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

Phase 2

Completed

Conditions: Cellulitis

Interventions: Drug: IV cefazolin plus oral probenecid and placebo cephalexin
Drug: Oral cephalexin and saline IV plus probenecid placebo

Registration Number: NCT01029782

Lead Sponsor: Kelowna General Hospital

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 206

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IV cefazolin plus oral probenecid and placebo cephalexin	IV cefazolin plus oral probenecid and placebo cephalexin	-
Oral cephalexin and saline IV plus probenecid placebo	Oral cephalexin and saline IV plus probenecid placebo	-

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (2): Kelowna General Hospital
🇨🇦
Kelowna, British Columbia, Canada
Queen Elizabeth II Health Sciences Centre
🇨🇦
Halifax, Nova Scotia, Canada