Previous changes

March 2025 — minor update. Typographical error corrected in the topic summary. 

February 2025 — minor update. External reviewers comments on a range of issues relating to management and diagnosis of mastitis. 

August 2024 — minor update. Adverse effects of co-amoxiclav updated in line with manufacturer's SPC. Added information about considering the use of cold compresses for retroareolar inflammation 

May 2024 — minor update. Information added stating that concomitant treatment with clarithromycin and ivabradine is now contra-indicated and caution is now advised when co-administering clarithromycin with edoxaban, as per the manufacturer's updated SPC.

December 2023 — minor update. Update to drug interactions section for erythromycin to include information on interactions with Lomitapide and Corticosteroids, as per the manufacturer's Summary of Product Characteristics (SPC).

November 2023 — minor update. Interactions section for flucloxacillin updated in line with updated manufacturer's summary of product characteristics.

September 2023 — minor update. The dose of metronidazole recommended for recurrent mastitis updated to reflect the availability of 400 mg dose.

July 2023 — minor update. The manufacturer's SPC for metronidazole has been updated to note that QT prolongation has been reported (unknown frequency), particularly when metronidazole was administered with drugs with the potential for prolonging the QT interval. The summary of manufacturer’s product characteristics for clarithromycin was updated to include a warning regarding concomitant treatment with domperidone (due to the risk of QT prolongation and cardiac arrhythmias).

May 2023 — minor update. Added potential adverse effects of co-amoxiclav to include Kounis syndrome (an allergic reaction which can result in myocardial infarction), aseptic meningitis, linear IgA disease (renal deposition of IgA), and drug-induced enterocolitis syndrome (all of unknown frequency). These adverse effects were noted in an update to the manufacturer’s summary of product characteristics.

January 2023 — minor update. Recommendation on emptying the affected breast in lactating women has been removed to align with the Academy of Breastfeeding Medicine Clinical Protocol 36, The Mastitis Spectrum, 2022. 

December 2020 to January 2021 — reviewed. A literature search was conducted in December 2020 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. The topic has undergone restructuring. No major changes to the recommendations have been made.

October 2018 — minor update. Adverse effects updated within prescribing information - metronidazole. 

September 2015 — minor update. The Prescribing information section has been updated to reflect manufacturer's Summary of Product Characteristics in relation to a drug interaction between macrolides and calcium channel blockers.

August 2015 — reviewed. A literature search was conducted in July 2015 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 recommendations have been made. However, the scope of the topic has been changed as follows: The topic now includes information on the management of non-lactating women (in addition to lactating women). The age of the topic has been changed from 10 years to 14 years onwards.

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.

June 2011 — minor update. The 2010/2011 QIPP options for local implementation have been added to this topic. 

January 2011 — updated. Advice regarding infant attachment and the management of full breast, breast engorgement, nipple problems, or a blocked duct is now covered in the separate CKS topic on Breastfeeding problems.

February to May 2010 — this is a new CKS topic. The evidence base has been reviewed in detail, and recommendations are clearly justified and transparently linked to the supporting evidence.

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 December 2025. 

HTAs (Health Technology Assessments)

No new HTAs since 1 December 2025. 

Economic appraisals

No new economic appraisals relevant to England since 1 December 2025. 

Systematic reviews and meta-analyses

No new systematic reviews or meta-analyses published since 1 December 2025. 

Primary evidence

No new primary evidence which reaches the CKS threshold for inclusion published since 1 December 2025. 

New policies

No new national policies or guidelines since 1 December 2025. 

New safety alerts

No new safety alerts since 1 December 2025. 

Changes in product availability

No changes in product availability since 1 December 2025. 

Predisposing factors for mastitis in lactating women

• Milk stasis is the primary cause of mastitis in lactating women. Predisposing factors include:
  • Poor infant attachment to the breast, for example, due to a short frenulum (tongue-tie) in the infant — this may also lead to nipple damage, which can cause pain and provide an entry point for bacteria.
  • Reduced number or duration of feeds, for example, due to:
    • Partial bottle feeding, changes in feeding regime (common when the infant first starts to sleep through the night), and rapid weaning from breast milk.
    • Painful breasts.
    • Use of a dummy or bottle — this may also result in poor infant attachment to the breast.
    • Having a preferred breast for feeding, leading to milk accumulation in the other breast.
    • Maternal stress and fatigue.
  • Pressure on the breast, for example, from tight clothing or bra, baby sling straps, or prone sleeping position.
• Other predisposing factors include:
  • A 2020 systematic review found 42 risk factors commonly associated with lactational mastitis, but divided them conceptually into three categories: factors directly related to anatomical/breastfeeding factors and behaviours, socio-demographic factors, and other factors (these include smoking).
  • The most consistent factor was nipple damage (often reported as cracked nipples), and this was found to be significantly associated with lactational mastitis in all eight studies investigating this association.
  • Participant's age was examined as a risk factor for lactational mastitis; however, the findings about the existence of an association and its direction were not consistent.
• Recurrence of lactational mastitis is common. Predisposing factors include:
  • Staphylococcus aureus carriage — asymptomatic carriage of S. aureus on a person's skin or mucous membranes (colonization) is implicated in recurrent infections. For more information, see Scenario: Staphylococcal carriage in the CKS topic on Boils, carbuncles, and staphylococcal carriage.
  • Previous mastitis — this association is thought to be due to inadequate treatment of previous mastitis (which can lead to a recurrence of more severe mastitis or a breast abscess) and/or inadequate management of predisposing factors.

[Wilson, 2020; ACOG, 2023; HSE, 2023; Blackmon, 2024; WHO, 2025]   

Predisposing factors for mastitis in non-lactating women

• Smoking is a major predisposing factor for periductal mastitis. Nicotine and other toxins found in cigarette smoke accumulate in the breasts causing damage to the ducts (directly or by a localized hypoxic effect).
• Other predisposing factors for non-lactational mastitis include:
  • Nipple damage, for example, from nipple piercing or skin conditions such as eczema, infection, or Raynaud's disease — this can cause pain and provide an entry point for bacteria.
  • Trauma to the breast — may damage the duct and gland tissue.
  • Underlying breast abnormality, such as ductal abnormality, cyst, or tumour — can cause persistent poor drainage of part of the breast, leading to breast infection.
  • Immunosuppression — women with diabetes mellitus or HIV infection, and those on immunosuppressive therapy, are at increased risk for developing breast infections.
  • Shaving or plucking areolar hair — pulling hair from the areola may result in the formation of a boil or an abscess, with potential for more widespread infection.
  • Foreign body — materials such as silicone and paraffin, which are used for both breast augmentation and reconstruction, may cause a foreign body-type reaction in the breast.
• Predisposing factors for granulomatous mastitis include bacterial infections (Corynebacterium spp.), childbirth, oral contraceptive use, trauma, autoimmune disease, hyperprolactinaemia, tuberculosis, sarcoidosis, and diabetes mellitus.
• Recurrence of non-lactational mastitis is common. Predisposing factors include:
  • Staphylococcus aureus carriage — asymptomatic carriage of S. aureus on a person's skin or mucous membranes (colonization) is implicated in recurrent infections. For more information, see Scenario: Staphylococcal carriage in the CKS topic on Boils, carbuncles, and staphylococcal carriage. Up to 30% of cases may be polymicrobial (associated, for example, with Enterobacteriaceae, Peptostreptococcus, Propionibacterium and Bacteroides.
  • Previous mastitis — this association is thought to be due to inadequate treatment of previous mastitis (which can lead to a recurrence of more severe mastitis or a breast abscess) and/or inadequate management of predisposing factors.

[Oliveira, 2021; Blackmon, 2024; Dilaveri, 2024]

Predisposing factors for breast abscess

• Predisposing factors for breast abscess include:
  • Previous mastitis — this association is thought to be due to:
    • Delayed, inadequate, or inappropriate treatment of previous mastitis — can lead to complications, including a breast abscess.
    • Sudden cessation of breastfeeding in women with lactational mastitis — without effective milk removal, infectious mastitis is likely to progress to an abscess.
  • Immunosuppression — women with diabetes mellitus or HIV infection, and those on immunosuppressive therapy, are at risk for developing recurrent breast infections.
  • Staphylococcus aureus carriage — asymptomatic carriage of S. aureus on a person's skin or mucous membranes (colonization) is implicated in recurrent infections. For more information, see Scenario: Staphylococcal carriage in the CKS topic on Boils, carbuncles, and staphylococcal carriage.
  • Socio-economic status — there is some evidence of a higher incidence of breast abscess (especially lactational) in low-income women compared with higher-income women.
  • Smoking is an independent predictor of periductal and peripheral mastitis and abscess.
  • Poor hygiene — better maternal and infant hygiene reduces the risk of abscess formation.
  • Breast abscess may also be more common in women who are primiparous, aged over 30 years, and following post-term delivery.

[Li, 2022; Toomey, 2023; Courtney, 2024]

Basis for recommendation

The information on when to suspect mastitis is based on expert opinion in the Academy of Breastfeeding Medicine clinical protocol The Mastitis Spectrum [ABM, 2022], the American College of Obstetricians and Gynaecologists guideline Breastfeeding challenges [ACOG, 2023], the Health Service Executive Ireland factsheet Mastitis: Fact sheet for Health Care Professionals [HSE, 2023], the World Health Organization (WHO) model chapter for textbooks for medical students and allied health professionals Infant and young child feeding [WHO, 2025], and review articles on lactational mastitis [Wilson, 2020; Blackmon, 2024]. 

Distinguishing between granulomatous mastitis and breast cancer

• The advice that due to overlapping clinical features, a biopsy is required to distinguish between granulomatous mastitis and breast cancer is based on expert opinion in review articles on mastitis [Rashid, 2023; Blackmon, 2024].
• A 2024 review states that imaging features from mammography and MRI, such as age, internal blood flow, calcification, and edge, enhancement characteristics, are important factors for differentiating the two [Peng, 2024].

Distinguishing between infectious and non-infectious mastitis

• CKS pragmatically suggests that if these features are present, an infectious cause is more likely.
• Expert opinion provides no consensus on distinguishing infectious and inflammatory mastitis, as a systemic inflammatory response (including systemic features such as fever) may also occur in the absence of infection [ABM, 2022].

Basis for recommendation

The information on clinical features of a breast abscess is based on expert opinion in the Academy of Breastfeeding Medicine clinical protocol The Mastitis Spectrum [ABM, 2022] Health Service Executive Ireland factsheet Mastitis: Fact sheet for Health Care Professionals [HSE, 2023], the World Health Organization (WHO) model chapter for textbooks for medical students and allied health professionals Infant and young child feeding [WHO, 2025] and the review articles Breast abscess [Pileri, 2022; Toomey, 2023].

Basis for recommendation

The recommendations on investigations for mastitis are largely based on expert opinion in the Academy of Breastfeeding Medicine (ABM) guideline ABM Clinical protocol: the mastitis spectrum [ABM, 2022], the Health Service Executive Ireland Mastitis: Fact sheet for Health Care Professionals [HSE, 2023], and review articles [Toomey, 2023; Blackmon, 2024].

Breast milk culture 

• Breast milk culture is not routinely recommended in primary care for women with mastitis because [ABM, 2022]:
  • The presence of bacteria in the milk does not necessarily indicate infection.
  • Many women with mastitis may not have pathogenic organisms in their milk.
  • Bacterial counts are not always reliable, for example because breast milk from non-infected areas of the breast may dilute or flush out the pathogen, or the flow of milk from the infected area may be obstructed.
• The recommendations on when breast milk culture should be performed are based on expert opinion in the Academy of Breastfeeding Medicine (ABM) guideline ABM Clinical protocol: the mastitis spectrum [ABM, 2022], the Health Service Executive Ireland Mastitis: Fact sheet for Health Care Professionals [HSE, 2023] .
• The information on how a sample of breast milk should be collected is taken from expert opinion in the ABM guideline ABM Clinical protocol: the mastitis spectrum [ABM, 2022], the Health Service Executive Ireland Mastitis: Fact sheet for Health Care Professionals [HSE, 2023].

Urgent secondary care referral for all women with a breast abscess

• The recommendation to arrange urgent secondary care referral for all women with a breast abscess is based on expert opinion in the WHO model chapter for textbooks for medical students and allied health professionals Infant and young child feeding [WHO, 2025] and in review articles [Toomey, 2023; Blackmon, 2024; Courtney, 2024].
  • Ultrasound examination is required to accurately diagnose a breast abscess and may identify more than one collection of pus that may otherwise be missed [Rashid, 2023].

Basis for recommendation

The information on the differential diagnoses of mastitis and breast abscess is based on expert opinion within the WHO Model chapter for textbooks for medical students and allied health professionals Infant and young child feeding [WHO, 2025], the National Institute for Health and Care Excellence (NICE) guideline Postnatal care [NICE, 2025], as well as review articles on mastitis and breast pain [Oliveira, 2021; Toomey, 2023; Blackmon, 2024; Tahir, 2025], a review article on necrotizing fasciitis of the breast [Yilmaz, 2022], the Cochrane systematic review protocol Treatments for breast engorgement during lactation [Zakarija-Grkovic, 2020], and a case report where breast abscess mimicked malignancy [Devanabanda, 2024].

When should I arrange immediate admission or referral for a woman with lactational mastitis?

• Arrange hospital admission if:
  • There are signs of sepsis (such as tachycardia, fever, and chills).
  • The infection progresses rapidly.
  • The woman is haemodynamically unstable or immunocompromised.
    • If appropriate and depending on the woman's wishes, the infant can be admitted with her to allow continuation of breastfeeding.
• Arrange a suspected cancer pathway referral if there is an underlying mass or breast cancer is suspected.
• Refer urgently to a general surgeon if a breast abscess is suspected.

How should I manage a woman with lactational mastitis in primary care?

If immediate admission or referral is not indicated:

• Reassure the woman that her breast should return to normal size, shape, and function after treatment.
• To relieve pain and discomfort:
  • Prescribe or advise a simple analgesic, such as paracetamol or ibuprofen. See the CKS topics on Analgesia - mild-to-moderate pain and NSAIDs - prescribing issues for detailed prescribing information.
  • Advise the application of cold compresses for approximately 10 minutes every hour when the retroareolar area is swollen and inflamed. 
  • Therapeutic ultrasound may help to reduce inflammation, but there is limited availability to provide this in some areas.
• Advise the woman to continue breastfeeding if possible (including from the affected breast). If necessary, involve a breastfeeding specialist to assist the woman in improving the infant's attachment to the breast. This will improve milk removal and prevent nipple damage.
  • If breastfeeding is too painful, or the infant refuses to breastfeed from the affected breast, advise the woman to hand express sufficient milk to match the infant's needs until she is able to resume breastfeeding from that breast.
  • Note that mothers using breast pumps should minimise usage and express only the volume their infant consumes, as breast pumps may worsen oedema.
    • For detailed information on expressing breast milk, see the CKS topic on Breastfeeding problems.
  • If the woman does not wish to continue breastfeeding, give advice on stopping breastfeeding.
• Identify and manage any predisposing factors for mastitis. For example:
  • Advise the woman to rest and to wear a supportive bra.
  • If there is nipple soreness or damage, see the CKS topic on Breastfeeding problems for detailed information on management.
• Prescribe an oral antibiotic if the woman has a nipple fissure that is infected, symptoms have not improved (or are worsening) after 24 hours despite effective milk removal, and/or breast milk culture is positive.
  • If breast milk culture results are available, treat with an antibiotic that the organism is sensitive to.
  • If breast milk culture results are not available:
    • Treat empirically with flucloxacillin 500 mg four times a day for 10–14 days.
    • If the woman is allergic to penicillin, prescribe either erythromycin 250 mg to 500 mg four times a day, or clarithromycin 500 mg twice a day for 10–14 days.
• Advise the woman to seek immediate medical advice if symptoms fail to settle after 48 hours of antibiotic treatment. See the section on Treatment failure/recurrence for further information.
• Give advice on measures to prevent recurrence.

How should I manage treatment failure or recurrence in a woman with lactational mastitis?

• If symptoms fail to settle after 48 hours of first-line antibiotic treatment:
  • Check that the woman has taken the antibiotic correctly.
  • Consider the possibility of an alternative diagnosis (such as breast cancer or a breast abscess) and the need for admission or referral.
    • If an abscess is suspected, be aware that malaise and fever may have subsided if antibiotics have been started.
  • If an alternative diagnosis is unlikely:
    • Send a sample of breast milk for microscopy, culture, and antibiotic sensitivity (if this has not already been done) — see the section on investigations for more information.
    • Prescribe a second-line antibiotic, co-amoxiclav 500/125 mg three times a day, for 10–14 days; review this choice when breast milk culture results become available. Seek specialist advice if the woman is allergic to penicillin.
• If mastitis recurs, manage as for treatment failure. In addition:
  • Identify and manage any predisposing factors, such as:
    • Nipple damage — see the CKS topic on Breastfeeding problems for detailed information on management.
    • Staphylococcus aureus carriage — send nasal swabs from both the woman and the infant to identify nasal carriage of S. aureus. See the CKS topic on Boils, carbuncles, and staphylococcal carriage for further information.
  • Ensure that the woman is aware of measures to prevent recurrence, such as having a good breastfeeding technique and maintaining good hygiene.

What advice should I give to prevent recurrence?

• Explain that good breastfeeding technique is necessary to prevent mastitis.
  • Advise the woman to:
    • Make sure the infant is attached to the breast correctly.
    • Feed on demand, both in terms of frequency and duration.
    • Avoid missed feeds, especially when the infant starts to sleep through the night.
    • Finish the first breast before offering the other.
    • Breastfeed exclusively for 4–6 months, if possible.
    • Avoid the use of a dummy, which may result in poor attachment to the breast.
    • For future pregnancies, start to breastfeed within an hour of delivery, if possible.
  • For detailed information on breastfeeding technique, see the CKS topic on Breastfeeding problems.
• Ensure that the woman knows:
  • How to express milk manually — for more information, see the CKS topic on Breastfeeding problems.
  • How to check breasts for lumps, redness, and tenderness.
  • How to recognize milk stasis.
  • What to do if milk stasis develops — rest, breastfeed frequently, and seek medical help if problems do not resolve within 24 hours.
• If the woman does not wish to continue breastfeeding, advise that she should:
  • Not stop breastfeeding abruptly.
  • Support the breasts with a comfortable bra.
  • Express enough milk to keep the breasts comfortable.
  • Take paracetamol or ibuprofen if pain occurs. See the CKS topics on Analgesia - mild-to-moderate pain and NSAIDs - prescribing issues for detailed prescribing information.
• Give advice on hygiene measures, such as: 
  • Thorough and frequent hand washing.
  • Ensuring that the breast pump is washed thoroughly with soap and hot water (and air dried) after every use.
  • Ensuring that potentially-contaminated nipple ointments or creams are discarded.

When should I arrange immediate admission or referral for a woman with non-lactational mastitis?

• Arrange hospital admission if:
  • There are signs of sepsis (such as tachycardia, fever, and chills).
  • The infection progresses rapidly.
  • The woman is haemodynamically unstable or immunocompromised.
• Arrange a suspected cancer pathway referral if there is an underlying mass or breast cancer is suspected.
• Refer urgently to a general surgeon if a breast abscess is suspected.

How should I manage a woman with non-lactational mastitis in primary care?

If immediate admission or referral is not indicated:

• Reassure the woman that her breast should return to normal size, shape, and function after adequate treatment.
• To relieve pain and discomfort:
  • Prescribe a simple analgesic, such as paracetamol or ibuprofen. See the CKS topics on Analgesia - mild-to-moderate pain and NSAIDs - prescribing issues for detailed information on prescribing these analgesics.
  • Advise the woman to use cold compresses on the breast, or bathe or shower in warm water, to relieve pain.
• Identify and manage any predisposing factors for mastitis. For example, if there is nipple damage, manage the underlying cause:
  • If a candidal infection is suspected, see the CKS topic on Fungal skin infection - body and groin for information on management.
  • If eczema is suspected, see the CKS topics on Eczema - atopic and Dermatitis - contact for information on management.
  • If Raynaud's disease of the nipple is suspected, see the CKS topic on Breastfeeding problems for information on management.
• Prescribe an oral antibiotic for all women with non-lactational mastitis:
  • Prescribe co-amoxiclav 500/125 mg three times a day for 10–14 days.
  • If the woman is allergic to penicillin, prescribe a combination of erythromycin (250 mg to 500 mg four times a day) or clarithromycin (500 mg twice a day) plus metronidazole (400 mg three times a day) for 10–14 days.
• Advise the woman to seek immediate medical advice if symptoms worsen or fail to settle after 48 hours of antibiotic treatment. See the section on Treatment failure/recurrence for further information.
• Give advice on measures to prevent recurrence.

How should I manage treatment failure or recurrence in a woman with non-lactational mastitis?

• If symptoms fail to settle after 48 hours of first-line antibiotic treatment:
  • Check that the woman has taken the antibiotic correctly.
  • Consider the possibility of an alternative diagnosis (such as breast cancer or a breast abscess) and refer accordingly.
    
    • If an abscess is suspected, be aware that malaise and fever may have subsided if antibiotics have been started.
  • Also consider the possibility of methicillin-resistant Staphylococcus aureus (MRSA) infection (risk factors include local prevalence and hospital-acquired infection) where first-line treatment is ineffective.
    • If MRSA is suspected, seek local microbiology advice regarding possible investigations and treatments.
  • Consider the need for referral or admission.
• If mastitis recurs, manage as for treatment failure. In addition:
  • Check that previous episodes of mastitis were managed appropriately.
  • If an alternative diagnosis is unlikely:
    • Prescribe co-amoxiclav 500/125 mg three times a day for 10–14 days.
    • If the woman is allergic to penicillin, prescribe a combination of erythromycin (250 mg to 500 mg four times a day) or clarithromycin (500 mg twice a day) plus metronidazole (400 mg three times a day) for 10–14 days.
    • If antibiotic treatment has failed more than once, seek advice from a local microbiologist regarding culture and sensitivity testing and/or alternative antibiotic treatment, and consider the possibility of an alternative diagnosis.
  • Identify and manage any predisposing factors, such as:
    • Nipple damage from skin conditions such as psoriasis, eczema, infection, or Raynaud's disease of the nipple — see the section on First-line management for more information.
  • Ensure that the woman is aware of measures to prevent recurrence, such as stopping smoking and maintaining good hygiene.
  • Consider referring the woman to secondary care (using clinical judgement to determine the urgency) if there is no obvious cause for recurrence (such as continued smoking or nipple piercing).

What advice should I give to prevent recurrence?

• Advise women who smoke to stop — smoking is a major risk factor for periductal mastitis. See the CKS topic on Smoking cessation for detailed information.
• Give advice on hygiene measures, including thorough and frequent hand washing and removal of nipple rings (due to potential bacterial contamination).

How should I manage a woman with a breast abscess

• Refer the woman urgently to a general surgeon for:
  • Confirmation of the diagnosis (by ultrasound).
  • Drainage of the abscess (by ultrasound-guided needle aspiration or surgical drainage).
  • Culture of fluid from the abscess, which will be used to guide the choice of antibiotic.
• Advise lactating women to continue breastfeeding if possible (including from the affected breast).
  • If this is too painful, or the infant refuses to breastfeed from the affected breast, advise the woman to express the milk (by hand or with a breast pump) until she is able to resume breastfeeding from that breast.
    • For detailed information on how breast milk should be expressed, see the CKS topic on Breastfeeding problems.

Contraindications and cautions

• Do not prescribe flucloxacillin to people with a history of:
  • A true penicillin hypersensitivity. Gastrointestinal adverse effects alone (such as nausea, vomiting, or diarrhoea) do not constitute an allergy to penicillin.
  • Hypersensitivity to cephalosporins.
  • Penicillin-associated hepatic dysfunction.
• Prescribe flucloxacillin with caution to people with:
  
  • Hepatic impairment.
  • Renal impairment — consider dose reduction or a reduction in dosing interval of flucloxacillin in severe renal failure due to the risk of neurotoxicity.

[BNF, 2025; EMC, 2025a]

Adverse effects

• Nausea, vomiting, skin rash, and diarrhoea are the most common adverse effects of flucloxacillin.
  • Consider pseudomembranous colitis if a person develops severe diarrhoea during or after treatment with flucloxacillin. For more information, see the CKS topic on Diarrhoea - antibiotic associated.
• Anaphylaxis (delayed or immediate) is a serious but rare adverse effect of flucloxacillin. For more information, see the CKS topic on Angio-oedema and anaphylaxis.
• 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.

[BNF, 2025; EMC, 2025a]

Drug interactions

• Methotrexate — methotrexate clearance may be reduced, causing an increased risk of toxicity, however, serious interactions are uncommon. 
  • Standard routine monitoring will identify any decreases in elimination in people on high-dose regimens. For people on low-dose regimens, consult local or national guidelines/protocols for monitoring and management.
• Coumarin and indanedione anticoagulants (warfarin, phenidione) — consider increased monitoring of international normalized ratio (INR) and adjust the dose accordingly.
• Posaconazole, voriconazole — concentrations of antifungal is greatly decreased. If concurrent use is unavoidable, monitor for decreased efficacy and consider increasing the dose of the azole (although this may not resolve the issue). 
• Probenecid — concomitant administration may result in increased levels of flucloxacillin.
• Live cholera vaccine — efficacy of vaccine may be reduced. Avoid flucloxacillin from 14 days before to 10 days after receiving live cholera vaccine.
• Live typhoid vaccine — immune response to vaccine may be reduced. Avoid flucloxacillin from 3 days before to 3 days after receiving live typhoid vaccine.

[BNF, 2025; Preston, 2025]

Contraindications and cautions

• Do not prescribe clarithromycin or erythromycin to people:
  • With known hypersensitivity to clarithromycin or erythromycin.
  • Taking certain drugs that prolong the QT interval — macrolides can also prolong the QT interval, which is a risk factor for Torsades de pointes.
  • With a history of QT prolongation or ventricular cardiac arrhythmia, including Torsades de pointes.
  • With hypokalaemia — due to the risk of prolongation of the QT interval.
• Do not prescribe clarithromycin to people with severe hepatic impairment if they also have renal impairment.
• Do not prescribe erythromycin to people with:
  • Porphyria.
  • Hypomagnesaemia.
• Prescribe clarithromycin and erythromycin with caution in people with:
  • Coronary artery disease, severe cardiac insufficiency, conduction disturbances, or clinically relevant bradycardia.
  • Impaired hepatic function (or concomitantly receiving potentially hepatotoxic drugs) – clarithromycin and erythromycin are principally excreted by the liver.
  • Myasthenia gravis — macrolides may aggravate symptoms.
• Prescribe clarithromycin with caution in people with:
  
  • Hypomagnesaemia.
  • Severe renal impairment (eGFR less than 30 mL/min/1.73m²).
    • Use half the normal dose. Avoid Klaricid XL® or clarithromycin modified-release preparations.
• Be aware of drug interactions with erythromycin and clarithromycin.

[MHRA, 2020; EMC, 2024; EMC, 2025b]

Adverse effects

• Nausea, vomiting, abdominal discomfort, and diarrhoea are the most common adverse effects of macrolides, but they are mild and less frequent with clarithromycin than with erythromycin.
  • Consider pseudomembranous colitis if a person develops severe diarrhoea during or after treatment with erythromycin or clarithromycin. For more information, see the CKS topic on Diarrhoea - antibiotic associated.
• Anaphylaxis is rarely associated with erythromycin and clarithromycin. For more information, see the CKS topic on Angio-oedema and anaphylaxis.
• Hepatotoxicity (including cholestatic jaundice) and rash have rarely been reported following treatment with erythromycin or clarithromycin.
• Reversible hearing loss (sometimes with tinnitus) can occur after large doses of erythromycin and clarithromycin.
• Other adverse effects reported rarely or very rarely include pancreatitis, QT interval prolongation, arrhythmias, Stevens-Johnson syndrome, and toxic epidermal necrolysis.

[EMC, 2024; BNF, 2025; EMC, 2025b]

Drug interactions

• Key drug interactions with erythromycin and clarithromycin include: 
  • Antidiabetic drugs and insulin — the 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.
  • Calcium channel blockers (CCBs) — due to an increased risk of hypotension, caution is advised with the concurrent use of macrolides and CCBs metabolised by CYP3A4 (such as verapamil, amlodipine, and diltiazem).
  • Carbamazepine — macrolides can raise plasma carbamazepine levels.
    • For erythromycin — avoid concurrent use with carbamazepine unless carbamazepine levels can be closely monitored, and suitable dose adjustments made. Symptoms of carbamazepine toxicity (for example nausea, vomiting, dizziness, ataxia, and confusion) commonly begin within 1–3 days of starting erythromycin and usually resolve within 5 days of stopping erythromycin.
    • For clarithromycin — reduce carbamazepine dose by 30–50% and monitor plasma levels within 3–5 days of concurrent treatment with carbamazepine.
  • Corticosteroids — levels of corticosteroids may be increased. Monitor for corticosteroid adverse effects (such as moon face, weight gain, hyperglycaemia), and adjust the corticosteroid dose or stop the macrolide as appropriate. 
  • Drugs that prolong the QT interval (such as antiarrhythmics, antipsychotics,comperidone, and tricyclic antidepressants) — all macrolides can prolong the QT interval, and concomitant use of drugs that prolong the QT interval is not recommended.
    • Seek advice from a microbiologist regarding a suitable alternative antibiotic.
  • Drugs that cause hypokalaemia (such as diuretics, corticosteroids, short-acting beta-2 agonists) — hypokalaemia is a risk factor for QT interval prolongation.
    • Seek advice from a microbiologist regarding a suitable alternative antibiotic.
  • Edoxaban — manufacturer advises caution with concurrent treatment with edoxaban, particularly in those with a high risk of bleeding.
  • Ivabradine — concomitant treatment is contra-indicated, owing to CYP3A4 inhibition by clarithromycin which can cause elevated levels of ivabradine.
  • Lomitapide — concurrent use with erythromycin increases transaminase levels and is contraindicated.
  • Rivaroxaban — erythromycin may increase levels of rivaroxaban, increasing the risk of bleeding. 
  • Statins — there is an increased risk of myopathy (due to cytochrome P450 enzyme CYP3A4 inhibition) if clarithromycin or erythromycin is taken with atorvastatin or simvastatin.
    • For simvastatin — do not prescribe clarithromycin or erythromycin to a person taking simvastatin, as simvastatin is extensively metabolized by CYP3A4. If treatment with clarithromycin or erythromycin cannot be avoided, stop treatment with simvastatin during the course of the treatment.
    • For atorvastatin — avoid concurrent use with clarithromycin or erythromycin, as atorvastatin is moderately metabolized by CYP3A4. If concurrent use cannot be avoided, prescribe the lowest starting dose of atorvastatin (10 mg), and advise the person to report any muscle pain, tenderness, or weakness.
    • Other statins — clinically significant drug interactions resulting from cytochrome P450-mediated metabolism are not expected for rosuvastatin and pravastatin as they are not metabolized to a clinically significant extent by the cytochrome P450 system. Fluvastatin is not dependent on CYP3A metabolism; therefore, interaction with clarithromycin is unlikely. Nevertheless, advise the person to report any muscle pain, tenderness, or weakness.
  • Theophylline — erythromycin increases plasma concentrations of theophylline and theophylline may also reduce absorption of oral erythromycin.
    • Check theophylline levels 48 hours after starting erythromycin, and adjust the dose of theophylline accordingly.
    • This interaction is less likely with clarithromycin unless theophylline levels are at the higher end of the therapeutic range.
  • Warfarin — occasionally and unpredictably, the effects of warfarin may be markedly increased by macrolides.
    • Monitor the international normalized ratio (INR), and adjust the warfarin dose accordingly.

Contraceptives — additional contraceptive precautions are not required during or after a course of clarithromycin or erythromycin.

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 and Contraception - progestogen-only methods.

[MHRA, 2020; CoSRH, 2022; BNF, 2025; Preston, 2025]

Contraindications and cautions

• Do not prescribe co-amoxiclav to people with a history of:
  • A true penicillin hypersensitivity. Gastrointestinal adverse effects alone (such as nausea, vomiting, or diarrhoea) do not constitute an allergy to penicillin.
  • Penicillin-associated hepatic dysfunction.
• Prescribe co-amoxiclav with caution to people with:
  • Hypersensitivity to cephalosporins.
  • Hepatic impairment.
  • Chronic kidney disease (CKD) — reduce the dose if the estimated glomerular filtration rate (eGFR) is 30 mL/minute/1.73 m² or less.

[BNF, 2025; EMC, 2026]

Adverse effects

• Gastrointestinal — diarrhoea (very common), nausea and vomiting (common), drug-induced enterocolitis syndrome (unknown frequency).
  • Very rarely: antibiotic-associated colitis.
• Nervous system — headache, dizziness (uncommon), aseptic meningitis (unknown frequency).
• Skin — skin rash, urticaria, pruritus (uncommon), drug reaction with eosinophilia and systemic symptoms (DRESS) (unknown frequency).
  • Very rarely: erythema multiforme, Stevens–Johnson syndrome, toxic epidermal necrolysis, bullous and exfoliative dermatitis, acute generalized exanthematous pustulosis.
• Other rare, or very rare adverse effects include:
  • Hepatitis, cholestatic jaundice.
  • Hyperactivity, convulsions.
  • Hypersensitivity reactions (serious and occasionally fatal).  
  • Interstitial nephritis.
  • Linear IgA disease (renal deposition of IgA).  
  • Leucopenia, thrombocytopenia, haemolytic anaemia.
  • Kounis syndrome (an allergic reaction which can cause myocardial infarction). 
• Symmetrical Drug-related Intertriginous and Flexural Exanthema (SDRIFE) are adverse effects of unknown frequency.

[BNF, 2025; EMC, 2026]

Drug interactions

• Key drug interactions with co-amoxiclav include: 
  • Allopurinol — be aware that concomitant use of allopurinol and amoxicillin may increase the incidence of skin rashes.
  • Anticoagulants (for example warfarin) — prolongation of prothrombin time has been reported in people taking penicillins and warfarin concurrently.
    • Monitor the prothrombin time or international normalized ratio (INR) more closely with the addition or withdrawal of penicillin. Adjustment of the anticoagulant dose may be necessary.
  • Methotrexate — penicillins may reduce the excretion of methotrexate. The interaction is not usually serious and risk factors are unknown (even people on low doses of methotrexate have been affected).
    • 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.

Oral hormonal contraception — additional contraceptive precautions are not required during or after courses of penicillins.

• 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 and Contraception - progestogen-only methods.

[CoSRH, 2022; BNF, 2025; Preston, 2025]

Contraindications and cautions

• Do not prescribe metronidazole to a person with:
  • Known metronidazole or nitroimidazole hypersensitivity.
  • 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). For people with Cockayne syndrome specialist advice should therefore be sought before prescribing metronidazole. 
• Prescribe oral metronidazole with caution:
  • In people with active or chronic severe peripheral and central nervous system disease (due to the risk of neurological aggravation).
  • In people with severe liver disease and hepatic encephalopathy (due to substantial impairment of metronidazole clearance) — the daily dose should be reduced to one-third and may be administered once daily.
  • For prolonged use (longer than 10 days) — may be associated with peripheral neuropathy or leucopenia, although both effects are usually reversible.
    • The manufacturer recommends that a full blood count should be carried out regularly in a person taking metronidazole for longer than 10 days, and the person should be monitored for adverse reactions, such as peripheral or central neuropathy (including paraesthesia, ataxia, dizziness, or seizures).

[BNF, 2025; EMC, 2025c]

Adverse effects

• Gastrointestinal disturbances (including nausea and vomiting), taste disturbances, furred tongue, oral mucositis, and anorexia are possible adverse effects of metronidazole.
  • Very rarely, hepatitis, jaundice, pancreatitis, drowsiness, dizziness, headache, ataxia, psychotic disorders, darkening of urine, thrombocytopenia, pancytopenia, myalgia, arthralgia, visual disturbances, rash, pruritis, and erythema multiforme have been reported.
• Advise the person not to drive or operate machinery if drowsiness, dizziness, confusion, hallucinations, convulsions, or transient visual disturbances occur.
• Severe bullous skin reactions such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) or acute generalized exanthematous pustulosis (AGEP) have been reported. If symptoms/signs are present, treatment must be immediately discontinued.

[BNF, 2025; EMC, 2025c]

Drug interactions

• Key drug interactions associated with oral metronidazole include:
  • Alcohol — some people taking oral metronidazole experience a disulfiram-like reaction (flushing, increased respiratory rate, increased pulse rate, nausea, headache, and dizziness) with alcohol.
    • Although there is no conclusive evidence to support this interaction, warn the person that they might experience this reaction if they drink alcohol whilst taking metronidazole. Alcohol should be avoided during treatment with metronidazole and for at least 48 hours afterwards.
  • Anticoagulants — the anticoagulant effects of warfarin can be markedly increased by metronidazole.
    • Monitor the international normalized ratio (INR) if metronidazole is given with warfarin and adjust the warfarin dose accordingly.
    • Warn the person of the possible risk of increased bruising and bleeding and advise them on when to seek medical help.
  • Ciclosporin — people receiving ciclosporin are at risk of elevated serum ciclosporin levels.
    • When co-administration of metronidazole and ciclosporin are necessary, serum ciclosporin and creatinine levels should be closely monitored.
  • Lithium — raised lithium levels accompanied by evidence of possible renal damage has been reported in people treated simultaneously with lithium and metronidazole.
    • Before starting metronidazole in a person taking lithium, seek specialist advice about tapering or stopping lithium treatment. If concurrent treatment is unavoidable, plasma concentrations of lithium, creatinine, and electrolytes should be monitored closely.
  • The manufacturers SPC also notes that QT prolongation has been reported (unknown frequency), particularly when metronidazole was administered with drugs with the potential for prolonging the QT interval.

Contraceptives — additional contraceptive precautions are not required during or after courses of metronidazole.

• 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 and Contraception - progestogen-only methods.

[CoSRH, 2022; BNF, 2025; Preston, 2025]