INTRODUCTION:

Cellulitis is a common problem caused by spreading bacterial inflammation of the skin, with redness, pain, and lymphangitis. Up to 40% of affected people have systemic illness. Erysipelas is a form of cellulitis with marked superficial inflammation, typically affecting the lower limbs and the face. The most common pathogens in adults are streptococci and Staphylococcus aureus. Cellulitis and erysipelas can result in local necrosis and abscess formation. Around one quarter of affected people have more than one episode of cellulitis within 3 years.

METHODS AND OUTCOMES:

We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of treatments to prevent recurrence of cellulitis and erysipelas? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2015 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview).

RESULTS:

At this update, searching of electronic databases retrieved 323 studies. After deduplication and removal of conference abstracts, 184 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 170 studies and the further review of 14 full publications. Of the 14 full articles evaluated, one systematic review was added at this update. We performed a GRADE evaluation for one PICO combination.

CONCLUSIONS:

In this systematic overview, we categorised the efficacy for two interventions based on information about to the effectiveness and safety of antibiotics and treatment of predisposing factors.

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ANTECEDENTES:

La celulitis y la erisipela se consideran por lo general manifestaciones de la misma enfermedad, una infección de la piel asociada con dolor intenso y síntomas sistémicos. En las guías se sugieren diversos tratamientos con antibióticos.

OBJETIVOS:

Evaluar la eficacia y la seguridad de las intervenciones para la celulitis adquirida en forma no quirúrgica.

ESTRATEGIA DE BÚSQUEDA:

En mayo 2010, se hicieron búsquedas de ensayos controlados aleatorios en el Registro Especializado del Grupo Cochrane de Piel (Cochrane Skin Group), en el Registro Cochrane Central de Ensayos Controlados (Cochrane Central Register of Controlled Trials) en The Cochrane Library, MEDLINE, EMBASE y en las bases de datos de ensayos en curso.

CRITERIOS DE SELECCIÓN:

Se seleccionaron los ensayos controlados aleatorios que comparaban dos o más intervenciones diferentes para la celulitis.

OBTENCIÓN Y ANÁLISIS DE LOS DATOS:

Dos autores, de forma independiente, evaluaron la calidad de los ensayos y extrajeron los datos.

RESULTADOS PRINCIPALES:

Se incluyeron 25 estudios con un total de 2488 participantes. Por lo común, se informó el resultado primario “síntomas calificados por el participante o el médico de cabecera o la proporción libre de síntomas”. Ninguno de los dos ensayos examinó los mismos fármacos, por lo tanto se agruparon tipos similares de fármacos.
Se encontró que los macrólidos/estreptograminas fueron más efectivos que los antibióticos con penicilina (cociente de riesgos [CR] 0,84; IC del 95%: 0,73 a 0,97). En tres ensayos con 419 personas, dos de estos estudios usaron un macrólido oral en comparación con penicilina intravenosa (iv) y demostraron que los tratamientos orales pueden ser más efectivos que los tratamientos iv (CR 0,85; IC del 95%: 0,73 a 0,98).
Tres estudios con un total de 88 personas que compararon una penicilina con una cefalosporina no revelaron ninguna diferencia en el efecto del tratamiento (CR 0,99; IC del 95%: 0,68 a 1,43).
Seis ensayos que incluyeron a 538 personas y que compararon diferentes generaciones de cefalosporina, no mostraron diferencias en el efecto del tratamiento (CR 1,00; IC del 95%: 0,94 a 1,06).
Sólo se encontraron estudios individuales pequeños en cuanto a la duración del tratamiento con antibióticos, la vía intramuscular versus intravenosa, el agregado de corticosteroides al tratamiento con antibióticos en comparación con el antibiótico solo, y el tratamiento con vibración, por lo cual no hubo pruebas suficientes para establecer conclusiones. Sólo dos estudios investigaron tratamientos para la celulitis grave y los mismos seleccionaron antibióticos diferentes para sus comparaciones, de manera que no es posible establecer conclusiones firmes.

CONCLUSIONES DE LOS AUTORES:

No es posible definir el mejor tratamiento para la celulitis y la mayoría de las recomendaciones se basan en ensayos individuales. Se necesitan ensayos para evaluar la eficacia de los antibióticos orales en comparación con los antibióticos intravenosos en el contexto de la comunidad ya que hay consecuencias en el servicio en cuanto al costo y la comodidad.

OBJECTIVES:

Because of the difficulty of obtaining bacterial cultures from patients with cellulitis and erysipelas, the microbiology of these common infections remains incompletely defined. Given the emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) over the past decade the proportion of infections due to S. aureus has become particularly relevant.

METHODS:

OVID was used to search Medline using the focused subject headings "cellulitis", "erysipelas" and "soft tissue infections". All references that involved adult patients with cellulitis or erysipelas and reported associated bacteremias and specific pathogens were included in the review.

RESULTS:

For erysipelas, 4.6% of 607 patients had positive blood cultures, of which 46% were Streptococcus pyogenes, 29% were other β-hemolytic streptococci, 14% were Staphylococcus aureus, and 11% were Gram-negative organisms. For cellulitis, 7.9% of 1578 patients had positive blood cultures of which 19% were Streptococcus pyogenes, 38% were other β-hemolytic streptococci, 14% were Staphylococcus aureus, and 28% were Gram-negative organisms.

CONCLUSIONS:

Although the strength of our conclusions are somewhat limited by the heterogeneity of included cases, our results support the traditional view that cellulitis and erysipelas are primarily due to streptococcal species, with a smaller proportion due to S. aureus. Our results also argue against the current distinction between cellulitis and erysipelas in terms of the relative proportion of infections due to S. aureus.

BACKGROUND:

Erysipelas and cellulitis (hereafter referred to as 'cellulitis') are common bacterial skin infections usually affecting the lower extremities. Despite their burden of morbidity, the evidence for different prevention strategies is unclear.

OBJECTIVES:

To assess the beneficial and adverse effects of antibiotic prophylaxis or other prophylactic interventions for the prevention of recurrent episodes of cellulitis in adults aged over 16.

SEARCH METHODS:

We searched the following databases up to June 2016: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and LILACS. We also searched five trials registry databases, and checked reference lists of included studies and reviews for further references to relevant randomised controlled trials (RCTs). We searched two sets of dermatology conference proceedings, and BIOSIS Previews.

SELECTION CRITERIA:

Randomised controlled trials evaluating any therapy for the prevention of recurrent cellulitis.

DATA COLLECTION AND ANALYSIS:

Two authors independently carried out study selection, data extraction, assessment of risks of bias, and analyses. Our primary prespecified outcome was recurrence of cellulitis when on treatment and after treatment. Our secondary outcomes included incidence rate, time to next episode, hospitalisation, quality of life, development of resistance to antibiotics, adverse reactions and mortality.

MAIN RESULTS:

We included six trials, with a total of 573 evaluable participants, who were aged on average between 50 and 70. There were few previous episodes of cellulitis in those recruited to the trials, ranging between one and four episodes per study.Five of the six included trials assessed prevention with antibiotics in participants with cellulitis of the legs, and one assessed selenium in participants with cellulitis of the arms. Among the studies assessing antibiotics, one study evaluated oral erythromycin (n = 32) and four studies assessed penicillin (n = 481). Treatment duration varied from six to 18 months, and two studies continued to follow up participants after discontinuation of prophylaxis, with a follow-up period of up to one and a half to two years. Four studies were single-centre, and two were multicentre; they were conducted in five countries: the UK, Sweden, Tunisia, Israel, and Austria.Based on five trials, antibiotic prophylaxis (at the end of the treatment phase ('on prophylaxis')) decreased the risk of cellulitis recurrence by 69%, compared to no treatment or placebo (risk ratio (RR) 0.31, 95% confidence interval (CI) 0.13 to 0.72; n = 513; P = 0.007), number needed to treat for an additional beneficial outcome (NNTB) six, (95% CI 5 to 15), and we rated the certainty of evidence for this outcome as moderate.Under prophylactic treatment and compared to no treatment or placebo, antibiotic prophylaxis reduced the incidence rate of cellulitis by 56% (RR 0.44, 95% CI 0.22 to 0.89; four studies; n = 473; P value = 0.02; moderate-certainty evidence) and significantly decreased the rate until the next episode of cellulitis (hazard ratio (HR) 0.51, 95% CI 0.34 to 0.78; three studies; n = 437; P = 0.002; moderate-certainty evidence).The protective effects of antibiotic did not last after prophylaxis had been stopped ('post-prophylaxis') for risk of cellulitis recurrence (RR 0.88, 95% CI 0.59 to 1.31; two studies; n = 287; P = 0.52), incidence rate of cellulitis (RR 0.94, 95% CI 0.65 to 1.36; two studies; n = 287; P = 0.74), and rate until next episode of cellulitis (HR 0.78, 95% CI 0.39 to 1.56; two studies; n = 287). Evidence was of low certainty.Effects are relevant mainly for people after at least two episodes of leg cellulitis occurring within a period up to three years.We found no significant differences in adverse effects or hospitalisation between antibiotic and no treatment or placebo; for adverse effects: RR 0.87, 95% CI 0.58 to 1.30; four studies; n = 469; P = 0.48; for hospitalisation: RR 0.77, 95% CI 0.37 to 1.57; three studies; n = 429; P = 0.47, with certainty of evidence rated low for these outcomes. The existing data did not allow us to fully explore its impact on length of hospital stay.The common adverse reactions were gastrointestinal symptoms, mainly nausea and diarrhoea; rash (severe cutaneous adverse reactions were not reported); and thrush. Three studies reported adverse effects that led to discontinuation of the assigned therapy. In one study (erythromycin), three participants reported abdominal pain and nausea, so their treatment was changed to penicillin. In another study, two participants treated with penicillin withdrew from treatment due to diarrhoea or nausea. In one study, around 10% of participants stopped treatment due to pain at the injection site (the active treatment group was given intramuscular injections of benzathine penicillin).None of the included studies assessed the development of antimicrobial resistance or quality-of-life measures.With regard to the risks of bias, two included studies were at low risk of bias and we judged three others as being at high risk of bias, mainly due to lack of blinding.

AUTHORS' CONCLUSIONS:

In terms of recurrence, incidence, and time to next episode, antibiotic is probably an effective preventive treatment for recurrent cellulitis of the lower limbs in those under prophylactic treatment, compared with placebo or no treatment (moderate-certainty evidence). However, these preventive effects of antibiotics appear to diminish after they are discontinued (low-certainty evidence). Treatment with antibiotic does not trigger any serious adverse events, and those associated are minor, such as nausea and rash (low-certainty evidence). The evidence is limited to people with at least two past episodes of leg cellulitis within a time frame of up to three years, and none of the studies investigated other common interventions such as lymphoedema reduction methods or proper skin care. Larger, high-quality studies are warranted, including long-term follow-up and other prophylactic measures.

Recurrences of erysipelas are especially prevalent in patients suffering from local impairment of circulation and intervention might thus be of benefit. Therefore a prospective, randomized, open study was undertaken to evaluate whether daily antibiotic prophylaxis would reduce the risk of recurrence. Patients with venous insufficiency or lymphatic congestion who had suffered two or more episodes of erysipelas during the previous 3 years and were admitted to the Infectious Disease Department at Roslagstull Hospital, Stockholm, Sweden, between November 1988 and November 1991 were included. Fourty patients, 20 on prophylaxis and 20 controls were followed according to a life table analysis during a median time of 15 months. Phenoxymethylpenicillin was prescribed as daily prophylaxis (while erythromycin was given to patients allergic to penicillin). Recurrences of erysipelas appeared to be reduced by daily antibiotic prophylaxis but the effect was not dramatic (p = 0.06). Only in patients with a high recurrence rate continuous antibiotic prophylaxis against erysipelas is indicated.

The incidence of deep vein thrombosis (DVT) in patients with erysipelas and cellulitis of the lower extremities is unknown. As such, the indication and efficacy of prophylactic anticoagulation for prevention of DVT in these patients is unclear. The main goal of this review is to provide an estimate of the incidence of DVT in erysipelas and cellulitis based on existing literature. A comprehensive search of the electronic sources: MEDLINE, EMBASE, CINAHL, LILAC and Cochrane without any language limitation was performed from 1950 to April 2011 for articles focused on the occurrence of DVT in cellulitis or erysipelas of the lower extremities. The selected studies were divided into two groups according to presence or absence of systematic investigation for DVT. Those studies in which the patients received prophylactic or therapeutic anticoagulants before a diagnosis of DVT were excluded. The reported incidence rate of DVT in patients with erysipelas or cellulitis of the lower extremities is highly variable, ranging from 0 to 15%. In this review, the overall incidence rates of DVT in studies with and without systematic investigation for thromboembolism were 2.72% (95% CI.: 1.71-3.75%) and 0.68% (95% CI.: 0.27-1.07%), respectively. Given the low reported overall incidence of DVT, neither routine prophylactic anticoagulation nor systematic paraclinical investigation for DVT is indicated in low risk patients with erysipelas or cellulitis of the lower extremities. DVT should still be considered in patients with high pretest probability or other thromboembolic risk factors.

The exact place of prophylactic antimicrobial therapy in prevention of recurrent leg's erysipelas has not been determined. To evaluate efficacy and cost of antibioprophylaxis, 58 patients (34 women and 24 men), average 46.2 years, were randomly divided in 2 groups, during the period 1 January 1990 to 30 January 1993. The first group A (24 cases) received intramuscular benzathine penicillin, 1200000 UI every 15 days, the second group B (34 cases) received no prophylaxis for a similar period. The groups were not statistically different. 18 patients in group A and 26 patients in group B, completed follow up were evaluated. No patients in group A and 9 patients (34.6%) in group B relapsed after an average follow up time of 11.6 months. The main cost of treatment for one erysipela episode is 8.3 times higher than the calculated cost of prophylaxis for one year. Benzathine penicillin might be recommended in preventing attacks of recurrent leg's erysipelas.

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In a randomised, double-blind study, the efficacy of sodium selenite application in combination with physical therapy to relieve congestion was investigated in a cohort of 60 cancer patients with secondary lymphedema, with special reference to the development of the incidence of erysipelas. All of the patients investigated in this study had erysipelas infection of the skin. Selenium was administered in pharmacological doses. The duration of physical therapy was three weeks. Patients were under observation for a further three months. The incidence of erysipelas among our patients was 11%. During the three-week period of intensive treatment, there was not a single case of erysipelas in the treatment group, whereas there was one single case in the placebo group. In the follow-up period (3 months), once again there was not a single case of erysipelas in the treatment group, but 50% of the patients in the placebo group exhibited erysipelas. In spite of higher doses, the selenium level did not rise above normal values. Patients under long-term antibiotic therapy suffered no relapse when the antibiotic therapy was stopped and instead, selenium was administered. It could be shown, in addition, that by administration of a single high-dose of sodium selenite, inflammation could be immediately brought under control.