Tissue Penetration of Ceftolozane/Tazobactam in Diabetic Patients With Lower Limb Infections

This study will enroll 10 patients with diabetes who are admitted with a lower limb wound
infection and 6 healthy volunteer control participants. The study will take place in an
inpatient unit at Hartford Hospital for all patients and in the Clinical Research Center at
Hartford Hospital for all healthy volunteers. All participants will receive at least 3 doses
of ceftolozane/tazobactam 1.5g every 8 hours. A microdialysis probe (Mdialysis Inc., N.
Chelmsford MA) will be inserted into the subcutaneous soft tissue near the margin of the
wound (patients) or in the thigh (healthy volunteers). The microdialysis probe is perfused
with lactated Ringer's solution and samples are collected each hour for 8 hours after the
final dose. A peripheral intravenous catheter will be inserted into an arm vein to collect
blood samples simultaneously with microdialysis samples. Concentrations in tissue are
compared with blood to determine percent penetration.

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.