Daptomycin for the Treatment of Severe Necrotizing Soft-Tissue Infections

Inclusion/Exclusion Criteria

Inclusion criteria :

1. Read and sign the consent form. If patient is unable to sign, the consent will be obtained from a legally authorized representative.
2. Male or female > 18 years of age
3. If female of child bearing potential, negative pregnancy test
4. Surgical diagnosis of severe necrotizing fasciitis, severe necrotizing skin and soft tissue infections (e.g. Fournier's gangrene)

5. A) At least three of the following clinical signs and symptoms of local infection should be present:

   • pain out of proportion to clinical findings
   • tenderness to palpation
   • swelling
   • erythema
   • induration
   • pus formation

   B) At least 1 of the two systemic conditions should be present:

   • Elevated temps.[100.4] or reduced temps. [<96]
   • WBC counts > 12.00/cu.mm

6. Positive gram stain or wound culture obtained within 3 calendar days prior to the first dose of Daptomycin.

   • positive gram stain would include gram positive cocci or gram positive rods
   • positive wound culture would include growth of staphylococci and/or streptococci and/or enterococcus and/or clostridia (Clostridium perfringens ).
7. If the patient is on HMG-CoA reductase inhibitors then these agents will be discontinued at the study initiation and resumed after discontinuation of daptomycin.

Exclusion criteria:

1. If female, pregnant, or lactating and breast-feeding
2. Previous antibiotic therapy exceeding 72 hours duration, unless patient is worsening clinically or has gram positive pathogens cultured from wound that are resistant to current antibiotic therapy.
3. Sites of infection other than skin i.e., osteomyelitis, meningitis, bacteremia, etc.
4. Known to be allergic or intolerant to study medications
5. Expected to die in < 5 days
6. Significant renal impairment - creatinine clearance < 30m/min
7. A primary diagnosis of uncomplicated skin infections, such as cellulitis, minor post-op. wound infection, small decubitus ulcer etc.
8. Patients with baseline CPKs equal to or greater than 10 times upper limit of normal without myopathy and CPK elevation of greater than or equal to 5 times upper limit of normal with symptoms of myopathy
9. Documentation of myoglobinuria at onset of the study. The study will be conducted over a one-year period. We are anticipating enrollment of 25 patients on the study.

Criteria for withdrawal from the study:

1. If the patient complains of myalgias and has high CPK values as specified below.
2. If the patient develops myoglobinuria, CPKs equal to or 10 times upper limit of normal without myopathy and CPK elevation of greater than 5 times upper limit of normal with symptoms of myopathy.