Cellulitis
Conditions
Keywords
Cellulitis, Bactrim, Trimethoprim Sulfamethoxazole, MRSA, Methicillin-resistant Staphylococcus aureus
Brief summary
The primary aim of this study is to quantify the effectiveness of Bactrim as additional therapy for the treatment of uncomplicated cellulitis in adults, by comparing: standard therapy plus Bactrim, versus standard therapy plus placebo. The primary hypothesis of this study is that, in light of increasing CA-MRSA prevalence, subjects treated with standard therapy plus Bactrim will have higher cure rates than those treated with standard therapy plus placebo.
Interventions
DRUGtrimethoprim-sulfamethoxazole
Weight-based dosing in capsule or suspension form according to the following scale: 15-19 kg (33-42 lbs): trimethoprim-sulfamethoxazole 40/200 mg four times daily 20-24 kg (42-53 lbs): trimethoprim-sulfamethoxazole 60/300 mg four times daily 25-29 kg (53-64 lbs): trimethoprim-sulfamethoxazole 72/360 mg four times daily 29-60 kg (64-132 lbs): trimethoprim-sulfamethoxazole 80/400 mg four times daily 60 kg (132 lbs): trimethoprim-sulfamethoxazole 80/400 mg four times daily 60-80 kg (132-176 lbs): trimethoprim-sulfamethoxazole 160/800 mg three times daily \> 80 kg (176 lbs): trimethoprim-sulfamethoxazole 160/800 mg four times daily
DRUGCephalexin
Weight-based dosing in capsule or suspension form according to the following scale: 15-19 kg (33-42 lbs): Cephalexin 300 mg four times daily 20-24 kg (42-53 lbs): Cephalexin 400 mg four times daily 25-29 kg (53-64 lbs): Cephalexin 500 mg four times daily 29-60 kg (64-132 lbs): Cephalexin 500 mg four times daily 60-80 kg (132-176 lbs): Cephalexin 1000 mg three times daily \> 80 kg (176 lbs): Cephalexin 1000 mg four times daily
Sponsors
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Months to No maximum
Healthy volunteers
No
Inclusion criteria
* Must have cellulitis as defined here: 1. Definition A (preferred definition): Recent onset of soft tissue erythema, considered by the treating clinician to be bacterial in origin, and associated with signs of infection that include at least two of the following: pain, swelling, warmth, fever, lymphangitis, induration, or ulceration. 2. Definition B (ONLY for darkly-pigmented subjects who cannot use Definition A): Recent onset of soft tissue color change, pain, or swelling, considered by the treating clinician to be bacterial in origin, and at least one of the following: warmth, fever, induration, or ulceration * Clinical (non-research) attending physician agrees with treatment with cephalexin until 3 days after all symptoms gone, using our weight-based dosing * Responsible clinical attending physician comfortable with adding trimethoprim-sulfamethoxazole vs. placebo to the above * Subject understands the study and signs written informed consent. * Subject agrees to drink at least 1 liter of fluid per day. * Subject will commit to all follow-up appointments
Exclusion criteria
* Age \< 12 months or weight \<15 kg * Current skin infection has already been treated * Allergy to sulfa drugs * History of severe allergic reaction to penicillin (defined as anaphylactoid reaction, angioedema, bronchospasm) * Current use of any antibiotic (other than topicals) * Diabetes mellitus * Cellulitis complicated by underlying peripheral vascular disease * Renal insufficiency, defined as patient report, clinical suspicion, or creatinine\>1.3 or EGFR\<60 on the last-available set of chemistry results in our computer system * Hospital admission required * Presence of \> 1 cc of purulent discharge at any time * Cellulitis involving an indwelling vascular, enteric, or urinary catheter * Immunocompromise of any etiology * Pregnancy * Breast feeding * Facial cellulitis (infection is above the clavicles) * Cellulitis associated with marine or freshwater injury, or animal or human bite. (Insect bites not excluded.) * History of glucose-6-phosphate dehydrogenase deficiency * Taking coumadin (warfarin), methotrexate, cisapride, phenytoin (dilantin), digoxin, or dofetilide * Known megaloblastic anemia due to folate deficiency.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relative Efficacy | 12 +/- 2 days; 30 +/- 2 days | Proportion of subjects in each arm with successful treatment. Treatment success was assessed by physician examination at 12 +/- 2 days. Non-success was defined as subsequent hospitalization, change in antibiotics, surgical or needle drainage of an abscess, or recurrence of infection within 30 days. Cure was defined as resolution of all symptoms other than mild residual erythema or edema. We confirmed the determination of cure by telephone interview and medical record review at 30 +/- 2 days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression to Abscess | 12 +/- 2 days, 30 days +/- 2 days | Proportion of subjects in each arm with progression from cellulitis to abscess. |
Countries
United States
Participant flow
Recruitment details
We enrolled generally-healthy subjects with uncomplicated acute cellulitis from 6/2007 to 12/2011. Eligible subjects were adults and children presenting to EDs of 3 teaching hospitals in Boston, MA.
Pre-assignment details
Each subject was assigned randomly to a treatment group by the institutions' research pharmacies. The research pharmacies had no knowledge of subjects' clinical characteristics. Treating (non-research) clinicians, research clinicians, coordinators, and subjects had no knowledge of the randomization sequence.
Participants by arm
| Arm | Count |
|---|---|
| Trimethoprim-sulfamethoxazole Cephalexin plus trimethoprim-sulfamethoxazole | 76 |
| Placebo Cephalexin plus placebo | 77 |
| Total | 153 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Found ineligible | 3 | 2 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Trimethoprim-sulfamethoxazole | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 5 Participants | 3 Participants | 8 Participants |
| Age, Categorical >=65 years | 3 Participants | 5 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 69 Participants | 68 Participants | 137 Participants |
| Age Continuous | 32.43 years STANDARD_DEVIATION 15.15 | 37.03 years STANDARD_DEVIATION 15.07 | 34.71 years STANDARD_DEVIATION 15.23 |
| Region of Enrollment United States | 77 participants | 76 participants | 153 participants |
| Sex: Female, Male Female | 36 Participants | 39 Participants | 75 Participants |
| Sex: Female, Male Male | 41 Participants | 37 Participants | 78 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 36 / 73 | 39 / 73 |
| serious Total, serious adverse events | 0 / 73 | 1 / 73 |
Outcome results
Primary
Relative Efficacy
Proportion of subjects in each arm with successful treatment. Treatment success was assessed by physician examination at 12 +/- 2 days. Non-success was defined as subsequent hospitalization, change in antibiotics, surgical or needle drainage of an abscess, or recurrence of infection within 30 days. Cure was defined as resolution of all symptoms other than mild residual erythema or edema. We confirmed the determination of cure by telephone interview and medical record review at 30 +/- 2 days.
Time frame: 12 +/- 2 days; 30 +/- 2 days
Population: Of the 153 randomized subjects, 4 were randomized in error and did not receive study drug, 1 received two doses before it was discovered that he was ineligible, 1 was lost to follow up, and 1 withdrew voluntarily in the first few days after enrollment. This left 146 subjects for intent-to-treat analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trimethoprim-sulfamethoxazole | Relative Efficacy | 62 participants |
| Placebo | Relative Efficacy | 60 participants |
Comparison: The study was powered to detect a difference in cure rate of 98% in the intervention group vs. 85% in the control group, with 2-sided alpha 0.05. This would yield a number needed to treat of 7.7 for intervention vs. control, and required 144 subjects to achieve 80% power. No data were analyzed until study completion.p-value: <0.0595% CI: [-9.3, 15]Chi-squared
Secondary
Progression to Abscess
Proportion of subjects in each arm with progression from cellulitis to abscess.
Time frame: 12 +/- 2 days, 30 days +/- 2 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trimethoprim-sulfamethoxazole | Progression to Abscess | 5 participants |
| Placebo | Progression to Abscess | 5 participants |
Comparison: We assessed the rate of progression to abscess in the two groups.p-value: <0.0595% CI: [-6.5, 6.3]Chi-squared