Daptomycin for the Treatment of Severe Necrotizing Soft-Tissue Infections

• Status: Completed
• Trial end date: 2008-05-01
• Target enrollment: 0
• Participant gender: All

Summary

Daptomycin is a new antimicrobial agent which has activity against resistant Gram positive cocci including MRSA. The phase 3 clinical trials for skin and soft tissue infections (SSTI) with Staphylococci and Streptococci have already demonstrated that daptomycin was noninferior to the comparator agent (vancomycin or beta-lactams) (10). Although this clinical trial did not include any patients with clostridial infection, there is in vitro data to support the activity of daptomycin against a variety of clostridial species(11) ( Clostridium perfringens) Therefore, for this trial we will include patients with clostridial infections with this species. Additionally, the patients in the SSTI study were not as ill as the proposed study population. Therefore for treatment of such severe infections, we would like to use a higher dose of daptomycin (6mg/kg/dose). The reasons for using a higher dose of daptomycin in this subgroup are as follows:

1. Patients who are severely ill have an increased volume of distribution; and therefore have a lower serum concentration of daptomycin. These patients might require a higher dose of daptomycin to achieve the desired serum concentration.

2. One of the organisms involved in necrotizing fasciitis is enterococcus (both-fecalis and faecium). E.faecium has higher MICs to daptomycin and would require a higher dose of the drug to achieve adequate free (unbound) serum concentration of the drug.

3. Both necrotizing fasciitis and endocarditis are serious deep seated infections. The clinical trials for endocarditis are using 6mg/kg/dose of daptomycin.

Therefore for optimal treatment of necrotizing fasciitis, it is justifiable that we should use the higher dose of daptomycin.

Objective:

To evaluate the clinical and microbiological efficacy and safety of higher dose daptomycin therapy in the treatment of patients with severe necrotizing skin and soft tissue infections.

Type of Study:

Open label, single center study.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Maryland; University of Maryland, Baltimore
• Collaborator: Cubist Pharmaceuticals LLC
• Treatments: Daptomycin

Criteria

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.