Overview
This is a randomized, unblinded, single-centre study. After eventual surgical debridement
(not amputation), patients will be randomized to receive 1 of 2 targeted antibiotic regimens,
in the ratio 1:1.
For diabetic toe osteomyelitis, the patients will be randomized between a 3 and a 6 week's
arm, for soft tissue infections between 10 and 20 days. The final assessments used in the
primary efficacy analysis will be obtained at the test-of-cure (TOC) visit approximately 60
days after treatment is stopped.
Description
Diabetic foot infections (DFI) are frequent and are associated with a high burden of
morbidity, costs, recurrence risk or new episodes of infections. About two-third of recurrent
DFI may reveal other microorganisms than in the previous period, suggesting new episodes of
infection due to the underlying problem, and/or selection by prior antimicrobial therapy.
Osteomyelitis in the diabetic toe is almost always established by contiguous spread of
infection from a chronic ulcer. It occurs in up to 15% of patients with a diabetic foot ulcer
and about 20% of all DFI (and over half of severe infections) involve bone at presentation.
The severity of a diabetic foot infection is based on the local and systemic signs and
symptoms of infection and has been categorically defined in the Infectious Disease Society of
America guidelines for the "Diagnosis and Treatment of Diabetic Foot Infections" (IDSA
guidelines).
Knowing the potential for poor outcomes, many clinicians have tended to treat DFIs with a
long duration of antibiotic therapy, with many side effects, development and spreading of
antibiotic resistance, and associated costs. Data from recent comparative trials has shown
that 1-2 weeks is sufficient for most soft tissue infections, and 4 to 6 weeks appears
adequate in those with (unresected) infected bone. Retrospective reviews over the past two
decades have demonstrated that about two-thirds of selected patients with diabetic foot
osteomyelitis can achieve remission with antibiotic therapy alone (i.e., without bone
resection). One recent randomized trial found that treatment with only antibiotic therapy
(given for 90 days) gave similar clinical outcomes to treatment with conservative surgery
(removal only of the infected bone) along with just a short course of antibiotic therapy.
Another randomized trial compared a 6-week against 12-week course of antibiotic therapy,
without concomitant surgery, for diabetic foot osteomyelitis and also found similar outcomes.
Likewise, the optimal antibiotic duration for any skin and soft tissue infection is unknown.
According to some databases of University of Geneva Hospitals, among 378 skin and soft tissue
infections in 346, overall cure was achieved in 330 episodes (87%) after a median antibiotic
administration of 15 days. In multivariate Cox regression analysis, duration of antibiotic
therapy (HR 1.0, 95%CI 0.96-1.02) did not influence treatment failure among patients with
positive MRSA carriage.
Our study intends to optimize the duration of antibiotic therapy in DFI; for skin and soft
tissue infections as well as for diabetic toe osteomyelitis that is not amputated.
Eligibility
Inclusion Criteria:
- Age 18
- Diabetes mellitus
- Diabetic Foot Infections
- Surgical intervention to remove all necrotic tissue or tenotomy.
- Osteomyelitis limited to bone contact or cortical lesions in X-ray.
Exclusion Criteria:
- Implanted device.
- More than 96 hours of systemic antibiotic therapy prior to inclusion
- Amputation
- Destructive osteomyelitis
- Concomitant infections requiring more than 14 days of antibiotic therapy.
