Cellulitis - Acute - NICE CKS PDF

Cellulitis - acute - NICE CKS 06/04/2020, 20:47
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Cellulitis - acute
Last revised in December 2019 Next planned review by April 2024
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Changes
December 2019 — minor update. Text amended to clarify antibiotic choices for children with a true penicillin allergy.
October 2019 — minor update. The topic has been updated to align with the National Institue for Health and Care
Excellence (NICE) guideline Cellulitis and erysipelas: antimicrobial prescribing [NICE, 2019a (/cellulitis-acute#!references)].
April 2019 — reviewed. A literature search was conducted in March 2019 to identify evidence-based guidelines, UK policy,
systematic reviews, and key randomized controlled trials published since the last revision of this topic. No major changes to
the recommendations have been made. However, the topic has undergone minor restructuring, and a prescribing information
section has been added for doxycycline, which is now recommended as the first-line treatment for a person with a penicillin
allergy who is also taking a statin.
Previous changes Back to top
December 2016 — minor update. The dose of clarithromycin for people with severe renal impairment has been clarified, in
line with the manufacturer's Summary of Product Characteristics (SPC) [ABPI, 2016].
August 2016 — minor update. Information on the use of antibiotic treatment for cellulitis in children with varicella has been
added.
July 2015 — minor update. The information on the concurrent use of clarithromycin with statins has been clarified.
March to June 2015 — reviewed. A literature search was conducted in March 2015 to identify evidence-based guidelines,
UK policy, systematic reviews, and key randomized controlled trials (RCTs) published since the last revision of this topic. No
major changes to the recommendations have been made. However, the topic has undergone minor restructuring, and
prescribing information sections for the recommended antibiotics have been added.
September 2014 — minor update. Text inserted to include recommendations on the management of people with cellulitis
and varicella.
May 2014 — minor update. Minor correction to the basis for the recommendation on prescribing clarithromycin.
Recommendations in prescribing information have been clarified and links amended.
June 2013 — minor update. Text regarding the risk of pseudomembranous colitis with flucloxacillin has been amended.
February 2013 — minor update. The 2013 QIPP options for local implementation have been added to this topic.
October 2012 — minor update. The 2012 QIPP options for local implementation have been added to this topic.
https://cks.nice.org.uk/cellulitis-acute#!diagnosisSub Page 1 of 40
September 2012 — revised. A literature search was conducted in November 2011 to identify evidence-based guidelines, UK
policy, systematic reviews, and key RCTs published since the last revision of the topic. No major changes to clinical
recommendations have been made.
July 2011 — minor update. More exact paracetamol dosing for children has been introduced by the Medicines and
Healthcare products Regulatory Agency (MHRA). Prescriptions have been updated to reflect the revised dosing. Issued in
July 2011.
May 2011 — minor update. The 2010/2011 QIPP options for local implementation have been added to this topic. Issued in
June 2011.
November 2008 — minor update. Co-amoxiclav added as an antibiotic option for treatment of mild facial cellulitis that does
not require admission, in line with Health Protection Agency (HPA) recommendations. Issued in January 2009.
July to September 2008 — converted from CKS guidance to CKS topic structure. The evidence base has been reviewed in
detail, and recommendations are more clearly justified and transparently linked to the supporting
evidence. Recommendations and prescriptions on recurrent cellulitis have been removed, as they are now considered out of
scope. Other than this, there have been no major changes to the recommendations.
October 2006 — minor update. Analgesia prescriptions updated because new doses of ibuprofen for children are
recommended by the British National Formulary (BNF). Issued in October 2006.
June 2005 — written. Validated in September 2005 and issued in November 2005.
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Update
New evidence Back to top
Evidence-based guidelines
No new evidence-based guidelines since 1 March 2019.
HTAs (Health Technology Assessments)
No new HTAs since 1 March 2019.
Economic appraisals
No new economic appraisals relevant to England since 1 March 2019.
Systematic reviews and meta-analyses
No new systematic review or meta-analyses since 1 March 2019.
Primary evidence
No new randomized controlled trials published in the major journals since 1 March 2019.
New policies Back to top
No new national policies or guidelines since 1 March 2019.
New safety alerts Back to top
No new safety alerts since 1 March 2019.
Changes in product availability Back to top
No changes in product availability since 1 March 2019.
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Goals
To support primary healthcare professionals to:
Diagnose cellulitis and identify any underlying causes.

Assess the severity of cellulitis.
Treat people who can be managed in primary care with appropriate antibiotics.
Admit or refer to secondary care if appropriate.
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Outcome measures
No outcome measures were found during the review of this topic.
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Audit criteria
No audit criteria were found during the review of this topic.
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QOF indicators
No QOF indicators were found during the review of this topic.
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QIPP - Options for local implementation
Non-steroidal anti-inflammatory drugs (NSAIDs)
Review the appropriateness of non-steroidal anti-inflammatory drug (NSAID) prescribing widely and on a routine basis,
especially in people who are at higher risk of gastrointestinal, renal and cardiovascular morbidity and mortality (for
example, older people).
If an NSAID is needed, use ibuprofen (1200 mg a day or less) or naproxen (1000 mg a day or less). Use the lowest
effective dose and the shortest duration of treatment necessary to control symptoms.
Co-prescribe a proton pump inhibitor with NSAIDs for people who have osteoarthritis or rheumatoid arthritis, and think
about the use of gastroprotective treatment when prescribing NSAIDs for low back pain.
Antibiotic prescribing
Review and, if appropriate, revise prescribing and local policies that relate to antimicrobial stewardship to ensure these
are in line with the NICE guidelines on antimicrobial stewardship: systems and processes for effective antimicrobial
medicine use (http://www.nice.org.uk/guidance/ng15) and antimicrobial stewardship: changing risk-related behaviours in
the general population (http://www.nice.org.uk/guidance/ng63).
Optimise current prescribing practice and use implementation techniques to ensure prescribing is in line with
NICE antimicrobial prescribing guidelines (https://www.nice.org.uk/about/what-we-do/our-programmes/nice-
guidance/antimicrobial-prescribing-guidelines) or PHE guidance on managing common infections in primary care
(https://www.gov.uk/government/publications/managing-common-infections-guidance-for-primary-care), PHE
guidance Start smart − then focus (https://www.gov.uk/government/publications/antimicrobial-stewardship-start-smart-
then-focus), local trust antimicrobial guidelines and the Antimicrobial Stewardship in Primary Care collaboration TARGET
antibiotics toolkit (http://www.rcgp.org.uk/TARGETantibiotics).
Promote the Antibiotic Guardian (http://antibioticguardian.com/) call to action and the Keep Antibiotics Working campaign
(https://campaignresources.phe.gov.uk/resources/campaigns/58-keep-antibiotics-working).
[NICE, 2018 (/cellulitis-acute#!references); NICE, 2019b (/cellulitis-acute#!references)]
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NICE quality standards
No NICE quality standards were found during the review of this topic.
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What is it?
Cellulitis is an acute bacterial infection of the dermis and subcutaneous tissue.
The infected area is characterized by pain, warmth, swelling, and erythema. Blisters and bullae may form. Fever,
malaise, nausea, and rigors may accompany or precede the skin changes.
Cellulitis most commonly affects the lower limbs, but other areas, such as the upper limbs, face, ears, and trunk, can
also be affected [Dalal, 2017 (/cellulitis-acute#!references)].
[CREST, 2005 (/cellulitis-acute#!references); Raff, 2016 (/cellulitis-acute#!references); Dalal, 2017 (/cellulitis-

acute#!references); BMJ, 2018 (/cellulitis-acute#!references); PCDS, 2018 (/cellulitis-acute#!references); PHE, 2018a
(/cellulitis-acute#!references)]
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What causes it?
Cellulitis develops when microorganisms gain entry to the dermal and subcutaneous tissues via disruptions in the
cutaneous barrier.
The most common causative organisms are:
Streptococcus pyogenes.
Staphylococcus aureus.
Less common causative organisms include:
Pseudomonas aeruginosa — following exposure to contaminated hot tubs, sponges, or nail puncture.
Vibrio vulnificus — following salt water exposure.
Aeromonas hydrophila — following fresh water exposure.
Erysipelothrix rhusiopathiae — in butchers, vets, or fish handlers.
Mycobacterium marinum — in aquarium keepers.
Pasteurella multocida and Capnocytophaga canimorsus — following cat or dog bites.
Eikenella corrodens — following human bite or fist injuries.
Streptobacillus moniliformis — following rat bite.
Streptococcus pneumoniae, Haemophilus influenzae, gram negative bacilli, and anaerobes — following injury, burns,
and other co‐existing diseases (for example people who are immunocompromised, have diabetes, cancer,
or malnutrition).
[CREST, 2005 (/cellulitis-acute#!references); Raff, 2016 (/cellulitis-acute#!references); Dalal, 2017 (/cellulitis-

acute#!references); BMJ, 2018 (/cellulitis-acute#!references); Bystritsky, 2018 (/cellulitis-acute#!references); PCDS, 2018
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How common is it?
Epidemiological surveys report that the incidence of cellulitis ranges from 0.2 per 1000 person-years to 24.6 per
1000 person-years in different populations [Dalal, 2017 (/cellulitis-acute#!references)].
Recurrence of cellulitis is common, and each episode increases the likelihood of subsequent recurrence:
In a longitudinal cohort study of 36,276 people presenting with a first episode of lower limb cellulitis [Cannon, 2018a
(/cellulitis-acute#!references)]:
During the follow-up period, 4598 had at least one recurrence.
The cumulative incidence of first, second, and third recurrences at 12 months since previous infection was 6.3%,
17.2%, and 29.4%, respectively, and at 5 years was 13.9%, 35.9%, and 52.9%, respectively.
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What are the risk factors?
Most cases of cellulitis arise from bacterial infection through a break in the skin, for example from trauma (due to a
bite, burn, or laceration), leg ulceration, maceration or fungal infection between the toes, or a concomitant skin disorder
(such as atopic eczema). Other risk factors for cellulitis include [CREST, 2005 (/cellulitis-acute#!references); Dalal, 2017
(/cellulitis-acute#!references); Quirke, 2017 (/cellulitis-acute#!references); BMJ, 2018 (/cellulitis-acute#!references);
Bystritsky, 2018 (/cellulitis-acute#!references); PCDS, 2018 (/cellulitis-acute#!references)]:
Lymphoedema.
Leg oedema.
Venous insufficiency and history of venous surgery.
Obesity.
Pregnancy [PCDS, 2018 (/cellulitis-acute#!references)].
Risk factors for either rapid progression of cellulitis or delayed response to treatment include [Eron et al, 2003
(/cellulitis-acute#!references); Imohl et al, 2011 (/cellulitis-acute#!references); Dalal, 2017 (/cellulitis-acute#!references);
Bystritsky, 2018 (/cellulitis-acute#!references); PCDS, 2018 (/cellulitis-acute#!references)]:
Conditions that predispose to infection, including diabetes mellitus, chronic liver or renal disease, immunocompromise,
and neutropenia.
Chickenpox (varicella).
Alcohol misuse.
Neuropathy.
Risk factors for recurrent cellulitis include [Cannon, 2018a (/cellulitis-acute#!references); Cannon, 2018b (/cellulitis-
acute#!references)]:
Increasing age.
Previous cellulitis — due to persistence of other risk factors (such as lymphoedema) or residual lymphatic dysfunction
(caused by inflammation with each acute episode of cellulitis) [BMJ, 2018 (/cellulitis-acute#!references)].
Conditions that commonly result in chronic lymphoedema, such as [Eron et al, 2003 (/cellulitis-acute#!references)]:
Saphenous venectomy for coronary artery bypass grafting.
Pelvic surgery or irradiation.
Lymphadenectomy or node dissection.
Mastectomy.
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What are the complications?
Acute complications of cellulitis include:
Deep-seated infection, such as:
Necrotizing fasciitis — a destructive and rapidly progressive soft tissue infection that involves the deep
subcutaneous tissues and fascia (and occasionally muscles), which is characterized by extensive necrosis and
gangrene of the skin and underlying structures.
Myositis — inflammation of muscle due to infection.
Sepsis (which can be fatal).
Subcutaneous abscesses.
Post-streptococcal nephritis.
Chronic complications of cellulitis include:
Persistent leg ulceration.
Lymphoedema (cellulitis causes lymphatic inflammation leading to permanent damage).
Recurrent cellulitis.
[CREST, 2005 (/cellulitis-acute#!references); Dalal, 2017 (/cellulitis-acute#!references); BMJ, 2018 (/cellulitis-

acute#!references); PCDS, 2018 (/cellulitis-acute#!references)]
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What is the prognosis?
Most episodes of cellulitis resolve with treatment, and major complications (/cellulitis-acute#!backgroundSub:4)
are absent [BMJ, 2018 (/cellulitis-acute#!references)]. However, recurrence is common, and each episode increases the
likelihood of subsequent recurrence as well as the length of hospitalization [Cannon, 2018a (/cellulitis-acute#!references)]:
In a longitudinal cohort study of 36,276 people presenting with a first episode of lower limb cellulitis [Cannon, 2018a
(/cellulitis-acute#!references)]:
During the follow-up period, 4598 had at least one recurrence.
The cumulative incidence of first, second, and third recurrences at 12 months since previous infection was 6.3%,
17.2%, and 29.4%, respectively, and at 5 years was 13.9%, 35.9%, and 52.9%, respectively.
The length of hospitalization increased from 3 days for the primary episode to 4–5 days for first and all subsequent
recurrences, respectively.
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How should I diagnose cellulitis?
Take a history.
Ask about:
Symptoms experienced, including duration and severity.
Recent trauma to the skin, for example, a bite, burn, or laceration.
Underlying comorbidities (/cellulitis-acute#!backgroundSub:3) (such as diabetes mellitus) that predispose to
infection.
Predisposing conditions (/cellulitis-acute#!backgroundSub:1) or environmental conditions which may increase the
likelihood of specific pathogens (such as salt or fresh water exposure).
Examine the person.
Cellulitis is more commonly seen in the lower limbs and usually affects one limb (bilateral leg cellulitis is very rare).
Typical features include:
An acute onset of red, painful, hot, swollen, and tender skin, that spreads rapidly.
Fever, malaise, nausea, shivering, and rigors — these may accompany or even precede skin changes.
On examination:
There is usually an obvious skin break where the infecting organism may have entered, such as a wound, macerated
skin, fungal skin infection, an ulcer, or a concomitant skin disorder (such as atopic eczema).
There may be diffuse redness or a well-demarcated edge that can be marked with a pen in order to monitor
progress.
Blisters and bullae may be seen. Occasionally, there may be inflamed regional lymph nodes or associated
lymphangitis, characterized by the presence of red, linear streaks spreading proximally from the area of cellulitis. If
swelling is significant, the skin surface may develop a peau d’orange appearance.
Severe cellulitis can lead to ulceration and more deep-seated tissue damage.
Assess for underlying risk factors (/cellulitis-acute#!backgroundSub:3) (such as lymphoedema and leg oedema).
Exclude differential diagnoses (/cellulitis-acute#!diagnosisSub:1) (such as erysipelas, contact allergic dermatitis, deep
vein thrombosis, and cutaneous abscess).
If cellulitis is diagnosed, categorize the severity using the Eron classification system, to help guide management
(/cellulitis-acute#!management) decisions.
Class I — there are no signs of systemic toxicity and the person has no uncontrolled comorbidities.
Class II — the person is either systemically unwell or systemically well but with a comorbidity (for example peripheral
arterial disease, chronic venous insufficiency, or morbid obesity) which may complicate or delay resolution of infection.
Class III — the person has significant systemic upset, such as acute confusion, tachycardia, tachypnoea, hypotension,
or unstable comorbidities that may interfere with a response to treatment, or a limb-threatening infection due to
vascular compromize.
Class IV — the person has sepsis or a severe life-threatening infection, such as necrotizing fasciitis.
Investigations are not usually necessary but may be considered in certain cases and/or performed in secondary care
settings, for example:
A swab for culture — if there is an open wound, penetrating injury, drainage, or an obvious portal for microbial
entry, exposure to water borne-organisms, an infection acquired outside the UK or in severe cellulitis.
Be aware that swab cultures, especially those of chronic wounds or ulcers, are commonly polymicrobial or colonized
with multidrug-resistant pathogens that are not involved in the aetiology of underlying cellulitis.
Ultrasonography — for distinguishing nonpurulent cellulitis from cellulitis with underlying abscess and for identifying
drainable fluid collection, particularly if the clinical assessment is indeterminate.
A skin biopsy — if there is doubt about the diagnosis and to help identify any unusual pathogens in people who are
unresponsive to initial treatment.
White blood cell count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) — to detect acute
inflammation. Although nonspecific, most people with cellulitis will have elevations in white blood cell count, ESR, and
CRP levels. Normal results make a diagnosis of cellulitis less likely.
Other relevant tests — to exclude differential diagnoses (/cellulitis-acute#!diagnosisSub:1) (such as deep vein
thrombosis, septic arthritis, and acute gout).
Basis for recommendation Back to top
These recommendations are based largely on the Clinical Resource Efficiency Support Team (CREST) Guidelines on the
management of cellulitis [CREST, 2005 (/cellulitis-acute#!references)], the Primary Care Dermatology Society (PCDS)
guideline Cellulitis, erysipelas, and necrotising fasciitis [PCDS, 2018 (/cellulitis-acute#!references)], a Cochrane systematic
review on Interventions for the prevention of recurrent erysipelas and cellulitis [Dalal, 2017 (/cellulitis-acute#!references)], and
on expert opinion in review articles on cellulitis [Raff, 2016 (/cellulitis-acute#!references); Shriner, 2017 (/cellulitis-
acute#!references); BMJ, 2018 (/cellulitis-acute#!references); Bystritsky, 2018 (/cellulitis-acute#!references)].
The diagnosis of cellulitis can usually be made on history and examination alone, although investigations may be
considered in certain cases [CREST, 2005 (/cellulitis-acute#!references); Raff, 2016 (/cellulitis-acute#!references); Dalal,
2017 (/cellulitis-acute#!references); Shriner, 2017 (/cellulitis-acute#!references); BMJ, 2018 (/cellulitis-acute#!references);
Bystritsky, 2018 (/cellulitis-acute#!references)]. Experts advise that:
The value of microbiological culture in the management of cellulitis is limited. Needle aspirations taken from the
infected skin areas and then cultured are positive for bacterial growth in only 10% of cases [CREST, 2005 (/cellulitis-
acute#!references)]. A higher yield is noticed in surgically‐removed full‐thickness skin biopsies or other tissue
specimens from the lesion, with successful bacterial growth in 20–30% of cases [Dalal, 2017 (/cellulitis-
acute#!references)].
Swab cultures, especially those of chronic wounds or ulcers, are commonly polymicrobial or colonized with multidrug-
resistant pathogens that are not involved in the aetiology of underlying cellulitis [Raff, 2016 (/cellulitis-
Blood cultures are rarely positive, with only 2–4% of cultures showing positive bacterial growth [CREST, 2005
(/cellulitis-acute#!references); Dalal, 2017 (/cellulitis-acute#!references)], and contaminants may outnumber pathogens
[CREST, 2005 (/cellulitis-acute#!references)].
If bullae or abscesses form, culturing the fluid from inside these lesions yields an organism in more than 90% of
cases [Raff, 2016 (/cellulitis-acute#!references)].
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What else might it be?
Common conditions that present with unilateral redness and/or swelling include:
Deep venous thrombosis — characterized by pain and swelling of the calves without significant erythema. For more
information, see the CKS topic on Deep vein thrombosis (/deep-vein-thrombosis).
Septic arthritis — involvement of the joint and disproportionate pain with joint movement.
Acute gout — swelling, redness, warmth, and pain on passive movement. The skin around the joint may be inflamed.
For more information, see the CKS topic on Gout (/gout).
Ruptured Baker's cyst — may cause unilateral calf swelling.
Thrombophlebitis — venous inflammation with thrombus formation. May cause redness, inflammation, and pain. For
more information, see the CKS topic on Thrombophlebitis - superficial (/superficial-vein-thrombosis-superficial-
thrombophlebitis).
Cutaneous abscess — a hot, red, swollen and painful swelling, which may need incision and drainage.
Erysipelas — a form of cellulitis involving more superficial dermal structures distinguished clinically by raised and well
demarcated borders.
Chronic conditions (these are usually bilateral but if worse on one side, it may be difficult to exclude superimposed
cellulitis):
Varicose eczema/venous insufficiency — crusting, scaling, and itching.
Contact allergic dermatitis — can present acutely as erythematous, sore and tender areas of skin, sometimes with
blisters. For more information, see the CKS topic on Dermatitis - contact (/dermatitis-contact).
Lipodermatosclerosis — a painful, red, tender, warm, hard, and sometimes scaly rash that occurs in the absence of
significant systemic upset. It is most likely to occur in the lower leg in obese women with venous insufficiency. For
more information, see the CKS topic on Venous eczema and lipodermatosclerosis (/venous-eczema-and-
lipodermatosclerosis).
Cutaneous small vessel vasculitis — palpable purpura typically on the lower legs and ankles.
Lymphoedema — swelling (especially in the subcutaneous tissues) that occurs as a result of excess accumulation of
lymph due to inadequate drainage.
Oedema with blisters.
Panniculitis — inflammation of subcutaneous adipose tissue.
Other conditions include:
Drug reaction — characterized by itching and burning. There is usually a well-demarcated area of involvement and a
history of similar reaction with prior exposure to the same drug.
Necrotizing fasciitis — a destructive and rapidly progressive soft tissue infection that involves the deep subcutaneous
tissues, fascia, and occasionally muscles. The presenting signs are usually non-specific (redness, swelling, and
pyrexia). The person is usually systemically very unwell and has disproportionate pain.
Metastatic cancer (carcinoma erysipeloides) — a fixed, red patch often with a raised edge and oedema due to
lymphatic obstruction. A metastasis from breast cancer is the most common cause, but rarely it may be caused by
lung, ovarian, colonic, or pancreatic metastases, or malignant melanoma.
Wet gangrene — ischaemia of tissue with adjacent cellulitis due to putrefaction of dead tissue.
Erythema nodosum — painful, red, warm nodules and plaques on the shins, knees, and ankles.
Pyoderma gangrenosum — small, tender pustules or papules that ulcerate with a purple undermined edge and
surrounding redness, typically on the trunk or legs.
Eosinophilic cellulitis (Wells syndrome) — presents with large, indurated erythematous plaques, and less commonly
nodules, that evolve over several weeks. Most people have a blood eosinophilia.
Eosinophilic fasciitis — the acute inflammatory stage consists of pain, swelling, and tenderness of the distal limbs.
These findings are later replaced by induration, and eventually fibrosis with limitation of the movement of the hands and
feet. The affected skin is taut and firmly adherent to underlying tissue with dimpling and a peau d'orange appearance.
The condition has a symmetrical distribution, and there is a blood eosinophilia in 70% of cases.
The information on differential diagnoses is based on the Clinical Resource Efficiency Support Team (CREST) Guidelines on
the management of cellulitis [CREST, 2005 (/cellulitis-acute#!references)], the Primary Care Dermatology Society (PCDS)
guideline Cellulitis, erysipelas, and necrotising fasciitis [PCDS, 2018 (/cellulitis-acute#!references)], review articles on
cellulitis [Stevens et al, 2005 (/cellulitis-acute#!references); Gunderson, 2011 (/cellulitis-acute#!references); Raff, 2016
(/cellulitis-acute#!references); Shriner, 2017 (/cellulitis-acute#!references); BMJ, 2018 (/cellulitis-acute#!references);
Bystritsky, 2018 (/cellulitis-acute#!references)], and information in a medical dictionary [Pugh, 2000 (/cellulitis-
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Scenario: Management of acute cellulitis
From age 1 month onwards.
When should I admit or refer a person with cellulitis? Back to top
Arrange urgent hospital admission if the person:

Has Class IV cellulitis (sepsis or severe life-threatening infection, such as necrotizing fasciitis).
Has Class III cellulitis (significant systemic upset, such as acute confusion, tachycardia, tachypnoea, hypotension, or
unstable comorbidities, or a limb-threatening infection due to vascular compromize).
Has severe or rapidly deteriorating cellulitis (for example extensive areas of skin).
Is very young (under 1 year of age) or frail.
Is immunocompromized.
Has significant lymphoedema.
Has facial cellulitis (unless very mild).
Has suspected orbital or periorbital cellulitis (admit to ophthalmology).
Has Class II cellulitis (systemically unwell or systemically well but with a comorbidity).
Admission may not be necessary if the facilities and expertise are available in the community to give intravenous
antibiotics and monitor the person (check local guidelines).
Has symptoms or signs suggesting a more serious illness or condition (such as osteomyelitis, or septic arthritis).
Consider referring people to hospital, or seek specialist advice, if they:
Are severely unwell.
Have infection near the eyes or nose (including periorbital cellulitis).
Could have uncommon pathogens, for example, after a penetrating injury, exposure to water-borne organisms, or an
infection acquired outside the UK.
Have spreading infection that is not responding to an oral antibiotic.
Have lymphangitis.
Cannot take oral antibiotics (exploring locally available options for giving intravenous antibiotics at home or in the
community, rather than in hospital, where appropriate).
For cellulitis resulting from a wound contaminated with fresh water or sea water:
Seek specialist advice from a medical microbiologist.
Seek specialist advice or consider admission, depending on clinical judgement, if:
There is continuing or deteriorating systemic signs, with or without deteriorating local signs, after 2–3 days of treatment
(/cellulitis-acute#!scenarioRecommendation:1).
Symptoms are not improving (or are worsening) after 14 days of treatment (/cellulitis-
acute#!scenarioRecommendation:1).
If a person has recurrent episodes of cellulitis (more than two episodes at the same site within one year), consider
routine referral to secondary care for advice on the use of prophylactic antibiotics.
guideline Cellulitis, erysipelas, and necrotising fasciitis [PCDS, 2018 (/cellulitis-acute#!references)], the British Lymphology
Society Consensus Document on the Management of Cellulitis in Lymphoedema [British Lymphology Society, 2016
(/cellulitis-acute#!references)], the National Institute for Health and Care Excellence (NICE) guideline Cellulitis and erysipelas:
antimicrobial prescribing [NICE, 2019a (/cellulitis-acute#!references)], and on expert opinion in review articles on
cellulitis [Raff, 2016 (/cellulitis-acute#!references); Shriner, 2017 (/cellulitis-acute#!references); BMJ, 2018 (/cellulitis-
acute#!references); Bystritsky, 2018 (/cellulitis-acute#!references)].
Urgent admission to hospital
Most people who are admitted to secondary care will require intravenous (IV) antibiotics [CREST, 2005 (/cellulitis-
Severe localized infection or systemic features (which may indicate the development of bacteraemia) can be life
threatening (for example if they progress to necrotizing fasciitis).
Certain groups of people (for example the very young and old, and people with comorbidities) are more vulnerable to
life-threatening infection, so they require a lower threshold for admission.
People with cellulitis affecting anatomical areas where the consequence of tissue damage would be particularly critical
(for example facial cellulitis and periorbital cellulitis) require immediate assessment.
The CREST guideline recommends urgent referral to ophthalmology for people with suspected orbital or periorbital
cellulitis, as it is vital to distinguish between the two due to potential complications from orbital cellulitis (decreased
ocular motility, decreased visual acuity and cavernous sinus thrombosis) [CREST, 2005 (/cellulitis-
IV antibiotics in the community
Certain groups of people with cellulitis can be treated in the community with IV antibiotics followed by a course of oral
antibiotics, provided there is an organized service in place to administer the treatment and monitor the person [CREST,
2005 (/cellulitis-acute#!references)].
This includes people who are systemically ill with stable comorbidities that are unlikely to complicate treatment, and
people who are systemically well but have one or more comorbidities that may complicate or delay the resolution of
cellulitis (for example morbid obesity, peripheral arterial disease, or chronic venous insufficiency).
CKS advises that local guidelines are followed in areas where an outpatient parenteral antibiotic therapy (OPAT) service
exists.
A Cochrane systematic review on interventions for cellulitis and erysipelas (search date: May 2010) suggests the need for
further investigation into the efficacy of oral antibiotics compared with IV antibiotics as there are only a small number of
studies comparing the two [Kilburn et al, 2010 (/cellulitis-acute#!references)]. Evidence from a subsequent prospective
randomized non-inferiority trial (n = 47) suggests that oral antimicrobials are as effective as parenteral antimicrobials for
the treatment of uncomplicated cellulitis [Aboltins, 2015 (/cellulitis-acute#!references)].
Referral for people with recurrent cellulitis to consider antibiotic prophylaxis
The recommendation to consider specialist referral for people with recurrent cellulitis is based on limited and conflicting
evidence to support the routine use of prophylactic antibiotics for these people.
Expert opinion in the CREST guideline is that antibiotic prophylaxis should be considered in people who have had at
least two episodes of cellulitis at the same site, but acknowledges that this is based on weak and inconclusive
evidence [CREST, 2005 (/cellulitis-acute#!references)]. In addition, the British Lymphology Society and the PCDS
recommend considering antibiotic prophylaxis in people with lymphoedema who have 2 or more attacks of cellulitis per
year [British Lymphology Society, 2016 (/cellulitis-acute#!references); PCDS, 2018 (/cellulitis-acute#!references)].
A US guideline Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014
update published by the Infectious Diseases Society of America recommends considering prophylactic antibiotics in
people who have had 3–4 episodes of cellulitis per year, despite attempts to treat or control predisposing factors
[Stevens et al, 2014 (/cellulitis-acute#!references)].
A systematic review and meta-analysis identified five randomized controlled trials (RCTs, n = 535) that assessed the
efficacy of antibiotic prophylaxis in preventing recurrent cellulitis compared with placebo [Oh et al, 2014 (/cellulitis-
The evidence showed that antibiotic prophylaxis significantly reduced the number of episodes of recurrent cellulitis.
In the antibiotic prophylaxis group, 44 of 260 people had an episode of cellulitis compared with 97 of 275 people in
the placebo group (risk ratio 0.46; 95% CI 0.26 to 0.79, p value not available).
These results should be interpreted with caution, however, as there was heterogeneity between the studies
regarding the antibiotics used, route of administration, number of recurrences of cellulitis at study entry, and study
quality.
A small, double-blind RCT (n = 123) assessed whether a 6-month course of prophylactic low-dose penicillin prescribed
after only one episode of cellulitis could prevent further episodes [UK Dermatology Clinical Trials Network's PATCH trial
team et al, 2012 (/cellulitis-acute#!references)].
The evidence showed that antibiotic treatment reduced the risk of recurrence by 47%, but the result was not
statistically significant (95% CI 0.26 to 1.07; p = 0.08).
How should I manage acute cellulitis in primary care? Back to top
For people with Class I cellulitis (no signs of systemic toxicity and no uncontrolled comorbidities):
Prescribe a high-dose oral antibiotic treatment (/cellulitis-acute#!scenarioRecommendation:2).
Before treatment, draw around the extent of the infection with a permanent marker pen for future comparison and to
track the spread of infection. This may be difficult in people with lymphoedema as the rash is often blotchy.
Advise the person to:
Take paracetamol or ibuprofen for pain and fever. For detailed information on prescribing these analgesics, see the
CKS topic on Analgesia - mild-to-moderate pain (/analgesia-mild-to-moderate-pain).
Drink adequate fluids.
Seek immediate medical advice if antibiotics are not tolerated, the cellulitis becomes worse (there may be an
increase in the redness in the first 24–48 hours of treatment possibly due to release of toxins), or if systemic
symptoms develop or worsen.
Elevate the leg for comfort and to relieve oedema (where applicable).
Avoid the use of compression garments during acute cellulitis.
Manage any underlying risk factors (/cellulitis-acute#!backgroundSub:3) for cellulitis.
Manage breaks in the skin, for example, due to eczema, tinea pedis, or leg ulcers, which may become a portal of
entry for organisms. See the CKS topics on Eczema - atopic (/eczema-atopic), Venous eczema and
lipodermatosclerosis (/venous-eczema-and-lipodermatosclerosis), Fungal skin infection - foot (/fungal-skin-infection-
foot), and Leg ulcer - venous (/leg-ulcer-venous) for management information.
Manage venous insufficiency. See the CKS topic on Venous eczema and lipodermatosclerosis (/venous-eczema-
and-lipodermatosclerosis) for management information.
Consider referring people with lymphoedema to a specialist clinic.
Liaise with a district nurse if there is skin blistering, broken skin, exudate, or venous ulceration.
Identify and manage comorbidities (/cellulitis-acute#!backgroundSub:3) (such as diabetes mellitus) that may
cause the cellulitis to spread rapidly, or delay healing.
Advise on preventative measures to reduce the risk of recurrence, including:
Weight management if the person is obese. For more information, see the CKS topic on Obesity (/obesity).
The use of emollients to prevent dry skin and cracking.
Provide patient information on cellulitis. For example:
Cellulitis or erysipelas (http://www.bad.org.uk/shared/get-file.ashx?id=156&itemtype=document) published by
the British Association of Dermatologists (BAD, www.bad.org.uk (http://www.bad.org.uk/)).
About cellulitis (https://www.lymphoedema.org/index.php/cellulitis/about-cellulitis) published by the Lymphoedema
Support Network (www.lymphoedema.org (https://www.lymphoedema.org/)).
Cellulitis (https://www.nhs.uk/conditions/cellulitis/) published by NHS (www.nhs.uk (https://www.nhs.uk/)).
Review (/cellulitis-acute#!scenarioRecommendation:3) the person after 2-3 days depending on clinical judgement,
or if local symptoms deteriorate (such as redness or swelling beyond the initial presentation), have severe pain, or they
develop systemic symptoms.
If a person has recurrent episodes of cellulitis (more than two episodes at the same site within one year), consider
routine referral to secondary care for advice on the use of prophylactic antibiotics.
guideline Cellulitis, erysipelas, and necrotising fasciitis [PCDS, 2018 (/cellulitis-acute#!references)], the British Lymphology
Society Consensus Document on the Management of Cellulitis in Lymphoedema [British Lymphology Society, 2016
(/cellulitis-acute#!references)], a Cochrane systematic review on Interventions for the prevention of recurrent erysipelas and
cellulitis [Dalal, 2017 (/cellulitis-acute#!references)], the National Institute for Health and Care Excellence (NICE)
guideline Cellulitis and erysipelas: antimicrobial prescribing [NICE, 2019a (/cellulitis-acute#!references)], and expert opinion in
review articles on cellulitis [Imohl et al, 2011 (/cellulitis-acute#!references); Raff, 2016 (/cellulitis-acute#!references); Shriner,
2017 (/cellulitis-acute#!references); BMJ, 2018 (/cellulitis-acute#!references); Bystritsky, 2018 (/cellulitis-acute#!references)].
Giving advice and information
The recommended advice and information are consistent with advice in the CREST guideline [CREST, 2005 (/cellulitis-
acute#!references)] and are accepted as good clinical practice.
The rationale for elevating the leg is to reduce swelling and discomfort through the action of gravity.
The recommendation on avoiding compression garments is based on the CREST guideline [CREST, 2005 (/cellulitis-
acute#!references)] and the British Lymphology Society guideline [British Lymphology Society, 2016 (/cellulitis-
Referral for people with recurrent cellulitis to consider antibiotic prophylaxis
The recommendation to consider specialist referral for people with recurrent cellulitis is based on limited and conflicting
evidence to support the routine use of prophylactic antibiotics for these people.
Expert opinion in the CREST guideline is that antibiotic prophylaxis should be considered in people who have had at
least two episodes of cellulitis at the same site, but acknowledges that this is based on weak and inconclusive
evidence [CREST, 2005 (/cellulitis-acute#!references)]. In addition, the British Lymphology Society and the PCDS
recommend considering antibiotic prophylaxis in people with lymphoedema who have 2 or more attacks of cellulitis per
year [British Lymphology Society, 2016 (/cellulitis-acute#!references); PCDS, 2018 (/cellulitis-acute#!references)].
A US guideline Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014
update published by the Infectious Diseases Society of America recommends considering prophylactic antibiotics in
people who have had 3–4 episodes of cellulitis per year, despite attempts to treat or control predisposing factors
[Stevens et al, 2014 (/cellulitis-acute#!references)].
A systematic review and meta-analysis identified five randomized controlled trials (RCTs, n = 535) that assessed the
efficacy of antibiotic prophylaxis in preventing recurrent cellulitis compared with placebo [Oh et al, 2014 (/cellulitis-
The evidence showed that antibiotic prophylaxis significantly reduced the number of episodes of recurrent cellulitis
In the antibiotic prophylaxis group, 44 of 260 people had an episode of cellulitis compared with 97 of 275 people in
the placebo group (risk ratio 0.46; 95% CI 0.26 to 0.79, p value not available).
These results should be interpreted with caution, however, as there was heterogeneity between the studies
regarding the antibiotics used, route of administration, number of recurrences of cellulitis at study entry, and study
quality.
A small, double-blind RCT (n = 123) assessed whether a 6-month course of prophylactic low-dose penicillin prescribed
after only one episode of cellulitis could prevent further episodes [UK Dermatology Clinical Trials Network's PATCH trial
team et al, 2012 (/cellulitis-acute#!references)].
The evidence showed that antibiotic treatment reduced the risk of recurrence by 47%, but the result was not
statistically significant (95% CI 0.26 to 1.07; p = 0.08).
Which oral antibiotics should I prescribe? Back to top
Before treatment, mark the area of cellulitis, if possible. Draw around the extent of the infection with a permanent
marker pen for future comparison and to track the spread of infection. This may be difficult in people with
lymphoedema as the rash is often blotchy.
When choosing an antibiotic, take into account:

The severity of symptoms.
The site of infection (for example, near the eyes or nose).
The risk of uncommon pathogens (for example, from a penetrating injury, after exposure to water-borne organisms, or
an infection acquired outside the UK).
Previous microbiological results from a swab.
The person's meticillin-resistant Staphylococcus aureus (MRSA) status if known.
For adults with Class I cellulitis (no signs of systemic toxicity and no uncontrolled comorbidities):
Prescribe flucloxacillin 500–1000 mg four times daily for 5–7 days. If this is unsuitable, or the person has a penicillin
allergy, prescribe either:
Clarithromycin 500 mg twice daily for 5–7 days.
Doxycycline 200 mg on the first day then 100 mg once daily, for a total of 5–7 days.
Erythromycin (in pregnancy) 500 mg four times daily for 5–7 days.
For adults with infection near the eyes or nose who do not require admission or referral (/cellulitis-
acute#!scenarioRecommendation):
Prescribe co-amoxiclav 500/125 mg three times a day for 7 days. If this is unsuitable, or the person has a penicillin
allergy, prescribe:
Clarithromycin 500 mg twice daily for 5–7 days with metronidazole 400 mg three times daily for 7 days.
For adults with known lymphoedema who develop cellulitis but do not require admission or referral (/cellulitis-
acute#!scenarioRecommendation):
Prescribe amoxicillin 500 mg three times daily.
If there is any evidence of Staphylococcus aureus infection, for example, folliculitis, pus formation, or crusted
dermatitis, prescribe flucloxacillin 500 mg four times a day in addition to amoxicillin, or as an alternative.
If the person has a penicillin allergy, prescribe clarithromycin 500 mg twice daily.
Continue antibiotic treatment until all signs of acute inflammation have resolved. The course of antibiotics should be for
no less than 14 days from the time a definite clinical response is observed.
Skin changes (such as discolouration) may persist for months or longer following severe cellulitis and do not
necessarily require ongoing antibiotics.
For children aged 1 month and over with Class I cellulitis:
Prescribe flucloxacillin for 5–7 days (aged 1 month to 1 year, 62.5–125 mg four times daily; aged 2 to 9 years, 125–
250 mg four times daily; aged 10-17 years, 250–500 mg four times daily). If this is unsuitable prescribe:
Co-amoxiclav for 5–7 days (aged 1–11 months, 0.25 ml/ kg of 125/31 suspension three times a day [doubled dose
in severe infection]; aged 1–5 years, 0.25 ml/kg or 5 ml of 125/31 suspension three times a day [dose doubled in
severe infection]; aged 6 –11 years, 0.15 ml/kg or 5 ml of 250/62 suspension three times a day [dose doubled in
severe infection]; aged 12–17 years, 250/125 mg or 500/125 mg three times a day).
If the person has a true penicillin allergy, prescribe:
Clarithromycin for 5–7 days (under 8 kg, 7.5 mg/kg twice a day; 8–11 kg, 62.5 mg twice a day; 12-19 kg, 125 mg
twice a day; 20-29 kg, 187.5 mg twice a day; 30–40 kg, 250 mg twice a day; 12–17 years, 250–500 mg twice a day)
or
Erythromycin (in pregnancy) 250–500 mg four times a day for 5–7 days.
For children aged 1 month and over with infection near the eyes or nose, consider seeking specialist advice and
prescribe:
Co-amoxiclav three times daily for 7 days. If this is unsuitable, or the person has a penicillin allergy, prescribe either:
Clarithromycin twice daily for 7 days.
Clarithromycin plus metronidazole twice daily for 7 days if the presence of anaerobes is suspected (aged 1 month,
7.5 mg/kg twice a day; aged 2 months to 11 years, 7.5 mg/kg three times a day [maximum per dose 400 mg]; aged
12–17 years, 400 mg three times a day).
Review (/cellulitis-acute#!scenarioRecommendation:3) the person after 2-3 days depending on clinical judgement,
or if local symptoms deteriorate (such as redness or swelling beyond the initial presentation), have severe pain, or
they develop systemic symptoms.
See the sections on Amoxicillin (/cellulitis-acute#!prescribingInfoSub), Clarithromycin (/cellulitis-
acute#!prescribingInfoSub:5), Co-amoxiclav (/cellulitis-acute#!prescribingInfoSub:10), Doxycycline (/cellulitis-
acute#!prescribingInfoSub:15), Erythromycin (/cellulitis-acute#!prescribingInfoSub:20), Flucloxacillin (/cellulitis-
acute#!prescribingInfoSub:25), and Metronidazole (/cellulitis-acute#!prescribingInfoSub:30) for detailed
prescribing information.
Recording the extent of the cellulitis
This recommendation is based on expert opinion in the Clinical Resource Efficiency Support Team (CREST) Guidelines on
the management of cellulitis [CREST, 2005 (/cellulitis-acute#!references)], the British Lymphology Society Consensus
Document on the Management of Cellulitis in Lymphoedema [British Lymphology Society, 2016 (/cellulitis-
acute#!references)], the Primary Care Dermatology Society (PCDS) guideline Cellulitis, erysipelas, and necrotising fasciitis
[PCDS, 2018 (/cellulitis-acute#!references)], and in review article on cellulitis [Phoenix et al, 2012 (/cellulitis-
Choice of antibiotics and duration of treatment
The recommended choice of antibiotics is based on the National Institute for Health and Care Excellence (NICE)
guideline Cellulitis and erysipelas: antimicrobial prescribing [NICE, 2019a (/cellulitis-acute#!references)], the Public Health
England (PHE) Summary of antimicrobial prescribing guidance – managing common infections: PHE context, references
and rationales for Clinical Commissioning Groups, Commissioning Support Units and Primary Care Providers [PHE, 2018b
(/cellulitis-acute#!references)] and a joint National Institute for Health and Care Excellence (NICE) and PHE Summary of
antimicrobial prescribing guidance – managing common infections [NICE and PHE, 2019 (/cellulitis-acute#!references)].
The PHE summary is based largely on the CREST guideline [CREST, 2005 (/cellulitis-acute#!references)], and trial
evidence.
Most cases of cellulitis are caused by beta-haemolytic Streptococci or Staphylococcus aureus, so empirical treatment
should be active against these organisms [CREST, 2005 (/cellulitis-acute#!references); PHE, 2018b (/cellulitis-
Flucloxacillin is a relatively narrow-spectrum antibiotic licensed for the treatment of cellulitis and other soft tissue
infections [ABPI, 2018a (/cellulitis-acute#!references)]. At high doses, it is active against the large majority of
staphylococcal and streptococcal species that cause cellulitis [CREST, 2005 (/cellulitis-acute#!references)].
Clarithromycin is an erythromycin derivative with slightly greater activity than erythromycin [Joint Formulary
Committee, 2019 (/cellulitis-acute#!references)] and is recommended as an alternative to flucloxacillin if the person
is penicillin allergic [CREST, 2005 (/cellulitis-acute#!references)]. A systematic review of 15 studies (9 in people with
cellulitis or erysipelas) found that the efficacy of treatment of cellulitis or erysipelas was similar with a beta-lactam
and a macrolide. The risk of adverse effects was also similar for both groups of antibiotics [Ferreira, 2016 (/cellulitis-
Doxycycline 200mg is recommended as an alternative if the person is penicillin allergic and taking statins (for
example simvastatin or atorvastatin) [British Lymphology Society, 2016 (/cellulitis-acute#!references); NICE and PHE,
2019 (/cellulitis-acute#!references)], because there is an increased risk of myopathy if macrolides are taken with
cytochrome CYP3A4 inhibitors, such as simvastatin and atorvastatin [MHRA, 2008 (/cellulitis-acute#!references);
MHRA, 2014 (/cellulitis-acute#!references)].
Co-amoxiclav is recommended for empirical treatment of facial cellulitis as it has a broader spectrum of activity than
flucloxacillin and also covers anaerobes and other less common causes of facial cellulitis [Fisher, 2002 (/cellulitis-
acute#!references); PHE, 2018b (/cellulitis-acute#!references)]. PHE does not make any recommendations for people
who are penicillin allergic, so CKS recommends seeking advice from a microbiologist.
The recommendation for adults with known lymphoedema who develop cellulitis but do not require admission or referral is
based on the British Lymphology Society guideline [British Lymphology Society, 2016 (/cellulitis-acute#!references)].
How should I follow up a person on oral antibiotic treatment? Back to top
Review the person after 2-3 days depending on clinical judgement, or if local symptoms deteriorate (such as redness or
swelling beyond the initial presentation), have severe pain, or they develop systemic symptoms.
If there is continuing or deteriorating systemic signs, with or without deteriorating local signs, after 2-3 days of
antibiotic treatment:
Seek specialist advice or consider admission, depending on clinical judgement.
If there is no substantial improvement after 7 days of first-line oral antibiotic treatment (/cellulitis-
acute#!scenarioRecommendation:2) and the person is systemically well:
Assess adherence to treatment, and continue the first-line oral antibiotic for a further 7 days.
If a swab result is available, use sensitivity results to guide treatment.
If symptoms are not improving (or are worsening) after 14 days:
Exclude differential diagnoses (/cellulitis-acute#!diagnosisSub:1) or complicating conditions (/cellulitis-
acute#!backgroundSub:3) (such as diabetes mellitus) that may cause the cellulitis to spread rapidly, or delay healing.
Consider admission or seeking specialist advice, depending on clinical judgement.
management of cellulitis [CREST, 2005 (/cellulitis-acute#!references)], the British Lymphology Society Consensus Document
on the Management of Cellulitis in Lymphoedema [British Lymphology Society, 2016 (/cellulitis-acute#!references)], and a
joint National Institute for Health and Care Excellence (NICE) and Public Health England (PHE) Summary of antimicrobial
prescribing guidance – managing common infections [NICE and PHE, 2019 (/cellulitis-acute#!references)], and the
NICE guideline Cellulitis and erysipelas: antimicrobial prescribing [NICE, 2019a (/cellulitis-acute#!references)].
Duration of antibiotic treatment
There is a lack of evidence on the optimal duration of antibiotic treatment. Expert opinion in the CREST guideline is
that uncomplicated cases usually respond to 1–2 weeks of treatment [CREST, 2005 (/cellulitis-acute#!references)].
If there has been a slow response to treatment with oral antibiotics, expert opinion in the joint NICE and PHE guideline is
that the antibiotic course can be extended for a further 7 days [NICE and PHE, 2019 (/cellulitis-acute#!references)].
No improvement after two weeks of antibiotics
CKS could not find any evidence on the management of people who are not responding after 2 weeks of oral antibiotic
treatment. The recommendations to exclude differential diagnoses or complicating conditions and to consider admission
or seeking specialist advice are pragmatic, based on what CKS considers to be good clinical practice. In addition:
The British Lymphology Society guideline recommends hospital admission if the person develops signs of septicaemia,
or fails to respond to oral antibiotics [British Lymphology Society, 2016 (/cellulitis-acute#!references)].
Expert opinion in a review article on cellulitis is that failure to improve with appropriate first-line antibiotics should
prompt consideration for resistant organisms, differential diagnoses of cellulitis, or underlying complicating conditions,
such as immunosuppression, chronic liver disease, or chronic kidney disease [Raff, 2016 (/cellulitis-acute#!references)].
Back to top
Amoxicillin
What are the contraindications and cautions for amoxicillin? Back to top
Do not prescribe amoxicillin to people with:

A true penicillin hypersensitivity. Gastrointestinal adverse effects alone (such as nausea, vomiting, or diarrhoea)
do not constitute an allergy to penicillin. See the CKS topic on Angio-oedema and anaphylaxis (/angio-oedema-and-
anaphylaxis) for more information.
A history of severe immediate hypersensitivity reaction to cephalosporins — there is some evidence of partial cross-
allergenicity.
Prescribe amoxicillin with caution to people with:
Chronic kidney disease (CKD) — reduce the dose of amoxicillin based on the estimated glomerular filtration rate
(eGFR):
If the eGFR is 10–30 mL/minute/1.73 m2, prescribe a maximum of 500 mg twice a day.
If the eGFR is less than 10 mL/minute/1.73 m2, prescribe a maximum of 500 mg once a day.
Glandular fever (infective mononucleosis) — erythematous rashes common.
Acute lymphocytic leukaemia and chronic lymphocytic leukaemia — increased risk of erythematous rashes.
Cytomegalovirus infection — increased risk of erythematous rashes.
[ABPI, 2017a (/cellulitis-acute#!references); Joint Formulary Committee, 2019 (/cellulitis-acute#!references)]
What are the possible adverse effects of amoxicillin? Back to top
The most common adverse effects of amoxicillin are nausea, vomiting, skin rash, and diarrhoea.
Consider pseudomembranous colitis if a person develops severe diarrhoea during or after treatment with co-amoxiclav.
For more information, see the CKS topic on Diarrhoea - antibiotic associated (/diarrhoea-antibiotic-associated).
Anaphylaxis (immediate or delayed) is a serious but rare adverse effect of amoxicillin. For more information, see the
CKS topic on Angio-oedema and anaphylaxis (/angio-oedema-and-anaphylaxis).
Other adverse effects include:
Rare — hepatitis, cholestatic jaundice; hyperkinesia, dizziness, convulsions; interstitial nephritis; leucopenia,
thrombocytopenia, haemolytic anaemia.
Very rare — erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous and exfoliative
dermatitis and acute generalized exanthematous pustulosis.
Frequency not known — Jarisch–Herxheimer reaction.
What are the possible drug interactions of amoxicillin? Back to top
Possible drug interactions of co-amoxiclav include:

Allopurinol — be aware that concomitant use of allopurinol and co-amoxiclav may increase the incidence of skin
rashes.
Manufacturer advises to consider alternatives.
Anticoagulants (for example warfarin) — penicillins potentially alter the anticoagulant effect of warfarin.
Monitor the prothrombin time or international normalized ratio (INR) more closely with the addition or withdrawal of a
penicillin. Adjustment of the anticoagulant dose may be necessary.
Methotrexate — amoxicillin is predicted to increase the risk of toxicity when given with methotrexate.
If concurrent treatment is indicated, monitor methotrexate levels more closely. One recommendation is to carry out
twice weekly platelet and white cell counts for 2 weeks initially, with the measurement of methotrexate levels if
toxicity is suspected.
Probenecid — the renal tubular secretion of amoxicilin is decreased by probenecid. Concurrent use may result in
increased and prolonged blood levels of amoxicillin, but not of clavulanic acid.
Manufacturer recommends avoiding concurrent use.
Oral hormonal contraception — additional contraceptive precautions are not required during or after courses of
penicillins [FSRH, 2017 (/cellulitis-acute#!references)].
However, advise women on the importance of correct contraceptive practice if they experience vomiting or diarrhoea.
For further information, see the section on vomiting or diarrhoea in the CKS topics on Contraception - combined
hormonal methods (/contraception-combined-hormonal-methods) and Contraception - progestogen-only methods
(/contraception-progestogen-only-methods).
Pregnancy and breastfeeding Back to top
Pregnancy
Amoxicillin is not known to be harmful in pregnancy [Joint Formulary Committee, 2019 (/cellulitis-acute#!references)].
The vast majority of the large amount of available data shows no increased risk of congenital malformation,
spontaneous abortion, intrauterine death, low birth weight, preterm delivery, or neonatal complications following
maternal exposure to therapeutic doses of penicillins [UKTIS, 2017a (/cellulitis-acute#!references)].
Breastfeeding
Trace amounts of amoxicillin are found in breastmilk, but it is appropriate to use in women who are breastfeeding [Joint
Formulary Committee, 2019 (/cellulitis-acute#!references)].
Penicillins (and cephalosporins) are the antibiotics of choice in women who are breastfeeding [Kearney, 2016 (/cellulitis-
Back to top
Clarithromycin
What are the contraindications and cautions for clarithromycin? Back to top
Do not prescribe clarithromycin to:

People with:
Severe hepatic impairment in combination with renal impairment.
Hypokalaemia.
A history of QT prolongation or ventricular cardiac arrhythmia, including Torsades de pointes arrhythmias.
Pregnant or breastfeeding women (unless potential benefit outweighs risk). See the section on Pregnancy and
breastfeeding (/cellulitis-acute#!prescribingInfoSub:9) for more information.
Prescribe clarithromycin with caution to:
People with:
Impaired hepatic function — clarithromycin is principally excreted by the liver. Hepatic dysfunction including
increased liver enzymes and cholestatic hepatitis (with or without jaundice) has been rarely reported with its use.
Conditions which predispose to QT interval prolongation, such as electrolyte disturbances — macrolides can also
prolong the QT interval, increasing the risk of Torsades de pointes arrhythmias.
Chronic kidney disease (CKD) stages 4 and 5 — if the estimated glomerular filtration rate (eGFR) is less than
30 mL/minute/1.73 m2, prescribe half the normal dose, and avoid Klaricid XL® or clarithromycin M/R preparations.
Coronary artery disease, severe cardiac insufficiency, or bradycardia (heart rate less than 50 beats per minute) —
increased risk of QT prolongation.
Myasthenia gravis — clarithromycin may aggravate symptoms.
People concomitantly taking:
Potentially hepatotoxic drugs — clarithromycin is principally excreted by the liver. Hepatic dysfunction including
increased liver enzymes and cholestatic hepatitis (with or without jaundice) has been rarely reported with its use.
Drugs that prolong the QT interval, for example amiodarone, sotalol, and amisulpride — macrolides can also prolong
the QT interval, increasing the risk of Torsades de pointes arrhythmias.
[ABPI, 2018b (/cellulitis-acute#!references); ABPI, 2018c (/cellulitis-acute#!references); Joint Formulary Committee, 2019
What are the possible adverse effects of clarithromycin? Back to top
The most common adverse effects of clarithromycin include abdominal pain, nausea, vomiting, taste perversion, and
diarrhoea.
Consider pseudomembranous colitis if a person develops severe diarrhoea during or after treatment with
clarithromycin. For more information, see the CKS topic on Diarrhoea - antibiotic associated (/diarrhoea-antibiotic-
associated).
Reversible hearing loss (sometimes with tinnitus) can occur after large doses of clarithromycin.
Other adverse effects of macrolides, including clarithromycin, include:
Common or very common — decreased appetite, dizziness, gastrointestinal discomfort, gastrointestinal
disorders, headache, hearing impairment, insomnia, pancreatitis, paraesthesia, skin reactions, vasodilation, and vision
disorders.
Uncommon — angioedema, anxiety, arrhythmias, burping, candida infection, chest pain, constipation, drowsiness, dry
mouth eosinophilia, epistaxis, hepatic disorders, leucopenia, muscle complaints, neutropenia, oral disorders,
palpitations, QT interval prolongation, severe cutaneous adverse reactions (SCARs), thrombocytosis, tremor,
and vertigo.
Rare or very rare — myasthenia gravis, nephritis tubulointerstitial.
Frequency not known — abnormal dreams, agranulocytosis, altered smell, depersonalisation, depression, hallucination,
hypotension, mania, myopathy, psychotic disorder, renal failure, seizure, thrombocytopenia, tongue discolouration,
tooth discolouration, and urine discolouration.
[ABPI, 2018c (/cellulitis-acute#!references); Joint Formulary Committee, 2019 (/cellulitis-acute#!references)]
What are the possible drug interactions of clarithromycin? Back to top
Drug interactions of clarithromycin include:

Aminophylline — be aware that aminophylline is predicted to cause hypokalaemia (potentially increasing the risk of
torsade de pointes) when given with clarithromycin.
Calcium channel blockers (CCBs) — clarithromycin possibly inhibits the metabolism of CCBs, increasing the risk of
adverse effects, such as hypotension.
Carbamazepine — clarithromycin can increase carbamazepine levels, causing carbamazepine toxicity (which may
present as nausea and vomiting, ataxia, and drowsiness).
Monitor carbamazepine levels within 3–5 days of starting clarithromycin, and adjust dose accordingly.
Colchicine — clarithromycin possibly increases the risk of colchicine toxicity.
Stop or reduce the dose of colchicine.
Avoid concomitant use in renal or hepatic impairment.
Drugs that prolong the QT interval (such as amiodarone, amisulpride, fluconazole, sildenafil, and tricyclic
antidepressants) — macrolides can also prolong the QT interval, increasing the risk of arrhythmias (such as Torsades
de pointes).
Concurrent use of drugs that prolong the QT interval is not recommended.
Drugs that cause hypokalaemia (such as diuretics, corticosteroids, short-acting beta-2 agonists) — hypokalaemia is
a risk factor for QT prolongation.
Digoxin — clarithromycin increases the concentration of digoxin.
Monitor digoxin concentration.
Ergotamine and dihydroergotamine — concurrent use with clarithromycin may result in acute ergot toxicity.
Concurrent use is contraindicated.
Oral hypoglycaemic drugs and insulin — concurrent use of clarithromycin and antidiabetic drugs (such as
sulphonylureas and/or insulin) can result in significant hypoglycaemia.
Monitor blood glucose levels more regularly, and adjust the antidiabetic drug (and/or insulin) dose accordingly.
Statins — there is an increased risk of myopathy (due to cytochrome P450 enzyme CYP3A4 inhibition) [MHRA, 2008
(/cellulitis-acute#!references); MHRA, 2014 (/cellulitis-acute#!references)].
For simvastatin (potent CYP3A4 inhibitor) — concurrent use is contraindicated. If clarithromycin treatment cannot be
avoided, stop treatment with simvastatin during the course of the treatment.
For atorvastatin (moderate CYP3A4 inhibitor) — avoid concurrent use if possible. If clarithromycin treatment cannot
be avoided, stop treatment with simvastatin during the course of the treatment or prescribe the lowest starting dose
of atorvastatin (that is 10 mg) and do not exceed 20 mg atorvastatin daily. Advise the person to seek medical advice
if they experience symptoms of myopathy (for example muscle pain, tenderness, or weakness).
For pravastatin — prescribe clarithromycin with caution, and advise the person to report any muscle pain,
tenderness, or weakness.
Other statins — rosuvastatin is not associated with cytochrome P450 interactions, and clinically significant
interaction with clarithromycin is not expected for fluvastatin. Nevertheless, advise the person to report any muscle
pain, tenderness, or weakness.
Theophylline — clarithromycin possibly increases the plasma concentration of theophylline.
Consider a dose reduction of theophylline if toxicity is suspected (for example if headache, nausea, or palpitations
occur).
Quetiapine — clarithromycin possibly increases the plasma concentration of quetiapine.
Avoid concurrent use.
Warfarin — clarithromycin may enhance the effect of warfarin.
Increase monitoring of the international normalized ratio (INR) when both drugs are used (particularly in elderly
people), and adjust the warfarin dose accordingly.
Oral hormonal contraception — additional contraceptive precautions are not required during or after a course of
clarithromycin [FSRH, 2017 (/cellulitis-acute#!references)].
For a complete list of possible drug interactions of clarithromycin, see the electronic Medicines Compendium
(http://scribe.clarity.co.uk/www.medicines.org.uk/emc) (eMC) or the British National Formulary
(https://bnf.nice.org.uk/) (BNF).
Can clarithromycin be used during pregnancy and breastfeeding? Back to top
Pregnancy
The available data for clarithromycin do not suggest an increased risk of congenital malformation, but the possibility
cannot be excluded [UKTIS, 2017b (/cellulitis-acute#!references)].
The manufacturer advises that the use of clarithromycin is not advised in pregnancy, particularly in the first trimester,
unless the potential benefit outweighs the risk [ABPI, 2018c (/cellulitis-acute#!references); Joint Formulary Committee,
Breastfeeding
Clarithromycin is excreted into human breast milk. Epidemiologic evidence indicates that the risk of hypertrophic
pyloric stenosis in infants might be increased by use of maternal macrolides, especially in infants exposed in the first 2
weeks after birth [SPS, 2016a (/cellulitis-acute#!references)].
The manufacturer advises that the use of clarithromycin is not advised for breastfeeding women unless the potential
benefit outweighs the risk [ABPI, 2018c (/cellulitis-acute#!references); Joint Formulary Committee, 2019 (/cellulitis-
Back to top
Co-amoxiclav
What are the contraindications and cautions for co-amoxiclav? Back to top
Do not prescribe co-amoxiclav to people with:

A history of severe immediate hypersensitivity reaction to cephalosporins — there is some evidence of partial cross-
allergenicity.
A history of co-amoxiclav- or penicillin-associated jaundice or hepatic dysfunction.
Prescribe co-amoxiclav with caution in people with:
Hepatic impairment — monitor closely.
Chronic kidney disease (CKD) — reduce the dose of co-amoxiclav based on the estimated glomerular filtration rate
(eGFR):
2
If the eGFR is 10–30 mL/minute/1.73 m2, prescribe one 250/125 strength tablet every 12 hours or one 500/125
strength tablet every 12 hours.
If the eGFR is less than 10 mL/minute/1.73 m2, prescribe one 250/125 strength tablet every 24 hours or one 500/125
strength tablet every 24 hours.
Acute lymphocytic leukaemia, chronic lymphocytic leukaemia, cytomegalovirus infection, glandular fever — increased
risk of erythematous rashes.
[ABPI, 2018d (/cellulitis-acute#!references); Joint Formulary Committee, 2019 (/cellulitis-acute#!references)]
What are the possible adverse effects of co-amoxiclav? Back to top
The most common adverse effects of co-amoxiclav include nausea, vomiting, increased risk of infections (for
example fungal infection and vaginitis), and diarrhoea.
Consider pseudomembranous colitis if a person develops severe diarrhoea during or after treatment with co-amoxiclav.
Anaphylaxis (delayed or immediate) is a serious but rare adverse effect of co-amoxiclav. For more information, see the
Cholestatic jaundice can occur either during or shortly after the use of co-amoxiclav.
Cholestatic jaundice is more common in people above the age of 65 years and in men; these reactions have only rarely
been reported in children. Jaundice is usually self-limiting and very rarely fatal. The duration of treatment should be
appropriate to the indication and should not usually exceed 14 days.
Other adverse effects of co-amoxiclav include:
Uncommon — dizziness, dyspepsia, and headache.
Frequency unknown — akathisia, aseptic meningitis, black hairy tongue, crystalluria, haemorrhagic colitis, and
hypersensitivity vasculitis.
What are the possible drug interactions of co-amoxiclav? Back to top
Possible drug interactions of co-amoxiclav include:

Allopurinol — be aware that concomitant use of allopurinol and co-amoxiclav may increase the incidence of skin
rashes.
Manufacturer advises to consider alternatives.
Anticoagulants (for example warfarin) — penicillins potentially alter the anticoagulant effect of warfarin.
Methotrexate — amoxicillin is predicted to increase the risk of toxicity when given with methotrexate.
Probenecid — the renal tubular secretion of amoxicilin is decreased by probenecid. Concurrent use may result in
increased and prolonged blood levels of amoxicillin, but not of clavulanic acid.
Manufacturer recommends avoiding concurrent use.

Can co-amoxiclav be used during pregnancy and breastfeeding? Back to top
Pregnancy
Co-amoxiclav is not known to be harmful in pregnancy [Joint Formulary Committee, 2019 (/cellulitis-
Breastfeeding
Trace amounts of co-amoxiclav are found in breastmilk, but it is appropriate to use in women who are
breastfeeding [Joint Formulary Committee, 2019 (/cellulitis-acute#!references)].
Penicillins (and cephalosporins) are the antibiotics of choice in breastfeeding women [Kearney, 2016 (/cellulitis-
Back to top
Doxycycline
What are the contraindications and cautions for doxycyline? Back to top
Do not prescribe doxycycline to:

Women who are pregnant or breastfeeding, and children younger than 12 years of age — tetracyclines are deposited in
growing bone and teeth which can result in discolouration of teeth and occasionally dental hypoplasia.
Prescribe doxycycline with caution to people with:
Hepatic impairment and those receiving potentially hepatotoxic drugs.
Myasthenia gravis — tetracyclines may increase muscle weakness in people with myasthenia gravis.
Systemic lupus erythematosus (SLE) — tetracyclines may exacerbate SLE symptoms.
Renal impairment — avoid excessive doses.
[ABPI, 2017b (/cellulitis-acute#!references); Joint Formulary Committee, 2019 (/cellulitis-acute#!references)]
What are the possible adverse effects of doxycycline? Back to top
Common adverse effects of doxycycline include dyspnoea, hypotension, peripheral oedema, and tachycardia.
Other adverse effects of tetracyclines, including doxycycline, include:
Common or very common — angioedema, diarrhoea, headache, Henoch-Schönlein
purpura, hypersensitivity, nausea, pericarditis, photosensitivity reaction, skin reactions, exacerbation of systemic lupus
erythematosus, and vomiting.
Consider pseudomembranous colitis if a person develops severe diarrhoea during or after treatment with co-
amoxiclav. For more information, see the CKS topic on Diarrhoea - antibiotic associated (/diarrhoea-antibiotic-
associated).
Headache may indicate benign intracranial hypertension. Discontinue treatment if raised intracranial pressure
develops.
Uncommon — gastrointestinal discomfort.
Rare or very rare — arthralgia, decreased appetite, discolouration of thyroid tissue (no abnormalities of thyroid function
are known to occur), dysphagia, eosinophilia, flushing, gastrointestinal disorders, haemolytic anaemia, hepatic
disorders, idiopathic intracranial hypertension, increased risk of infection, myalgia, neutropenia, oral
disorders, pancreatitis, photoonycholysis, pseudomembranous enterocolitis, severe cutaneous adverse reactions
(SCARs), Stevens-Johnson syndrome, thrombocytopenia, tinnitus, and vision disorders.
Visual disorders may indicate benign intracranial hypertension. Discontinue treatment if raised intracranial pressure
develops.
Frequency unknown — dizziness and tooth discolouration.
What are the possible drug interactions of doxycycline? Back to top
Possible drug interactions of doxycycline include:

Antacids — antacids containing aluminium, bismuth, calcium, or magnesium decreasesthe absorption of doxycycline.
Manufacturer advises separate administration (for example by 2–3 hours).
Oral zinc, iron salts, or bismuth preparations — absorption of doxycycline may be impaired if it is taken with these
preparations.
Manufacturer advises separate administration (for example by 2–3 hours).
Retinoids — there is a possible increased risk of benign intracranial pressure if tetracyclines are used concurrently with
retinoids (such as isotretinoin).
Avoid the concurrent use of tetracyclines and retinoids.
tetracyclines [FSRH, 2017 (/cellulitis-acute#!references)].
For a complete list of possible drug interactions of doxycycline, see the electronic Medicines Compendium
Can doxycycline be used during pregnancy and breastfeeding? Back to top
Pregnancy
Doxycycline is contraindicated in women who are pregnant [ABPI, 2017b (/cellulitis-acute#!references); Joint Formulary
Committee, 2019 (/cellulitis-acute#!references)].
Exposure to doxycycline in early pregnancy has not been firmly associated with any specific malformations, but its use
in the second or third trimester can cause discolouration of the teeth [UKTIS, 2017c (/cellulitis-acute#!references)].
Effects on skeletal development have been reported in the first trimester in animal studies [Joint Formulary Committee,
Breastfeeding
The manufacturer states that doxycycline is contraindicated in breastfeeding women as it may cause permanent
discolouration of the teeth (yellow-grey-brown) [ABPI, 2017b (/cellulitis-acute#!references)].
The NHS Specialist Pharmacy Service (SPS) states that concerns about bone deposition of tetracyclines and possible
staining of infant’s dental enamel have not been confirmed, and are unlikely during short-term use [SPS, 2016b
(/cellulitis-acute#!references)]. In addition, absorption and therefore discoloration of teeth in the infant is also inhibited
by calcium in the breastmilk [SPS, 2016b (/cellulitis-acute#!references); Joint Formulary Committee, 2019 (/cellulitis-
The SPS states that If other antibiotics are not appropriate, tetracycline is the preferred drug from this group. Short-
term use (less than 3 weeks duration) is acceptable for most tetracyclines, but long-term use (for example in acne) is
not advisable [SPS, 2016b (/cellulitis-acute#!references)].
Back to top
Erythromycin
What are the contraindications and cautions for erythromycin? Back to top
Do not prescribe erythromycin to people:

With acute porphyrias.
Taking medicines that interact with erythromycin (for example, simvastatin, mizolastine, domperidone, cisapride,
pimozide, ergotamine, dihydroergotamine).
Prescribe erythromycin with caution to people with:
A predisposition to QT interval prolongation (for example, people with electrolyte disturbances or taking other
medicines that cause QT interval prolongation).
Myasthenia gravis.
Hepatic impairment.
Renal impairment — the maximum daily dose in adults with severe renal impairment is 1500 mg daily.
[ABPI, 2019 (/cellulitis-acute#!references); Joint Formulary Committee, 2019 (/cellulitis-acute#!references)]
What are the possible adverse effects of erythromycin? Back to top
Gastrointestinal (GI) — diarrhoea, GI discomfort/disorders, nausea, vomiting (common or very common); consipation
(uncommon).
Rare or very rare: antibiotic associated colitis.
Cardiovascular — QTc interval prolongation, torsades de pointes, palpitations and cardiac rhythm disorders including
ventricular tachyarrhythmias (uncommon).
Hepatobiliary — cholestatic hepatitis, jaundice, hepatic disfunction, hepatomegaly, hepatic failure, hepatocellular
hepatitis
Skin and subcutaneous tissues — skin reactions (common or very common); Stevens-Johnson syndrome, toxic
epidermal necrolysis, erythema multiforme (uncommon); acute generalised exanthematous pustulosis (AGEP) (frequency
unknown).
Other common adverse effects include:
Dizziness
Headache
Hearing impairment
Vasodilation
Vision disorders.
[ABPI, 2019 (/cellulitis-acute#!references); Joint Formulary Committee, 2019 (/cellulitis-acute#!references)]
What are the possible drug interactions of erythromycin? Back to top
Drug interactions for erythromycin include:
Aminophylline — aminophylline can cause hypokalaemia (potentially increasing the risk of torsade de pointes) when
given with erythromycin. Theophylline clearance may also be reduced if given concurrently with erythromycin. Monitor
theophylline levels after 48 hours and adjust the dose accordingly. Monitor potassium concentrations closely and the
effects of oral erythromycin to ensure they are adequate. Consider giving an alternative antibiotic.
Calcium channel blockers (amlodipine, diltiazem) — erythromycin possibly inhibits the metabolism of calcium channel
blockers, increasing the risk of adverse effects, such as hypotension. Monitor for adverse effects (for example,
bradycardia, hypotension, headache, oedema) and reduce the calcium-channel blocker dose as necessary.
Rifampicin — may induce the metabolism of clarithromycin, resulting in sub-therapeutic levels.
If concurrent use is necessary, monitor erythromycin efficacy closely.
Carbamazepine — erythromycin can increase carbamazepine levels, causing carbamazepine toxicity (which may
present as nausea and vomiting, ataxia, and drowsiness).
Avoid concurrent use, unless carbamazepine levels can be monitored closely. amino
Ciclosporin — levels are greatly increased by erythromycin. Monitor concentrations and effects (for example, renal
function) more frequently if erythromycin is started or stopped. Adjust the ciclosporin dose as required.
Cisapride, domperidone — levels may be raised, increasing the risk of potentially life-threatening arrhythmias (torsade
de pointes). Concurrent use is contraindicated.
Colchicine — erythromycin possibly increases the risk of colchicine toxicity.
Stop or reduce the dose of colchicine.
Avoid concomitant use in renal or hepatic impairment.
Drugs that prolong the QT interval (such as amiodarone, amisulpride, fluconazole, sildenafil, mizolastine,
hydroxyzine) — macrolides can also prolong the QT interval, increasing the risk of arrhythmias (such as Torsades de
pointes).
Concurrent use of drugs that prolong the QT interval is not recommended.
Drugs that cause hypokalaemia (such as diuretics, corticosteroids, short-acting beta-2 agonists) — hypokalaemia is
a risk factor for QT prolongation. Monitor potassium levels closely.
Digoxin — erythromycin may increase the concentration of digoxin.
Monitor digoxin concentration.
Ergot alkaloids (such as ergotamine and dihydroergotamine) — concurrent use with erythromycin may result in acute
ergot toxicity.
Concurrent use is contraindicated.
Protease inhibitors (ritonavir, saquinavir) — erythromycin levels may be increased. Monitor for adverse effects.
Statins — there is an increased risk of myopathy (due to cytochrome P450 enzyme CYP3A4 inhibition) [MHRA, 2008
(/cellulitis-acute#!references); MHRA, 2014 (/cellulitis-acute#!references)].
For simvastatin (potent CYP3A4 inhibitor) — concurrent use is contraindicated. If erythromycin treatment cannot be
avoided, stop treatment with simvastatin during the course of the treatment.
For atorvastatin (moderate CYP3A4 inhibitor) — avoid concurrent use if possible. If erythromycin treatment cannot
be avoided, stop treatment with simvastatin during the course of the treatment or prescribe the lowest starting dose
of atorvastatin (that is 10 mg) and do not exceed 20 mg atorvastatin daily. Advise the person to seek medical advice
if they experience symptoms of myopathy (for example muscle pain, tenderness, or weakness).
For pravastatin — prescribe erythromycin with caution, and advise the person to report any muscle pain,
tenderness, or weakness.
Theophylline — erythromycin possibly increases the plasma concentration of theophylline.
Monitor theophylline levesl after 48 hours and adjust the theophylline dose if necessary.
Quetiapine — erythromycin increases the plasma concentration of quetiapine and both drugs are associated with QT
interval prolongation.
Concurrent use is contraindicated, but if necessary, monitor for quetiapine adverse effects (for
example, somnolence, dry mouth, tachycardia) and reduce the dose if needed.
Warfarin — erythromycin may cause a minor increase in warfarin effects.
Consider increased monitoring of the international normalized ratio (INR) when both drugs are used (particularly in
elderly people), and adjust the warfarin dose accordingly.

Oral hormonal contraception — additional contraceptive precautions are not required during or after a course of
erythromycin [FSRH, 2017 (/cellulitis-acute#!references)].
For a complete list of possible drug interactions for erythromycin, see the electronic Medicines Compendium
[Preston, 2016 (/cellulitis-acute#!references)]
Can erythromycin be used during pregnancy and breastfeeding? Back to top
Pregnancy
The use of erythromycin in pregnancy is not known to be harmful — the considerable data for macrolides as a class, and
for erythromycin specifically, do not suggest an increased overall risk of congenital malformation or of cardiac
malformations specifically [Joint Formulary Committee, 2019 (/cellulitis-acute#!references); UKTIS, 2019 (/cellulitis-
However, the manufacturer states that [ABPI, 2019 (/cellulitis-acute#!references)]:
Observational studies in humans have reported cardiovascular malformations after exposure to medicinal products
containing erythromycin during early pregnancy.
There have been reports that maternal macrolide antibiotics exposure within 7 weeks of delivery may be associated
with a higher risk of infantile hypertrophic pyloric stenosis (IHPS).
Breastfeeding
Erythromycin is excreted in breast milk in small amounts and it is not known to be harmful [Joint Formulary Committee,
2019 (/cellulitis-acute#!references)] [LactMed, 2019 (/cellulitis-acute#!references)].
Monitor the infant for irritability and possible effects on the gastrointestinal flora, such as diarrhea, candidiasis (thrush,
nappy rash).
However, the manufacturer advises exercising caution due to reports of infantile hypertrophic pyloric stenosis in breast-
fed infants [ABPI, 2019 (/cellulitis-acute#!references)].
Back to top
Flucloxacillin
What are the contraindications and cautions for flucloxacillin? Back to top
Do not prescribe flucloxacillin to people with:

A hypersensitivity to cephalosporins — there is some evidence of partial cross-allergenicity.
A history of penicillin-associated jaundice or hepatic dysfunction.
Prescribe flucloxacillin with caution in people with:
Hepatic impairment (especially if they are 50 years of age or older, or have a serious underlying disease).
Severe renal impairment — reduce the dose of flucloxacillin, or the dosing interval, if the estimated glomerular filtration
2
rate (eGFR) is less than 10 mL/minute/1.73 m2, due to the risk of neurotoxicity.
What are the possible adverse effects of flucloxacillin? Back to top
The most common adverse effects of flucloxacillin include nausea, vomiting, skin rash, thrombocytopenia, and
diarrhoea.
Consider pseudomembranous colitis if a person develops severe diarrhoea during or after treatment with flucloxacillin.
Anaphylaxis (delayed or immediate) is a serious but rare adverse effect of flucloxacillin. For more information, see the
Hepatitis and cholestatic jaundice may occur very rarely after treatment with flucloxacillin. These reactions are related
neither to the dose nor to the route of administration of flucloxacillin, and the onset may be delayed for several weeks (up
to 2 months) after treatment has stopped. Risk factors include treatment for more than 2 weeks and increasing age [CSM,
1992 (/cellulitis-acute#!references); CSM, 2004 (/cellulitis-acute#!references)].
Other adverse effects of penicillins, including flucloxacillin, include:
Uncommon — leucopenia.
Rare or very rare — agranulocytosis, angioedema, arthralgia, eosinophilia, fever, haemolytic anaemia, myalgia, nephritis
tubulointerstitial, neutropenia, seizure, and severe cutaneous adverse reactions (SCARs).
What are the possible drug interactions of flucloxacillin? Back to top
Possible drug interactions of flucloxacillin include:

Anticoagulants (for example warfarin) — flucloxacillin potentially alters the anticoagulant effect of warfarin.
Methotrexate — flucloxacillin is predicted to increase the risk of toxicity when given with methotrexate, and both
flucloxacillin and methotrexate can increase the risk of hepatotoxicity.
Food — the absorption of flucloxacillin may be reduced by food.
Advise that flucloxacillin should be taken one hour before food or on an empty stomach.
Can flucloxacillin be used during pregnancy and breastfeeding? Back to top
Pregnancy
Penicillins are not known to be harmful in pregnancy [Joint Formulary Committee, 2019 (/cellulitis-acute#!references)].
Breastfeeding
Trace amounts of penicillins are found in breastmilk, but it is appropriate to use in women who are breastfeeding [Joint
Formulary Committee, 2019 (/cellulitis-acute#!references)].
Penicillins (and cephalosporins) are the antibiotics of choice in breastfeeding women [Kearney, 2016 (/cellulitis-
Back to top
Metronidazole
What are the contraindications and cautions for metronidazole? Back to top
Do not prescribe metronidazole in people with:

Known metronidazole or nitroimidazole hypersensitivity.
Prescribe metronidazole with caution in people with:
Cockayne syndrome — cases of severe hepatotoxicity/acute hepatic failure, including cases with a fatal outcome with
very rapid onset after treatment initiation in patients with Cockayne syndrome have been reported with products
containing metronidazole for systemic use (oral and suppositories).
Only prescribe after careful benefit-risk assessment and only if no alternative treatment is available. Liver function tests
must be performed just prior to the start of therapy, throughout and at the end of treatment until liver function is within
normal ranges, or until the baseline values are reached.
Active or chronic severe peripheral and central nervous system disease, as there is a risk of neurological aggravation.
Severe liver disease or hepatic encephalopathy — prescribe one-third of the daily dosage once daily.
What are the possible adverse effects of metronidazole? Back to top
Blood disorders — agranulocytosis, neutropenia, thrombocytopenia, pancytopenia (very rare).

Eye — transient diploplia, or myopia (very rare).
Gastrointestinal — nausea, vomiting, anorexia, epigastric pain, taste disturbances, furred tongue, oral mucositis
(unknown frequency).
Nervous system — drowsiness, dizziness, convulsions, headaches, encephalopathy (very rare)
Psychiatric — confusion, hallucinations (very rare).
Skin — rash, pruritus, flushing, erythema multiforme, Stevens-Johnson syndrome or toxic epidermal necrolysis, fixed drug
eruption (very rare).
Other rare, or very rare adverse effects include:
Anaphylaxis.
Darkening of urine.
Hearing impairment, tinnitus.
Liver enzyme increases, jaundice, pancreatitis.
Myalgia, arthralgia.
What are the possible drug interactions of metronidazole? Back to top
Alcohol — some people taking metronidazole experience a disulfiram-like reaction with alcohol.
Warn the person that they might experience this reaction if they drink alcohol whilst on metronidazole and for at least
48 hours afterwards.
Busulfan — plasma levels of busulfan may be increased leading to toxicity. Avoid high doses of busulfan. If conventional
doses of busulfan are given, monitor blood count weekly.
Ciclosporin — levels of ciclosporin may be increased. If co-administration of metronidazole and ciclosporin is necessary,
serum ciclosporin levels and serum creatinine should be closely monitored.
5-fluorouracil — metronidazole reduces the clearance of 5-fluorouracil, increasing the risk of toxicity.
Lithium — seek specialist advice regarding the use of metronidazole with lithium, as metronidazole increases the risk of
lithium toxicity. Lithium dose reduction may be required due to the risk of renal damage with concurrent use. Plasma
concentrations of lithium, creatinine, and electrolytes should be monitored if metronidazole and lithium are used
simultaneously.
metronidazole.
However, women should be advised about the importance of correct contraceptive practice if they experience vomiting
or diarrhoea. For further information, see the sections on vomiting or diarrhoea in the CKS topics on Contraception -
combined hormonal methods (/contraception-combined-hormonal-methods) and Contraception - progestogen-only
methods (/contraception-progestogen-only-methods).
Phenobarbital — the metabolism of metronidazole is increased significantly. The dose of metronidazole may need to be
increased.
Warfarin — the anticoagulant effects of warfarin may be increased by metronidazole.
Monitor the international normalized ratio (INR) and adjust the warfarin dose accordingly.
[Preston, 2016 (/cellulitis-acute#!references); ABPI, 2017c (/cellulitis-acute#!references); FSRH, 2017 (/cellulitis-

acute#!references); Joint Formulary Committee, 2019 (/cellulitis-acute#!references)]
Can metronidazole be used during pregnancy and breastfeeding? Back to top
Pregnancy
Metronidazole is not known to be harmful in pregnancy, however the manufacturer advises that it should only be used if
the benefit outweighs risks and that a single high dose regimen should be avoided.
Breastfeeding
Significant amounts of metronidazole are excreted in breastmilk, however it is compatible with breastfeeding, as it is of
low toxicity and quantities are far less than those used therapeutically in infants.
The manufacturer advises against the use of high-dose regimens.
Back to top
Analgesia
For detailed information on prescribing simple analgesics, see the CKS topics on Analgesia - mild-to-moderate pain
(/analgesia-mild-to-moderate-pain) and NSAIDs - prescribing issues (/nsaids-prescribing-issues).
Back to top
Search strategy
Scope of search
A literature search was conducted for guidelines and systematic reviews on primary care management of acute cellulitis.
Search dates
March 2015 - April 2019
Key search terms

The terms listed below are the core search terms that were used for EBSCOhost MEDLINE (searched 11th April 2019). These
were combined with filters to identify guidelines, systematic reviews and primary care relevant literature in EBSCOhost
MEDLINE. The strategy was adapted for The Cochrane Library databases.
S3 S1 OR S2
S2 AB cellulitis OR TI cellulitis
S1 (MH "Cellulitis+")
Sources of guidelines
National Institute for Health and Care Excellence (NICE) (https://www.nice.org.uk/)
Scottish Intercollegiate Guidelines Network (SIGN) (https://www.sign.ac.uk/)
Royal College of Physicians (https://www.rcplondon.ac.uk/)
Royal College of General Practitioners (https://www.rcgp.org.uk/)
Royal College of Nursing (https://www.rcn.org.uk/)
NICE Evidence (https://www.evidence.nhs.uk/)
World Health Organization (https://www.who.int/)
Guidelines International Network (https://www.g-i-n.net/)
TRIP database (http://www.tripdatabase.com/)
Agency for Healthcare Research and Quality (https://www.ahrq.gov/)
Institute for Clinical Systems Improvement (https://www.icsi.org/)
National Health and Medical Research Council (Australia) (https://www.nhmrc.gov.au/research-policy)
Royal Australian College of General Practitioners (https://www.racgp.org.au/clinical-resources/clinical-guidelines)
British Columbia Medical Association (https://www2.gov.bc.ca/gov/content/health/practitioner-professional-resources/bc-
guidelines)
Canadian Medical Association (https://www.cma.ca/)
Alberta Medical Association (http://www.topalbertadoctors.org/cpgs/)
Michigan Quality Improvement Consortium (http://mqic.org/guidelines.htm)
Singapore Ministry of Health (https://www.moh.gov.sg/resources-statistics)
National Resource for Infection Control (https://www.nric.org.uk/)
Patient UK Guideline links (https://patient.info/patientplus)
RefHELP NHS Lothian Referral Guidelines (https://apps.nhslothian.scot/refhelp)
Medline (with guideline filter)
Driver and Vehicle Licensing Agency (https://www.gov.uk/guidance/assessing-fitness-to-drive-a-guide-for-medical-
professionals)
NHS Health at Work (http://www.nhshealthatwork.co.uk/oh-guidelines.asp) (occupational health practice)
Sources of systematic reviews and meta-analyses
The Cochrane Library (https://www.cochranelibrary.com/):

Systematic reviews
Protocols
Database of Abstracts of Reviews of Effects
Medline (with systematic review filter)
EMBASE(with systematic review filter)
Sources of health technology assessments and economic appraisals

NIHR Health Technology Assessment programme (https://www.nihr.ac.uk/funding-and-support/funding-for-research-
studies/funding-programmes/health-technology-assessment/)
NHS Economic Evaluations
Health Technology Assessments
Canadian Agency for Drugs and Technologies in Health (https://www.cadth.ca/)
International Network of Agencies for Health Technology Assessment (http://www.inahta.org/)
Sources of randomized controlled trials

Central Register of Controlled Trials
Medline (with randomized controlled trial filter)
EMBASE (with randomized controlled trial filter)
Sources of evidence based reviews and evidence summaries

Bandolier (http://www.bandolier.org.uk/)
Drug and Therapeutics Bulletin (https://dtb.bmj.com/)
TRIP database (http://www.tripdatabase.com/)
Central Services Agency COMPASS Therapeutic Notes (http://www.medicinesni.com/index.asp)
Sources of national policy

Department of Health (https://www.gov.uk/government/organisations/department-of-health-and-social-care)
Health Management Information Consortium (HMIC)
Patient experiences
Healthtalk (http://www.healthtalk.org/)
BMJ - Patient Journeys (https://www.bmj.com/specialties/patient-journeys)
Patient.co.uk - Patient Topics (https://patient.info/health)
Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all
topics. Some of these resources are not freely available and require subscriptions to access content.
British National Formulary (https://bnf.nice.org.uk/) (BNF)

electronic Medicines Compendium (https://www.medicines.org.uk/emc) (eMC)
European Medicines Agency (https://www.ema.europa.eu/en) (EMEA)
LactMed (https://toxnet.nlm.nih.gov/newtoxnet/lactmed.htm)
Medicines and Healthcare products Regulatory Agency (https://www.gov.uk/government/organisations/medicines-and-

healthcare-products-regulatory-agency) (MHRA)
REPROTOX (http://www.reprotox.org/)
Scottish Medicines Consortium (https://www.scottishmedicines.org.uk/home)
Stockley's Drug Interactions (https://about.medicinescomplete.com/publication/stockleys-drug-interactions/)
TERIS (http://depts.washington.edu/terisdb/terisweb/index.html)
TOXBASE (https://www.toxbase.org/)
Micromedex (https://www.micromedexsolutions.com/home/dispatch)
UK Medicines Information (https://www.ukmi.nhs.uk/)
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Stakeholder engagement
Our policy
The external review process is an essential part of CKS topic development. Consultation with a wide range of stakeholders
provides quality assurance of the topic in terms of:
Clinical accuracy.
Consistency with other providers of clinical knowledge for primary care.
Accuracy of implementation of national guidance (in particular NICE guidelines).
Usability.
Principles of the consultation process

The process is inclusive and any individual may participate.
To participate, an individual must declare whether they have any competing interests or not. If they do not declare whether
or not they have competing interests, their comments will not be considered.
Comments received after the deadline will be considered, but they may not be acted upon before the clinical topic is
issued onto the website.
Comments are accepted in any format that is convenient to the reviewer, although an electronic format is encouraged.
External reviewers are not paid for commenting on the draft topics.
Discussion with an individual or an organization about the CKS response to their comments is only undertaken in
exceptional circumstances (at the discretion of the Clinical Editor or Editorial Steering Group).
All reviewers are thanked and offered a letter acknowledging their contribution for the purposes of appraisal/revalidation.
All reviewers are invited to be acknowledged on the website.All reviewers are given the opportunity to feedback about the
external review process, enabling improvements to be made where appropriate.
Stakeholders
Key stakeholders identified by the CKS team are invited to comment on draft CKS topics. Individuals and organizations
can also register an interest to feedback on a specific topic, or topics in a particular clinical area, through the Getting
involved (http://cks.clarity.co.uk/get-involved/) section of the Clarity Informatics (https://clarity.co.uk/) website.
Stakeholders identified from the following groups are invited to review draft topics:
Experts in the topic area.
Professional organizations and societies(for example, Royal Colleges).
Patient organizations, Clarity has established close links with groups such as Age UK and the Alzheimer’s Society
specifically for their input into new topic development, review of current topic content and advice on relevant areas of
expert knowledge.
Guideline development groups where the topic is an implementation of a guideline.
The British National Formulary team.
The editorial team that develop MeReC Publications.

Reviewers are provided with clear instructions about what to review, what comments are particularly helpful, how to
submit comments, and declaring interests.
Patient engagement
Clarity Informatics has enlisted the support and involvement of patients and lay persons at all stages in the process of
creating the content which include:
Topic selection
Scoping of topic
Selection of clinical scenarios
First draft internal review
Second draft internal review
External review
Final draft and pre-publication
Our lay and patient involvement includes membership on the editorial steering group, contacting expert patient groups,
organizations and individuals.
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Evidence exclusion criteria
Our policy
Scoping a literature search, and reviewing the evidence for CKS is a methodical and systematic process that is carried out
by the lead clinical author for each topic. Relevant evidence is gathered in order that the clinical author can make fully
informed decisions and recommendations. It is important to note that some evidence may be excluded for a variety of
reasons. These reasons may be applied across all CKS topics or may be specific to a given topic.
Studies identified during literature searches are reviewed to identify the most appropriate information to author a CKS topic,
ensuring any recommendations are based on the best evidence. We use the principles of the GRADE and PICOT approaches
to assess the quality of published research. We use the principles of AGREE II to assess the quality of published guidelines.
Standard exclusions for scoping literature:

Animal studies
Original research is not written in English
Possible exclusions for reviewed literature:

Sample size too small or study underpowered
Bias evident or promotional literature
Population not relevant
Intervention/treatment not relevant
Outcomes not relevant
Outcomes have no clear evidence of clinical effectiveness
Setting not relevant
Not relevant to UK
Incorrect study type
Review article
Duplicate reference
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Organizational, behavioural and financial barriers
Our policy
The CKS literature searches take into consideration the following concepts, which are discussed at the initial scoping of the
topic.
Feasibility
Studies are selected depending on whether the intervention under investigation is available in the NHS and can be
practically and safely undertaken in primary care.
Organizational and Financial Impact Analysis
Studies are selected and evaluated on whether the intervention under investigations may have an impact on local clinical
service provision or national impact on cost for the NHS. The principles of clinical budget impact analysis are adhered to,
evaluated and recorded by the author. The following factors are considered when making this assessment and analysis.
Eligible population
Current interventions
Likely uptake of new intervention or recommendation
Cost of the current or new intervention mix
Impact on other costs
Condition-related costs
In-direct costs and service impacts
Time dependencies
Cost-effectiveness or cost-benefit analysis studies are identified where available.
We also evaluate and include evidence from NICE accredited sources which provide economic evaluations of
recommendations, such as NICE guidelines. When a recommended action may not be possible because of resource
constraints, this is explicitly indicated to healthcare professionals by the wording of the CKS recommendation.
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Declarations of interest
Our policy
Clarity Informatics requests that all those involved in the writing and reviewing of topics, and those involved in the external
review process to declare any competing interests. Signed copies are securely held by Clarity Informatics and are available
on request with the permission of the individual. A copy of the declaration of interest form which participants are asked to
complete annually is also available on request. A brief outline of the declarations of interest policy is described here and full
details of the policy is available on the Clarity Informatics website (https://cks.clarity.co.uk/). Declarations of interests of the
authors are not routinely published, however competing interests of all those involved in the topic update or development are
listed below. Competing interests include:
Personal financial interests

Personal family interest
Personal non-financial interest
Non-personal financial gain or benefit
Although particular attention is given to interests that could result in financial gains or losses for the individual, competing
interests may also arise from academic competition or for political, personal, religious, and reputational reasons.An individual
is not obliged to seek out knowledge of work done for, or on behalf of, the healthcare industry within the departments for
which they are responsible if they would not normally expect to be informed.
Who should declare competing interests?

Any individual (or organization) involved in developing, reviewing, or commenting on clinical content, particularly the
recommendations should declare competing interests. This includes the authoring team members, expert advisers, external
reviewers of draft topics, individuals providing feedback on published topics, and Editorial Steering Group members.
Declarations of interest are completed annually for authoring team and editorial steering group members, and are completed
at the start of the topic update and development process for external stakeholders.
Competing interests declared for this topic:

None.
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Cellulitis - acute: Summary
Cellulitis is an acute bacterial infection of the dermis and subcutaneous tissue. The infected area, most commonly the
lower limb, is characterized by pain, warmth, swelling, and erythema. Blisters and bullae may form. Fever, malaise,
nausea, and rigors may accompany or precede the skin changes.
Cellulitis develops when microorganisms (most commonly Streptococcus pyogenes and Staphylococcus aureus) gain
entry to the dermal and subcutaneous tissues via disruptions in the cutaneous barrier. Risk factors include skin trauma,
ulceration, and obesity.
Complications of cellulitis include necrotizing fasciitis, sepsis, persistent leg ulceration, and recurrent cellulitis.
Most episodes of cellulitis resolve with treatment, and major complications are absent. However, recurrence is common,
and each episode increases the likelihood of subsequent recurrence.
The diagnosis of cellulitis can usually be made on history and examination alone. Investigations may be considered in
certain cases, for example, a swab for culture if there is an open wound, drainage, or an obvious portal for microbial
entry.
Differential diagnoses of cellulitis include deep venous thrombosis, septic arthritis, acute gout, and ruptured Baker's cyst.
The Eron classification of cellulitis is a useful guide for making management decisions:
Class I — there are no signs of systemic toxicity or uncontrolled comorbidities.
Class II — the person is either systemically unwell or systemically well but with a comorbidity (for example peripheral
arterial disease, chronic venous insufficiency, or morbid obesity) which may complicate or delay resolution of infection.
Class III — the person has significant systemic upset (such as acute confusion, tachycardia, hypotension), or unstable
comorbidities that may interfere with a response to treatment, or a limb-threatening infection due to vascular
compromise.
Class IV — the person has sepsis or a severe life-threatening infection, such as necrotizing fasciitis.
People with class I cellulitis can be managed in primary care with oral antibiotics.
People with class II cellulitis are suitable for short-term (up to 48 hours) hospitalization and discharge on outpatient
parenteral antibiotic therapy (OPAT), where this service is available.
Urgent hospital admission should be arranged for:
People with Class III or IV cellulitis.
People who are more vulnerable to life-threatening infection, for example, the very young and frail, and people with
comorbidities.
People with facial cellulitis (unless mild) or suspected orbital or periorbital cellulitis.
Primary care management of uncomplicated cellulitis includes:
Prescribing appropriate antibiotics.

Advising on the use of analgesia to treat pain, adequate fluid intake, elevating the leg for comfort and to relieve oedema
(where applicable), and when to seek immediate medical review (for example if antibiotics are not tolerated or systemic
symptoms develop or worsen).
Managing any underlying risk factors (such as breaks in the skin).
Identifying and managing comorbidities (such as diabetes mellitus) that may cause the cellulitis to spread rapidly, or
delay healing.
Advising on preventative measures to reduce the risk of recurrence, including weight loss (where applicable) and the
use of emollients to prevent dry skin and cracking.
Providing patient information on cellulitis.
Reviewing the person appropriately.
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Have I got the right topic?
From age 1 month onwards.
This CKS topic covers the management of acute cellulitis in primary care.
This CKS topic does not cover the detailed management of persistent or recurrent cellulitis, cellulitis associated with an
animal or human bite wound, or diabetic foot ulcer.
There are separate CKS topics on Bites - human and animal (/bites-human-and-animal), Boils, carbuncles, and
staphylococcal carriage (/boils-carbuncles-and-staphylococcal-carriage), Candida - skin (/candida-skin), Diabetes - type 1
(/diabetes-type-1), Diabetes - type 2 (/diabetes-type-2), Fungal skin infection - foot (/fungal-skin-infection-foot), Lacerations
(/lacerations), Leg ulcer - venous (/leg-ulcer-venous), Otitis externa (/otitis-externa), Paronychia - acute (/paronychia-
acute) and Whitlow (staphylococcal and herpetic) (/whitlow-staphylococcal-and-herpetic).
The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first
contact or primary healthcare.
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How up-to-date is this topic?
Changes
Update
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Goals and outcome measures
Goals
Outcome measures
Audit criteria
QOF indicators
QIPP - Options for local implementation
NICE quality standards
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Background information
Definition
Causes
Prevalence
Risk factors
Complications
Prognosis
Back to top
Diagnosis of acute cellulitis
Diagnosis
Differential diagnosis
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Management
Scenario: Management (/cellulitis-acute#!scenario): covers the management of acute cellulitis in primary care.
Back to top
Prescribing information
Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the
drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse
effects, see the electronic Medicines Compendium (http://www.medicines.org.uk/emc) (eMC), or the British National
Formulary (https://bnf.nice.org.uk/) (BNF).
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Supporting evidence
The recommendations in this CKS topic are based largely on Guidelines on the management of cellulitis published by the
Clinical Resource Efficiency Support Team [CREST, 2005 (/cellulitis-acute#!references)], and the National Institute for Health
and Care Excellence (NICE) guideline Cellulitis and erysipelas: antimicrobial prescribing [NICE, 2019a (/cellulitis-
Back to top
How this topic was developed
This section briefly describes the processes used in developing and updating this topic. Further details on the full process
can be found in the About Us (http://cks.nice.org.uk/development) section and on the Clarity Informatics
(https://clarity.co.uk/) website.
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References
Aboltins, C.A., Hutchinson, A.F., Sinnappu, R.N. et al. (2015) Oral versus parenteral antimicrobials for the treatment of
cellulitis: a randomized non-inferiority trial. Journal of Antimicrobial Chemotherapy 70(2), 581-586. [Abstract
(http://www.ncbi.nlm.nih.gov/pubmed/25336165?dopt=Abstract<https://www.ncbi.nlm.nih.gov/pubmed/25336165?
dopt=Abstract>)]
ABPI (2017a) SPC for amoxicillin 250 mg capsules. Electronic Medicines Compendium . Datapharm Communications Ltd.
.. www.medicines.org.uk/emc/ (https://www.medicines.org.uk/emc/) [Free Full-text
(https://www.medicines.org.uk/emc/medicine/25916)]
ABPI (2017b) SPC for coxycycline 100 mg Capsules. Electronic Medicines Compendium. Datapharm Communications
Ltd.. www.medicines.org.uk/emc (https://www.medicines.org.uk/emc) [Free Full-text
(https://www.medicines.org.uk/emc/medicine/33352)]
ABPI (2017c) SPC for Metronidazole 400 mg tablets. Electronic Medicines Compendium. Datapharm Communications Ltd.
www.medicines.org.uk (http://www.medicines.org.uk/)
ABPI (2018a) SPC for Flucloxacillin 250mg Capsules. Electronic Medicines Compendium. Datapharm Communications
Ltd.. www.medicines.org.uk/emc/ (https://www.medicines.org.uk/emc/)
ABPI (2018b) SPC for Klaricid XL 500mg tablets. Electronic Medicines Compendium. Datapharm Communications Ltd..
www.medicines.org.uk/emc/ (https://www.medicines.org.uk/emc/) [Free Full-text
(https://www.medicines.org.uk/emc/product/151/smpc)]
ABPI (2018c) SPC for Clarithromycin 250mg. Electronic Medicines Compendium. Datapharm Communications Ltd.
www.medicines.org.uk/emc/ (https://www.medicines.org.uk/emc/)
ABPI (2018d) SPC for Augmentin 375 mg tablets. Electronic Medicines Compendium. Datapharm Communications Ltd..
www.medicines.org.uk/emc/ (https://www.medicines.org.uk/emc/) [Free Full-text
ABPI (2019) SPC for Erythromycin 250 mg gastro-resistant tablets. Electronic Medicines Compendium. Datapharm
Communications Ltd. www.medicines.org.uk/emc/ (https://www.medicines.org.uk/emc/) [Free Full-text
BMJ (2018) Cellulitis. BMJ Best Practice. bestpractice.bmj.com/info/ (https://bestpractice.bmj.com/info/)
British Lymphology Society (2016) Consensus document on the management of cellulitis in lymphoedema. British
Lymphology Society. www.lymphoedema.org (http://www.lymphoedema.org) [Free Full-text
(https://www.lymphoedema.org/images/pdf/CellulitisConsensus.pdf)]
Bystritsky, R. and Chambers, H. (2018) Cellulitis and Soft Tissue Infections. Annals of Internal Medicine 168(3), Itc17-Itc32.
Cannon, J., Dyer, J. and Carapetis, J. et al. (2018a) Epidemiology and risk factors for recurrent severe lower limb cellulitis:
a longitudinal cohort study. Clinical Microbiology And Infection 24(10), 1084-1088.
Cannon, J., Rajakaruna, G., Dyer, J. et al. (2018b) Severe lower limb cellulitis: defining the epidemiology and risk factors
for primary episodes in a population-based case-control study. Clinical Microbiology And Infection 24(10), 1089-1094.
CREST (2005) Guidelines on the management of cellulitis in adults. Clinical Resource Efficiency Support Team.. www.gain-
ni.org (http://www.gain-ni.org) [Free Full-text (http://www.gain-ni.org/index.php/crest-cellulitis-guidelines)]
CSM (1992) Flucloxacillin-induced cholestatic jaundice. Current Problems. 35(Nov), 2.
CSM (2004) Reminder: flucloxacillin and serious hepatic disorders. Current Problems in Pharmacovigilance. 30(Oct), 9.
Dalal, A., Eskin‐Schwartz, M. and Mimouni, D. et al. (2017) Interventions for the prevention of recurrent erysipelas and
cellulitis (Cochrane Review/Cochrane Intervention Protocol). John Wiley & Sons, Ltd. www.cochranelibrary.com/
(http://www.cochranelibrary.com/) [Free Full-text
(https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD009758.pub2/full)]
Eron,L.J., Lipsky,B.A., Low,D.E., et al. (2003) Managing skin and soft tissue infections: expert panel recommendations on
key decision points. Journal of Antimicrobial Chemotherapy. 52(Suppl 1), i3-i17.
Ferreira, A., Bolland, M.J. and Thomas, M.G. (2016) Meta-analysis of randomised trials comparing a penicillin or
cephalosporin with a macrolide or lincosamide in the treatment of cellulitis or erysipelas. Infection 44(5), 607-615.
[Abstract (http://www.ncbi.nlm.nih.gov/pubmed/27085865)]
Fisher, R.G. and Benjamin, D.K Jr. (2002) Facial cellulitis in childhood: a changing spectrum. Southern Medical Journal
95(7), 672-674.
FSRH (2017) Drug interactions with hormonal contraception. Faculty of Sexual and Reproductive Healthcare. www.fsrh.org
(https://www.fsrh.org/) [Free Full-text (https://www.fsrh.org/documents/ceu-clinical-guidance-drug-interactions-with-
hormonal/)]
Gunderson,C.G. (2011) Cellulitis: definition, etiology, and clinical features. American Journal of Medicine. 124(12), 1113-
1122. [Abstract (http://www.ncbi.nlm.nih.gov/pubmed/22014791)]
Imohl,M., van der Linden,M., Reinert,R. and Ritter,K. (2011) Invasive group A streptococcal disease and association with
varicella in Germany, 1996-2009. FEMS Immunology & Medical Microbiology. 62(1), 101-109. [Abstract
(http://www.ncbi.nlm.nih.gov/pubmed/21314732)]
Joint Formulary Committee (2019) British National Formulary (online). BMJ Group and Pharmaceutical Press.
bnf.nice.org.uk (https://bnf.nice.org.uk/)
Kearney, L. (2016) Are penicillins and cephalosporins safe in breastfeeding?. Specialist Pharmacy Service.
www.sps.nhs.uk/ (http://www.sps.nhs.uk/) [Free Full-text (https://www.sps.nhs.uk/articles/are-penicillins-and-
cephalosporins-safe-in-breast-feeding/)]
Kilburn,S.,A., Featherstone,P., Higgins,B. and Brindle,R. (2010) Interventions for cellulitis and erysipelas (Cochrane
Review). The Cochrane Library. John Wiley & Sons, Ltd. www.thecochranelibrary.com (http://www.thecochranelibrary.com)
[Free Full-text (https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004299.pub2/abstract)]
LactMed (2019) Erythromycin. National Library of Medicine. www.toxnet.nlm.nih.gov/ (https://www.toxnet.nlm.nih.gov/)
MHRA (2008) Statins: interactions, and updated advice for atorvastatin. Drug Safety Update. 1(6), 2-4.
MHRA (2014) Statins: interactions, and updated advice for atorvastatin. Drug Safety Update 1(6), 2. [Free Full-text
(https://www.gov.uk/drug-safety-update/statins-interactions-and-updated-advice-for-atorvastatin#contents)]
NICE and PHE (2019) Summary of antimicrobial prescribing guidance – managing common infections. National Institute for
Health and Care Excellence. www.nice.org.uk (http://www.nice.org.uk) [Free Full-text
(https://www.nice.org.uk/about/what-we-do/our-programmes/nice-guidance/antimicrobial-prescribing-guidelines)]
NICE (2018) Antimicrobial stewardship: prescribing antibiotics. Key therapeutic topic (KTT9). National Institute for Health
and Care Excellence. www.nice.org.uk (http://www.nice.org.uk) [Free Full-text
(https://www.nice.org.uk/advice/ktt9/chapter/Options-for-local-implementation)]
NICE (2019a) Cellulitis and erysipelas: antimicrobial prescribing. National Institute for Health and Care Excellence.
www.nice.org.uk (http://www.nice.org.uk/) [Free Full-text (http://www.nice.org.uk/guidance/ng141)]
NICE (2019b) Antimicrobial stewardship: prescribing antibiotics (Key therapeutic topics). National Institute for Health and
Care Excellence. www.nice.org.uk (http://www.nice.org.uk) [Free Full-text
(https://www.nice.org.uk/advice/ktt9/chapter/Evidence-context)]
Oh,C., Ko,H., Lee,H., et al. (2014) Antibiotic prophylaxis for preventing recurrent cellulitis: a systematic review and meta-
analysis. Journal of Infection. 69(1), 26-34. [Abstract (http://www.ncbi.nlm.nih.gov/pubmed/24576824?dopt=Abstract)]
PCDS (2018) Cellulitis, erysipelas, and necrotising fasciitis. Primary Care Dermatology Society. www.pcds.org.uk
(http://www.pcds.org.uk) [Free Full-text (http://www.pcds.org.uk/clinical-guidance/cellulitis-and-erysipelas)]
PHE (2018a) UK Standards for Microbiology Investigations. Investigation of swabs from skin and superficial soft tissue
infections. Public Health England. www.gov.uk (http://www.gov.uk) [Free Full-text
(https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/766634/B_11i6.5.pdf)]
PHE (2018b) Summary of antimicrobial prescribing guidance - managing common infections: PHE context, references and
rationales for Clinical Commissioning Groups, Commissioning Support Units and Primary Care Providers. Public Health
England. www.gov.uk (http://www.gov.uk) [Free Full-text
(https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/777505/Common_Infect_-
_PHE_context_references_and_rationale_Feb_2019.pdf)]
Phoenix,G., Das,S. and Joshi,M. (2012) Diagnosis and management of cellulitis. BMJ. 345(e4955).
Preston, C.L. (Eds.) (2016) Stockley's drug interactions 2015: pocket companion. London: Pharmaceutical Press.
Pugh, M. (Eds.) (2000) Stedman's medical dictionary. Baltimore, MD: Lippincott Williams & Wilkins..
Quirke, M., Ayoub, F., McCabe, A. et al. (2017) Risk factors for nonpurulent leg cellulitis: a systematic review and meta-
analysis. British Journal Of Dermatology 177(2), 382-394. [Abstract (http://www.ncbi.nlm.nih.gov/pubmed/27864837)]
Raff, A. B. and Kroshinsky. D. (2016) Cellulitis: A Review. Jama 316(3), 325-337.
Shriner, A. and Wilkie, L. (2017) Pediatric Cellulitis: A Red-Hot Concern 46(7), e265-e269.
Fenner, S. (2016a) Safety in lactation: macrolides. Specialist Pharmacy Service. www.sps.nhs.uk/
(https://www.sps.nhs.uk/)
Fenner, S. (2016b) Safety in lactation: tetracyclines. Specialist Pharmacy Service. www.sps.nhs.uk/
(https://www.sps.nhs.uk/) [Free Full-text (https://www.sps.nhs.uk/articles/safety-in-lactation-tetracyclines/)]
Stevens,D.L., Bisno,A.L., Chambers,H.F., et al. (2005) Practice guidelines for the diagnosis and management of skin and
soft-tissue infections. Clinical Infectious Diseases. 41(10), 1373-1406.
Stevens,D., Bisno,A., Chambers,H., et al. (2014) Practice guidelines for the diagnosis and management of skin and soft
tissue infections: 2014 update by the Infectious Diseases Society of America. Clinical Infectious Diseases. 59(2), 147-159.
[Abstract (http://www.ncbi.nlm.nih.gov/pubmed/24947530)]
UK Dermatology Clinical Trials Network's PATCH trial team, Thomas,K., Crook,A., Foster,K., et al. (2012) Prophylactic
antibiotics for the prevention of cellulitis (erysipelas) of the leg: results of the UK Dermatology Clinical Trials Network's
PATCH II trial. British Journal of Dermatology. 166(1), 169-178. [Abstract (http://www.ncbi.nlm.nih.gov/pubmed/21910701?
dopt=Abstract)]
UKTIS (2017a) Use of penicillins in pregnancy. UK teratology information service. www.medicinesinpregnancy.org/

(http://www.medicinesinpregnancy.org/) [Free Full-text (http://www.medicinesinpregnancy.org/bumps/monographs/USE-
OF-PENICILLINS-IN-PREGNANCY/)]
UKTIS (2017b) Use of macrolides in pregnancy. UK Teratology Information Service. [Free Full-text
(http://www.medicinesinpregnancy.org/bumps/monographs/USE-OF-MACROLIDES-IN-PREGNANCY)]
UKTIS (2017c) Use of tetracycline in pregnancy. UK Teratology Information Service (UKTIS). [Free Full-text
(http://www.medicinesinpregnancy.org/bumps/monographs/USE-OF-TETRACYCLINE-IN-PREGNANCY/)]
UKTIS (2019) Use of erythromycin in pregnancy. UK Teratology Information Service. www.medicinesinpregnancy.org
(http://www.medicinesinpregnancy.org/) [Free Full-text (http://www.medicinesinpregnancy.org/bumps/monographs/USE-
OF-ERYTHROMYCIN-IN-PREGNANCY/)]
© NICE (National Institute for Health and Care Excellence) 2020. All rights reserved. Subject to Notice of rights (https://www.nice.org.uk/terms-
and-conditions#notice-of-rights).

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Cellulitis - acute - NICE CKS 06/04/2020, 20:47

Read about our approach to COVID-19 (https://www.nice.org.uk/covid-19)

Previous changes Back to top

New evidence Back to top

No new evidence-based guidelines since 1 March 2019.

HTAs (Health Technology Assessments)

No new HTAs since 1 March 2019.

No new economic appraisals relevant to England since 1 March 2019.

Systematic reviews and meta-analyses

No new systematic review or meta-analyses since 1 March 2019.

New policies Back to top

No new national policies or guidelines since 1 March 2019.

New safety alerts Back to top

No new safety alerts since 1 March 2019.

Changes in product availability Back to top

No changes in product availability since 1 March 2019.

Diagnose cellulitis and identify any underlying causes.

​Non-steroidal anti-inflammatory drugs (NSAIDs)

[NICE, 2018 (/cellulitis-acute#!references); NICE, 2019b (/cellulitis-acute#!references)] ​

[CREST, 2005 (/cellulitis-acute#!references); Raﬀ, 2016 (/cellulitis-acute#!references); Dalal, 2017 (/cellulitis-

[CREST, 2005 (/cellulitis-acute#!references); Raﬀ, 2016 (/cellulitis-acute#!references); Dalal, 2017 (/cellulitis-

[CREST, 2005 (/cellulitis-acute#!references); Dalal, 2017 (/cellulitis-acute#!references); BMJ, 2018 (/cellulitis-

Basis for recommendation Back to top

Basis for recommendation Back to top

When should I admit or refer a person with cellulitis? Back to top

Arrange urgent hospital admission if the person:

Basis for recommendation Back to top

Urgent admission to hospital

IV antibiotics in the community

Referral for people with recurrent cellulitis to consider antibiotic prophylaxis

How should I manage acute cellulitis in primary care? Back to top

Basis for recommendation Back to top

Giving advice and information

Referral for people with recurrent cellulitis to consider antibiotic prophylaxis

Which oral antibiotics should I prescribe? Back to top

When choosing an antibiotic, take into account:

Basis for recommendation Back to top

Recording the extent of the cellulitis

Choice of antibiotics and duration of treatment

How should I follow up a person on oral antibiotic treatment? Back to top

Basis for recommendation Back to top

Duration of antibiotic treatment

No improvement after two weeks of antibiotics

Do not prescribe amoxicillin to people with:

[ABPI, 2017a (/cellulitis-acute#!references); Joint Formulary Committee, 2019 (/cellulitis-acute#!references)]

What are the possible adverse eﬀects of amoxicillin? Back to top

[ABPI, 2017a (/cellulitis-acute#!references); Joint Formulary Committee, 2019 (/cellulitis-acute#!references)]

What are the possible drug interactions of amoxicillin? Back to top

Possible drug interactions of co-amoxiclav include:

[ABPI, 2017a (/cellulitis-acute#!references); Joint Formulary Committee, 2019 (/cellulitis-acute#!references)]

Pregnancy and breastfeeding Back to top

Do not prescribe clarithromycin to:

What are the possible adverse eﬀects of clarithromycin? Back to top

[ABPI, 2018c (/cellulitis-acute#!references); Joint Formulary Committee, 2019 (/cellulitis-acute#!references)]

What are the possible drug interactions of clarithromycin? Back to top

Drug interactions of clarithromycin include:

[ABPI, 2018c (/cellulitis-acute#!references); Joint Formulary Committee, 2019 (/cellulitis-acute#!references)]

Can clarithromycin be used during pregnancy and breastfeeding? Back to top

Do not prescribe co-amoxiclav to people with:

[ABPI, 2018d (/cellulitis-acute#!references); Joint Formulary Committee, 2019 (/cellulitis-acute#!references)]

What are the possible adverse eﬀects of co-amoxiclav? Back to top

[ABPI, 2018d (/cellulitis-acute#!references); Joint Formulary Committee, 2019 (/cellulitis-acute#!references)]

What are the possible drug interactions of co-amoxiclav? Back to top

Non-steroidal anti-inflammatory drugs (NSAIDs)

[NICE, 2018 (/cellulitis-acute#!references); NICE, 2019b (/cellulitis-acute#!references)]

[ABPI, 2019 (/cellulitis-acute#!references); Joint Formulary Committee, 2019 (/cellulitis-acute#!references)]