Comparison of Intravenous Cefazolin Plus Oral Probenecid With Oral Cephalexin for the Treatment of Cellulitis

Intravenous Cefazolin Plus Oral Probenecid vs. Oral Cephalexin for the Treatment of Cellulitis: a Randomized Controlled Trial

The purpose of this study is to determine whether oral cephalexin is equivalent to intravenous cefazolin plus oral probenecid for the treatment of uncomplicated skin and soft tissue infections in patients that present to the emergency department.

Study Overview

• Status: Completed
• Conditions: Cellulitis
• Intervention / Treatment: Drug: IV cefazolin plus oral probenecid and placebo cephalexin; Drug: Oral cephalexin and saline IV plus probenecid placebo

Detailed Description

Skin and soft tissue infections (SSTIs) are a common reason for presentation to an Emergency Department (ED) in Canada. Although many patients with mild SSTI are able to be managed at home with oral antibiotics, those with mild-moderate infections are often treated with parenteral antibiotics. Current practice patterns in Canadian EDs indicate this patient population is often treated with intravenous cefazolin once daily along with oral probenecid and return to the ED or other ambulatory setting for daily medication administration and assessment. This parenteral regimen has been found to result in success rates comparable to studies which have evaluated treatment success with oral antibiotics in this patient population (89-97%). Although successful outcome can be achieved with this approach, it is often inconvenient for the patient to return to the ED/ambulatory care unit daily and does contribute to overall ED/ambulatory care visit volumes and overall health care costs. Unfortunately, there has never been a study which has evaluated the relative efficacy and safety or oral antibiotics to the aforementioned parenteral approach in this patient population and thus there remains a significant knowledge gap which must be addressed before a change in current practice can be explored.

The objective of the study is to determine whether oral cephalexin is equivalent to intravenous cefazolin plus oral probenecid for the treatment of uncomplicated SSTIs in patients that present to the ED. This study will be a prospective, multi-centered, randomized controlled non-inferiority trial comparing cephalexin 500 mg orally four times to cefazolin 2 g IV plus probenecid 1 g orally, in patients presenting to the ED with presumed diagnosis of SSTI. The primary outcome will be to compare the proportion of patients failing therapy for their cellulitis after 72 hours of antibiotic treatment with oral cephalexin or IV cefazolin/oral probenecid 1 g daily. Secondary outcomes include the clinical cure rate at 7 days, percentage of patients requiring hospital admission, percentage of patients stepped down to oral antibiotics on or before day 7 of therapy, percentage of patients requiring an additional antibiotic prescription on day 7, and the frequency of adverse events.

• Study Type: Interventional
• Enrollment (Actual): 206
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 1T2
      • Kelowna General Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Queen Elizabeth II Health Sciences Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients presenting to the emergency department with a presumed diagnosis of mild to moderate skin and soft tissue infection
• Deemed well enough to be treated as an outpatient
• 19 years of age or older

Exclusion Criteria:

• known allergy to study drugs
• known chronic kidney disease with a creatinine clearance <30 mL/min
• known previous methicillin-resistant staphylococcus aureus (MRSA) infection
• use of antibiotics for greater than 24 hours in the past 7 days
• wound/abscess requiring operative debridement or incision and drainage
• suspected necrotizing fasciitis, osteomyelitis or septic arthritis
• febrile neutropenia
• concomitant documented bacteremia
• Two or more signs of systemic sepsis
• new altered mental status
• infections at a site involving prosthetic materials
• animal or human bite wound infections
• post-operative wound infections
• known peripheral vascular disease
• superficial thrombophlebitis
• pregnant/breastfeeding
• obesity (BMI > 30 kg/m2)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: IV cefazolin plus oral probenecid and placebo cephalexin	Drug: IV cefazolin plus oral probenecid and placebo cephalexin; Intravenous cefazolin 2 g IV plus probenecid 1 g daily plus cephalexin placebo orally four times daily.
Active Comparator: Oral cephalexin and saline IV plus probenecid placebo	Drug: Oral cephalexin and saline IV plus probenecid placebo; Cephalexin 500 mg orally four times daily plus saline IV and oral probenecid placebo daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The Number of Patients Failing Therapy After 72 Hours of Antibiotic Treatment With Oral Cephalexin or Intravenous Cefazolin Plus Oral Probenecid.	72 hours

Collaborators and Investigators

• Sponsor: Kelowna General Hospital
• Collaborators: Capital Health, Canada; Canadian Society of Hospital Pharmacists; Interior Health Authority, Canada
• Investigators: Principal Investigator: Dawn Dalen, PharmD, Interior Health; Principal Investigator: Peter Zed, PharmD, Capital Health, Canada

Publications and helpful links

General Publications

• Dalen D, Fry A, Campbell SG, Eppler J, Zed PJ. Intravenous cefazolin plus oral probenecid versus oral cephalexin for the treatment of skin and soft tissue infections: a double-blind, non-inferiority, randomised controlled trial. Emerg Med J. 2018 Aug;35(8):492-498. doi: 10.1136/emermed-2017-207420. Epub 2018 Jun 18.

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: December 9, 2009
• First Submitted That Met QC Criteria: December 9, 2009
• First Posted (Estimate): December 10, 2009

Study Record Updates

• Last Update Posted (Actual): August 13, 2018
• Last Update Submitted That Met QC Criteria: August 10, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Emergency Department; Probenecid; Cellulitis; Cefazolin; Cephalexin
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Inflammation; Connective Tissue Diseases; Skin Diseases, Infectious; Suppuration; Cellulitis; Anti-Infective Agents; Antirheumatic Agents; Anti-Bacterial Agents; Gout Suppressants; Renal Agents; Uricosuric Agents; Cefazolin; Cephalexin; Probenecid
• Other Study ID Numbers: KGHQEII-0001