Abstract
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 a quarter of affected people have more than one episode of cellulitis within 3 years.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for cellulitis and erysipelas? 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 May 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 14 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics, comparative effects of different antibiotic regimens, duration of antibiotics, and treatment of predisposing factors.
Key Points
Cellulitis is a common problem caused by spreading bacterial inflammation of the skin, with redness, pain, and lymphangitis. Up to 40% of people have systemic illness.
Erysipelas is a form of cellulitis with marked superficial inflammation, typically affecting the lower limbs and the face.
Risk factors include lymphoedema, leg ulcer, toe web intertrigo, and traumatic wounds.
The most common pathogens in adults are streptococci and Staphylococcus aureus.
Cellulitis and erysipelas can result in local necrosis and abscess formation. Around a quarter of people have more than one episode of cellulitis within 3 years.
Antibiotics cure 50−100% of infections, but we don't know which antibiotic regimen is most successful.
We don't know whether antibiotics are as effective when given orally as when given intravenously, or whether intramuscular administration is more effective than intravenous.
A 5-day course of antibiotics may be as effective as a 10-day course at curing the infection and preventing early recurrence.
Although there is consensus that treatment of predisposing factors can prevent recurrence of cellulitis or erysipelas, we found no studies that assessed the benefits of this approach.
About this condition
Definition
Cellulitis is a spreading bacterial infection of the dermis and subcutaneous tissues. It causes local signs of inflammation, such as warmth, erythema, pain, lymphangitis, and frequently systemic upset with fever and raised white blood cell count. Erysipelas is a form of cellulitis and is characterised by pronounced superficial inflammation. The term erysipelas is commonly used when the face is affected. The lower limbs are by far the most common sites affected by cellulitis and erysipelas, but any area, such as the ears, trunk, fingers, and toes, can be affected.
Incidence/ Prevalence
We found no validated recent data on the incidence of cellulitis or erysipelas worldwide. UK hospital incidence data reported 69,576 episodes of cellulitis and 516 episodes of erysipelas in 2004-2005. Cellulitis infections of the limb accounted for most of these infections (58,824 episodes).
Aetiology/ Risk factors
The most common infective organisms for cellulitis and erysipelas in adults are streptococci (particularly Streptococcus pyogenes) and Staphylococcus aureus. In children, Haemophilus influenzae was a frequent cause before the introduction of the Haemophilus influenzae type B vaccination. Several risk factors for cellulitis and erysipelas have been identified in a case-control study (167 cases and 294 controls): lymphoedema (OR 71.2, 95% CI 5.6 to 908.0), leg ulcer (OR 62.5, 95% CI 7.0 to 556.0), toe web intertrigo (OR 13.9, 95% CI 7.2 to 27.0), and traumatic wounds (OR 10.7, 95% CI 4.8 to 23.8).
Prognosis
Cellulitis can spread through the bloodstream and lymphatic system. A retrospective case study of people admitted to hospital with cellulitis found that systemic symptoms, such as fever and raised white blood cell count, were present in up to 42% of cases at presentation. Lymphatic involvement can lead to obstruction and damage of the lymphatic system that predisposes to recurrent cellulitis. Recurrence can occur rapidly, or after months or years. One prospective cohort study found that 29% of people with erysipelas had a recurrent episode within 3 years. Local necrosis and abscess formation can also occur. It is not known whether the prognosis of erysipelas differs from cellulitis. We found no evidence about factors that predict recurrence, or a better or worse outcome. We found no good evidence on the prognosis of untreated cellulitis.
Aims of intervention
To reduce the severity and duration of infection; to relieve pain and systemic symptoms; to restore the skin to its premorbid state; to prevent recurrence; to minimise adverse effects of treatment.
Outcomes
Duration and severity of symptoms (pain, swelling, erythema, and fever); clinical cure (defined as the absence of pain, swelling, and erythema); recurrence; adverse effects of treatment. We found no standard scales of severity in cellulitis or erysipelas.
Methods
BMJ Clinical Evidence search and appraisal May 2007. The following databases were used to identify studies for this systematic review: Medline 1966 to May 2007, Embase 1980 to May 2007, and The Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials 2007, Issue 2. Additional searches were carried out using these websites: NHS Centre for Reviews and Dissemination (CRD) — for Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA), Turning Research into Practice (TRIP), and National Institute for Health and Clinical Excellence (NICE). We also searched for retractions of studies included in this review. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the author for additional assessment, using pre-determined criteria to identify relevant studies. Study design criteria for inclusion in this review were: published systematic reviews and RCTs in any language, at least single blinded and containing more than 20 individuals, of whom more than 80% were followed up. There was no minimum length of follow-up required to include studies. We excluded all studies described as "open", "open label", or not blinded unless blinding was impossible. In addition we use a regular surveillance protocol to capture harms alerts from organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are added to the reviews as required. We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table ).
Table.
Important outcomes | Cure rates, relapse rates, adverse effects | ||||||||
Number of studies (participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
What are the effects of treatments for cellulitis and erysipelas? | |||||||||
1 (58) | Cure rates | Ceftriaxone v flucloxacillin | 4 | –3 | 0 | 0 | 0 | Very low | Quality points deducted for sparse data, no intention-to-treat analysis, and poor follow-up |
1 (81) | Symptom severity | Intravenous flucloxacillin plus intravenous benzylpenicillin v intravenous flucloxacillin | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and no intention-to-treat analysis. |
1 (112) | Clinical cure | Intravenous benzylpenicillin v intramuscular bipenicillin | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
1 (132) | Clinical cure | Cefazolin plus oral probenecid v ceftriazone | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
1 (69) | Clinical cure | Penicillin v roxithromycin | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
3 subgroup analysis (237) | Clinical cure | Oral azithromycin v oral erythromycin/oral cloxacillin/cefalexin | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for subgroup analysis of RCT |
1 subgroup analysis (34) | Clinical cure | Cefdinir v cefalexin | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and subgroup analysis of RCT |
1 subgroup analysis (11) | Clinical cure | Oral amoxicillin–clavulanate potassium v oral fleroxacin | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and subgroup analysis of RCT |
1 subgroup analysis (39) | Clinical cure | Fleroxacin v ceftazidime | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and subgroup analysis of RCT |
1 subgroup analysis (20) | Clinical cure | Ampicillin/sulbactam v cefazolin | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and subgroup analysis of RCT |
1 (73) | Clinical efficacy | Oral v intravenous penicillin | 4 | –3 | 0 | 0 | 0 | Very low | Quality points deducted for sparse data, incomplete reporting of results, quasi-randomisation, and uncertainty about methods of measuring outcomes |
1 (87) | Clinical cure rates | Different durations of antibiotics v each other | 4 | –1 | 0 | 0 | 0 | Moderate | Quality point deducted for sparse data |
What are the effects of treatments to prevent recurrence of cellulitis and erysipelas? | |||||||||
2 (72) | Recurrence rates | Antibiotics v no treatment | 4 | –1 | 0 | –1 | 0 | Low | Quality point deducted for sparse data. Directness point deducted for inclusion of predisposing conditions |
Type of evidence: 4 = RCT; 2 = Observational; 1 = Non-analytical/expert opinion. Consistency: similarity of results across studies Directness: generalisability of population or outcomes Effect size: based on relative risk or odds ratio
Glossary
- Low-quality evidence
Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
- Moderate-quality evidence
Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
- Very low-quality evidence
Any estimate of effect is very uncertain.
Disclaimer
The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients.To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.
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