Review
Antibiotic prophylaxis for preventing recurrent cellulitis: A systematic review and meta-analysis

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Summary

Importance

A significant proportion of patients who have had a first episode of erysipelas or uncomplicated cellulitis will subsequently develop a recurrence. There is disagreement about how effective antibiotic prophylaxis is for preventing recurrent cellulitis.

Objective

To determine if antibiotic prophylaxis is effective in preventing recurrent cellulitis compared to no prophylaxis using a systematic review and meta-analysis.

Data sources

Studies in any language identified by searching Medline, EMBASE, Cochrane Library, CINAHL, TRIP database, clinical practice guidelines websites, and ongoing trials databases up to 31st August 2012. Search terms included cellulitis, erysipelas, controlled clinical trial, randomized, placebo, clinical trials, randomly, and trial.

Study selection

Only controlled trials comparing antibiotic prophylaxis to no antibiotic prophylaxis in patients age 16 years and above, and after 1 or more episodes of cellulitis, were included.

Data extraction and synthesis

Independent extraction of articles was done by 2 investigators using predefined data extraction templates, including study quality indicators. PROSPERO registration number: CRD42012002528. Meta-analyses were done using random-effects models.

Main outcomes and measures

The primary outcome was the number of patients with a recurrence of cellulitis. Secondary outcomes were (1) the time to next episode of recurrence, (2) quality of life measures, and (3) adverse events (e.g. allergic reactions, nausea).

Results

Five randomized controlled trials (n = 535), with 260 patients in the intervention arm and 275 in the comparator group met our inclusion criteria. 44 patients (8%) in the antibiotic prophylaxis group and 97 patients (18%) in the comparator group had an episode of cellulitis. Antibiotic prophylaxis significantly reduced the number of patients having recurrent cellulitis, with a risk ratio (RR) of 0.46 (95% CI 0.26–0.79). None of the studies reported severe adverse effects to antibiotics. There was methodological heterogeneity amongst the studies in terms of types of antibiotic used, delivery modes, number of recurrences of cellulitis at study entry, and study quality.

Conclusion and relevance

Antibiotic prophylaxis can prevent recurrent cellulitis. Future research should aim to identify the ideal type, dosage, and duration of antibiotics for prophylaxis, as well as to identify the group of patients who will benefit most from antibiotic prophylaxis.

Introduction

Cellulitis of the lower extremities is an acute, painful and potentially serious infection of the skin and subcutaneous tissue associated with significant morbidity1, 2 and healthcare costs.3, 4, 5 Erysipelas or uncomplicated cellulitis refers to non-suppurative, acute and spreading skin infection. Specifically, erysipelas tends to be more superficial and has prominent lymphatic involvement; while cellulitis extends deeper and involves subcutaneous tissues. We will use the terms erysipelas and cellulitis interchangeably in this paper. Risk factors for developing cellulitis of the leg include prior history of cellulitis, lymphoedema, toe web maceration, obesity and diabetes.6, 7, 8, 9

Cellulitis is typically caused by b-haemolytic streptococci of group A, less often by group B, C, or G streptococci or Staphylococcus aureus.10, 11 Prior history of cellulitis is strongly associated with acute cellulitis.7, 12

An attack of acute cellulitis may lead to a vicious circle of impaired lymphatic function leading to increased susceptibility to further recurrences of cellulitis.13

However, the causal association is not clear.14, 15

In 2003, 428,274 patients were hospitalized in the US with a principle diagnosis of cellulitis, with cellulitis being responsible for 1.1% of all hospital discharges.16 Sixteen to 30% of patients who have had a first episode of erysipelas or uncomplicated cellulitis will subsequently develop a recurrence.17, 18, 19

There is disagreement about how effective antibiotic prophylaxis is for preventing recurrent cellulitis. We undertook a systematic review and meta-analysis to evaluate the level and quality of available evidence regarding the efficacy and reported adverse effects of antibiotic prophylaxis against recurrent cellulitis.

Section snippets

Methods

This systematic review protocol was registered with PROSPERO on 11th September 2012 with registration number CRD42012002528.

Results

Our literature search yielded 1472 articles from all sources. Fig. 1 shows the numbers of studies screened, resulting in five studies that matched our criteria.21, 22, 23, 24, 25, 26 Of these, two studies were done by the UK's ‘Prophylactic Antibiotics for the Treatment of Cellulitis at Home’ (PATCH) group.24, 25, 26

There were 535 participants from all five studies, with 260 participants taking antibiotics and 275 participants on placebo or not taking any antibiotics. There were 209 males and

Discussion

Antibiotic prophylaxis reduced the risk of recurrent cellulitis compared to no antibiotic prophylaxis, with an RR of 0.46 (95% CI 0.26–0.79) in patients with a history of cellulitis. This review also suggests that in patients with two or more baseline episodes of cellulitis, antibiotic prophylaxis seemed to half the recurrence of cellulitis as compared to no antibiotic prophylaxis; while not statistically significant (RR 0.35, 95% CI 0.12–1.02) this finding hints to a possibly clinically

Funding

Nasia Safdar is supported by a MERIT award from the Department of Veterans Affairs. The views in this paper do not necessarily represent the views of the authors' employers, nor the Department of Veterans Affairs.

Acknowledgements

The authors would like to thank Dr Melina Willlson for her translation work in Ref. 21.

References (38)

  • M. Chakroun et al.

    Benzathine penicillin prophylaxis in recurrent erysipelas

    Med Mal Infect

    (1994)
  • M. Kremer et al.

    Long-term antimicrobial therapy in the prevention of recurrent soft-tissue infections

    J Infect

    (1991)
  • S. Bitnun

    Prophylactic antibiotics in recurrent erysipelas

    Lancet

    (1985)
  • N.H. Cox et al.

    Management and morbidity of cellulitis of the leg

    J R Soc Med

    (1998)
  • K. Carter et al.

    Cellulitis and treatment: a qualitative study of experiences

    Br J Nurs

    (2007)
  • N.J. Levell et al.

    Severe lower limb cellulitis is best diagnosed by dermatologists and managed with shared care between primary and secondary care

    Br J Dermatol

    (2011)
  • M.N. Haan et al.

    The impact of aging and chronic disease on use of hospital and outpatient services in a large HMO: 1971–1991

    J Am Geriatr Soc

    (1997)
  • W.G. Goettsch et al.

    Burden of illness of bacterial cellulitis and erysipelas of the leg in the Netherlands

    J Eur Acad Dermatol Venereol

    (2006)
  • A. Dupuy et al.

    Risk factors for erysipelas of the leg (cellulitis): case-control study

    BMJ

    (1999)
  • J.C. Roujeau et al.

    Chronic dermatomycoses of the foot as risk factors for acute bacterial cellulitis of the leg: a case-control study

    Dermatology

    (2004)
  • M. Mokni et al.

    Risk factors for erysipelas of the leg in Tunisia: a multicenter case-control study

    Dermatology

    (2006)
  • S.J. Eells et al.

    Non-suppurative cellulitis: risk factors and its association with Staphylococcus aureus colonization in an area of endemic community-associated methicillin-resistant S. aureus infections

    Epidemiol Infect

    (2011)
  • A.L. Bisno et al.

    Streptococcal infections of skin and soft tissue

    N Engl J Med

    (1996)
  • E.W. 3rd Hook et al.

    Microbiologic evaluation of cutaneous cellulitis in adults

    Arch Intern Med

    (1986)
  • S. Björnsdóttir et al.

    Risk factors for acute cellulitis of the lower limb: a prospective case-control study

    Clin Infect Dis

    (2005)
  • N.H. Cox

    Oedema as a risk factor for multiple episodes of cellulitis/erysipelas of the lower leg: a series with community follow-up

    Br J Dermatol

    (2006)
  • R.J. Damstra et al.

    Erysipelas as a sign of subclinical primary lymphoedema: a prospective quantitative scintigraphic study of 40 patients with unilateral erysipelas of the leg

    Br J Dermatol

    (2008)
  • J.K. Soo et al.

    Lymphatic abnormalities demonstrated by lymphoscintigraphy after lower limb cellulitis

    Br J Dermatol

    (2008)
  • Agency for Healthcare Research and Quality Healthcare costs and utilization project

    (2006)
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