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Child health Infections and infestations

Scarlet fever

Last revised in September 2024

Scarlet fever is a notifiable infectious disease caused by toxin-producing strains of the group A streptococcus bacterium (Streptococcus pyogenes).

Scarlet fever: Summary

  • Scarlet fever (or 'scarlatina') is an notifiable infectious disease caused by toxin-producing strains of the bacterium Streptococcus pyogenes, also known as group A streptococcus (GAS).
    • The incubation period is usually 2–3 days. People can be infectious for 2–3 weeks after the onset of symptoms, unless they are treated.
    • It is highly contagious and is transmitted when a person's mouth, throat, or nose comes into contact with infected saliva or mucus by aerosol transmission or by direct contact.
    • An outbreak is defined as 'a credible report of two or more probable or confirmed scarlet fever cases attending the same school or nursery or other childcare setting, notified within 10 days of each other (two maximum incubation periods), with an epidemiological link between cases, for example they are in the same class or year group'.
  • People who are at increased risk of invasive Group A streptococcal infection (iGAS) and complications include:
    • People aged 75 years or over, people who are immunocompromised or immunosuppressed, people with comorbidities such as skin breakdown, people with diabetes mellitus, cardiovascular disease, or underlying malignancy, people who develop chickenpox with active lesions within 7 days prior to diagnosis of iGAS infection in the index case, or within 48 hours of commencing antibiotics by the iGAS case if exposure is ongoing, or influenza, and people who inject drugs or are alcohol dependent.
    • Pregnant women.
    • Postpartum women (within 28 days of giving birth).
    • Neonates (aged up to 28 days). 
  • Scarlet fever can occur at any age but is most common in children between 2–8 years of age. There has been an increase in notified cases since 2013/14.
  • Complications may include:
    • Suppurative complications due to local spread, such as otitis media, peritonsillar abscess, and acute sinusitis.
    • Non-suppurative (immune-mediated) complications, such as acute rheumatic fever and acute post-streptococcal glomerulonephritis.
    • Invasive GAS infection, such as pneumonia, meningitis, streptococcal toxic shock syndrome, or necrotizing fasciitis.
  • In most cases, the clinical features of infection resolve over about 1 week.
  • A diagnosis of scarlet fever should be suspected if there is:
    • Initial sore throat, fever, headache, fatigue, nausea, and vomiting.
    • A pinpoint, sandpaper-like blanching rash that develops on the trunk within 48 hours after initial symptoms, before spreading to the rest of the body and flexures.
    • Possible strawberry tongue, cervical lymphadenopathy, circumoral pallor.
  • Throat swabs and blood tests are not routinely indicated for the diagnosis of scarlet fever.
  • Management of suspected or confirmed scarlet fever should include:
    • Arranging urgent hospital admission if a person has severe symptoms or a suspected serious complication (or is at risk of serious complications).
    • Offering appropriate oral antibiotics promptly, such as phenoxymethylpenicillin for 10 days first-line.
    • Notifying the local health protection team promptly.
    • Advising the person or family/carers about appropriate self-care measures, and strategies to reduce the risk of cross-infection.
    • Arranging follow up if symptoms worsen or have not improved after 7 days. 
    • Considering seeking local health protection team advice if a person is a high-risk contact.

Have I got the right topic?

From age 1 month onwards.

This CKS topic covers the diagnosis and management of scarlet fever in primary care. 

This CKS topic does not cover the management of infections caused by other group A beta-haemolytic streptococci, such as Streptococcus pyogenes, or the specialist management of complications of scarlet fever, such as acute rheumatic fever and glomerulonephritis. 

There are separate CKS topics on Measles, Parvovirus B19 infection, Rubella, and Sore throat - acute.

The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary healthcare.

How up-to-date is this topic?

Changes

September 2024 — reviewed. A literature search was conducted in September 2024 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials (RCTs) published since the last revision of this topic. There have been no changes to the recommendations. 

Previous changes

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

July 2023 — minor update. 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).

April 2023 — minor update. Antibiotic recommendations updated in line with the UKHSA guideline Scarlet fever: managing outbreaks in schools and nurseries. 

February 2023 — minor update. Antibiotic recommendations updated in line with the UKHSA guideline Scarlet fever: managing outbreaks in schools and nurseries. A prescribing section for azithromycin has been added and prescribing information for erythromycin has been combined with the section on clarithromycin.  

December 2022 — minor update. Antibiotic recommendations updated in line with the UKHSA Group A streptococcus in children. Interim clinical guidance summary issued on December 16. Typographical error in prescribing section amended. 

April 2022 — minor update. Drug interactions with azithromycin to include hydroxychloroquine and chloroquine added in line with the manufacturer's summary of product characteristics. 

March 2020 — reviewed. A literature search was conducted in February 2020 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of the topic. The topic has undergone minor restructuring. A new section on Risk factors has been added to the Background information section. The section on Admission has been deleted and the content incorporated into the section on Management. Recommendations have been updated in line with current evidence. No major changes to the recommendations have been made.

June 2018 — minor update. Prescribing information updated with information regarding azithromycin interacting with colchicine.  

September 2015 to October 2015 — reviewed. A literature search was conducted in September 2015 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. Changes to the recommendations are based on guidelines from Public Health England (PHE, 2015), and include the use of azithromycin instead of erythromycin as treatment for scarlet fever in people who are allergic to penicillin.

July 2015 — minor update. Statins have been included in the list of drugs metabolized by cytochrome P450 isoenzymes that interact with erythromycin and clarithromycin. 

May 2014 — minor update. Links to prescriptions have been removed and replaced with text on the doses of antibiotics. 

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. 

July 2011 — minor update. More exact paracetamol dosing for children has been introduced by the Medicines and Healthcare products Regulatory Agency (MHRA). Prescriptions have been updated to reflect the revised dosing. 

May 2010 — minor update to state that the Health Protection Agency should be notified following clinical diagnosis of scarlet fever. 

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.

Update

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 September 2024.

HTAs (Health Technology Assessments)

No new HTAs since 1 September 2024.

Economic Appraisals

No new economic appraisals relevant to England since 1 September 2024.

Systematic reviews and meta-analyses

No new systematic reviews or meta-analysis which reach the CKS threshold for inclusion since 1 September 2024.

Primary evidence

No new primary evidence which reaches the CKS threshold for inclusion published since 1 September 2024.

New policies

No new national policies or guidelines since 1 September 2024.

New safety alerts

No new safety alerts since 1 September 2024.

Changes in product availability

No changes in product availability since 1 September 2024.

Goals and outcome measures

Goals

To support primary healthcare professionals to: 

  • Be aware when to suspect scarlet fever in children and adults.
  • Treat scarlet fever promptly with appropriate antibiotics.
  • Give information and self-care advice on the management of scarlet fever.
  • Arrange hospital admission if there is a suspected serious complication or seek specialist advice, depending on clinical judgement.

Outcome measures

No outcome measures were found during the review of this topic.

Audit criteria

No audit criteria were found during the review of this topic.

QOF indicators

No QOF indicators were found during the review of this topic.

QIPP - Options for local implementation

No QIPP indicators were found during the review of this topic.

NICE Quality standards

No NICE Quality standards were found during the review of this topic.

Background information

What is it?

  • Scarlet fever (or 'scarlatina') is a notifiable infectious disease caused by the bacterium Streptococcus pyogenes, also known as group A streptococcus (GAS).
    • It typically causes a sore throat, fever, and extensive red, sandpaper-like rash.
  • An outbreak of scarlet fever is defined as a 'credible report of two or more probable or confirmed scarlet fever cases attending the same school or nursery or other childcare setting, notified within 10 days of each other (two maximum incubation periods), with an epidemiological link between cases, for example, they are in the same class or year group'.

[UKHSA, 2023a]

How is it transmitted?

  • Scarlet fever is caused by toxin-producing strains of Streptococcus pyogenes, also known as Group A streptococcus (GAS).
    • GAS bacteria can colonize mucosal surfaces or skin. Asymptomatic pharyngeal carriage of S. pyogenes occurs in 3–26% of healthy children.
    • The incubation period is usually 2–3 days but can range from 1–6 days. 
    • When GAS causes infection, the primary site is usually the throat, which results in pharyngitis. 
    • The clinical manifestations associated with scarlet fever are due to exotoxin or superantigen release by the bacteria.
  • Scarlet fever is highly contagious and is spread through aerosol transmission of infected saliva or mucus (by breathing infected airborne droplets produced through coughing or sneezing), or by direct contact with contaminated surfaces (including cups, utensils, taps, and handles).
    • The risk of transmission of S. pyogenes from index cases to contacts depends on the duration of exposure and the distance from the index case. 
    • Outbreaks in nurseries, schools, and other institutions may occur where there is close contact between people. 
    • People can be infectious for 2–3 weeks after the onset of symptoms unless they are treated. 

[Wong, 2012; UKHSA, 2019; Wessels, 2022; UKHSA, 2023a]

What are the risk factors?

  • People who are at increased risk of invasive Group A Streptococcal infection (iGAS) and complications include:
    • People:
      • Aged 75 years or over. 
      • Who are immunocompromised or immunosuppressed. 
      • With comorbidities such as skin breakdown, diabetes mellitus, cardiovascular disease, or underlying malignancy.
      • Who develop chickenpox with active lesions within 7 days prior to diagnosis of iGAS infection in the index case, or within 48 hours of commencing antibiotics by the iGAS case if exposure is ongoing, or influenza.
      • Who inject drugs or are alcohol dependent.
    • Pregnant women.
    • Postpartum women (within 28 days of giving birth).
    • Neonates (aged up to 28 days). 

[Wong, 2012; UKHSA, 2023b; UKHSA, 2023a] 

How common is it?

  • Scarlet fever can occur at any age but is most common in children aged 2–8 years (median age 4 years).
    • Incidence is seasonal, and in the UK most cases occur between December and May, peaking in March or April.
    • Routine national surveillance data for invasive and non-invasive GAS infections suggests a cyclical pattern with higher incidence peaks evident in notifications approximately every 4 years.
  • In England in 2022/23 from week 37 (mid-September 2022) to week 36 (mid-September 2023) there was an exceptionally high level of scarlet fever activity with 61,442 notifications and a peak of 10,069 notifications in week 49. 
    • Data for the 2023/24 season show scarlet fever infections in line with normal seasonal patterns up to week 28 (July 2024) with a peak of 3.88 cases per 100,000 population reported in March 2024.  
  • There was also an exceptionally high number of invasive Group A Streptococcus (iGAS) infections reported in 2022/23 with a total of 4412 cases. 
    • The highest rate of infections was in those aged 75 years and over (22.9 per 100,000 population), followed by those aged under 1 year (18.3 per 100,000 population).
    • There have been 2631 iGAS notifications in 2023/24 (up to week 28), which is higher than average but within the range for the same previous 5 seasons (2107/18 to 2021/22), and compares with 3998 in the same period last season. 
      • The highest rate of iGAS infection is in people aged 75 years and over (8.8 per 100,000 population), followed by those aged under 1 year (6.4 per 100,000 population), and people aged 65–74 years (4.0 per 100,000).
      • The rate in people aged 75 years and older is considerably higher than the range of 1.5–3.9 in the previous 5 seasons (2017/18 to 2021/22). 

[UKHSA, 2023a; UKHSA, 2024a; UKHSA, 2024b]

What are the complications?

Serious complications of scarlet fever are generally rare.

  • Suppurative complications are due to local spread of the infection and tend to occur early in the course of infection: 
    • Acute sinusitis and mastoiditis — see the CKS topic on Sinusitis for more information.
    • Otitis media — see the CKS topic on Otitis media - acute for more information.
    • Throat infection and abscess (peritonsillar or retropharyngeal abscess) — see the CKS topic on Sore throat - acute for more information.
  • Non-suppurative (immune-mediated) complications tend to occur later in the course of infection, particularly in untreated people, and include: 
    • Acute post-streptococcal glomerulonephritis — this typically occurs 1-3 weeks or more after the acute initial infection. Most people recover without long-term renal impairment, but some may need dialysis or transplant. 
    • Acute rheumatic fever — this can cause carditis and endocarditis (leading to valvular heart disease) and reactive arthritis.
  • Invasive Group A streptococcal (iGAS) infections may be life-threatening and include:

[Wong, 2012; UKHSA, 2019; RHD Australia, 2022; Wessels, 2022; UKHSA, 2023a; UKHSA, 2023c; BMJ Best Practice, 2024a] 

What is the prognosis?

  • Scarlet fever is usually a mild and self-limiting illness — in most cases, the clinical features of infection, including rash, resolve over about 1 week. However, some people experience severe infections or complications.  
  • Once a person has had scarlet fever recurrence is unlikely. 

[UKHSA, 2019; UKHSA, 2023a]

Diagnosis of scarlet fever

When should I suspect a diagnosis of scarlet fever?

Suspect a diagnosis of scarlet fever if there are typical clinical features present.

  • Initial clinical features may be non-specific and include: 
    • Sore throat. 
    • Fever (typically greater than 38.3°C).  
    • Headache, fatigue, nausea, and vomiting. 
  • A blanching rash usually develops on the chest and stomach within 48 hours before spreading to the rest of the body and flexures. 
    • The rash has a sandpaper-like texture. 
    • On white skin, the rash looks pink and red, while on brown and black skin, it may be harder to see a change in colour.
    • The rash is characteristically red, generalized and pinpoint (punctate). 
    • It may be accentuated in the skin folds of the neck, axillae, groin, elbows, and knees with a deep red, linear appearance (Pastia's lines). 
    • The palms and soles are typically spared. 
    • The skin may peel after the rash resolves — particularly at the tips of the fingers and toes and less commonly on the trunk and limbs.
  • Examination may also reveal: 
    • Strawberry tongue — initially, the tongue is covered with a white coat through which enlarged papillae may be seen, which peels a few days later, leaving the tongue looking red and swollen.  
    • Cervical lymphadenopathy. 
    • Flushed face, with marked circumoral pallor. 
    • Pharyngitis and small red spots (petechiae) on the soft palate. 
  • Be alert for clinical features of scarlet fever in people who are at increased risk of invasive Group A streptococcal (iGAS) infection and its complications. 
  • Consider an alternative diagnosis if symptoms and signs are atypical, particularly in older children and adults.

Basis for recommendation

These recommendations are based on the UK Health Security Agency (UKHSA) publications Guidelines for the public health management of scarlet fever outbreaks in schools, nurseries and other childcare settings [UKHSA, 2023a], and Scarlet fever: symptoms, diagnosis and treatment [UKHSA, 2019], and expert opinion in a narrative review Streptococcus pyogenes and re-emergence of scarlet fever as a public health problem [Wong, 2012], a chapter on Streptococcus pyogenes: Pharyngitis and scarlet fever in a medical textbook [Wessels, 2022], and what CKS considers good medical practice.

  • The UKHSA recommends that healthcare professionals should maintain a high level of suspicion of invasive group A streptococcus (iGAS), especially in people at high risk [UKHSA, 2023a].
    • It notes that there is an increased risk of iGAS disease, especially when there are concomitant outbreaks of chickenpox or influenza with GAS infection, but advises that chickenpox is the most common risk factor for iGAS disease in children.

When is laboratory testing needed to confirm scarlet fever?

Throat swabs and blood tests are not routinely indicated for the diagnosis of scarlet fever. 

  • Consider taking a throat swab for culture of Group A streptococcus (GAS) (prior to starting treatment) if: 
    • There is uncertainty about the clinical diagnosis. 
    • A case is suspected to be part of an outbreak — the local health protection team should advise primary care if a local outbreak is suspected and when testing is appropriate.
    • There is a true allergy to penicillin, to determine antimicrobial susceptibility, depending on clinical judgement. 
    • A case is in regular contact with vulnerable people who are at high risk of complications, such as healthcare workers. 
  • Measurement of serum anti-streptolysin O (ASO) antibody titres is not useful in acute infection but may be helpful in the diagnosis of postinfection complications, such as acute rheumatic fever or glomerulonephritis. 

Basis for recommendation

These recommendations are based on the UK Health Security Agency (UKHSA) Guidelines for the public health management of scarlet fever outbreaks in schools, nurseries and other childcare settings [UKHSA, 2023a], and expert opinion in a chapter on Streptococcus pyogenes: Pharyngitis and scarlet fever in a medical textbook [Wessels, 2022].

Measuring serum anti-streptolysin O (ASO) antibody titres

  • The information that serology is not useful for the acute diagnosis of S. pyogenes pharyngitis is based on expert opinion in a medical textbook [Wessels, 2022]. However, serum assays for antibodies to Streptococcus pyogenes antigens are useful for retrospective diagnosis of a preceding S. pyogenes infection in cases of suspected acute rheumatic fever or poststreptococcal glomerulonephritis. 
    • A rise in specific antibodies only begins 7–14 days after the onset of infection, reaching maximum levels at 3–4 weeks.
  • The UKHSA does not make a recommendation on the measurement of antibody titres in people with suspected scarlet fever [UKHSA, 2023a]. 

What else might it be?

Alternative diagnoses that may present similarly to scarlet fever include:

  • Glandular fever (infective mononucleosis) — this presents with fever, sore throat, and lymphadenopathy and may be accompanied by a rash. For more information, see the CKS topic on Glandular fever (infectious mononucleosis). 
  • Hand, foot and mouth disease — this presents with a low-grade fever, lesions in the mouth and/or a rash on the body. For more information, see the CKS topic on Hand, foot, and mouth disease.
  • Kawasaki disease — this may be a cause of fever that has lasted 5 days or longer, and may also present with an erythematous polymorphous rash, strawberry tongue, cervical lymphadenopathy, bilateral conjunctivitis, and oedema, erythema, and skin peeling of the hands and feet. See the CKS topic on Feverish children - risk assessment and management for more information.
  • Measles — this causes a characteristic erythematous and maculopapular rash that may become confluent as it progresses. It appears on the face and behind the ears first before spreading to the trunk and limbs over the course of about 3–4 days. It is usually accompanied by severe symptoms of viraemia (malaise, fever, loss of appetite, cough, rhinorrhoea, and conjunctivitis), and sore throat is not prominent. See the CKS topic on Measles for more information. 
  • Parvovirus B19 infection — this often presents with a diffuse erythematous facial rash appearing on one or both cheeks (resembling a 'slapped cheek') in children. An erythematous maculopapular rash on the trunk, back, and limbs may develop a few days after the facial rash. See the CKS topic on Parvovirus B19 infection for more information. 
  • Pityriasis rosea — this usually starts with a herald patch before a generalized eruption. For more information, see the CKS topic on Pityriasis rosea. 
  • Roseola infantum (herpesvirus type 6) — this causes a generalized pink papular or maculopapular rash. It usually starts on the trunk before spreading to the face and limbs. 
  • Rubella — this typically causes a non-confluent, maculopapular rash that starts behind the ears, spreads to the face and neck, and then to the trunk and extremities. The rash is transient, lasting between 3–5 days, and there may be associated cervical lymphadenopathy. See the CKS topic on Rubella for more information.
  • Staphylococcal toxic shock syndrome (TSS) — this is a potentially life-threatening condition. Symptoms include diffuse erythroderma of the skin and mucous membranes, particularly of the palms and soles, acute mental state changes (for example, confusion, agitation, change in consciousness), myocarditis, peritonitis and endophthalmitis. Risk factors include recent tampon use. 
  • Enterovirus and adenovirus infections — these are common causes of erythematous maculopapular viral rashes. 
  • Allergic reactions, adverse drug reactions — for more information, see the CKS topic on Adverse drug reactions. 

Basis for recommendation

This information is based on the UK Health Security Agency (UKHSA) Guidelines for the public health management of scarlet fever outbreaks in schools, nurseries and other childcare settings [UKHSA, 2023a], expert opinion in a chapter on Streptococcus pyogenes: Pharyngitis and scarlet fever in a medical textbook [Wessels, 2022], the BMJ Best Practice guides Scarlet fever [BMJ Best Practice, 2024a], and Assessment of rash in children [BMJ Best Practice, 2024b], and expert opinion in a narrative review Common skin rashes in children [Allmon, 2015].

Management

Scenario: Management of scarlet fever

From age 1 month onwards.

How should I manage suspected or confirmed scarlet fever?

For people with a suspected or confirmed diagnosis of scarlet fever:

  • Arrange urgent hospital admission if a person has:
    • Severe symptoms that cannot be managed in primary care. 
    • A suspected serious or life-threatening complication. 
    • A high risk of developing complications, depending on clinical judgement.
  • If the person does not need hospital admission, prescribe appropriate antibiotics promptly.
    • Offer a 10-day course of phenoxymethylpenicillin (penicillin V) first-line. 
    • Second-line options for people with penicillin allergy are: 
      • Birth to 6 months — clarithromycin for 10 days.
      • Non-pregnant adults and children aged 6 months to 17 years — azithromycin for 5 days, or clarithromycin for 10 days.
      • Pregnant or postpartum (within 28 days of childbirth) — erythromycin for 10 days.
  • Notify the local health protection team promptly within 3 days by completing a notification form if a diagnosis of scarlet fever is suspected. 
  • Advise the person or family/carers about appropriate self-care measures.
    • Advise on sources of information and support, such as:
    • Advise on the use of over-the-counter paracetamol or ibuprofen for symptom relief if there are no contraindications. See the CKS topics on Analgesia - mild-to-moderate pain and NSAIDs - prescribing issues for more information.
    • Encourage the person to drink adequate fluids.
    • Advise to clean and cover any skin breaks, including bites, cuts, grazes, or wounds. 
  • Advise the person or family/carers on measures to reduce the risk of cross-infection:
    • Exclusion from nursery, school, or work is needed for at least 24 hours after starting appropriate antibiotic treatment. 
    • Effective and frequent handwashing is needed (for example, before eating food, after using the toilet, after play, and after sneezing and disposing of tissues).
    • Avoid sharing eating utensils and towels, and dispose of tissues promptly. 
    • Avoid contact with people at high risk of complications of scarlet fever. 
  • Advise the person to arrange follow-up if symptoms worsen or have not improved after 7 days. 
    • Advise them to be aware of possible complications of scarlet fever in the first few weeks after infection, and to seek immediate medical advice if suspected.
    • Maintain a low threshold for prompt referral to secondary care for children presenting with persistent or worsening symptoms.
  • Consider seeking local health protection team advice if a person is a high-risk contact.
    • The specialist team may advise whether exclusion from work, school, or nursery and/or antibiotic prophylaxis is necessary (for example in people with severe immunosuppression). See the UKHSA website information Contacts: UKHSA health protection teams for contact details of the local health protection team. 
    • Advise that high-risk contacts should seek immediate medical advice if they develop any clinical features of Group A streptococcal (GAS) infection or its complications. 
    • Routine testing of asymptomatic household contacts is not recommended. 

Basis for recommendation

These recommendations are based on the UK Health Security Agency (UKHSA) publications Guidelines for the public health management of scarlet fever outbreaks in schools, nurseries and other childcare settings [UKHSA, 2023a], and Scarlet fever: symptoms, diagnosis and treatment [UKHSA, 2019], expert opinion in a narrative review Streptococcus pyogenes and re-emergence of scarlet fever as a public health problem [Wong, 2012], and what CKS considers good medical practice.

Urgent hospital admission
  • The recommendations on when to consider hospital admission are pragmatic as severe invasive Group A streptococcal (iGAS) infections carry a substantial risk of mortality, and people who develop a serious complication, or who are at potential high risk of developing complications require specialist management. This approach is supported by the expert opinion of previous external reviewers of this topic.
Prescribing appropriate antibiotic treatment promptly
  • The recommendation to treat people with suspected scarlet fever promptly with antibiotics is based on the UKHSA guideline, which advises that prompt treatment with appropriate antibiotics significantly reduces the risk of complications. It also advises that exclusion from work or school is no longer necessary 24 hours after starting antibiotic treatment [UKHSA, 2023a].
    • Antibiotic treatment achieves a high rate (>90%) of clearance of pharyngeal GAS 24 hours after initiation of therapy [UKHSA, 2023b].
    • Left untreated, people can remain infectious for 2-3 weeks after symptoms appear [UKHSA, 2019]. 
Managing close contacts 
  • The information that routine testing of asymptomatic household contacts is not recommended is extrapolated from the UKHSA guidelines [UKHSA, 2023a; UKHSA, 2019].
  • The recommendation that close contacts at risk of iGAS should seek immediate medical advice if they develop symptoms is extrapolated from expert opinion in a narrative review, which advises that education and monitoring of close contacts for early symptoms of infection are important, especially within 30 days after the diagnosis in the index patient [Wong, 2012]. 
    • This is supported by a retrospective cohort study that compared the incidence of iGAS infection among household contacts of people with scarlet fever, with the background incidence of iGAS infection in England. It recorded the 60-day incidence rate of iGAS in household contacts of people with scarlet fever (n = 73,344) diagnosed with or without laboratory confirmation of GAS infection, and found the absolute risk was low, but was 12.2-fold higher than the background rate. It concluded that clinicians should have increasing awareness of the risk for iGAS in scarlet fever contacts when assessing people, to improve early identification and treatment of cases [Watts, 2019].
    • The UKHSA also advises that household contacts of scarlet fever cases have a low, but increased risk of iGAS disease in the 2 months after the onset of scarlet fever in the initial case and clinicians should advise patients, or their parents or guardians, to be vigilant for any symptoms which might suggest these complications and to seek medical help immediately if concerned [UKHSA, 2023a].
  • Antibiotic prophylaxis is not routinely recommended for contacts of non-invasive GAS infection in school and nursery settings as there is no good evidence of its effectiveness in routine outbreak control in this setting [UKHSA, 2023a]. However, it may be considered by the local health protection team in some cases, and is recommended to treat household outbreaks of iGAS infection [UKHSA, 2023b].
Follow-up
  • The recommendations on follow-up are pragmatic, based on what CKS considers to be good medical practice. This approach is supported by the expert opinion of previous external reviewers of this topic.

Prescribing information

Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC), or the British National Formulary (BNF).

Azithromycin

Dose

  • Adults: 500 mg once daily for 5 days.
  • Children aged:
    • 6 months to 11 years — 12 mg/kg once daily (max 500 mg per dose) for 5 days.
    • 12-17 years — 500 mg once daily for 5 days.   

[BNF, 2024; UKHSA, 2023a]

Contraindications and cautions

  • Prescribe azithromycin with caution in people:
    • Who may be predisposed to prolongation of the QT interval. For example people:
      • With congenital or documented acquired QT prolongation.
      • Currently receiving treatment with other active substances known to prolong the QT interval such as antiarrhythmics of classes IA and III.
      • With electrolyte disturbance, particularly in cases of hypokalaemia and hypomagnesaemia.
      • With clinically relevant bradycardia, cardiac arrhythmia, or severe cardiac insufficiency, including Torsades de pointes.
    • Hepatic impairment.
    • With severe renal impairment.
    • With myasthenia gravis — macrolides may aggravate symptoms.

[BNF, 2024; EMC, 2024a]

Adverse effects

  • Gastrointestinal 
    • Very common: diarrhoea, abdominal pain, nausea.
    • Common: vomiting, dyspepsia.
  • Nervous system 
    • Common: headache, dizziness, dysgeusia, paraesthesia.
    • Frequency unknown: convulsions, hyperactivity, syncope, myasthenia gravis.
  • Psychiatric 
    • Uncommon: nervousness, insomnia.
    • Rare or very rare: agitation, aggression, anxiety, delirium, hallucination.
  • Skin and subcutaneous tissue
    • Common: rash, pruritus.
    • Rare, or very rare: drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme.
  • Other adverse effects include: 
    • Anaphylaxis.
    • Arrhythmias.
    • Arthralgia.
    • Deafness. 
    • Eye discomfort.
    • Hepatitis, cholestatic jaundice.
    • Pancreatitis. 
    • QT interval prolongation.

[BNF, 2024; EMC, 2024a]

Drug interactions

  • Antacids — plasma concentrations of azithromycin may be reduced. Simultaneous administration should be avoided. Azithromycin should be taken at least 1 hour before, or 2 hours after antacids
  • Apixaban — azithromycin is predicted to increase the exposure to apixaban, increasing its effects. Monitor patients for signs of bleeding.
  • Dabigatran — azithromycin is predicted to increase levels of dabigatran. Monitor for signs and symptoms of bleeding, particularly in those with renal impairment and stop dabigatran if bleeding occurs.
  • Digoxin — azithromycin may increase digoxin levels. Monitor for signs of digoxin adverse effects and adjust dose if required.
  • Edoxaban — levels may be increased by azithromycin. Monitor for signs of bleeding or anaemia. 
  • Ergot derivatives — there is a theoretical possibility of ergot toxicity if taken concomitantly with azithromycin. The manufacturer of azithromycin recommends avoiding concurrent use.
  • Rifabutin — concurrent use with azithromycin may increase the risk of neutropenia. Monitor for toxicity (in particular uveitis) and white blood cells. Advise patients to report any signs or symptoms of neutropenia (fever, sore throat, swollen glands, mouth ulcers, infections).
  • Statins — there is a possible increased risk of myopathy.
    • Advise the person to report any muscle pain, tenderness, or weakness.
  • Warfarin — isolated cases of increased INRs reported. Consider increased INR monitoring. 
  • Drugs that cause hypokalaemia (such as beta2-agonists, corticosteroids, thiazide and loop diuretics) — increased risk of torsades de pointes. Monitor potassium levels closely.
  • Drugs that prolong the QT interval — all macrolides can prolong the QT interval. 
    • Hydroxyzine, domperidone, mizolastine — concurrent use is contraindicated.
    • Amiodarone, disopyramide, haloperidol, sotalol — if concurrent use is unavoidable consider ECG monitoring.
  • Live cholera vaccines — the efficacy of the live vaccine may be affected. Avoid concurrent use and for 14 days before, and for 10 days after, live cholera vaccines.
  • Live typhoid vaccines — the immune response to the vaccine may be reduced. Antibacterials should be stopped from 3 days before to 3 days after receiving live typhoid vaccines.

[Preston, 2024]

Pregnancy and breastfeeding

Pregnancy

  • There are limited data available on the use of azithromycin in women who are pregnant. The manufacturer advises that azithromycin should only be used during pregnancy if clinically needed and the benefit of treatment is expected to outweigh any small increased risks which may exist. 

Breastfeeding

  • Azithromycin is excreted in breastmilk, but no adverse effects have been observed in breastfed infants.
  • The manufacturer advises that a decision must be made whether to discontinue breastfeeding or to discontinue/abstain from azithromycin therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

[BNF, 2024; EMC, 2024a]

Clarithromycin and erythromycin

Dose

  • Adults: 250–500 mg twice daily for 10 days.
  • Children aged 1 month to 11 years weighing:
    • Up to 8 kg  — 7.5 mg/kg twice daily for 10 days.
    • 8-11 kg — 62.5 mg twice daily for 10 days.
    • 12-19 kg — 125 mg twice daily for 10 days.
    • 20-29 kg — 187.5 mg twice daily for 10 days.
    • 30-40 kg — 250 mg twice daily for 10 days.
  • Children aged 12-17 years — 250-500 mg twice daily for 10 days. 

[BNF, 2024]  [UKHSA, 2023a]

Contraindications and cautions

  • Do not prescribe clarithromycin to people with:
    • A history of QT prolongation or ventricular cardiac arrhythmia, including torsades de pointes.
    • Conditions that predispose to QT interval prolongation, such as electrolyte disturbances (hypokalaemia or hypomagnesaemia) or the use of some medications that prolong the QT interval.
    • Severe hepatic impairment in combination with renal impairment.
  • Prescribe clarithromycin with caution to people with:
    • Hepatic impairment (or concurrently receiving potentially hepatotoxic drugs).
    • Moderate to severe renal impairment.
      • For immediate-release preparations: if creatinine clearance (CrCl) is less than 30 mL/minute, prescribe half the normal dose and use for a maximum duration of 14 days.
      • For modified-release preparations: if CrCl is 30–60 mL/minute, prescribe half the normal dose. Avoid if CrCl is less than 30 mL/minute.
    • Myasthenia gravis — macrolides may aggravate weakness symptoms.
    • Other risk factors for QT prolongation, such as:
      • Coronary artery disease, severe cardiac insufficiency, conduction disturbances, or clinically relevant bradycardia.
      • The use of some medications associated with QT prolongation other than those which are contraindicated. 

[BNF, 2024; EMC, 2024b]

Adverse effects

  • Cardiac 
    • Uncommon: cardiac arrest, atrial fibrillation, QT interval prolongation.
    • Rarely: torsades de pointes, ventricular tachycardia, ventricular fibrillation.
  • Gastrointestinal 
    • Common: diarrhoea, vomiting, dyspepsia, nausea, abdominal pain.
    • Uncommon: gastritis, glossitis, constipation, dry mouth.
    • Rarely: pancreatitis, pseudomembranous colitis. For more information, see the CKS topic on Diarrhoea - antibiotic associated.
  • Nervous system 
    • Common: headache, dysgeusia.
    • Uncommon: dizziness, somnolence, tremor.
    • Rarely: convulsions, paraesthesia.
  • Psychiatric 
    • Common: insomnia.
    • Uncommon: anxiety, nervousness.
    • Rarely or very rarely: psychotic disorders, depression, mania, hallucination.
  • Skin and subcutaneous tissue 
    • Common: rash, hyperhidrosis. 
    • Uncommon: pruritus, urticaria.
    • Rarely, or very rarely: drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalised exanthematous pustulosis (AGEP).
  • Other adverse effects reported rarely, or very rarely, include: 
    • Anaphylaxis.
    • Deafness.
    • Hepatic failure, jaundice.
    • Pancreatitis. 
    • Renal failure, interstitial nephritis.
    • Rhabdomyolysis, myopathy.

[BNF, 2024; EMC, 2024b]

Drug interactions

  • CYP3A enzyme inducers (for example, rifampicin, rifabutin, carbamazepine, phenobarbital) — these decrease exposure to clarithromycin, while their plasma levels may be increased. 
    • Carbamazepine — clarithromycin greatly and rapidly increases carbamazepine concentrations despite dose reductions of up to 40%. Several cases of toxicity have been reported. Monitor carbamazepine concentrations and adjust the dose if necessary. Advise patients to report any symptoms of toxicity (dizziness, diplopia, ataxia, mental confusion).
    • Rifabutin — concentrations of rifabutin are increased and concurrent use increases the risk of uveitis and neutropenia. Monitor for increased rifabutin adverse effects and consider reducing dose of rifabutin. Advise patients to report any signs or symptoms of neutropenia (fever, sore throat, swollen glands, mouth ulcers, infections).
  • Concurrent use with clarithromycin increases exposure to the following drugs: 
    • Calcium channel blockers (verapamil, amlodipine, diltiazem) —  monitor for adverse effects (for example, bradycardia, hypotension, headache, oedema) and reduce the calcium-channel blocker dose as necessary.
    • Ciclosporin — if concurrent use is necessary, monitor ciclosporin levels and effects (for example on renal function), and adjust the dose accordingly.
    • Colchicine — levels are moderately increased. The manufacturer advises against concurrent use.  
    • Daridorexant — avoid concurrent use.
    • Digoxin — significant increases in digoxin concentrations. Monitor for signs of adverse effects, measure digoxin levels and reduce the digoxin dose if required.
    • Eletriptan — concurrent use is contraindicated.
    • Eplerenone, finerenone — concurrent use is contraindicated.
    • Ivabradine — concurrent use is contraindicated. 
    • Lomitapide — concurrent use is contraindicated. 
    • Midazolam — reduce oral dose by 50 to 75%, and advise patients about sedative risk. 
    • Oral anticoagulants (such as direct-acting oral anticoagulants [DOACs] and warfarin). 
      • DOACs — monitor for signs and symptoms of bleeding or anaemia, especially, in elderly people and those with renal impairment. 
      • Warfarin — a few clinically significant interactions have been reported. Consider increased INR monitoring. 
    • Quetiapine — concurrent use is contraindicated.
    • Ranolazine — may increase risk of QT interval prolongation. Avoid concurrent use.  
    • Rimegepant — avoid concurrent use. 
    • Statins —  increased risk of myopathy.
      • Lovastatin, simvastatin — concurrent use is contraindicated. If treatment with clarithromycin cannot be avoided, stop treatment with statin temporarily.
      • Atorvastatin — levels moderately increased with concurrent use. Temporarily withhold statin, or if necessary, reduce dose and warn patients to report any unexplained muscle pain or weakness. 
    • Tacrolimus — large increases in tacrolimus concentrations and renal toxicity have been reported with clarithromycin. Both clarithromycin and tacrolimus have been associated with QT prolongation or torsade de pointes but an effect is not established. Monitor the concentrations and effects (e.g. on renal function) of tacrolimus more frequently if clarithromycin is started or stopped, adjusting the tacrolimus dose as necessary.
    • Ticagrelor — avoid concurrent use.
  • Ergot alkaloids — concurrent administration is contraindicated, due to the risk of acute ergot toxicity.
  • Hydroxychloroquine, chloroquine — concurrent use is associated with an increased risk of cardiovascular events (including angina or chest pain and heart failure) and cardiovascular mortality. Consider the benefits and risks before prescribing macrolides to people being treated with hydroxychloroquine or chloroquine. If there is a clinical need, use caution in patients with risk factors for cardiac events and follow advice in the product information for each medicine.
  • Oral hypoglycaemic drugs (sulfonylureas) and insulin — the concurrent use of clarithromycin and oral hypoglycaemic drugs and/or insulin can result in significant hypoglycaemia. Monitor blood glucose levels.
  • Drugs that cause hypokalaemia — hypokalaemia is a risk factor for QT prolongation.
    • Avoid concurrent treatment with drugs that increase the risk of hypokalaemia, such as diuretics, corticosteroids, and short-acting beta-2 agonists.
  • Drugs that prolong the QT interval amisulpride, fluconazole, sildenafil) — macrolides can also prolong the QT interval, increasing the risk of arrhythmias (such as torsades de pointes).
    • Domperidone, dronedarone, hydroxyzine, mizolastine, pimozide — concurrent use is contraindicated.
    • Amiodarone, disopyramide, haloperidol — if concurrent use is unavoidable consider ECG monitoring.
  • Live cholera vaccines — the efficacy of the live vaccine may be affected. Avoid concurrent use and for 14 days before, and for 10 days after, live cholera vaccines.
  • Live typhoid vaccines — the immune response to the vaccine may be reduced. Antibacterials should be stopped from 3 days before to 3 days after receiving live typhoid vaccines.

[MHRA, 2020; Preston, 2024]

Pregnancy and breastfeeding

Pregnancy

  • The safety of clarithromycin in pregnancy has not been established. Avoid (especially in the first trimester), unless the potential benefits outweigh the possible risks.

Breastfeeding

  • Clarithromycin is excreted into breastmilk in small amounts. An exclusively breastfed infant would receive about 1.7% of the maternal weight-adjusted dose of clarithromycin.
  • However, the manufacturer advises that the safety has not been established and it should be avoided unless the potential benefit outweighs the risk.  

[BNF, 2024; EMC, 2024b]

Title

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Dose

  • For women who are pregnant or postpartum (within 28 days of childbirth): 250–500 mg four times daily for 10 days. 

[BNF, 2024; UKHSA, 2023a]

Contraindications and cautions

  • Do not prescribe erythromycin to people with: 
    • Acute porphyrias.
    • A history of QT interval prolongation (congenital or acquired) or ventricular cardiac arrhythmia, including torsades de pointes.
    • Electrolyte disturbances (such as hypokalaemia or hypomagnesaemia) — due to the risk of arrhythmia associated with QT interval prolongation.
  • Prescribe erythromycin with caution to people with:
    • Cardiac disease or heart failure, conduction disturbances or clinically relevant bradycardia, or taking other medicines associated with QT interval prolongation.
    • Hepatic impairment.
    • Myasthenia gravis.

[MHRA, 2020; BNF, 2024; EMC, 2024c]

Adverse effects

  • Gastrointestinal 
    • Common or very common: diarrhoea, gastrointestinal discomfort/disorders, nausea, vomiting, pancreatitis. 
    • Rare or very rare: antibiotic-associated colitis.
  • Cardiovascular 
    • Uncommon: QTc interval prolongation, torsades de pointes, palpitations and cardiac rhythm disorders, including ventricular tachyarrhythmias. 
  • Skin and subcutaneous tissues 
    • Common or very common: skin reactions. 
    • Frequency unknown: acute generalised exanthematous pustulosis (AGEP), Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, angioedema, skin eruptions, pruritus, urticaria, exanthema.
  • Other adverse effects include:
    • Dizziness, headache.
    • Hearing impairment, tinnitus.
    • Hepatic disorders.
    • Interstitial nephritis.
    • Vasodilation.
    • Vision disorders.

[BNF, 2024; EMC, 2024c]

Drug interactions

  • Aminophylline, theophylline — aminophylline can cause hypokalaemia (potentially increasing the risk of torsade de pointes) when given with erythromycin. Theophylline clearance (from aminophylline) can be reduced if given concurrently with erythromycin. Oral erythromycin exposure may be reduced by theophylline. Monitor theophylline levels after 48 hours and adjust the dose accordingly. Monitor potassium concentrations closely and the effects of oral erythromycin to ensure they are adequate. Consider giving an alternative antibiotic. 
  • Carbamazepine — erythromycin greatly and rapidly increases carbamazepine levels, which can cause carbamazepine toxicity. Avoid concurrent use, unless carbamazepine levels can be monitored closely, and advise patients to report symptoms of toxicity (dizziness, diplopia, ataxia, mental confusion). 
  • Ergot alkaloids (such as ergotamine and dihydroergotamine) — concurrent use with erythromycin may result in acute ergot toxicity. 
    • Concurrent use is contraindicated.
  • Hydroxychloroquine, chloroquine — concurrent use is associated with an increased risk of cardiovascular events (including angina or chest pain and heart failure) and cardiovascular mortality. Consider the benefits and risks before prescribing macrolides to people being treated with hydroxychloroquine or chloroquine. If there is a clinical need, use caution in patients with risk factors for cardiac events and follow advice in the product information for each medicine.
  • Protease inhibitors (ritonavir, saquinavir) — erythromycin levels may be increased. Monitor for adverse effects. 
  • Rifampicin — may induce the metabolism of clarithromycin. Avoid concurrent use and for 2 weeks after stopping rifampicin.
    • If concurrent use is necessary, monitor erythromycin efficacy closely.
  • Concurrent use with erythromycin increases exposure to the following drugs:
    • Calcium channel blockers (amlodipine, diltiazem) — erythromycin possibly inhibits the metabolism of calcium channel blockers, increasing the risk of adverse effects, such as hypotension. Monitor for adverse effects (for example, bradycardia, hypotension, headache, oedema) and reduce the calcium channel blocker dose as necessary.
    • Ciclosporin — levels are greatly increased by erythromycin. Monitor concentrations and effects (for example, renal function) more frequently if erythromycin is started or stopped. Adjust the ciclosporin dose as required. 
    • Colchicine — erythromycin possibly increases the risk of colchicine toxicity. Concurrent use is contraindicated in renal or hepatic impairment.
    • 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. 
    • Coumarin anticoagulants (such as warfarin) — erythromycin may cause a minor increase in warfarin effects. Consider increased monitoring of INR, especially within the first 3 days of starting erythromycin.  
    • Domperidone — levels may be raised, increasing the risk of potentially life-threatening arrhythmias (torsade de pointes). Concurrent use is contraindicated.
    • Digoxin — erythromycin may increase the concentration of digoxin. Monitor for signs of digoxin adverse effects. Measure digoxin concentration and adjust dose if necessary.
    • Edoxaban — erythromycin slightly increases edoxaban levels. Decrease dose of edoxaban to 30 mg once daily. Monitor for signs and symptoms of bleeding. 
    • Lomitapide — concurrent use is contraindicated.
    • Rivaroxaban — exposure to rivaroxaban is increased. Monitor for signs and symptoms of bleeding or anaemia, especially in elderly people and those with renal impairment.
    • Quetiapine — erythromycin increases the plasma concentration of quetiapine and both drugs are associated with QT interval prolongation.
      • Concurrent use is contraindicated, but if necessary, monitor for quetiapine adverse effects (for example, somnolence, dry mouth, tachycardia) and reduce the dose if needed.
    • Statins — there is an increased risk of myopathy (due to cytochrome P450 enzyme CYP3A4 inhibition) [MHRA, 2014].    
      • Lovastatin, simvastatin  — concurrent use is contraindicated. If erythromycin treatment cannot be avoided, withhold the statin during the course of the treatment.
      • Atorvastatin — levels of atorvastatin increased slightly with concurrent use. Temporarily withhold the statin, or if necessary give the lowest dose of statin and advise the person to seek medical advice if they experience symptoms of myopathy (for example muscle pain, tenderness, or weakness).
      • Pravastatin — prescribe erythromycin with caution, and advise the person to report any muscle pain, tenderness, or weakness.
  • Drugs that prolong the QT interval — macrolides can also prolong the QT interval, increasing the risk of arrhythmias (such as torsades de pointed).
    • Domperidone, hydroxyzine, mizolastine, pimozide — concurrent use is contraindicated.
    • Amiodarone, disopyramide, dronedarone, haloperidol — if concurrent use is unavoidable consider ECG monitoring.
  • Drugs that cause hypokalaemia (such as diuretics, corticosteroids, short-acting beta-2 agonists) — hypokalaemia is a risk factor for QT prolongation. Monitor potassium levels closely. 
  • Live cholera vaccines — the efficacy of the live vaccine may be affected. Avoid concurrent use and for 14 days before, and for 10 days after, live cholera vaccines.
  • Live typhoid vaccines — the immune response to the vaccine may be reduced. Antibacterials should be stopped from 3 days before to 3 days after receiving live typhoid vaccines.

[MHRA, 2022; Preston, 2024]

Pregnancy and breastfeeding

Pregnancy

  • Erythromycin should only be used if the potential benefits outweigh the possible risks.  
    • The majority of data do not provide evidence that macrolide use during pregnancy increases the risk of adverse pregnancy outcomes. However, a limited number of studies have described small increased risks of malformation and miscarriage. Macrolide use should be reserved for compelling indications where there are no suitable alternatives with adequate pregnancy safety data, and should only be used if the expected benefits outweigh any small increased risks [UKTIS, 2020]. 
  • The manufacturer advises that erythromycin should only be used during pregnancy if clinically needed and the benefit of treatment outweighs any small increased risks.

Breastfeeding

  • Erythromycin is excreted in breast milk in small amounts and it is not known to be harmful. 
  • However, the manufacturer advises exercising caution due to reports of infantile hypertrophic pyloric stenosis in breast-fed infants. 

[BNF, 2024; EMC, 2024c]

Phenoxymethylpenicillin

Dose

  • Adults: 500 mg four times daily, or 1000 mg twice daily (increased if necessary up to 1000 mg four times daily) for 10 days.
  • Children aged: 
    • 1-11 months — 62.5 mg 4 times daily, or 125 mg twice daily for 10 days. 
    • 1-5 years — 125 mg 4 times daily, or 250 mg twice daily for 10 days. 
    • 6-11 years — 250 mg 4 times daily, or 500 mg twice daily for 10 days. 
    • 12-17 years — 500 mg 4 times daily, or 1000 mg twice daily for 10 days. 

[UKHSA, 2023a; BNF, 2024]

Contraindications and cautions

  • Do not prescribe phenoxymethylpenicillin to people with:
    • A history of anaphylaxis, urticaria, or rash immediately after penicillin administration due to risk of immediate hypersensitivity.
      • Note: People with a history of a minor rash (i.e. non-confluent, non-pruritic rash restricted to a small area of the body), or a rash that occurs more than 72 hours after penicillin administration are probably not allergic to penicillin and in these individuals, a penicillin should not be withheld unnecessarily for serious infections.
  • Prescribe phenoxymethylpenicillin with caution to people with a history of:
    • Atopic allergy (e.g. asthma, eczema, hay fever) — these people are at increased risk of anaphylactic reactions.
    • Cephalosporin-sensitivity, as there is some evidence of partial cross-sensitivity to cephalosporins and penicillins.
    • Markedly impaired renal function. 

[BNF, 2024; EMC, 2024d]

Adverse effects

  • Common or very common adverse effects include:
    • Diarrhoea — consider pseudomembranous colitis if a person develops sustained severe diarrhoea. For more information, see the CKS topic on Diarrhoea - antibiotic associated.
    • Nausea, vomiting, abdominal pain.
    • Hypersensitivity reactions.
    • Rash.
    • Reduced appetite.
    • Urticaria.
  • Rare or very rare adverse effects include:
    • Anaphylaxis, angioedema, arthralgia, serum sickness.
    • CNS toxicity (including convulsions).
    • Coagulation disorders. 
    • Haemolytic anaemia, leucopenia, thrombocytopenia, neutropenia.
    • Interstitial nephritis. 
    • Toxic epidermal necrolysis, exfoliative dermatitis, severe skin reactions (such as Stevens-Johnson syndrome).

[BNF, 2024; EMC, 2024d]

Drug interactions

  • Food — phenoxymethylpenicillin should be taken on an empty stomach, or one hour before food. 
  • Methotrexate — phenoxymethylpenicillin may reduce methotrexate clearance, causing an increased risk of toxicity.
    • Routine high dose monitoring will identify decreased elimination and should be managed according to local guidelines. Consult local guidelines for people taking low dose methotrexate for monitoring and management.
  • Coumarin anticoagulants — isolated cases of increased prothrombin time have occurred. Consider monitoring INR more frequently if penicillins are started or stopped.
  • Live cholera vaccines — the efficacy of the live vaccine may be affected. Avoid concurrent use and for 14 days before, and for 10 days after, live cholera vaccines.
  • Live typhoid vaccines — the immune response to the vaccine may be reduced. Antibacterials should be stopped from 3 days before to 3 days after receiving live typhoid vaccines.

[Preston, 2024]

Pregnancy and breastfeeding

Pregnancy

  • Phenoxymethylpenicillin is not known to be harmful in pregnancy.

Breastfeeding

  • Trace amounts of phenoxymethylpenicillin are found in breastmilk – however, it is appropriate to use.

[BNF, 2024; EMC, 2024d]

Supporting evidence

This CKS topic is largely based on the UK Health Security Agency (UKHSA) publications Guidelines for the public health management of scarlet fever outbreaks in schools, nurseries and other childcare settings [UKHSA, 2023a], and Scarlet fever: symptoms, diagnosis and treatment [UKHSA, 2019], and expert opinion in a narrative review Streptococcus pyogenes and re-emergence of scarlet fever as a public health problem [Wong, 2012], and a chapter on Streptococcus pyogenes: Pharyngitis and scarlet fever in a medical textbook [Wessels, 2022]. The rationale for the individual recommendations is discussed in the relevant basis for recommendation sections.

How this topic was developed

This section briefly describes the processes used in developing and updating this topic. Further details on the full process can be found in the About Us section and on the Clarity Informatics website.

Search strategy

A literature search was conducted for guidelines and systematic reviews on primary care management of scarlet fever.

Search dates

January 2020 - September 2024

Key search terms

The terms listed below are the core search terms that were used for EBSCOhost MEDLINE (searched 30th January 2020). These were combined with filters to identify guidelines, systematic reviews and primary care relevant literature in EBSCOhost MEDLINE. The strategy was adapted for The Cochrane Library databases. 

S4    S1 OR S2 OR S3 
S3    AB scarlatina OR TI scarlatina 
S2    AB scarlet fever OR TI scarlet fever 
S1    (MH "Scarlet Fever") 

Sources of guidelines

Sources of systematic reviews and meta-analyses

  • The Cochrane Library:
    • Systematic reviews
    • Protocols
    • Database of Abstracts of Reviews of Effects
  • Medline (with systematic review filter)
  • EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

Sources of randomized controlled trials

  • The Cochrane Library:
    • Central Register of Controlled Trials
  • Medline (with randomized controlled trial filter)
  • EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

Sources of national policy

Patient experiences

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

Stakeholder engagement

Our policy

The external review process is an essential part of CKS topic development. Consultation with a wide range of stakeholders provides quality assurance of the topic in terms of:

  • Clinical accuracy.
  • Consistency with other providers of clinical knowledge for primary care.
  • Accuracy of implementation of national guidance (in particular NICE guidelines).
  • Usability.

Principles of the consultation process

  • The process is inclusive and any individual may participate.
  • To participate, an individual must declare whether they have any competing interests or not. If they do not declare whether or not they have competing interests, their comments will not be considered.
  • Comments received after the deadline will be considered, but they may not be acted upon before the clinical topic is issued onto the website.
  • Comments are accepted in any format that is convenient to the reviewer, although an electronic format is encouraged.
  • External reviewers are not paid for commenting on the draft topics.
  • Discussion with an individual or an organization about the CKS response to their comments is only undertaken in exceptional circumstances (at the discretion of the Clinical Editor or Editorial Steering Group).
  • All reviewers are thanked and offered a letter acknowledging their contribution for the purposes of appraisal/revalidation.
  • All reviewers are invited to be acknowledged on the website. All reviewers are given the opportunity to feedback about the external review process, enabling improvements to be made where appropriate.

Stakeholders

  • Key stakeholders identified by the CKS team are invited to comment on draft CKS topics. Individuals and organizations can also register an interest to feedback on a specific topic, or topics in a particular clinical area, through the Getting involved section of the Clarity Informatics website.
  • Stakeholders identified from the following groups are invited to review draft topics:
    • Experts in the topic area.
    • Professional organizations and societies (for example, Royal Colleges).
    • Patient organizations, Clarity has established close links with groups such as Age UK and the Alzheimer’s Society specifically for their input into new topic development, review of current topic content and advice on relevant areas of expert knowledge.
    • Guideline development groups where the topic is an implementation of a guideline.
    • The British National Formulary team.
    • The editorial team that develop MeReC Publications.
  • Reviewers are provided with clear instructions about what to review, what comments are particularly helpful, how to submit comments, and declaring interests.

Patient engagement

Clarity Informatics has enlisted the support and involvement of patients and lay persons at all stages in the process of creating the content which include:

  • Topic selection
  • Scoping of topic
  • Selection of clinical scenarios
  • First draft internal review
  • Second draft internal review
  • External review
  • Final draft and pre-publication

Our lay and patient involvement includes membership on the editorial steering group, contacting expert patient groups, organizations and individuals.

Evidence exclusion criteria

Our policy

Scoping a literature search, and reviewing the evidence for CKS is a methodical and systematic process that is carried out by the lead clinical author for each topic. Relevant evidence is gathered in order that the clinical author can make fully informed decisions and recommendations. It is important to note that some evidence may be excluded for a variety of reasons. These reasons may be applied across all CKS topics or may be specific to a given topic.

Studies identified during literature searches are reviewed to identify the most appropriate information to author a CKS topic, ensuring any recommendations are based on the best evidence. We use the principles of the GRADE and PICOT approaches to assess the quality of published research. We use the principles of AGREE II to assess the quality of published guidelines.

Standard exclusions for scoping literature:

  • Animal studies
  • Original research is not written in English

Possible exclusions for reviewed literature:

  • Sample size too small or study underpowered
  • Bias evident or promotional literature
  • Population not relevant
  • Intervention/treatment not relevant
  • Outcomes not relevant
  • Outcomes have no clear evidence of clinical effectiveness
  • Setting not relevant
  • Not relevant to UK
  • Incorrect study type
  • Review article
  • Duplicate reference

Organizational, behavioural and financial barriers

Our policy

The CKS literature searches take into consideration the following concepts, which are discussed at the initial scoping of the topic.

  • Feasibility
    • Studies are selected depending on whether the intervention under investigation is available in the NHS and can be practically and safely undertaken in primary care.
  • Organizational and Financial Impact Analysis
  • Studies are selected and evaluated on whether the intervention under investigations may have an impact on local clinical service provision or national impact on cost for the NHS. The principles of clinical budget impact analysis are adhered to, evaluated and recorded by the author. The following factors are considered when making this assessment and analysis.
    • Eligible population
    • Current interventions
    • Likely uptake of new intervention or recommendation
    • Cost of the current or new intervention mix
    • Impact on other costs
    • Condition-related costs
    • In-direct costs and service impacts
    • Time dependencies
  • Cost-effectiveness or cost-benefit analysis studies are identified where available. 

We also evaluate and include evidence from NICE accredited sources which provide economic evaluations of recommendations, such as NICE guidelines. When a recommended action may not be possible because of resource constraints, this is explicitly indicated to healthcare professionals by the wording of the CKS recommendation.

Declarations of interest

Our policy

Clarity Informatics requests that all those involved in the writing and reviewing of topics, and those involved in the external review process to declare any competing interests. Signed copies are securely held by Clarity Informatics and are available on request with the permission of the individual. A copy of the declaration of interest form which participants are asked to complete annually is also available on request. A brief outline of the declarations of interest policy is described here and full details of the policy is available on the Clarity Informatics website. Declarations of interests of the authors are not routinely published, however competing interests of all those involved in the topic update or development are listed below. Competing interests include:

  • Personal financial interests
  • Personal family interest
  • Personal non-financial interest
  • Non-personal financial gain or benefit

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Competing interests declared for this topic:

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