This study will determine the tissue penetration of a broad-spectrum orally bioavailable carbapenem, tebipenem pivoxil hydrobromide (SPR994) (Spero Therapeutics, Inc.), 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.
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 3 to 7 doses of tebipenem pivoxil hydrobromide (300 mg or 600 mg orally every 8 hours depending on renal function). 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 normal saline solution and samples are collected for the 8 hours following 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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
12
Tebipenem 300 mg or 600 mg will be administered orally every 8 hours for total of 3 to 7 doses
Hartford Hospital
Hartford, Connecticut, United States
Tebipenem Pivoxil Hydrobromide Tissue Penetration
The ratio of tebipenem tissue concentrations to blood concentrations following the final tebipenem dose
Time frame: 8 hours
Tebipenem Pivoxil Hydrobromide Area Under the Curve (AUC) in Tissue
The area under the drug concentration-time curve (AUC) in tissue reflects the actual tissue exposure to drug after administration of a dose of the drug and is expressed in mg\*h/L. Venous blood will be obtained via peripheral intravenous catheter immediately before administration of the last dose (pre-dose timepoint), and at 9 time-points post-dose. Dialysate samples of 120μL will be collected in 200µL microvials simultaneously with plasma samples.
Time frame: 8 hours
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