Dr Caroline Ward summarises updated NICE guidance on assessing and prescribing for impetigo, cellulitis and erysipelas, leg ulcer infection, and diabetic foot infections in primary care

Photograph of Dr Caroline Ward

Dr Caroline Ward

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Read this article to learn more about:

  • diagnosing impetigo, cellulitis, erysipelas, leg ulcer infections, and diabetic foot infections
  • antimicrobial treatment options for these conditions
  • when to reassess and refer.

NICE has recently published three antimicrobial prescribing guidelines covering the management of infective skin conditions: impetigo,1 cellulitis and erysipelas,2 and leg ulcer infection.3 NICE has also included a new and updated section on antimicrobial prescribing in its diabetic foot infection guideline.4 The guidelines aim to optimise antibiotic use, reduce antibiotic resistance, and reduce variations in practice. There are links to useful visual summaries of the recommendations in each respective guideline.1–4

This article summarises each of the guidelines and updates for primary care, highlighting common themes and important differences in management.

Note: Not all of the treatments discussed in this article currently (June 2020) have UK marketing authorisation. The prescriber should follow relevant professional guidance, taking full responsibility for all clinical decisions. Informed consent should be obtained and documented. See the General Medical Council’s guidance on Good practice in prescribing and managing medicines and devices5 for further information.

Impetigo

Impetigo is a common superficial bacterial infection of the skin that is most often seen in children; the non-bullous form is most common in children aged 2–5 years, whereas bullous impetigo is more common in children under 2 years of age.6 Lesions can develop anywhere on the body but are most common on the face. It is a self-limiting, non-scarring condition, which usually resolves in 2–3 weeks without treatment. Complications are uncommon; however, untreated individuals remain infectious. In order to prevent outbreaks, children should be excluded from school or other childcare institutions until lesions are crusted and healed, or for 48 hours after commencing treatment. Good hygiene measures (e.g. washing hands regularly and using separate towels) help prevent spread of impetigo to other areas of the body and to other people.6

The two main clinical forms of impetigo are:1

  • non-bullous impetigo (see Figure 1; accounts for around 70% of cases7)
  • bullous impetigo (see Figure 2).

Impetigo is usually caused by Staphylococcus aureus, Streptococcus pyogenes or a combination of both. Lesions begin as thin-walled vesicles or pustules, which release exudate forming a characteristic golden crust.1

impet6_web

Figure 1: Non-bullous impetigo

© DermNet NZ.

Reproduced with permission.

Bullous impetigo is caused by toxin production, causing loss of cell adhesion in the superficial skin surface resulting in fluid filled lesions.8 Impetigo caused by methicillin-resistant Staphylococcus aureus (MRSA) is becoming increasingly common.

impet-bull_crop

Figure 2: Bullous impetigo

© Prof Raimo Suhonen, DermNet NZ

Reproduced with permission.

Primary care treatment of impetigo

Topical treatment

Topical hydrogen peroxide 1% cream (an antiseptic available on prescription or over the counter) is now recommended by NICE to be considered as first-line treatment for people with localised non-bullous impetigo who are not systemically unwell or at high risk of complications, as it was found to be as effective as topical antibiotics.1 Use of topical antibiotics can lead to a rapid development of antimicrobial resistance in causative organisms, therefore using hydrogen peroxide 1% cream is antibiotic-sparing and may reduce clinical challenges associated with development of resistance. NICE does note that other topical antiseptics are available to treat superficial skin infections; however there was no published evidence found to support their use in impetigo.1

Topical versus oral antibiotics

Table 1 in this article summarises the treatment choices for impetigo recommended by NICE.1 See NG153 (Tables 1 and 2) for detailed information and considerations, as well as dosages in different age groups, and consult individual summaries of product characteristics in the British National Formulary (BNF) or BNF for children for appropriate use and dosing.1

Topical antibiotics are as effective as oral antibiotics for treating impetigo. Topical treatments are likely to cause fewer side-effects, and applying a cream is usually straightforward for localised impetigo. Palatability and frequency of dosing of oral antibiotic liquids can be challenging in young children. In widespread non-bullous impetigo, clinicians should choose either a topical or oral antibiotic treatment after considering the distribution of the lesions and the wishes of the patient or parent/carer. Whether topical or oral treatment is used, a 5-day course should be prescribed; this can be increased to 7 days based on clinical judgement, depending on the severity and number of lesions.1

Combination treatment

Combination treatment with an oral and a topical antibiotic is no more effective in impetigo than either treatment alone. Combination treatment should therefore be avoided due to increased risk of adverse events and development of antimicrobial resistance.1

Table 1: Treatment choices in impetigo1
ConditionInitial treatmentSecond-line treatmentTreatment choices (for 5 days)

Localised non-bullous impetigo

Antiseptic: hydrogen peroxide 1% cream

Topical antibiotic

Topical

First choice:

  • Hydrogen peroxide 1% b.d./t.d.s

Hydrogen peroxide unsuitable (e.g. near eyes) or ineffective

  • Fusidic acid 2% t.d.s

Fusidic acid resistance suspected or confirmed:

  • Mupirocin 2% t.d.s

Oral antibiotics (immediate release; dosage dependent on age)

First choice:

  • Flucloxacillin q.d.s

Penicillin allergy:

  • Clarithromycin b.d.
  • Erythromycin (in pregnancy) q.d.s

Widespread non-bullous impetigo

Topical or oral antibiotic

Consider patient/parental preferences, practicalities of administration and potential side-effects

If topical antibiotic is unsuccessful, offer an oral antibiotic

Consider a skin swab for microbiological testing if initial treatment fails

Bullous impetigo or patient is systemically unwell or at high risk of complications

Oral antibiotic

Consider referral or seeking specialist advice referral, particularly in babies aged under 1 year 

 

Recurrent impetigo

Oral antibiotic

Consider seeking specialist advice or hospital referral for people who have impetigo that recurs frequently

Perform a skin swab

Consider a nasal swab and treatment for decolonisation[A]

Review antibiotic with swab result and change to a narrow-spectrum antibiotic if possible

[A] Decolonisation is the use of topical treatments (antiseptic body wash, nasal ointment, or a combination of both) and personal hygiene measures to remove the bacteria causing the infection from the body.

Cellulitis and erysipelas

Cellulitis is an acute bacterial infection of the dermis and subcutaneous tissue.9 Erysipelas is a superficial infection affecting the upper layers of the skin.9 Symptoms and signs can overlap so it is not always easy to differentiate them clinically; however, the recommended treatment is the same for both.2 In cellulitis and erysipelas, the most common causative pathogens are Streptococcus pyogenes and Staphylococcus aureus. Common organisms include: Streptococcus pneumoniae, Haemophilus influenza, Gram-negative bacilli and anaerobes.9

Diagnosis of cellulitis can be clinically challenging as many conditions can mimic the signs and symptoms. Antibiotics will always be indicated in cellulitis, therefore it is important to ensure as far as possible that the diagnosis is correct prior to treatment in order to limit unnecessary use of antimicrobials.

Cellulitis is more commonly seen in the lower limbs and usually affects only one limb. Bilateral cellulitis is very rare9 and should prompt a rethink of the diagnosis. Infection around the eyes or the nose (the triangle from the bridge of the nose to the corners of the mouth, or immediately around the eyes, including periorbital cellulitis) is of greater concern because of the risk of a serious intracranial complication.2

Typical features are an acute onset of red, painful, hot, swollen, and tender skin that spreads rapidly. Fever, malaise, nausea, shivering, and rigors may accompany or precede skin changes.9 Clinicians should consider marking the extent of infection with a single-use surgical marker pen prior to treatment in order to assist the monitoring of response to treatment.2

Table 2 shows some common differential diagnoses for cellulitis (NB these lists are not exhaustive).9

Table 2: Common differential diagnoses of cellulitis9
Unilateral leg erythemaBilateral leg erythema[A]
  • Deep vein thrombosis
  • Septic arthritis
  • Acute gout
  • Ruptured Baker’s cyst
  • Thrombophlebitis
  • Cutaneous abscess
  • Erysipelas
  • Varicose eczema/venous insufficiency
  • Contact dermatitis
  • Lipodermatosclerosis
  • Cutaneous small vessel vasculitis
  • Lymphoedema
  • Oedema with blisters
  • Panniculitis

[A] Usually bilateral but if worse on one side, it may be difficult to exclude superimposed cellulitis

Leg ulcer infection

As with cellulitis, diagnosis of infection within a leg ulcer can be challenging. Few leg ulcers are clinically infected, but most are colonised by bacteria.3 Antibiotics do not promote healing when a leg ulcer is not infected,3 therefore correct identification of infection is key to maintaining antimicrobial stewardship.

There are many causes of leg ulcer, and it is important that any underlying conditions, such as venous insufficiency and oedema, are managed optimally to promote healing and prevent infection.3

Symptoms and signs of an infected leg ulcer include redness or swelling spreading beyond the ulcer, localised warmth, increased pain, or fever.3

Diabetic foot infection

Diabetic foot infection can lead to serious complications that can be limb-threatening. It is important that treatment is initiated promptly and managed/monitored in the appropriate setting.

As with leg ulcers, most diabetic foot wounds are likely to be colonised with bacteria. Diabetic foot infection has at least two of the following:4

  • local swelling or induration
  • erythema
  • local tenderness or pain
  • local warmth
  • purulent discharge.

Treatment is based on the severity of foot infection and is classified into mild, moderate, and severe:4

  • mild: local infection with 0.5 cm to less than 2 cm erythema around the ulcer. Other causes of inflammatory response (e.g. trauma, gout, acute Charcot neuro-osteoarthropathy, fracture, thrombosis, and venous stasis) should be excluded
  • moderate: local infection with more than 2 cm erythema around the ulcer or involving deeper structures (such as abscess, osteomyelitis, septic arthritis, or fasciitis) and no signs of systemic inflammatory response
  • severe: local infection with signs of a systemic inflammatory response (e.g. temperature of more than 38°C or less than 36°C, increased heart rate, or increased respiratory rate). 

Many moderate and all severe infections should be referred to hospital, and all infections not referred to hospital require urgent (within 1 working day) referral to the local diabetic foot services.4

Taking swabs for microbiological sampling

Swabbing of skin infections should be undertaken judiciously due to the possibility of culturing colonising rather than infective organisms, leading to the initiation of inappropriate treatment.

Impetigo, cellulitis, and leg ulcers often have predictable infective organisms and therefore empirical antibiotic treatment without swabbing is suitable in most cases. See Table 1 (above) and Table 3 for further details of when swabbing is appropriate for these conditions.

In people with diabetic foot infection, prompt empirical treatment of the infection is necessary to prevent serious complications, including limb-threatening infections. However, it is important that a deep swab is taken for microbiological testing before, or as close as possible to, the start of antibiotic treatment. This allows empirical antibiotic treatment to be changed if needed when results are available.4

Primary care treatment of cellulitis and erysipelas, infected leg ulcer, and diabetic foot infection in adults

Table 3 summarises the initial management and antibiotic choices in adults with cellulitis, leg ulcer infection, and diabetic foot infection as these conditions most commonly present in adults. See NG141, Table 2, for treatment of cellulitis infections in under 18s;2 specialist advice should be sought regarding prescribing for any suspected diabetic foot infection or leg ulcer in children and young people aged under 18 years.3,4

Table 3: Summary of initial management of and antibiotic treatment for skin infection in adults2–4
ConditionSwab recommendationsFirst choice antibiotic 
(immediate release)
Second choice antibiotic or penicillin allergy
(immediate release)
Course length (days)

Cellulitis and erysipelas near the eyes/nose[A],[B]

Swab only if skin broken and uncommon pathogen suspected (e.g. exposure to water-borne organisms or infection acquired outside the UK)

Co-amoxiclav 500/125 mg t.d.s

Clarithromycin 500 mg with metronidazole 400 mg t.d.s

7[C]

Cellulitis and erysipelas

Flucloxacillin 500 mg to 1 g q.d.s[D]

Clarithromycin 500 mg b.d.

Doxycycline 200 mg on day 1 then 100 mg o.d.

In pregnancy: erythromycin 500 mg q.d.s

5–7[C]

Leg ulcer

Do not take a sample for microbiological testing at initial presentation, even if the ulcer might be infected. If the infection is worsening or not improving as expected, consider microbiological testing.

Doxycycline 200 mg on day 1 then 100 mg o.d. (can be increased to 200 mg daily)

Clarithromycin 500 mg b.d.

In pregnancy: erythromycin 500 mg q.d.s

(Alternative choices in leg ulcer: co-amoxiclav 500/125 mg t.d.s or

Co-trimoxazole (in penicillin allergy) 960 mg b.d.)[E]

7[C]

Mild diabetic foot infection

Deep swab from wound base at initial presentation

Review antibiotic when swab results available, change according to results, using a narrow-spectrum antibiotic, if appropriate

May require admission or investigation to rule out underlying deep-seated infection

Refer to local diabetic foot service within 1 working day if not admitted

Moderate diabetic foot infection

Flucloxacillin 1 g q.d.s[D] +/- metronidazole 400 mg t.d.s

Co-amoxiclav 500/125 mg t.d.s

Penicillin allergy:

Co-trimoxazole 960 mg b.d.[C] +/- metronidazole 400 mg t.d.s[E]

Refer to hospital if no/incomplete response to initial treatment

Mini-mum of 7

Severe diabetic foot infection

Refer to hospital immediately

[A] Consider seeking specialist advice. Give oral antibiotics first line if the person can take oral medicines, and the severity of their symptoms does not require intravenous antibiotics.

[B] Infection around the eyes or the nose (the triangle from the bridge of the nose to the corners of the mouth, or immediately around the eyes including periorbital cellulitis) is of more concern because of risk of a serious intracranial complication.

[C] In cellulitis and mild diabetic foot infection, a longer course (up to 14 days in total) may be needed based on clinical assessment. However, skin does take time to return to normal, and full resolution at 5 to 7 days is not expected.

[D] The upper dose of 1 g 4 times a day would be off-label, as defined in the NICE glossary.

[E] Use would be off-label. See British National Formulary (BNF) for information on monitoring of patient parameters.

Reassessment

It is important to counsel patients to seek medical attention if they become systemically unwell or infection is rapidly worsening at any time.

Diabetic foot infection can lead to serious limb-threating complications so should be reassessed at 1–2 days if not improving.4

Cellulitis and leg ulcer infections should be reassessed if symptoms worsen rapidly, the person becomes systemically very unwell, or there is no improvement after 2–3 days.2

Impetigo is generally a self-limiting condition so reassessment can be delayed until the end of the 5-day initial treatment period unless symptoms worsen rapidly or significantly at any time.1

When reassessing unresponsive skin infections, it is important to reconsider whether the initial diagnosis is correct; for example, herpes simplex can mimic impetigo, and many conditions can present as cellulitis.1

Hospital referral

Consider hospital referral or seeking specialist advice for all those with symptoms or signs of a more serious condition such as osteomyelitis, septic arthritis, necrotising fasciitis, limb ischaemia, gangrene, and for those who are systemically unwell, at high risk of complications, have spreading infection not responding to oral antibiotics, or who cannot take oral antibiotics.1–4,9

Also consider referral or specialist advice for immunocompromised people with widespread impetigo and those with bullous impetigo, particularly babies.1

Necrotising fasciitis

In any patient presenting with skin infection, it is vital to exclude necrotising fasciitis, a rare but destructive and rapidly progressive infection that involves deep tissues, fascia, and muscles.10 Necrotising fasciitis has a significant mortality rate and may require extensive surgical debridement.10 The presenting signs are often non-specific (redness, swelling, and pyrexia); however, patients may be systemically unwell. The key symptom is pain disproportionate to the clinical signs.10 Immediate surgical referral and admission to hospital is vital if the condition is suspected.

Summary

The NICE guidelines discussed in this article provide recommendations on the use of antimicrobials for infective skin conditions, with the aim of optimising antibiotic use and reducing antibiotic resistance. Topical and oral antibiotics are equally effective in treating non-bullous impetigo. The recommended first-line treatment for localised non-bullous impetigo is now hydrogen peroxide 1% cream rather than an antibiotic. Skin swabs at initial presentation are unnecessary for most cases of impetigo, cellulitis, and leg ulcers, but may be considered if there is no response to initial treatment or if infection recurs. Swabbing and outpatient referral or hospital admission should be undertaken at initial presentation for all diabetic foot infections. It is vital not to miss rare but serious underlying complications such as necrotising fasciitis.

Dr Caroline Ward

GP and member of the NICE managing common infections advisory committee

COVID-19 considerations

  • Current guidance states that anyone with symptoms of COVID-19 needs to self-isolate for 7 days. If fever persists at 7 days, they must remain in self-isolation until their temperature returns to normal. Other household members need to self-isolate for 14 days; if anyone else in the household starts displaying symptoms, they need to stay at home for at least 7 days from when the symptoms appear, regardless of what day they are on in the original 14 day isolation period.11

Remote consultations

  • Many patients with the conditions discussed in this article will be suitable to be managed remotely in primary care via telephone consultation, but remote assessment is likely to be enhanced by video consultation or photographs
  • In cellulitis, patients can be asked to draw around erythematous margins to monitor response to treatment
  • Some patients may have thermometers and blood-pressure monitoring equipment at home and may be able to provide readings. However, it is important to bear in mind that these devices are unlikely to have been recently calibrated. It is advisable to ask about the type of equipment used, as forehead chemical thermometers are unreliable.12 Automated blood pressure cuffs may read inaccurately in those with pulse irregularity such as atrial fibrillation13
  • A face-to-face review should be considered if the patient is febrile, or feels very unwell, or is not responding to initial treatment
  • It is important to ask about symptoms that may indicate sepsis, such as:14
    • recent fever or rigors
    • signs of dehydration, such as reduced urine output in the past 18 hours
    • altered behaviour, mental state, irritability (in children), or new confusion (in adults)
    • sudden change or deterioration in functional ability
    • possible risk factors for sepsis, including co-morbidities and drug treatments
    • possible risk factors for antibiotic resistance, such as recent or previous antibiotic therapy, previous hospital admissions, and residency in a care home
    • immunisation status (particularly in infants and young children)
  • It remains important to assess and take swabs in diabetic foot infections, so these patients may be less suitable for remote assessment.

Implementation actions for STPs and ICSs

written by Dr David Jenner, GP, Cullompton, Devon

The following implementation actions are designed to support STPs and ICSs with the challenges involved with implementing new guidance at a system level. Our aim is to help you consider how to deliver improvements to healthcare within the available resources. 

  • Review the NICE recommendations highlighted in this article in a multi-professional forum 
  • Update local joint formularies to reflect local policy and choices
  • Consider local education programmes for primary care professionals, particularly around the use of 1% hydrogen peroxide cream in localised, non-bullous impetigo, as few professionals will be familiar with this treatment
  • Publish information leaflets for parents of children with impetigo to explain infectivity and why antibiotics are not being used
  • Ensure that any local care pathways for management of diabetic foot infections reflect recommendations in NG19 and set out clear thresholds for referral to specialist care
  • Facilitate remote consultation options, particularly video consultation, for assessment of skin infections where COVID-19 risk is high.

STP=sustainability and transformation partnership; ICS=integrated care system; NG=NICE guideline

Implementation actions for clinical pharmacists in general practice

written by Nicola Cree, Pharmaceutical Services Manager, Soar Beyond Ltd

The following implementation actions are designed to support clinical pharmacists in general practice with implementing the guidance at a practice level.

Practice pharmacists are well placed to help embed and audit new antibiotic prescribing guidance into primary care. The Network Contract DES[A] states that a key responsibility of PCN pharmacists is to ‘provide leadership on person-centred medicines optimisation (including ensuring prescribers in the practice conserve antibiotics in line with local antimicrobial stewardship guidance)’. To achieve this:

  • provide initial training to practice staff to support implementation of the guidance
  • audit antimicrobial prescribing practices in the skin conditions covered by the guidelines to assess prescribing practice, including the type of antibiotic prescribed and the length of the course
  • report audit findings to practice staff to help highlight where changes in prescribing habits can support improvements in antimicrobial stewardship.

Some clinical pharmacists will also be involved in running minor illness clinics (if appropriately trained to undertake this activity in practice). These pharmacists should:

  • be familiar with the signs and symptoms, management and red flag symptoms for infective skin conditions and follow the NICE guidelines when prescribing
  • lead by example and champion antibiotic stewardship in their role
  • have clear objectives, when creating an audit, about the outcomes you expect to measure, how you will measure the outcomes, and how you will analyse and provide feedback.

Further guidance on the role of practice pharmacists in antimicrobial stewardship is available from the SMART website. If you have clinical pharmacists in your practice or organisation, contact Soar Beyond to see how we can support with their clinical delivery, training and development soarbeyond.co.uk

DES=Directed Enhanced Services; PCN=Primary Care Network

[A] NHS England and NHS Improvement.Network Contract Directed Enhanced Service Contract specification 2020/21 – PCN Requirements and Entitlements. March 2020. Available at:  www.england.nhs.uk/wp-content/uploads/2020/03/network-contract-des-specification-pcn-requirements-entitlements-2020-21.pdf

References

  1. NICE.Impetigo: antimicrobial prescribing. NICE Guideline 153. NICE, 2020. Available at: www.nice.org.uk/ng153
  2. NICE. Cellulitis and erysipelas: antimicrobial prescribing. NICE Guideline 141. NICE, 2019. Available at: www.nice.org.uk/ng141
  3. NICE. Leg ulcer infection: antimicrobial prescribing. NICE Guideline 152. NICE, 2020. Available at: www.nice.org.uk/ng152
  4. NICE. Diabetic foot problems: prevention and management. NICE Guideline 19. NICE, 2015 (updated 2019). Available at: www.nice.org.uk/ng19
  5. General Medical Council. Good practice in prescribing and managing medicines and devices. GMC, 2013. Available at: www.gmc-uk.org/ethical-guidance/ethical-guidance-for-doctors/prescribing-and-managing-medicines-and-devices
  6. Primary Care Dermatology Society. Impetigo. PCDS, 2015 (last updated 2018). www.pcds.org.uk/clinical-guidance/impetigo (accessed 22 May 2020).
  7. Hartman-Adams H, Banvard C, Juckett G. Impetigo: diagnosis and treatment. Am Fam Physician 2014; 90 (4): 229–235.
  8. DermNetNZ. Impetigo. dermnetnz.org/topics/impetigo/ (accessed 22 May 2020).
  9. NICE. Cellulitis—acute. NICE Clinical Knowledge Summary. NICE, 2019. Available at: cks.nice.org.uk/cellulitis-acute (accessed 26 May 2020).
  10. Diab J, Bannan A, Pollitt T. Necrotising fasciitis. BMJ 2020; 369: m1428.
  11. Public Health England. Stay at home: guidance for households with possible or confirmed coronavirus (COVID-19) infection. PHE, 2020 (updated 28 May 2020). Available at: www.gov.uk/government/publications/covid-19-stay-at-home-guidance/stay-at-home-guidance-for-households-with-possible-coronavirus-covid-19-infection
  12. NICE. Fever in under 5s: assessment and initial management. NICE Guideline 143. NICE, 2019. Available at: www.nice.org.uk/ng143
  13. NICE. Hypertension in adults: diagnosis and management. NICE Guideline 136. NICE, 2019. Available at: www.nice.org.uk/ng136
  14. NICE. Sepsis. NICE Clinical Knowledge Summary. NICE, 2020. Available at: cks.nice.org.uk/sepsis