Recommendations

Urgent

Think 'Could this be sepsis' based on acute deterioration in a patient in whom there is clinical evidence or strong suspicion of infection.[27][28][29]

  • Use a systematic approach, alongside your clinical judgement, for assessment; urgently consult a senior clinical decision-maker (e.g., ST4 level doctor in the UK) if you suspect sepsis.[27][28][29][30]

  • Refer to local guidelines for the recommended approach at your institution for assessment and management of the patient with suspected sepsis.

In practice, treat cellulitis and erysipelas similarly, with empirical antibiotics.[21] 

Urgently (in practice, within 30 minutes of initial clinical assessment) refer for senior review patients presenting to hospital with: 

  • Necrotising fasciitis. These patients will usually be managed by surgery or orthopaedics depending on local policy.[20] See  Necrotising fasciitis 

  • Orbital or peri-orbital cellulitis. These patients will usually be managed by ophthalmology. See  Peri-orbital and orbital cellulitis

Prioritise any underlying serious conditions that may be associated with the cellulitis such as:[21]

In the community , refer patients to hospital if they have any symptoms or signs suggesting a more serious illness or condition, such as necrotising fasciitis, septic arthritis, osteomyelitis, or orbital cellulitis.[21]

Key Recommendations

Admit patients with:

  • Signs of systemic illness, such as:

    • Confusion[20][23] 

    • Tachycardia[20][23]

    • Tachypnoea[23]

    • Hypotension[20][23]

  • Suspected sepsis[23]

  • Spreading cellulitis or erysipelas not responding to oral medication[21][23]

  • Severe immunocompromising factors[23]

  • Poor adherence to therapy[23]

  • A comorbidity that may complicate or delay their recovery, or that is unstable[23]

  • Limb-threatening infection due to vascular compromise[23]

  • Necrotising fasciitis[20][23]

  • Orbital cellulitis.

Before treating, outline the area of infection with a single-use surgical marker pen so you can track progress over time.[23]

Provide adequate analgesia.[23]

Consider whether the patient needs hydration.[23]

Manage underlying conditions that may predispose to cellulitis or erysipelas.[20][21][23]

Full recommendations

Think 'Could this be sepsis' based on acute deterioration in a patient in whom there is clinical evidence or strong suspicion of infection.[27][28][29] See  Sepsis in adults

  • The patient may present with non-specific or non-localised symptoms (e.g., acutely unwell with a normal temperature) or there may be severe signs with evidence of multi-organ dysfunction and shock.[27][28][29]

  • Remember that sepsis represents the severe, life-threatening end of infection.[35]

Use a systematic approach (e.g., National Early Warning Score 2 [NEWS2]), alongside your clinical judgement, to assess the risk of deterioration due to sepsis.[28][29][36][37] Consult local guidelines for the recommended approach at your institution.

Arrange urgent review by a senior clinical decision-maker (e.g., ST4 level doctor in the UK) if you suspect sepsis:[30]

  • Within 30 minutes for a patient who is critically ill (e.g., NEWS2 score of 7 or more, evidence of septic shock, or other significant clinical concerns).

  • Within 1 hour for a patient who is severely ill (e.g., NEWS2 score of 5 or 6).

Follow your local protocol for investigation and treatment of all patients with suspected sepsis, or those at risk. Start treatment promptly. Determine urgency of treatment according to likelihood of infection and severity of illness, or according to your local protocol.[30][37]

Necrotising fasciitis is life-threatening, so give empirical broad-spectrum antibiotics and refer (in practice, within 30 minutes of initial clinical assessment) for senior review, or to surgery or orthopaedics where patients with this condition are usually managed.[20] See  Necrotising fasciitis

Orbital cellulitis can be sight-threatening, so for orbital or peri-orbital cellulitis, give empirical broad-spectrum antibiotics and refer (in practice, within 30 minutes of initial clinical assessment) for senior review or to ophthalmology, where patients with these conditions are usually managed. See  Peri-orbital and orbital cellulitis

For concurrent:

Decide whether your patient needs admission based on the Eron severity classification.[23][42] See Severity assessment under Diagnosis recommendations for information on the Eron severity classification.

Admission criteria based on Eron severity classification[23][42]

Classification

Site of management

Class I

Outpatient

Class II

Admit to hospital for up to 48 hours and discharge on outpatient parenteral antimicrobial therapy, if available

Class III and IV

Admit until clinical improvement is evident and comorbidities are stabilised

Other indications for admission include:

  • Signs of systemic illness, such as:[23] 

    • Confusion[20][23] 

    • Tachycardia[20][23]

    • Tachypnoea[23]

    • Hypotension[20][23]

  • Suspected sepsis[23]

  • Spreading cellulitis or erysipelas not responding to oral medication[20] 

  • Severe immunocompromising factors[20] 

  • Limb-threatening infection due to vascular compromise[23] 

  • Necrotising fasciitis[20][23]

  • Orbital cellulitis.

Be aware that some of these presentations require urgent referral. See Physical examination under Diagnostic recommendations for more information.

Consider admitting, or referring for specialist advice, patients with:

  • Rapid progression of symptoms

  • Lymphangitis[21]

  • Facial cellulitis (unless mild)

  • Infection near the eyes or nose, including peri-orbital cellulitis[21] 

  • Suspected unusual pathogens[21]

  • Symptoms and signs of osteomyelitis[21]

  • Symptoms and signs of septic arthritis[21]

  • A comorbidity that may complicate or delay recovery, or that is unstable[23] 

  • Poor adherence to therapy[20]

  • Inability to take oral antibiotics.[21]

Prescribe adequate pain relief.[23] This may be paracetamol, or a non-steroidal anti-inflammatory drug (NSAID; e.g., ibuprofen, diclofenac). In view of their habit-forming risk, opioids are reserved as a last resort in practice. 

Practical tip

Be cautious and monitor renal function closely when prescribing NSAIDs to older people and people with comorbidities such as hypertension and heart disease. Be aware that NSAIDs may increase the risk of acute kidney injury in people with sepsis.

Monitor and manage fever with an antipyretic, such as paracetamol, if clinically indicated.[23]

  • In practice, this means treating the fever if it is making the patient feel more unwell. Do not treat the fever merely to maintain euthermia.

Consider whether your patient needs intravenous or oral hydration.[23]

Before treating, consider drawing around the edge of the infection with a single-use surgical marker pen to monitor progress. Note that the extent of the infection may be less clear on darker skin tones.[21]

Elevate an affected lower leg to reduce pain, swelling, and damage to the venous system.[23] Consider using a bed cradle.[23] 

Consider thromboprophylaxis based on risk stratification as for all admitted patients in your hospital. Follow your local protocol.

Proactively aspirate and/or deroof any blisters using aseptic technique.[23] Send aspirate for microbiological processing. If in doubt, seek specialist advice.[23]

Manage wound exudate if the skin ulcerates.[23] In practice, use absorbent but non-adhesive dressings according to your local wound management protocols.

Monitor inflammatory markers to assess response to treatment.[23] In practice, take blood for processing every 24 to 48 hours. 

Practical tip

Do not prescribe compression bandages in the acute phase of cellulitis.[23] 

Manage any underlying conditions that may predispose to cellulitis, such as:[20][21][57]

Refer patients with chronic lymphoedema to lymphoedema services.[23]

Treat cellulitis and erysipelas with empirical antibiotics.[21] 

  • Aim to start antibiotics immediately after taking samples for microbiological testing if this is indicated.[32][33][34]

  • There is little high-quality evidence to indicate the most appropriate antibiotics, routes of administration, or duration of treatment for cellulitis and erysipelas.[58] [ Cochrane Clinical Answers logo ] ​​​

  • Offer an antibiotic that is effective against streptococci and Staphylococcus aureus (the most common bacteria causing cellulitis and erysipelas) in the first instance, but note that infection can also be caused by Streptococcus pneumoniae, Haemophilus influenzae, gram-negative bacilli, and anaerobes.[21]

  • Consult your local antibiotic protocol to determine the most appropriate choice, based on local pathogen prevalence and antibiotic resistance patterns.[59]

  • Take account, also, of individual patient factors, including:

    • Symptom severity[21]

    • Infection site[21]

    • Potential uncommon pathogens (e.g., from a penetrating injury, exposure to water-borne organisms, or infection acquired outside the UK)[21]

    • Previous microbiological results from a swab[21]

    • The patient’s MRSA status (if known)[21]

    • History of anaphylactic reaction or immediate urticarial rash to a penicillin.[23] 

  • Seek specialist advice for patients with immunocompromising factors.

Practical tip

Current or recent antibiotic therapy may also influence your treatment choice. In practice, if a patient comes to you with no clinical improvement after a few days of taking oral antibiotics for cellulitis, have a low threshold for adding in a second antibiotic, or changing to intravenous administration. In practice, ask a senior clinician if you are in doubt about how to proceed if a previous antibiotic has been given.

It is worth taking a swab if the wound is open or wet to check whether the organisms may be resistant to their current treatment. Bear in mind that some increase in redness may occur in the first 24 to 48 hours after starting treatment.[21] This may be due to toxin release.[23] 

Evidence: Choice of empirical antibiotic

There is no difference in clinical outcomes between most antibiotics from systematic review and randomised controlled trial (RCT) evidence. The UK National Institute for Health and Care Excellence (NICE) guidance is therefore based on expert experience, resistance data, and general principles of antimicrobial stewardship.

In September 2019 NICE conducted an evidence review on antimicrobial prescribing in cellulitis that included the choice of antibiotic in adults.[60] 

  • NICE identified four systematic reviews (SRs; three with meta-analysis) and five additional RCTs.

    • All RCTs were multicentre, international studies.

    • Two SRs were of adults only; the other two included children as well. Four RCTs were in adults (three studies: ≥18 years old; one study: ≥65 years old), and the age-range of the other RCT was unclear.

    • Two SRs were in people with cellulitis or erysipelas only; two were in people with skin and skin-structure infections with cellulitis analysed as a subgroup. One RCT was in people with cellulitis or erysipelas and a comorbid condition. The other four RCTs were in people with complicated skin and skin-structure infections with cellulitis analysed as a subgroup, and therefore they may have been underpowered with limited outcomes reported.

    • There were differences in the definition of cellulitis, severity of infection (and how this was defined), setting, and length of follow-up.

    • Three SRs and three RCTs did not report the site of infection.

  • Overall there was no difference for all except one comparison and outcome. Therefore, NICE based its recommendations on expert experience regarding severity and site of infection, risk of complications, and resistance data, and by considering broader guidance on antimicrobial stewardship.[59][61][62]

A systematic review with some meta-analysis (search date December 2018) assessed RCT evidence of antibiotic treatment of cellulitis and erysipelas in adults and children.[58]

  • The review found 36 studies on choice of antibiotic, all of which were considered low-quality evidence.

  • One third of studies had cellulitis as a primary diagnosis; the rest reported it as a subgroup.

  • The review concluded that there was no evidence for any antibiotic over another, including antibiotics with activity against MRSA.

Before treating, consider drawing around the edge of the infection with a single-use surgical marker pen to monitor progress. Note that the extent of the infection may be less clear on darker skin tones.[21][Figure caption and citation for the preceding image starts]: Drawing around the edge of the infectionEdwards G, et al. BMJ. 2020;368:m54 [Citation ends].Drawing around the edge of the infection

Immunocompromising factors

For those who have immunocompromising factors, seek specialist advice. Recommendations from the Infectious Diseases Society of America include broad-spectrum empirical antibiotics.[20]

Route of administration

For patients with mild symptoms of Eron class I severity, give antibiotics orally if the patient can tolerate this.[21][23]

For patients with more severe symptoms, Eron classes II to IV, give antibiotics intravenously.[21][23] See Severity assessment under Diagnosis recommendations for information on the Eron severity classification. 

Practical tip

Do not use topical antibiotics for cellulitis.[23] 

Severe infection

For patients with severe infection, give intravenous flucloxacillin in the first instance.[21] If flucloxacillin is unsuitable (e.g., patient has a penicillin allergy), give intravenous clarithromycin.[21]

Alternative antibiotics for severe infection include:[21]

  • Amoxicillin/clavulanate, or

  • Cefuroxime, or

  • Clindamycin, or

  • Ceftriaxone (only for ambulatory care).

Infection around the eyes and nose

For patients with infection around the eyes and nose (the triangle from the bridge of the nose to the corners of the mouth, or immediately around the eyes, which is associated with risk of a serious intracranial complication), consider seeking specialist advice regardless of severity and give oral or intravenous:[21]

  • Amoxicillin/clavulanate as a first choice, or

  • Clarithromycin plus metronidazole.

MRSA

For patients with suspected or confirmed MRSA infection, add in one of the following antibiotics to the first-line antibiotic regimen:[21]

  • Vancomycin

  • Teicoplanin

  • Linezolid (specialist use only).

Non-severe infection

For patients with mild disease give oral flucloxacillin as a first choice, unless the patient is unable to take oral antibiotics.[21]

For patients with penicillin allergy or if flucloxacillin is unsuitable, give:[21]

  • Clarithromycin, or

  • Doxycycline.

Immersion injuries

For patients with fresh-water exposure, add an antibiotic with Aeromonas hydrophila cover, such as ciprofloxacin to the first-line antibiotic regimen.[23] In practice, considering the safety issues with fluoroquinolones, alternative antibiotics include doxycycline or trimethoprim/sulfamethoxazole. Seek advice from microbiology.

More info: EMA and MHRA restrictions on the use of fluoroquinolone antibiotics

In November 2018, the European Medicines Agency (EMA) completed a review of serious, disabling, and potentially irreversible adverse effects associated with systemic and inhaled fluoroquinolone antibiotics. These adverse effects include tendonitis, tendon rupture, arthralgia, neuropathies, and other musculoskeletal or nervous system effects.

  • As a consequence of this review, the EMA now recommends that fluoroquinolone antibiotics be restricted for use in serious, life-threatening bacterial infections only. Furthermore, it recommends that fluoroquinolones should not be used for mild to moderate infections unless other appropriate antibiotics for the specific infection cannot be used, and should not be used in non-severe, non-bacterial, or self-limiting infections. Patients who are older, have renal impairment, or have had a solid organ transplant, and those being treated with a corticosteroid are at a higher risk of tendon damage. Co-administration of a fluoroquinolone and a corticosteroid should be avoided.[63] The UK-based Medicines and Healthcare products Regulatory Agency (MHRA) supports these recommendations.[64]

  • Consult with a microbiologist about whether a fluoroquinolone is an appropriate option for your patient.

For patients with salt-water exposure, add an antibiotic with Vibrio vulnificus cover, such as doxycycline, to the first-line antibiotic regimen.[25]

If the patient is already on doxycycline for first-line empirical treatment, use a combination of doxycycline plus ciprofloxacin for both fresh-water and salt-water exposure.

Bites

Use antibiotics targeted against likely organisms, depending on the source of the bite. See  Animal bites.

Switch to pathogen-targeted antibiotics in line with microbiology culture and sensitivity results when they become available.[59]

Consult a microbiologist or an infectious diseases consultant about appropriate antibiotic choices in line with local protocols.

Review intravenous antibiotics by 48 hours and consider switching to oral antibiotics if possible.[21]

Consider switching from intravenous to oral antibiotics when:[23] 

  • The patient’s temperature is settling

  • Redness is reducing

  • Comorbidities are stable

  • Inflammatory markers are falling.

In practice, start oral antibiotics that:

  • Have the same spectrum of activity as the intravenous antibiotics that achieved clinical response

  • Are in line with microbiology culture and sensitivity results.

Prescribe antibiotics for a total of 5 to 7 days (7 days if the area around the nose and eyes is involved) and for 10 days in patients with risk factors.[20][21][65] See the Risk factors section under Epidemiology

In practice, for patients with immersion injuries, continue treatment for at least 7 days, but you may decide to narrow treatment when a pathogen has been identified.

A longer course of antibiotics may be needed based on clinical assessment.[21]

Reassess your patient if:[21]

  • Symptoms worsen, for example:

    • Significant redness and swelling spreading beyond 48 hours after initial presentation

    • Pain becomes severe

  • You suspect systemic involvement

  • There is no improvement within 2 to 3 days.

Practical tip

Some increase in redness may occur in the first 24 to 48 hours after starting treatment.[21] This may be due to toxin release.[23]

Even after an effective course of antibiotics, complete resolution at 5 to 7 days is unlikely. The skin may take several weeks to return to normal.[21]

If the patient’s condition is not improving, consider whether:[21]

  • The diagnosis is correct; consider other possible diagnoses

  • You have managed any underlying conditions optimally

  • There are symptoms or signs that suggest more serious illness; these may need onward referral

  • Results from microbiological testing support your empirical treatment; change the antibiotic if necessary

  • Bacterial resistance may have developed due to previous antibiotics; if so, a change in treatment may be required

  • A swab for microbiological testing might be helpful if this has not been done already (if skin is broken).

If there is no improvement in symptoms and signs after 48 hours, or the diagnosis is in doubt, seek advice from a senior colleague, a microbiologist, a dermatologist, or a surgeon.[23]

Intravenous antibiotics can be administered in the community if the patient has the necessary support and this resource is available in your area. [21][23]

Practical tip

In practice, whether the patient has been treated in hospital or has been receiving intravenous treatment at home, check for signs of re-emerging infection 24 to 48 hours after starting oral antibiotic treatment.

Recurrent cellulitis and erysipelas

Address any predisposing factors. See the Risk factors section under Epidemiology

  • Patients with an episode of cellulitis have annual recurrence rates of 8% to 20%, with the risk being higher if the legs were involved.[20] 

Do not routinely offer antibiotic prophylaxis.[21]

Consult with a dermatologist or an infectious diseases consultant about whether to prescribe a 6-month trial of phenoxymethylpenicillin prophylaxis in adults treated at least twice in hospital for cellulitis or erysipelas in the previous 12 months.[21][23] [ Cochrane Clinical Answers logo ] ​​[Evidence B] Low-dose erythromycin can be used in patients with penicillin allergy. Tell patients that their prophylaxis should be reviewed at least every 6 months.[21]

In patients with chronic oedema and cellulitis, compression therapy may help reduce recurrence.[66]

Practical tip

Based on expert opinion and resistance data, the UK National Institute for Health and Care Excellence suggests avoiding the use of the same antibiotic for treatment and prophylaxis.[21]

Patient information

See the Patient discussions section.

Refer to hospital or seek specialist advice for patients with:[21]

  • Severe systemic symptoms

  • Infection near the eyes or nose (including peri-orbital cellulitis)

  • A penetrating injury

  • Exposure to water-borne organisms

  • Infection from outside the UK

  • Infection that is spreading despite oral antibiotics

  • Lymphangitis

  • Inability to tolerate oral antibiotics (and if intravenous antibiotics cannot be given at home or in the community).

Advise the patient to access healthcare advice for reassessment and consideration of admission if:[21]

  • Symptoms worsen, for example:

    • Significant redness and swelling spreading beyond 48 hours after initial presentation

    • Pain becomes severe

  • Symptoms develop suggesting systemic involvement

  • There is no improvement within 2 to 3 days.

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