenous antibacterial agent or an oral antibacterial agent.
Hindfoot	Intravenous Antibacterial Agent	Individuals with an infection on the hindfoot are randomized to an intravenous antibacterial agent or an oral antibacterial agent.
Hindfoot	Oral Antibacterial Agent	Individuals with an infection on the hindfoot are randomized to an intravenous antibacterial agent or an oral antibacterial agent.
Toe	Intravenous Antibacterial Agent	Individuals with an infection on the toe are randomized to an intravenous antibacterial agent or an oral antibacterial agent.
Toe	Oral Antibacterial Agent	Individuals with an infection on the toe are randomized to an intravenous antibacterial agent or an oral antibacterial agent.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Bone Infection	Six Months	Six months following completion of treatment, the researchers record evidence of bone infection for each participant. A negative diagnosis is made when there is (i) an absence of infection based on clinical examination and (ii) down-trending of inflammatory markers. Otherwise, a positive diagnosis is made.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Ulcer Resolution	Six Months	Six months following completion of treatment, the researchers record whether each participant's ulcer has resolved.