Tissue Penetration of Ceftolozane/Tazobactam in Diabetic Patients With Lower Limb Infections
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Ceftolozane Tissue Penetration
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Diabetic Wound Infection
Participants with a documented history of Type 1 or Type 2 diabetes and a mild to moderate (Grade 2 or 3) wound infection of the lower limb will receive at least 3 doses of intravenous ceftolozane/tazobactam 1.5g every 8 hours, followed by sampling of interstitial tissue fluid at the margin of the wound by a microdialysis probe over 8 hours.
干预措施: Ceftolozane/tazobactam (Drug)
Diabetic Wound Infection
Participants with a documented history of Type 1 or Type 2 diabetes and a mild to moderate (Grade 2 or 3) wound infection of the lower limb will receive at least 3 doses of intravenous ceftolozane/tazobactam 1.5g every 8 hours, followed by sampling of interstitial tissue fluid at the margin of the wound by a microdialysis probe over 8 hours.
干预措施: Microdialysis Catheter Insertion (Procedure)
Healthy Volunteer
Participants will be male or female healthy adult volunteers with no significant medical or medication history. Participants will receive at least 3 doses of intravenous ceftolozane/tazobactam 1.5g every 8 hours, followed by sampling of interstitial tissue fluid in the thigh by a microdialysis probe over 8 hours.
干预措施: Ceftolozane/tazobactam (Drug)
Healthy Volunteer
Participants will be male or female healthy adult volunteers with no significant medical or medication history. Participants will receive at least 3 doses of intravenous ceftolozane/tazobactam 1.5g every 8 hours, followed by sampling of interstitial tissue fluid in the thigh by a microdialysis probe over 8 hours.
干预措施: Microdialysis Catheter Insertion (Procedure)
结局指标
主要结局
Ceftolozane Tissue Penetration
时间窗: 16-24 hours
The ratio of ceftolozane tissue concentration area under the curve (AUC) to plasma concentrations AUC following the final (i.e., 3rd) ceftolozane/tazobactam dose. Note. Ceftolozane/tazobactam doses were administered at 0, 8, and 16 hours. Plasma and dialysate concentrations were determined at hours 16, 17, 18, 19, 20, 21, 22, 23, and 24 hours after the first dose for determination of ceftolozane AUC in blood and tissue.
Tazobactam Tissue Penetration
时间窗: 16-24 hours
The ratio of tazobactam tissue concentration area under the curve (AUC) to plasma concentration AUC following the final (3rd) ceftolozane/tazobactam dose. Note. Ceftolozane/tazobactam doses were administered at 0, 8, and 16 hours. Plasma and dialysate concentrations were determined at hours 16, 17, 18, 19, 20, 21, 22, 23, and 24 hours after the first dose for determination of tazobactam AUC in blood and tissue.
次要结局
- Ceftolozane Area Under the Curve (AUC) in Tissue(16 to 24 hours post-dose)
- Tazobactam AUC in Tissue(16 to 24 hours post-dose)
- Ceftolozane Total Drug AUC in Plasma(16 to 24 hours post-dose)
- Tazobactam Total Drug AUC in Plasma(16 to 24 hours post-dose)
- Number of Participants With Adverse Events(Duration of study (34 hours))