Cellulitis
Conditions
Keywords
Cellulitis, Emergency Department, Cefazolin, Probenecid, Cephalexin
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.
Interventions
DRUGIV cefazolin plus oral probenecid and placebo cephalexin
Intravenous cefazolin 2 g IV plus probenecid 1 g daily plus cephalexin placebo orally four times daily.
DRUGOral cephalexin and saline IV plus probenecid placebo
Cephalexin 500 mg orally four times daily plus saline IV and oral probenecid placebo daily
Sponsors
Canadian Society of Hospital Pharmacists
Capital Health, Canada
Interior Health Authority, Canada
Kelowna General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| 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 |
Countries
Canada
Participant flow
Recruitment details
Patients were included if they presented to the ED with presumed diagnosis of mild-moderate SSTI and were deemed well enough to be treated as outpatients and be able to return to the ED daily.
Participants by arm
| Arm | Count |
|---|---|
| IV Cefazolin Plus Oral Probenecid and Placebo Cephalexin 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. | 102 |
| Oral Cephalexin and Saline IV Plus Probenecid Placebo Oral cephalexin and saline IV plus probenecid placebo: Cephalexin 500 mg orally four times daily plus saline IV and oral probenecid placebo daily | 101 |
| Total | 203 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Diagnosis changed | 1 | 1 |
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Oral Cephalexin and Saline IV Plus Probenecid Placebo | Total | IV Cefazolin Plus Oral Probenecid and Placebo Cephalexin |
|---|---|---|---|
| Age, Continuous | 52.01 years STANDARD_DEVIATION 19.64 | 53.62 years STANDARD_DEVIATION 18.72 | 55.21 years STANDARD_DEVIATION 17.71 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment Canada | 101 participants | 203 participants | 102 participants |
| Sex: Female, Male Female | 30 Participants | 66 Participants | 36 Participants |
| Sex: Female, Male Male | 71 Participants | 137 Participants | 66 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 102 | 0 / 101 |
| other Total, other adverse events | 4 / 102 | 5 / 101 |
| serious Total, serious adverse events | 0 / 102 | 0 / 101 |
Outcome results
Primary
The Number of Patients Failing Therapy After 72 Hours of Antibiotic Treatment With Oral Cephalexin or Intravenous Cefazolin Plus Oral Probenecid.
Time frame: 72 hours
Population: Per-Protocol Analysis at 72 hours.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IV Cefazolin Plus Oral Probenecid and Placebo Cephalexin | The Number of Patients Failing Therapy After 72 Hours of Antibiotic Treatment With Oral Cephalexin or Intravenous Cefazolin Plus Oral Probenecid. | 6 Participants |
| Oral Cephalexin and Saline IV Plus Probenecid Placebo | The Number of Patients Failing Therapy After 72 Hours of Antibiotic Treatment With Oral Cephalexin or Intravenous Cefazolin Plus Oral Probenecid. | 4 Participants |