Tissue Penetration of Ceftolozane/Tazobactam in Diabetic Patients With Lower Limb Infections
Condition: Diabetes; Wound Infection; Healthy Volunteers
MeSH terms: Infections; Wound Infection
Intervention: Ceftolozane/tazobactam; Microdialysis Catheter Insertion
Intervention description: 3 or more doses of ceftolozane/tazobactam intravenously administered over 60 minutes every 8 hours; A 20 kila-Dalton microdialysis probe (63 MD catheter; MDialysis Inc., N. Chelmsford, MA) will be inserted into the subcutaneous tissue at the margin of the wound (patient group) or in the thigh tissue (healthy volunteers). The probe will be left in place for the final dose and all tissue sampling procedures thereafter. This probe is perfused with a physiologic solution to collect interstitial fluid samples. The probe will then be removed after completion of sample collection.
Intervention MeSH terms: Tazobactam; Ceftolozane; Ceftolozane, tazobactam drug combination
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This study will determine the tissue penetration of ceftolozane/tazobactam (Zerbaxa, Merck &
      Co.), a novel β-lactam/β-lactamase combination antibiotic, into the extracellular,
      interstitial fluid of soft tissue in diabetic patients with lower limb wound infections.
      Penetration will be compared with a group of healthy volunteer control participants.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Experimental: Type 1 or Type 2 diabetes and a mild to moderate (Grade 2 or 3) wound
             infection of the lower limb

          -  Active Comparator: Healthy Adult Volunteer

        Exclusion Criteria:

        All Participants:

          -  Less than 18 years of age

          -  History of hypersensitivity to ceftolozane/tazobactam, piperacillin/tazobactam, or any
             β-lactam antibiotic

          -  History of hypersensitivity to lidocaine or lidocaine derivatives

          -  Females who are pregnant or breastfeeding

          -  Concomitant receipt of any β-lactams antibiotic

          -  Concomitant receipt of probenecid

          -  Reduced kidney function defined as creatinine clearance of ≤ 50 mL/min

          -  Any other reason felt by the investigator to potentially affect the outcomes of the
             study

        Experimental Group Only:

          -  No palpable pedal pulses present

          -  Participants likely to require multiple surgical interventions during the study
             period, which therefore could affect placement of the microdialysis catheter

        Active Comparator Group Only:

          -  Positive urine drug screen (cocaine, tetrahydrocannabinol, opiates, benzodiazepines,
             and amphetamines)

          -  History of regular alcohol consumption exceeding 7 drinks/week for females or 14
             drinks/week for men (1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of
             hard liquor) within 6 months of screening.

          -  Use of tobacco- or nicotine-containing products in excess of the equivalence of 5
             cigarettes per day.

          -  Use of prescription or nonprescription drugs, vitamins, or dietary supplements within
             7 days or 5 half-lives (whichever is longer) prior to the first dose of study
             medication, with the exception of acetaminophen at doses of ≤ 1 g/day. Herbal
             supplements, hormonal methods of contraception (including oral and transdermal
             contraceptives, injectable progesterone, progestin subdermal implants,
             progesterone-releasing intrauterine devices (IUDs), postcoital contraceptive methods),
             and hormone replacement therapy must be discontinued at least 14 days prior to the
             first dose of study medication. Depo-Provera® must be discontinued at least 6 months
             prior to the first dose of study medication.