Leg ulcer infection antimicrobial prescribing guide

Leg ulcer infection:
antimicrobial prescribing
NICE guideline
Published: 11 February 2020
www.nice.org.uk/guidance/ng152
© NICE 2024. All rights reserved. Subject to Notice of rights (https://www.nice.org.uk/terms-and-

conditions#notice-of-rights).
Leg ulcer infection: antimicrobial prescribing (NG152)
Your responsibility
The recommendations in this guideline represent the view of NICE, arrived at after careful
consideration of the evidence available. When exercising their judgement, professionals
and practitioners are expected to take this guideline fully into account, alongside the
individual needs, preferences and values of their patients or the people using their service.
It is not mandatory to apply the recommendations, and the guideline does not override the
responsibility to make decisions appropriate to the circumstances of the individual, in
consultation with them and their families and carers or guardian.
All problems (adverse events) related to a medicine or medical device used for treatment
or in a procedure should be reported to the Medicines and Healthcare products Regulatory
Agency using the Yellow Card Scheme.
Local commissioners and providers of healthcare have a responsibility to enable the

guideline to be applied when individual professionals and people using services wish to
use it. They should do so in the context of local and national priorities for funding and
developing services, and in light of their duties to have due regard to the need to eliminate
unlawful discrimination, to advance equality of opportunity and to reduce health
inequalities. Nothing in this guideline should be interpreted in a way that would be
inconsistent with complying with those duties.
Commissioners and providers have a responsibility to promote an environmentally

sustainable health and care system and should assess and reduce the environmental
impact of implementing NICE recommendations wherever possible.
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Contents
Overview ................................................................................................................................... 4
Who is it for? ........................................................................................................................................ 4
Recommendations .................................................................................................................... 5
1.1 Managing leg ulcer infection in adults.......................................................................................... 5
1.2 Choice of antibiotic ....................................................................................................................... 7
Terms used in the guideline ............................................................................................................... 11
Recommendation for research ................................................................................................ 12
1 Topical treatments for infected leg ulcer ....................................................................................... 12
Rationales .................................................................................................................................. 13
Treatment ............................................................................................................................................. 13
Reassessment ..................................................................................................................................... 15
Referral or seeking specialist advice ................................................................................................. 16
Choice of antibiotic ............................................................................................................................. 17
Context ...................................................................................................................................... 21
Summary of the evidence........................................................................................................ 22
Topical antiseptics .............................................................................................................................. 23
Antibiotics ............................................................................................................................................ 26
Choice of antibiotic ............................................................................................................................. 27
Antibiotic course length, dosage and route of administration ....................................................... 27
Other considerations................................................................................................................ 28
Medicines safety ................................................................................................................................. 28
Medicines adherence.......................................................................................................................... 29
Resource implications ......................................................................................................................... 29
Finding more information and committee details .................................................................. 30
Update information .................................................................................................................. 31
Overview
This guideline sets out an antimicrobial prescribing strategy for adults with leg ulcer
infection. It aims to optimise antibiotic use and reduce antibiotic resistance.
See a 2-page visual summary of the recommendations, including a table to support

prescribing decisions.
We have also produced guidelines on cellulitis and erysipelas and antimicrobial

stewardship: systems and processes for effective antimicrobial medicine use.
The recommendations in this guideline were developed before the COVID-19 pandemic.
Who is it for?
• Healthcare professionals
• Adults with leg ulcer infection, their families and carers
Recommendations
1.1 Managing leg ulcer infection in adults
Treatment
1.1.1 Be aware that:
• there are many causes of leg ulcers: underlying conditions, such as venous
insufficiency and oedema, should be managed to promote healing
• most leg ulcers are not clinically infected but are likely to be colonised with
bacteria
• antibiotics do not help to promote healing when a leg ulcer is not clinically
infected.
1.1.2 Do not take a sample for microbiological testing from a leg ulcer at initial
presentation, even if it might be infected.
1.1.3 Only offer an antibiotic for adults with a leg ulcer when there are symptoms or
signs of infection (for example, redness or swelling spreading beyond the ulcer,
localised warmth, increased pain or fever). When choosing an antibiotic (see the
recommendations on choice of antibiotic) take account of:
• the severity of symptoms or signs
• the risk of developing complications
• previous antibiotic use.
1.1.4 Give oral antibiotics if the person can take oral medicines, and the severity of
their condition does not require intravenous antibiotics.
1.1.5 If intravenous antibiotics are given, review by 48 hours and consider switching to
oral antibiotics if possible.
For a short explanation of why the committee made these recommendations, see the
rationale section on treatment.
For more details, see the summary of the evidence on antibiotics and topical
antiseptics.
Advice
1.1.6 When prescribing antibiotics for an infected leg ulcer in adults, give advice to
seek medical help if symptoms or signs of the infection worsen rapidly or
significantly at any time, or do not start to improve within 2 to 3 days of starting
treatment.
Reassessment
1.1.7 Reassess an infected leg ulcer in adults if:
• symptoms or signs of the infection worsen rapidly or significantly at any time,

or do not start to improve within 2 to 3 days
• the person becomes systemically unwell or has severe pain out of proportion
to the infection.
1.1.8 When reassessing an infected leg ulcer in adults, take account of previous
antibiotic use, which may have led to resistant bacteria.
1.1.9 Be aware that it will take some time for a leg ulcer infection to resolve, with full
resolution not expected until after the antibiotic course is completed.
1.1.10 Consider sending a sample from the leg ulcer (after cleaning) for microbiological
testing if symptoms or signs of the infection are worsening or have not improved
as expected.
1.1.11 When microbiological results are available:
• review the choice of antibiotic(s) and
• change the antibiotic(s) according to results if symptoms or signs of the

infection are not improving, using a narrow-spectrum antibiotic if possible.
rationale section on reassessment.
Referral or seeking specialist advice

1.1.12 Refer adults with an infected leg ulcer to hospital if they have any symptoms or
signs suggesting a more serious illness or condition, such as sepsis, necrotising
fasciitis or osteomyelitis.
1.1.13 Consider referring or seeking specialist advice for adults with an infected leg
ulcer if they:
• have a higher risk of complications because of comorbidities, such as

diabetes or immunosuppression
• have lymphangitis
• have spreading infection that is not responding to oral antibiotics
• cannot take oral antibiotics (exploring locally available options for giving
intravenous or intramuscular antibiotics at home or in the community, rather
than in hospital, where appropriate).
rationale section on referral or seeking specialist advice.
1.2 Choice of antibiotic

1.2.1 When prescribing antibiotics for an infected leg ulcer in adults aged 18 years and
over, follow the recommendations in table 1.
Table 1 Antibiotics for adults aged 18 years and over

Treatment Antibiotic, dosage and course length
Flucloxacillin:
500 mg to 1 g four times a day for 7 days
First-choice oral antibiotic (In February 2020, 1 g four times a day was off
label. See NICE's information on prescribing
medicines.)
Doxycycline:
200 mg on the first day, then 100 mg once a
day (can be increased to 200 mg daily) for
Alternative first-choice oral antibiotics 7 days in total
for penicillin allergy or if flucloxacillin
Clarithromycin:
unsuitable
500 mg twice a day for 7 days
Erythromycin (in pregnancy):
500 mg four times a day for 7 days
Co-amoxiclav:
500/125 mg three times a day for 7 days
Co-trimoxazole (in penicillin allergy):
Second-choice oral antibiotics (guided
by microbiological results when 960 mg twice a day for 7 days
available) (In February 2020, co-trimoxazole was off
label for leg ulcer infection. See NICE's
information on prescribing medicines. See the
BNF for information on monitoring.)
Flucloxacillin:
1 g to 2 g four times a day intravenously
with or without
Gentamicin:
Initially, 5 mg/kg to 7 mg/kg once daily
intravenously, subsequent doses if needed
according to serum gentamicin concentration
(see the BNF for information on monitoring)
and/or
Metronidazole:
400 mg three times a day orally or 500 mg
three times a day intravenously
Co-amoxiclav:
1.2 g three times a day intravenously
with or without
First-choice antibiotics if severely
Gentamicin:
unwell (guided by microbiological
results if available)
Co-trimoxazole (in penicillin allergy):
960 mg twice a day intravenously (increased
to 1.44 g twice a day if severe infection)
(In February 2020, co-trimoxazole was off
label for leg ulcer infection. See NICE's
information on prescribing medicines. See the
BNF for information on monitoring.)
with or without
Gentamicin:
and/or
Metronidazole:
Piperacillin with tazobactam:

4.5 g three times a day intravenously
(increased to 4.5 g four times a day if severe
infection)
Second-choice antibiotics if severely
unwell (guided by microbiological Ceftriaxone:
results when available or following 2 g once a day intravenously
specialist advice) with or without
Metronidazole:
Vancomycin:
15 mg/kg to 20 mg/kg two or three times a day
intravenously (maximum 2 g per dose),
adjusted according to serum vancomycin
concentration (see the BNF for information on
Antibiotics to be added if meticillin- monitoring)
resistant Staphylococcus aureus Teicoplanin:
infection is suspected or confirmed Initially 6 mg/kg every 12 hours for
(combination therapy with antibiotics three doses, then 6 mg/kg once a day
listed above) intravenously (see the BNF for information on
monitoring)
Linezolid (if vancomycin or teicoplanin cannot
be used; specialist advice only):
600 mg twice a day orally or intravenously
See the BNF for appropriate use and dosing in specific populations, for example, people
with hepatic or renal impairment, in pregnancy and breastfeeding, and when administering
intravenous (or, where appropriate, intramuscular) antibiotics.
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Review intravenous antibiotics by 48 hours and consider switching to oral antibiotics if

possible.
Erythromycin is preferred if a macrolide is needed in pregnancy, for example, if there is

true penicillin allergy and the benefits of antibiotic treatment outweigh the harms. See the
Medicines and Healthcare products Regulatory Agency (MHRA) Public Assessment Report
on the safety of macrolide antibiotics in pregnancy.
For a short explanation of why the committee made the recommendation, see the
rationale section on choice of antibiotic.
For more detail, see the summary of the evidence on choice of antibiotic.
Terms used in the guideline
Leg ulcer
A leg ulcer is a long-lasting (chronic) open wound that takes more than 4 to 6 weeks to
heal. Leg ulcers usually develop on the lower leg, between the shin and the ankle.
Necrotising fasciitis
This is a rare but serious bacterial infection that affects the tissue beneath the skin and
surrounding muscles and organs (fascia). Early symptoms can include intense pain that is
out of proportion to any damage to the skin, and fever. The most common cause is group
A streptococcus.
Osteomyelitis
This is an infection of the bone. It can be very painful and most commonly occurs in the
long bones of the leg. It can also occur in other bones, such as those in the back or arms.
Anyone can develop osteomyelitis, but certain people are more at risk, including people
with diabetes and those with a weakened immune system.
Recommendation for research

The guideline committee has made the following recommendation for research.
1 Topical treatments for infected leg ulcer

What is the clinical effectiveness of topical treatments (antibiotics and antiseptics)
compared with oral antibiotics for the treatment of infected leg ulcer?
For a short explanation of why the committee made the recommendation for research,
see the rationale on treatment.
For more details, see the summary of the evidence on antibiotics and topical
antiseptics.
Rationales
The recommendations in this guideline are for adults and are based on the evidence
identified and the experience of the committee. No evidence was found for children with
leg ulcers and recommendations were made for adults only.
Treatment
Why the committee made the recommendations

Recommendations 1.1.1 to 1.1.5
The committee agreed that health professionals should be aware that there are many
causes of leg ulcers and that, although most leg ulcers are colonised by bacteria, few are
infected. They discussed that it is important to ensure that underlying conditions, such as
venous insufficiency and oedema, are managed appropriately.
The committee discussed that antibiotics should only be offered for adults with a leg ulcer
when there are symptoms or signs of infection. They agreed that there was no difference
in outcomes between treatment with antibiotics and standard care in people with
uninfected leg ulcers (although this was from a small, very low-quality study with no
details reported on dosage or route of administration).
Evidence showed no difference in complete healing of the leg ulcer with antibiotics
compared with standard care or placebo. However, in all but 1 study, the ulcer was either
uninfected or the infection status was unclear. No study stated that children and young
people (under 18 years) were included. The committee agreed that this age group are very
unlikely to develop a leg ulcer and if they do the cause is likely to be from a condition that
needs specialist management. Therefore, it was not appropriate to extrapolate evidence
for adults to children and young people and so the committee made recommendations for
adults only.
The committee agreed that antibiotics should be offered to all adults with a leg ulcer if
there are symptoms or signs of an infection, because untreated infection causes delays in
ulcer healing, affecting quality of life and sometimes resulting in hospital admission. The
committee discussed that studies did not use consistent criteria for identifying infection in
ulcers, and some signs of infection (such as localised redness, discharge and unpleasant
smell) could be present in all leg ulcers, regardless of infection status, especially once
compression is removed. Therefore, they agreed that the symptoms or signs to use to
determine if the ulcer is infected may include redness or swelling spreading beyond the
ulcer, localised warmth, increased pain or fever. The committee noted that healthcare
professionals should be aware that redness, 1 of the signs of infection, may be less visible
on darker skin tones.
Based on experience, the committee agreed that antibiotic choice will depend on the
severity of symptoms or signs of infection (for example, how rapidly the infection is
progressing or expanding), the person's risk of complications (possibly because of
comorbidities, such as diabetes or immunosuppression) and any previous antibiotic use
(which may have led to antimicrobial resistance).
In line with the NICE guideline on antimicrobial stewardship: systems and processes for
effective antimicrobial medicine use and Public Health England's antimicrobial
stewardship: start smart – then focus toolkit, oral antibiotics should be given first if the
person can take them, and if the severity of their infection does not require intravenous
antibiotics. The use of intravenous antibiotics should be reviewed by 48 hours (taking into
account the person's response to treatment and any microbiological results) and switched
to oral treatment where possible.
The committee discussed and agreed that samples for microbiological testing should not
routinely be taken from a leg ulcer at initial presentation, whether it is thought to be
infected or not. Most leg ulcers are colonised by bacteria, and bacterial growth from a
sample is likely regardless of infection status. Universal sampling could lead to
inappropriate antibiotic prescribing. If the leg ulcer is clinically infected, the most likely
causative organism is Staphylococcus aureus, which would be covered by empirical
treatment with flucloxacillin.
Topical antiseptics
Evidence comparing antibiotics with povidone-iodine (an antiseptic) for leg ulcer infection
was limited by small sample size. Most of the evidence was in adults with unclear infection
status or uninfected leg ulcer.
There was some evidence of effect for cadexomer-iodine and silver dressings in people
with infected leg ulcer (compared with standard care and non-adherent foam dressing
respectively). But there were severe limitations, including an unclear definition of 'infection'
(1 being reliant on laboratory growth and the other stating that inflammation was the only
symptom required). For the comparison of silver dressings and foam dressings, the only
sign of infection required was inflammation, there were very wide confidence intervals,
and both study arms had the option to use antibiotics (and the number of people taking
systemic antibiotics was not reported). Silver dressings can be expensive and could have
considerable resource impact. Therefore, because of the inadequate definition of infection,
the confounding issue of antibiotic use, the uncertainty of the effect estimate and the
potential cost, the committee agreed not to recommend silver dressings.
The committee were also concerned about the adverse effects with cadexomer-iodine.
These were mainly local skin irritation, rash and pain, all of which can make leg ulcers
worse. No adverse effects were reported for silver dressings, but this may have been
because of the small sample size. The committee were also aware of issues with the
availability of iodine-based preparations, particularly in community settings.
In clinical practice, topical antiseptics are used for leg ulcers, often to manage minor,
localised infections. However, the committee agreed that they could not make any
recommendations on the use topical antiseptics for treating infected leg ulcers because of
the limitations of the evidence and the unclear benefit. The inability to differentiate
between a more localised or widespread infection both in the evidence and in clinical
practice makes it difficult to define any place in therapy for topical antiseptics. The
committee decided that it was appropriate to make a recommendation for research on the
effectiveness of topical treatments (antiseptics and antibiotics) compared with oral
antibiotics.
Return to recommendations
Reassessment

Recommendations 1.1.7 to 1.1.11
Based on experience, the committee agreed when adults with an infected leg ulcer should
be reassessed. If symptoms of the infection worsen rapidly or significantly at any time, or
do not start to improve within 2 to 3 days, this may indicate that the person has a more
serious illness requiring referral, or a resistant infection (possibly because of previous

antibiotic use). People with leg ulcers have routine reviews, often by nurses. However, this
review and any decision on the need for further antibiotics should take into account the
fact that a leg ulcer infection will take some time to resolve even after a course of effective
antibiotics.
The committee agreed that adults should be reassessed if they have severe pain out of
proportion to the infection because this can be a symptom of necrotising fasciitis, which is
a rare but serious bacterial infection.
Although microbiological sampling is not required at initial presentation, the committee

agreed that it is appropriate to consider this if symptoms or signs of the infection are
worsening or have not improved as expected. This will guide future antibiotic choice if the
person has a resistant infection. The committee agreed that before microbiological
sampling the wound should be cleaned to remove surface contaminants, slough or
necrotic tissue, in line with Public Health England's guidance on venous leg ulcers:
infection diagnosis and microbiological investigation guide for primary care.
When microbiological results are available, the choice of antibiotic should be reviewed and
changed according to results if symptoms or signs of the infection are not improving, using
a narrow-spectrum antibiotic if appropriate to minimise the risk of antimicrobial resistance.
Referral or seeking specialist advice

Recommendations 1.1.12 and 1.1.13
Based on experience, the committee agreed that adults with symptoms or signs
suggesting a more serious illness or condition should be referred to hospital. Some people
may have an infected leg ulcer that is more difficult to treat, for example, because they
have a higher risk of complications or other underlying conditions, or they have a resistant
infection. In these cases, referral or specialist advice should be considered (which may
include giving intravenous antibiotics or adopting other non-antimicrobial management
strategies).
Choice of antibiotic
Recommendation 1.2.1

There was very limited evidence on the choice of antibiotics in adults with an infected leg
ulcer. Only 1 study compared antibiotics with standard care, and this was limited by the
criteria for diagnosing infection. It was unclear whether wounds had symptoms and signs
of clinical infection at baseline or whether they were just colonised with bacteria.
Based on experience, current practice and resistance data, the committee agreed that the
first-choice oral antibiotic in adults with an infected leg ulcer is flucloxacillin (a penicillin).
This is a relatively narrow-spectrum penicillin, which has good penetration for skin and
soft tissue infections and is effective against gram-positive organisms, including the most
common causative organism Staphylococcus aureus.
The alternative first-choice antibiotics in adults with penicillin allergy or in whom

flucloxacillin is unsuitable are doxycycline (a tetracycline), or clarithromycin or
erythromycin (in pregnancy), which are macrolides. These all have a similar spectrum of
activity to flucloxacillin. The committee agreed that the doses provided in the prescribing
table were suitable for people with poor vascular flow.
The committee discussed the MHRA Public Assessment Report on the safety of macrolide
antibiotics in pregnancy. This found that the available evidence is insufficient to confirm
with certainty whether there is a small increased risk of birth defects or miscarriage when
macrolides are taken in early pregnancy. They agreed with the UK Teratology Information
Service monograph on the use of macrolides in pregnancy. They decided that there should
be an informed discussion of the potential benefits and harms of treatment. Then, after
such a discussion, macrolides can be used if there is a compelling clinical need and there
are no suitable alternatives with adequate pregnancy safety data. Erythromycin is the
preferred choice if a macrolide is needed during pregnancy, for example, if there is true
penicillin allergy and the benefits of antibiotic treatment outweigh the harms. This is
because there is more documented experience of its use than for other macrolides.
The committee agreed that the second-choice oral antibiotics if the first-choice oral
antibiotics are not effective (guided by microbiological results when available) are the
broader-spectrum antibiotics co-amoxiclav (a penicillin with a beta-lactamase inhibitor) or
co-trimoxazole (in penicillin allergy). These are more active against gram-negative
organisms. The presence of gram-negative organisms may be a reason why an infected
leg ulcer is not healing; these antibiotics are therefore appropriate second-choice
antibiotics. However, the committee noted that it is important to only use broad-spectrum
antibiotics if first-choice antibiotics are not effective. Broad-spectrum antibiotics can
create a selective advantage for bacteria resistant to these agents, allowing such strains
to proliferate and spread. By disrupting normal flora, broad-spectrum antibiotics can also
leave people susceptible to harmful bacteria such as Clostridium difficile in community
settings. The committee discussed that cephalosporins are not an appropriate option as a
second-choice oral antibiotic because they do not provide adequate cover for anaerobes.
Oral antibiotics should be given first line if possible. But based on experience and
resistance data, the committee agreed that several intravenous antibiotics (or
combinations of antibiotics) can be used for adults who are severely unwell or unable to
take oral antibiotics. This enables antibiotics to be selected based on individual patient
factors, likely pathogens, and antibiotic susceptibilities from microbiological results (if
known).
In people who are severely unwell, broader antimicrobial cover is needed because both
anaerobes and gram-negative bacteria may be present. However, in line with the principles
of antimicrobial stewardship, narrower-spectrum antibiotics should be used where
possible.
For adults with an infected leg ulcer who require intravenous antibiotics, the committee
agreed that flucloxacillin was the most appropriate first choice, with or without the
addition of gentamicin (a broad-spectrum aminoglycoside) and/or metronidazole.
The committee agreed that additional choices would be:
• co-amoxiclav with or without gentamicin
• co-trimoxazole with or without gentamicin and/or metronidazole (if penicillin allergy).
The committee discussed that metronidazole (which is used for anaerobic bacteria) may
be useful for people with leg ulcers related to arterial disease or diabetes. These people
may have a reduced blood supply that can encourage anaerobic bacterial growth. Because
metronidazole has good oral bioavailability, this could be given orally instead of
intravenously if people were able to take oral antibiotics.
Second choice intravenous antibiotics (guided by microbiological results when available or

following specialist advice) are:
• piperacillin with tazobactam (a penicillin with a beta-lactamase inhibitor) or
• ceftriaxone (a third-generation cephalosporin) with metronidazole.
The committee discussed that intravenous ceftriaxone may be given as an outpatient

without the need for hospital admission.
Meticillin-resistant Staphylococcus aureus (MRSA) may be found on swabbing, but the

current likelihood of MRSA infection is very low. The committee agreed that if MRSA
infection is suspected or confirmed, 1 of the following intravenous antibiotics with activity
against MRSA should be added to the treatment regimen:
• vancomycin (a glycopeptide) or
• teicoplanin or
• linezolid (an oxazolidinone; if vancomycin or teicoplanin cannot be used, following

specialist advice only).
Course length and dosage and route of administration
There was very little evidence on antibiotic dosage, course length and route of
administration. Therefore, recommendations were based on the committee's experience of
current practice. Flucloxacillin has poor oral bioavailability and in people with an infected
leg ulcer who could have impaired circulation, a higher (off-label dose) of up to 1 g, 4 times
a day orally, may be needed to adequately treat the infection.
The committee agreed that the shortest course that is likely to be effective should be
prescribed to minimise adverse effects and reduce the risk of antimicrobial resistance, but
that this should be balanced against the need for a course length that provides effective
treatment.
In the absence of evidence for optimum course length, the committee agreed, based on
experience and extrapolation of evidence from people with cellulitis and diabetic foot
infection, that a course of 7 days is appropriate for most people with an infected leg ulcer.
They discussed that a decision for a longer course of antibiotics may be made on review if
the infection is not improving, particularly for people with poor healing and a higher risk of
complications because of comorbidities. However, 7 days should be adequate for most
people if their wound and any underlying condition is being managed appropriately. Any
decision on the need for further antibiotics should take into account the fact that a leg
ulcer infection will take some time to resolve, even after a course of effective antibiotics.
The committee also discussed safety concerns around longer courses of flucloxacillin or
co-amoxiclav, particularly in older people, because of the risk of cholestatic jaundice or
hepatitis.
In line with the NICE guideline on antimicrobial stewardship and Public Heath England's
antimicrobial stewardship: start smart – then focus toolkit, oral antibiotics should be given
first line if the person can take them, and the severity of their condition does not require
intravenous antibiotics. The use of intravenous antibiotics should be reviewed by 48 hours
(taking into account the person's response to treatment and any microbiological results)
and switched to oral treatment where possible.
Return to recommendation
Context
A leg ulcer is a long-lasting (chronic) open wound that takes more than 4 to 6 weeks to
heal. Leg ulcers usually develop on the lower leg, between the shin and the ankle.
Studies suggest that 80% to 100% of leg ulcers may have bacteria (usually Staphylococcus
aureus or Pseudomonas aeruginosa) present in the wound, but this does not necessarily
mean the wound is infected.
Summary of the evidence

This is a summary of the evidence. For full details see the evidence review and expert
testimony.
The review protocol included a population of adults, young people and children with
infected leg ulcers. There was minimal evidence for this population (2 small studies),
therefore the population was expanded to people with leg ulcers that had an unclear
infection status or were not infected. For antiseptic and antibiotics, the results have been
presented separately for people with:
• an infected leg ulcer
• a leg ulcer with unclear infection status
• an uninfected leg ulcer.
All the evidence is based on 1 systematic review of antibiotics and antiseptics for venous
leg ulcers (O'Meara et al. 2014), which included 45 randomised controlled trials (RCTs).
Nine of these were not included in the review because 8 contained ineligible interventions
and 1 study was withdrawn from publication. Seven RCTs included people exclusively with
leg ulcer infection (however 5 of these RCTs had an uncertain definition of infection); 14
RCTs included people with leg ulcers of unclear infection status and 15 studies included
people with leg ulcers that were not infected.
No studies included in the review stated that they included children. The committee
discussed that leg ulcer infection in children and young people is extremely rare, and
usually a result of an underlying illness that requires specialist management. Therefore,
they agreed not to extrapolate the evidence to children and young people.
Standard care is the care given in addition to the intervention and/or the control. The
included studies were limited because the definition of standard care for each study varied
widely, full details of what composed standard care is noted in the GRADE tables
(appendix H of the evidence review).
Topical antiseptics
Iodine-based preparations
Infected leg ulcer
In a single RCT, cadexomer-iodine was significantly better than standard care at reducing
the average size of the ulcers, the amount of pain experienced from the ulcers and
reducing or eliminating the presence of Staphylococcus aureus at 6 weeks.
There was no significant difference for:
• cadexomer-iodine compared with silver dressing for the frequency of complete

healing at 12 weeks and for participant satisfaction (neither group reported any
adverse effects)
• povidone-iodine plus compression compared with moist or foam dressings plus

compression for complete healing at 4 months.
Unclear leg ulcer infection status
Cadexomer-iodine (topical application) was significantly better than standard care (varied
by RCT) for the frequency of complete healing at 4 to 12 weeks, mean percentage change
ulcer area and mean rate of ulcer healing. However, adverse events were significantly
more common in the cadexomer-iodine group.
Uninfected leg ulcer
Cadexomer-iodine was not significantly different from hydrocolloid dressing or paraffin

gauze for the frequency of complete healing at 12 weeks, neither group reported any
adverse effects.
Povidone-iodine plus compression was not significantly different from hydrocolloid plus
compression for the frequency of complete healing at 4 months.
Povidone-iodine 10% solution plus compression was significantly better for time to healing
than hydrocolloid plus compression.
Peroxide-based preparations
Benzoyl peroxide (10% and 20%) was significantly better than a saline dressing for
reducing average ulcer size at 42 days. Data on adverse effects were limited and poorly
reported.
Hydrogen peroxide 1% cream was significantly better for median decrease in ulcer area
compared with placebo cream at 10-day follow up. Data on adverse effects were limited
and poorly reported.
Honey-based preparations
Honey (calcium alginate dressing impregnated with Manuka honey) was not significantly
different from standard care for:
• complete healing at 12 weeks
• incidence of ulcer infection during 12 weeks of treatment.
There were significantly more adverse effects in the honey group than the standard care
group.
Honey (topical Manuka honey) was not significantly different from hydrogel (3 g/20 cm2
applied weekly) for the eradication of meticillin-resistant Staphylococcus aureus (MRSA) at
4 weeks.
Silver-based preparations
Infected leg ulcer
Silver dressing plus compression was significantly better than non-adhesive plus
compression dressing for:
• complete healing at 9 weeks
• proportion of adults who were pain free at the end of the trial.
Silver dressings were not significantly different from non-adhesive dressings for adverse
effects.
There was no significant difference between the following comparisons for complete
healing (4 to 12 weeks):
• silver sulfadiazine (1% cream) plus compression compared with non-adherent dressing
plus compression
• silver impregnated dressings (with or without compression) compared with non-

antimicrobial dressings (with or without compression)
• silver-impregnated polyurethane foam dressing plus compression compared with

5-layer silver impregnated dressing plus compression.
Silver dressings were not significantly different from non-antimicrobial dressings for
adverse effects.
There was no significant difference for:
• silver sulfadiazine (1% cream) with non-adhesive foam dressing and compression
compared with placebo cream with non-adherent dressing and compression for
complete healing at 4 weeks
• silver sulfadiazine (1% cream) compared with standard care for median time to healing
• silver dressing plus compression compared with low-adherent dressing for complete
healing at 4 to 12 weeks, 6 months or 12 months, or for ulcer recurrence within
12 months
• silver dressings compared with non-antimicrobial dressings for adverse effects.
Silver dressing plus compression was significantly better than non-antimicrobial dressings
plus compression for reducing ulcer surface area when measured using square
centimetres at 4 weeks, but was not significantly different when measured as a
percentage change. The healing rate (cm2 per day) in these 2 RCTs was not significantly
different.
Antibiotics
Antibiotics compared with standard care or placebo
Infected leg ulcer
Ciprofloxacin was not significantly different from standard care for the frequency of
complete healing, emergence of antibiotic-resistant strains or bacterial eradication at
3 months.
For the frequency of complete healing (unclear follow-up time), there was no significant
difference between:
• ciprofloxacin and placebo or
• trimethoprim and placebo.
Emergence of resistance was significantly higher with ciprofloxacin than with placebo, but
there was no significant difference in the emergence of resistance with trimethoprim
compared with placebo.
There was no significant difference between:
• systemic antibiotics (co-trimoxazole, gentamicin or amikacin according to sensitivities)

and standard care for the outcomes of complete healing at 3 weeks, complete
eventual healing or bacterial eradication
• topical mupirocin compared with standard care for frequency of complete healing at
12 weeks or for the eradication of gram-positive bacteria.
Data on adverse effects were limited and poorly reported.
Antibiotics compared with antiseptics
Infected leg ulcer
Amoxicillin with compression was not significantly different from povidone-iodine alone or
with compression for complete healing at 12 weeks in people with an infected leg ulcer.
No data on adverse effects were reported.
Choice of antibiotic

Ciprofloxacin was not significantly different from trimethoprim for the frequency of
complete healing.
Limited data on adverse effects were reported. However, ciprofloxacin and trimethoprim
increased the emergence of antimicrobial resistance compared with standard care or
placebo. This finding was statistically significant for ciprofloxacin, but did not reach
significance for trimethoprim.
Antibiotic course length, dosage and route of

administration
No evidence from systematic reviews or RCTs was identified.
Other considerations
Medicines safety
Antibiotic-associated diarrhoea is estimated to occur in 2% to 25% of people taking
antibiotics, depending on the antibiotic used (NICE clinical knowledge summary on
diarrhoea – antibiotic associated).
About 10% of the general population claim to have a penicillin allergy; this is often because
of a skin rash that occurred while taking a course of penicillin as a child. Fewer than 10% of
people who think they are allergic to penicillin are truly allergic. See the NICE guideline on
drug allergy: diagnosis and management for more information.
Cholestatic jaundice and hepatitis can occur with flucloxacillin up to 2 months after
stopping treatment, with risk factors being increasing age and use for more than 14 days
(British national formulary [BNF] flucloxacillin). Cholestatic jaundice can also occur with
co-amoxiclav, and is more common in people over 65 years and in men; treatment should
not usually exceed 14 days (BNF co-amoxiclav).
People with a history of immediate hypersensitivity to penicillin may also react to

cephalosporins and other beta-lactam antibiotics (BNF phenoxymethylpenicillin).
Macrolides (for example, clarithromycin) should be used with caution in people with a
predisposition to QT interval prolongation. Nausea, vomiting, abdominal discomfort, and
diarrhoea are the most common side effects of macrolides. These are less frequent with
clarithromycin than with erythromycin (BNF erythromycin).
Tetracyclines (for example, doxycycline) can deposit in growing bone and teeth (by
binding to calcium) causing staining and occasionally dental hypoplasia. They should not
be given to pregnant women or women who are breastfeeding, and use in children under
12 years is either contraindicated or cautioned for use in severe or life-threatening
infections where there are no alternatives. People should be advised to avoid exposure to
sunlight or sun lamps because of photosensitivity reactions (BNF doxycycline).
Co-trimoxazole is associated with rare but serious side effects, including blood disorders
and Stevens−Johnson syndrome. It is cautioned for use in older people because there is
an increased risk of serious side effects, and in those with a predisposition to

hyperkalaemia. Monitoring of blood counts is recommended with prolonged treatment
(BNF co-trimoxazole).
Aminoglycoside (for example, gentamicin) doses are based on body weight and renal
function. Ototoxicity and nephrotoxicity are important side effects to consider, and
whenever possible treatment should not exceed 7 days (BNF gentamicin).
Glycopeptide (for example, vancomycin and teicoplanin) doses are based on body weight.
Therapeutic drug monitoring and monitoring of various patient parameters, including blood
count, urinalysis, auditory function, hepatic function and renal function, is recommended,
depending on the particular glycopeptide (BNF vancomycin).
Severe optic neuropathy can occur with linezolid, particularly if used for longer than
28 days. Blood disorders have also been reported, and weekly full blood counts are
recommended (BNF linezolid).
See the electronic medicines compendium's summaries of product characteristics for

information on contraindications, cautions and adverse effects of individual medicines.
Medicines adherence
Medicines adherence may be a problem for some people taking antibiotics that need
frequent dosing or longer treatment duration (see the NICE clinical guideline on medicines
adherence).
Resource implications
Recommended antibiotics are available as generic formulations. See NHS Drug tariff and
BNF for costs.
See the evidence review for more information.
Finding more information and committee

details
To find NICE guidance on related topics, including guidance in development, see the NICE
topic pages on injuries, accidents and wounds and antimicrobial stewardship.
For full details of the evidence and the guideline committee's discussions, see the
evidence review. You can also find information about how the guideline was developed,
including details of the committee.
NICE has produced tools and resources to help you put this guideline into practice. For
general help and advice on putting our guidelines into practice, see resources to help you
put NICE guidance into practice.
Update information
Minor changes since publication
January 2022: We made minor wording changes to reflect updated advice on the use of
macrolides in pregnancy.
November 2020: We amended table 1 to clarify that the gentamicin dosage is once daily.
ISBN: 978-1-4731-3678-6

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© NICE 2024. All rights reserved. Subject to Notice of rights (https://www.nice.org.uk/terms-and-

Local commissioners and providers of healthcare have a responsibility to enable the

Commissioners and providers have a responsibility to promote an environmentally

Who is it for? ........................................................................................................................................ 4

1.1 Managing leg ulcer infection in adults.......................................................................................... 5

1.2 Choice of antibiotic ....................................................................................................................... 7

Terms used in the guideline ............................................................................................................... 11

Recommendation for research ................................................................................................ 12

1 Topical treatments for infected leg ulcer ....................................................................................... 12

Referral or seeking specialist advice ................................................................................................. 16

Choice of antibiotic ............................................................................................................................. 17

Summary of the evidence........................................................................................................ 22

Topical antiseptics .............................................................................................................................. 23

Choice of antibiotic ............................................................................................................................. 27

Antibiotic course length, dosage and route of administration ....................................................... 27

Medicines safety ................................................................................................................................. 28

Resource implications ......................................................................................................................... 29

Finding more information and committee details .................................................................. 30

Update information .................................................................................................................. 31

See a 2-page visual summary of the recommendations, including a table to support

We have also produced guidelines on cellulitis and erysipelas and antimicrobial

• Adults with leg ulcer infection, their families and carers

• the severity of symptoms or signs

• the risk of developing complications

• previous antibiotic use.

• symptoms or signs of the infection worsen rapidly or significantly at any time,

1.1.11 When microbiological results are available:

• review the choice of antibiotic(s) and

• change the antibiotic(s) according to results if symptoms or signs of the

Referral or seeking specialist advice

• have a higher risk of complications because of comorbidities, such as

• have spreading infection that is not responding to oral antibiotics

1.2 Choice of antibiotic

Table 1 Antibiotics for adults aged 18 years and over

Treatment Antibiotic, dosage and course length

Treatment Antibiotic, dosage and course length

Piperacillin with tazobactam:

Review intravenous antibiotics by 48 hours and consider switching to oral antibiotics if

Erythromycin is preferred if a macrolide is needed in pregnancy, for example, if there is

Terms used in the guideline

Recommendation for research

1 Topical treatments for infected leg ulcer

Why the committee made the recommendations

Why the committee made the recommendations

serious illness requiring referral, or a resistant infection (possibly because of previous

Although microbiological sampling is not required at initial presentation, the committee

Referral or seeking specialist advice

Why the committee made the recommendations

Why the committee made the recommendations

The alternative first-choice antibiotics in adults with penicillin allergy or in whom

The committee agreed that additional choices would be:

• co-amoxiclav with or without gentamicin

• co-trimoxazole with or without gentamicin and/or metronidazole (if penicillin allergy).

intravenously if people were able to take oral antibiotics.

Second choice intravenous antibiotics (guided by microbiological results when available or

• piperacillin with tazobactam (a penicillin with a beta-lactamase inhibitor) or

• ceftriaxone (a third-generation cephalosporin) with metronidazole.

The committee discussed that intravenous ceftriaxone may be given as an outpatient

Meticillin-resistant Staphylococcus aureus (MRSA) may be found on swabbing, but the