Cellulitis, Erysipelas
Conditions
Keywords
antibiotics, flucloxacillin, therapy duration, cellulitis, erysipelas, skin infections, hospital
Brief summary
Cellulitis is among the most common infections leading to hospitalization, yet the optimal duration of therapy remains ill defined. Pragmatically, Dutch guidelines advise 10-14 days of antibiotics, which is the current standard of care. Recently it has been shown that antibiotic treatment for pneumonia and urinary tract infections can safely and significantly be shortened. Importantly, in an outpatient setting, treatment of uncomplicated cellulitis with 5 days of antibiotics was as effective as 10 days. We hypothesize that there is no difference in outcomes when patients hospitalized with cellulitis are treated with either a short-course (6 days) or standard-course (12 days) of antibiotics.
Interventions
DRUGFlucloxacillin
DRUGPlacebo (for flucloxacillin)
Sugar capsule manufactured to mimic flucloxacillin 500mg capsules
Sponsors
ZonMw: The Netherlands Organisation for Health Research and Development
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Admitted to receive intravenous antibiotics for cellulitis/erysipelas * 18 years of age or older * Capable of giving written informed consent, able to comply with study requirements and restrictions
Exclusion criteria
* Allergy for flucloxacillin, other beta-lactam antibiotics or one of the additives, or flucloxacillin induced hepatitis or liver enzyme disorders. * Concurrent use of antibiotics for other indications * Alternative diagnosis accounting for the clinical presentation. * All cases involving any of the following complicating factors: * Use of antibiotics with Gram-positive activity for more than 4 days in the past 7 days * Intensive care unit admission during the last 7 days * Severe peripheral arterial disease (Fontaine IV) * Severe cellulitis necessitating surgical debridement or fascial biopsy * Necrotizing fasciitis * Periorbital or perirectal involvement * Surgery * Life expectancy less than one month * Risk factors associated with Gram-negative pathogens as a causative agent: * Chronic or macerated infra-malleolar ulcers, or infra-malleolar ulcers with previous antibiotic treatment, in patients with diabetes mellitus. * Neutropenia * Cirrhosis (Child-Pugh class B or C) * Intravenous drug use * Human or animal bite * Skin laceration acquired in fresh or salt open water * Fish fin or bone injuries
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1/2: Resolution... | day 14 | Resolution of cellulitis at day 14, defined as disappearance of warmth and tenderness at the site of infection, with substantial improvement in erythema and edema |
| Part 2/2: ...without relapse | day 28 | No recurrence by day 28, defined as the need for additional antibiotic therapy for cellulitis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective speed of recovery | Up to 90 days | Improvement in cellulitis severity score (a 7 item scoring system, each with a score between 0-3; items are erythema, warmth, tenderness, edema, ulceration, drainage and fluctuance). Determined at day 1, day 2-3, day 5-6, day 14, and day 28 |
| Recurrence at day 90 | 90 days | Recurrence of cellulitis by day 90, defined as the need for additional antibiotic therapy for cellulitis |
| Health related Quality of Life | Up to 90 days | Using questionnaires Dutch SF-36 and EQ-5D at day 1, day 28, and day 90 |
| Health care resource utilisation | Up to 90 days | Determined by total antibiotic use and effect on direct and indirect health-care associated costs, using modified versions of iMTA's Productivity Cost Questionnaire (iPCQ) and Medical Consumption Questionnaire (iMCQ). Measured at day 5-6, day 28 and day 90. |
| Subjective speed of recovery | Up to 90 days | Visual Analog Scales (0-10) on pain and on swelling. Determined at day 1, day 2-3, day 5-6, day 14, day 28, and day 90 |
| Additional antibiotic usage | Up to 90 days | Total usage of additional antibiotics for cellulitis between the end of treatment and day 90. |
| Time to relapse | Up to 90 days | Time between end of treatment and the need for additional antibiotics for cellulitis |
| Resolution without relapse | day 28 | Other operators used to define resolution at day 14 (no fever; reduction in combined erythema/edema/warmth/tenderness score of at least 2 points, or reach 0) and relapse at day 28 (no fever; stable or further improved combined score; no new antibiotics for cellulitis) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Per protocol analysis of the resolution without relapse secondary outcome | up to 28 days | Like secondary outcome, but the following will be included: (i) patients with treatment failure, who have received at least 24 hours of study medication, and (ii) patients with treatment success, who have received at least 80% of study medication. Cured is defined as above (under secondary outcome). Indeterminate is (i) receiving \<80% of study drug for reasons other than unblinding/requiring new AB for cellulitis/being unable to continue due to adverse effects, (ii) acquired a concomitant infection outside of the skin requiring antibiotic treatment, (iii) were lost to follow-up, or (iv) died unrelated to the primary diagnosis. Patients who are not cured nor indeterminate are failures. |
| Sensitivity analyses of the resolution without relapse secondary outcome | up to 28 days | Similar, but requiring further improvement of symptoms by either 1 or 2 points by day 28, instead of just stability of symptoms. |
| Adjustments for baseline covariates | up to day 28 | Sensitivity analysis, adjusting the primary outcome for baseline covariates |
| Diabetes mellitus subgroup analysis | up to day 28 | Analysis to see if having diabetes mellitus influences outcome, using a regression analysis with interaction term for diabetes. |
| Per protocol analysis | up to 28 days | Like main outcome, but the following will be included: (i) patients with treatment failure, who have received at least 24 hours of study medication, and (ii) patients with treatment success, who have received at least 80% of study medication. Treatment failure is defined as the persistence or progression of signs and symptoms of the acute process after randomization, or the inability to complete the study owing to adverse events. The response is deemed indeterminate when the patients (i) received less than 80% of the study drug for reasons other than treatment failure, (ii) acquired a concomitant infection outside of the skin requiring antibiotic treatment, (iii) were lost to follow-up, or (iv) died unrelated to the primary diagnosis. |
| Cellulitis severity score subgroup analysis | up to day 28 | Analysis to see if the height of the cellulitis severity score influences outcome, using a regression analysis with interaction term for severity score. |
Countries
Netherlands
Outcome results
None listed