NIHR Signal Long-term antibiotics likely to reduce risk of recurrent cellulitis

Published on 17 October 2017

Antibiotics may reduce the risk of leg cellulitis by about two thirds, in adults who have had at least two previous episodes, but only while they take the antibiotics. There is limited evidence measuring the efficacy of other forms of prevention.

A review of five studies showed that the risk of developing repeated cellulitis was reduced in participants who were taking long-term (more than six months) penicillin or erythromycin, compared with a control group. Once the antibiotic course had finished, participants’ risk of recurrent cellulitis was no different from the control group.

Cellulitis is a bacterial skin infection that spreads and worsens quickly. Risk of recurrence is high in people with a predisposing condition such as poor leg circulation.

This review explored the effectiveness of various preventative interventions for recurrent cellulitis. It highlights the need to explore non-pharmacological options, such as compression stockings, moisturisers or exercise. These could be cheaper and avoid the risk of increasing antibiotic resistance, but few studies of these options were identified.

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Why was this study needed?

Cellulitis is a bacterial infection that is painful and can spread rapidly under the skin. It’s a common condition, particularly in those with underlying disease, poor circulation or a weak immune system and can progress to cause serious illness.

People who are hospitalised for cellulitis are likely to be readmitted due to a repeat occurrence at a later date. Studies have shown that as many as 45% of these people experience a recurrence within three years.

Existing guidelines recommend antibiotics to prevent recurrent cellulitis. They also advise careful skin care and treating conditions such as fungal infections and dryness that can allow bacteria through the skin.

This study aimed to explore and assess the available interventions that prevent recurrent cellulitis in adults.

What did this study do?

This systematic review analysed and pooled the results of five studies (514 participants). They assessed antibiotic use compared to placebo or no prophylaxis in adults who had at least two episodes of leg cellulitis in the previous three years. Those with cellulitis due to poor lymphatic drainage were excluded.

Participants receiving antibiotics were treated for between six and 18 months with either penicillin (four studies) or erythromycin (one study). The primary outcome was at least one episode of cellulitis within at least three months after randomisation. Follow-up was up to three years.

The review assessed the trials as moderate-quality. They took place in five countries (two studies in the UK). Three studies had a high risk of bias, because clinicians, participants or assessors were aware of the treatment type. Antibiotic type and dosage were not consistent across studies.

What did it find?

  • Results from five trials (513 participants) found that people receiving antibiotics were 69% less likely to have a repeat episode of cellulitis; 13.6% had a recurrence compared to 31.5% of the control group (relative risk [RR] 0.31, 95% confidence interval [CI] 0.13 to 0.72). A clinician would need to treat six people with antibiotics in order for one episode of cellulitis to be prevented (number needed to treat is six, 95% CI 5 to 15 at a control event rate 83/263 [32%]).
  • There were 56% fewer infections over the study period in the antibiotic group (88 infections) compared with the control group (168 infections), (RR 0.44, 95% CI 0.22 to 0.89).
  • Antibiotics did not have a long-term effect on preventing repeated cellulitis. Participants who had finished their course of antibiotics showed no difference in the risk of getting cellulitis again compared to the control group, during a follow up of 18 months to two years (RR 0.88, 95% CI 0.59 to 1.31). This result came from two studies (287 participants).
  • There was no significant difference in the number of adverse events between the control and treatment groups (RR 0.87, 95% CI 0.58 to 1.30).

What does current guidance say on this issue?

NICE’s Clinical Knowledge Summary service recommends treating underlying risk factors such as breaks in the skin, oedema and obesity, to prevent recurrence of cellulitis. It advises considering referral to secondary care for advice on prophylactic antibiotics if someone has more than two episodes of cellulitis on the same site within a year.

The Clinical Resource Efficiency Support Team published guidelines on the management of cellulitis in 2005. They recommend antibiotic prophylaxis in those who have had at least two episodes of cellulitis at the same site.

What are the implications?

This review looked for prophylactic interventions for recurrent cellulitis but found most evidence for the use of antibiotics. Further evidence on alternative strategies such as compression stockings or exercises would be useful, given the need to prescribe antibiotics carefully.

These results, although in line with current guidance, are applicable to a narrow population as the studies did not include people with lymphoedema. Antibiotic prophylaxis only seems effective whilst treatment is on-going.

Studies comparing specific antibiotics for all cellulitis cases would give a clearer picture on the most effective way to prevent recurrence and allow researchers to address the issues of antibiotic guardianship.

Citation and Funding

Dalal A, Eskin-Schwartz M, Mimouni D, et al. Interventions for the prevention of recurrent erysipelas and cellulitis. Cochrane Database Syst Rev. 2017;6:CD009758.

Cochrane UK and the Cochrane Skin Group are supported by the NIHR infrastructure funding.

Bibliography

Cox NH. Oedema as a risk factor for multiple episodes of cellulitis/erysipelas of the lower leg: a series with community follow-up. Br J of Dermatol. 2006;155(5):947-50.

CREST. Guidelines on the management of cellulitis in adults. Belfast: Clinical Resource Efficiency Support Team; 2005.

NICE CKS. Cellulitis – acute. London: National Institute for Health and Care Excellence Clinical Knowledge Summaries; 2015.

Patient. Cellulitis and Erysipelas. Leeds: Patient Platform Limited; 2015.

Why was this study needed?

Cellulitis is a bacterial infection that is painful and can spread rapidly under the skin. It’s a common condition, particularly in those with underlying disease, poor circulation or a weak immune system and can progress to cause serious illness.

People who are hospitalised for cellulitis are likely to be readmitted due to a repeat occurrence at a later date. Studies have shown that as many as 45% of these people experience a recurrence within three years.

Existing guidelines recommend antibiotics to prevent recurrent cellulitis. They also advise careful skin care and treating conditions such as fungal infections and dryness that can allow bacteria through the skin.

This study aimed to explore and assess the available interventions that prevent recurrent cellulitis in adults.

What did this study do?

This systematic review analysed and pooled the results of five studies (514 participants). They assessed antibiotic use compared to placebo or no prophylaxis in adults who had at least two episodes of leg cellulitis in the previous three years. Those with cellulitis due to poor lymphatic drainage were excluded.

Participants receiving antibiotics were treated for between six and 18 months with either penicillin (four studies) or erythromycin (one study). The primary outcome was at least one episode of cellulitis within at least three months after randomisation. Follow-up was up to three years.

The review assessed the trials as moderate-quality. They took place in five countries (two studies in the UK). Three studies had a high risk of bias, because clinicians, participants or assessors were aware of the treatment type. Antibiotic type and dosage were not consistent across studies.

What did it find?

  • Results from five trials (513 participants) found that people receiving antibiotics were 69% less likely to have a repeat episode of cellulitis; 13.6% had a recurrence compared to 31.5% of the control group (relative risk [RR] 0.31, 95% confidence interval [CI] 0.13 to 0.72). A clinician would need to treat six people with antibiotics in order for one episode of cellulitis to be prevented (number needed to treat is six, 95% CI 5 to 15 at a control event rate 83/263 [32%]).
  • There were 56% fewer infections over the study period in the antibiotic group (88 infections) compared with the control group (168 infections), (RR 0.44, 95% CI 0.22 to 0.89).
  • Antibiotics did not have a long-term effect on preventing repeated cellulitis. Participants who had finished their course of antibiotics showed no difference in the risk of getting cellulitis again compared to the control group, during a follow up of 18 months to two years (RR 0.88, 95% CI 0.59 to 1.31). This result came from two studies (287 participants).
  • There was no significant difference in the number of adverse events between the control and treatment groups (RR 0.87, 95% CI 0.58 to 1.30).

What does current guidance say on this issue?

NICE’s Clinical Knowledge Summary service recommends treating underlying risk factors such as breaks in the skin, oedema and obesity, to prevent recurrence of cellulitis. It advises considering referral to secondary care for advice on prophylactic antibiotics if someone has more than two episodes of cellulitis on the same site within a year.

The Clinical Resource Efficiency Support Team published guidelines on the management of cellulitis in 2005. They recommend antibiotic prophylaxis in those who have had at least two episodes of cellulitis at the same site.

What are the implications?

This review looked for prophylactic interventions for recurrent cellulitis but found most evidence for the use of antibiotics. Further evidence on alternative strategies such as compression stockings or exercises would be useful, given the need to prescribe antibiotics carefully.

These results, although in line with current guidance, are applicable to a narrow population as the studies did not include people with lymphoedema. Antibiotic prophylaxis only seems effective whilst treatment is on-going.

Studies comparing specific antibiotics for all cellulitis cases would give a clearer picture on the most effective way to prevent recurrence and allow researchers to address the issues of antibiotic guardianship.

Citation and Funding

Dalal A, Eskin-Schwartz M, Mimouni D, et al. Interventions for the prevention of recurrent erysipelas and cellulitis. Cochrane Database Syst Rev. 2017;6:CD009758.

Cochrane UK and the Cochrane Skin Group are supported by the NIHR infrastructure funding.

Bibliography

Cox NH. Oedema as a risk factor for multiple episodes of cellulitis/erysipelas of the lower leg: a series with community follow-up. Br J of Dermatol. 2006;155(5):947-50.

CREST. Guidelines on the management of cellulitis in adults. Belfast: Clinical Resource Efficiency Support Team; 2005.

NICE CKS. Cellulitis – acute. London: National Institute for Health and Care Excellence Clinical Knowledge Summaries; 2015.

Patient. Cellulitis and Erysipelas. Leeds: Patient Platform Limited; 2015.

Interventions for the prevention of recurrent erysipelas and cellulitis

Published on 21 June 2017

Dalal, A.,Eskin-Schwartz, M.,Mimouni, D.,Ray, S.,Days, W.,Hodak, E.,Leibovici, L.,Paul, M.

Cochrane Database Syst Rev Volume 6 , 2017

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.

Erysipelas is a form of cellulitis that affects more superficial layers of skin. It is often difficult to distinguish erysipelas from cellulitis so the study refers to both conditions as cellulitis.

Expert commentary

Cellulitis is a common infection, often associated with underlying risk factors. It can be difficult to treat, requiring longer courses or several antibiotics and affecting the quality of life, so the idea of prophylaxis is attractive.

Unfortunately, the results are not overwhelming: a relatively modest reduction in infections, recurrence when treatment ceases, and little effect on hospitalisation (suggesting serious infections may not be prevented).

Community parenteral antibiotic therapy is gaining ground and is a useful strategy for some. Low-dose prophylaxis can still benefit those most frequently affected and may provide better antimicrobial stewardship than repeated high-dose antibiotics.

Dr James Larcombe, GP, NHS Durham Dales, Easington and Sedgefield CCG