Previous changes

August 2024 — minor update. Adverse effects of co-amoxiclav updated in line with manufacturer's SPC.

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.

March 2024 — minor update. Adverse effects of doxycycline updated in line with manufacturer's SPC.

February 2024 — minor update. Neurotoxicity has been added as a possible adverse effect of cefaclor treatment in line with 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). Information about the onset of action of beta-2 agonists aligned to SPC.

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.

March 2022 — reviewed. A literature search was conducted in February 2022 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.

August 2021 — minor update. Threshold for immediate admission to hospital for children with bronchiolitis changed from 92% oxygen saturation to 90% as a response to the partial update of the NICE Bronchiolitis in children guideline [NG9]. 

January 2021 — minor update. Contraindications and drug interactions for erythromycin have been updated in line with an MHRA drug safety update. 

January to February 2017 — reviewed. A literature search was conducted in January 2017 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.

November 2016 — minor update. The National Institute for Health and Care Excellence (NICE) quality standards for bronchiolitis in chidren have been added to this topic.

February 2013 — minor update. The 2013 QIPP options for local implementation have been added to this topic.

October 2012 — reviewed. A literature search was conducted in August 2012 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of the topic. Changes to clinical recommendations have been made including the general assessment of a child with a cough, and the management of a child with community-acquired pneumonia.

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

February 2011 — topic structure revised to ensure consistency across CKS topics — no changes to clinical recommendations have been made.

November 2010 — minor update. The recommendations regarding the management of children under the age of 5 years with viral wheeze have been updated. 

April 2009 — minor typographical corrections. 

July to November 2007 — this is a new CKS topic that has been developed following a full literature review. The management of community-acquired pneumonia in children was previously covered in the CKS guidance on Chest infections. This CKS topic provides information on the management of viral-induced wheeze/possible asthma and bronchiolitis, which were not covered by the previous CKS guidance.

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 February 2022.

HTAs (Health Technology Assessments)

No new HTAs since 1 February 2022.

Economic appraisals

No new economic appraisals relevant to England since 1 February 2022.

Systematic reviews and meta-analyses

• Armarego, M., Forde, H., Wills, K., and Beggs, S.A. (2024) High‐flow nasal cannula therapy for infants with bronchiolitis. Cochrane Library. https://www.cochranelibrary.com/ [Free Full-text]

Primary evidence

Little, P., Becque, T., Hay, A.D., et al. (2023) Predicting illness progression for children with lower respiratory infections in primary care: a prospective cohort and observational study. British Journal of General Practice. https://bjgp.org/ [Free Full-text]

New policies

No new national policies or guidelines since 1 February 2022.

New safety alerts

No new safety alerts since 1 February 2022.

Changes in product availability

No changes in product availability since 1 February 2022.

Basis for recommendation

Recommendations on diagnosing the cause of cough in children are based on expert opinion in the BMJ article Community-acquired pneumonia in children [Haq, 2017] the National Institute for Health and Care Excellence (NICE) guidelines Fever in under 5s: assessment and initial management [NICE, 2019a], and Bronchiolitis in children: diagnosis and management [NICE, 2021a], the review article Coughing children in family practice and primary care: a systematic review of prevalence, aetiology and prognosis[Bergmann, 2021] and the Scottish Intercollegiate Guidelines Network/British Thoracic Society British guideline on the management of asthma [BTS/SIGN, 2019].

Basis for recommendation

Information on the differential diagnosis of cough with chest signs in children is based on expert opinion from medical text book - the Oxford Handbook of General Practice (Respiratory medicine) [Simon, 2020], from the Scottish Intercollegiate Guidelines Network/British Thoracic Society British guideline on the management of asthma [BTS/SIGN, 2019] and in the review article Coughing children in family practice and primary care: a systematic review of prevalence, aetiology and prognosis [Bergmann, 2021]

How should I manage a child with viral-induced wheeze or an infective exacerbation of asthma?

• Determine the severity of the attack, bearing in mind that children in a severe or life-threatening condition sometimes do not appear to be distressed.
  • Note the child's degree of agitation and consciousness. Agitation and behavioural changes in a child may be a sign of hypoxia. 
  • Look for signs of exhaustion (inability to complete sentences, if applicable), cyanosis (bluish lips or extremities), and involvement of accessory muscles of respiration while the child is at rest.
  • Examine the child's chest, and record their respiratory rate, pulse, and blood pressure. 
  • Record the child's peak expiratory flow rate (if they are old and well enough to comply) and use the best of three recordings compared to their best  (if measured within the last two years) or predicted PEFR value. 
  • Measure the child's oxygen saturation in room air using pulse oximetry (if available). 
  • The severity of an attack is graded as follows:
    • Moderate – PEFR at least 50% best or predicted and normal speech (if applicable), with no acute severe or life-threatening features.
    • Acute severe – PEFR less than 50% best or predicted, or respiratory rate of at least 25/min in children over the age of 12 years, 30/min in children between the ages of 5 and 12 years, and 40/min in children between 2 and 5 years old, or pulse rate of at least 110/min in children over the age of 12 years, 125/min in children between the ages of 5 and 12 years, and 140/min in children between 2 and 5 years old, or inability to complete sentences in one breath (if applicable), or accessory muscle use, or inability to feed, with oxygen saturation of at least 92%.
    • Life-threatening – PEFR  less than 33% best or predicted, or oxygen saturation of less than 92%, or altered consciousness, or exhaustion, or cardiac arrhythmia, or hypotension, or cyanosis, or poor respiratory effort, or silent chest, or confusion.
• Consider the need for hospital admission. The threshold for admission should be low in children:
  • Admit all children with life-threatening features.
  • Admit children with any feature of a severe attack persisting after initial bronchodilator treatment.
  • Admit children with a moderate attack with worsening symptoms despite initial bronchodilator treatment and/or who have had a previous near-fatal asthma attack.
  • Other factors that lower the threshold for hospital admission include the infant/child having been born prematurely, any significant medical history, such as congenital heart disease, chronic lung disease of prematurity, cystic fibrosis, bronchiectasis, and immune deficiency, and the ability of the child's carers to cope with the ill child (in particular, assess the carer's experience, their level of anxiety, and the time they have available to care for the child).
• While awaiting admission to hospital:
  • Give controlled supplementary oxygen to all children with life-threatening asthma or an oxygen saturation <94% using a face mask, Venturi mask, or nasal cannulae. Adjust flow rates as necessary to maintain an oxygen saturation of 94–98% but do not delay oxygen administration in the absence of pulse oximetry.
  • Treat with a short-acting beta-₂ agonist:
    • For life-threatening or severe attacks, give nebulized salbutamol (5 mg to all children aged over 5 years, and 2.5 mg to children aged  2–5 years).  Ideally, nebulizers should be oxygen driven (flow rate of 6 L /min usually needed) to avoid worsening hypoxia. If an oxygen-driven nebulizer is unavailable, deliver by air-driven nebulizer, although be alert that oxygen desaturation may occur. Continuous nebulization is preferred in severe obstruction, but not all nebulizer systems can do this. When using intermittent nebulization, repeat salbutamol administration every 20–30 minutes. When using a continuous nebulizer, give the dose over 30–60 minutes.
    • If a nebulizer is not available, or if the attack is of mild-moderate severity, use a pressurized metered-dose inhaler with a large-volume spacer. Children under the age of three years are likely to require a face mask connected to the mouthpiece of a spacer for successful drug delivery. A short pause between puffs may be necessary to avoid hyperventilation with puffs given one at a time and inhaled with five tidal breaths. Give a puff every 30–60 seconds, up to 10 puffs. If the response is poor, give further doses while awaiting hospital admission, and switch to a nebulizer if available.
  • Monitor peak expiratory flow rate (if the child can comply) and oxygen saturation (if available) to assess response to treatment.
• If the child does not require hospital admission:
  • Use a short-acting beta-₂ agonist via a large-volume spacer to relieve acute symptoms. Give a puff every 30–60 seconds, up to 10 puffs. Each puff should be given one at a time and inhaled with five tidal breaths. Repeat every 10–20 minutes according to clinical response.
  • If the child responds favourably to bronchodilator treatment, prescribe a short-acting beta-₂ agonist and spacer device to use at home as required.
  • If the child has an existing asthma diagnosis, or if asthma is suspected (for example if wheezing has also been observed in response to triggers other than viral infection, and/or there is a personal or family history of atopy), prescribe a short course of oral prednisolone. For information on doses, see the section on Prescribing information.
  • Prescribe antibiotics if symptoms and signs suggest a bacterial infection. Amoxicillin is first-line treatment, with doxycycline an alternative for those aged 12 years and over if amoxicillin is contraindicated or not tolerated. Other alternatives include cefaclor, or a macrolide such as erythromycin, azithromycin, or clarithromycin. Duration of treatment is usually five days. For information on dosing, please see the section on Prescribing information.
  • Provide self-care advice.
    • Advise the parents/carers to use either paracetamol or ibuprofen to treat a child who is distressed due to fever. Antipyretic medications should not be used with the sole aim of reducing body temperature, and should be continued for only as long as the child appears distressed.
    • Advise the parents/carers to consider changing to the other medication if the child's distress is not alleviated, but not to give both medications simultaneously, and to only alternate the medications if the distress persists, or recurs before the next dose is due.
    • Advise them not attempt to reduce fever by under-dressing the child or with use of tepid sponging.
    • Advise them to encourage the child to take fluids regularly. For infants that are breastfed, advise continued breastfeeding.
  • For children managed at home, advise parents/carers to check on the child regularly, including through the night and to seek medical advice if they are unable to cope, or if the child deteriorates, particularly if:
    • Breathing rate increases or there are any episodes of apnoea or signs of increased effort of breathing.
    • A baby takes less than 50% of its normal feeds, or there are signs of dehydration such as dry mouth or infrequent passage of urine.
    • A baby becomes less responsive or difficult to rouse.
    • There is persistent worsening of fever.
• Follow-up the child within 48 hours of presentation, if not admitted to hospital. Follow-up all children admitted to hospital within 2 working days of discharge.
  • Review symptoms and check peak expiratory flow if the child is old enough to comply.
  • Advise the child and/or the parents/carers on recognizing symptoms of a respiratory tract infection that could trigger a further attack, as well as early signs of an attack (such as worsening symptoms or peak flow readings), and to seek medical help if symptoms are not controlled.
  • If the child or their parent/carer smokes, advise them to stop.
  • For children with mild intermittent wheeze and other respiratory symptoms that occur only with viral upper respiratory infections, consider managing without use of maintenance treatment, but plan a review after an agreed interval.
  • For children with more severe, recurrent attacks of wheezing consider prescribing a low dose inhaled corticosteroid or leukotriene receptor antagonist. 
  • For information on management of children with suspected or confirmed asthma, see the CKS topic on Asthma.

How should I manage a child with bronchiolitis?

• Determine the severity of the child's condition:
  • Note the degree of agitation and consciousness. Agitation and behavioural changes in a child may be a sign of hypoxia. 
  • Look for signs of exhaustion, cyanosis (bluish lips or extremities), and involvement of accessory muscles of respiration while the child is at rest.
  • Examine the child's chest, and record their respiratory rate, pulse, and blood pressure. 
  • Measure the child's oxygen saturation in room air using pulse oximetry (if available). 
  • Assess the child's hydration status by measuring capillary refill time, examining skin turgor and dryness of mucous membranes, and ascertaining urine output.
• Immediately refer children with bronchiolitis for emergency hospital care (usually by 999 ambulance) if there are any of the following:
  • Apnoea (observed or reported).
  • Child looks seriously unwell.
  • Severe respiratory distress, for example grunting, marked chest recession, or a respiratory rate of over 70 breaths/minute.
  • Central cyanosis. 
  • Note: Impending respiratory failure may be indicated by listlessness or decreased respiratory effort, recurrent apnoea, and/or failure to maintain adequate oxygen saturation despite oxygen supplementation.
• Consider referral for children with any of the following:
  • Respiratory rate of over 60 breaths/minute.
  • Difficulty with breastfeeding or inadequate oral fluid intake (50–75% of usual volume).
  • Clinical dehydration (indicated by reduced skin turgor and/or a capillary refill time of more than three seconds, and/or dry mucous membranes, and/or reduced urine output).
  • Persistent oxygen saturation of less than 92% when breathing air.
  • Factors which should lower the threshold for hospital admission include:
    • Chronic lung disease (including bronchopulmonary dysplasia).
    • Haemodynamically significant congenital heart disease.
    • Neuromuscular disorders.
    • Immunodeficiency.
    • Age under three months.
    • The infant having been born prematurely, particularly before 32 gestational weeks.
    • Factors that might affect a carer's ability to look after a child with bronchiolitis, such as adverse social circumstances, or concerns about the skill and confidence of the carer in looking after a child with bronchiolitis at home, or the carer being able to spot red flag symptoms.
    • Longer distance to healthcare in case of deterioration.
• While awaiting admission to hospital:
  • Give controlled supplementary oxygen to all children whose oxygen saturation is persistently less than 92%.
• If the child does not require hospital admission:
  • Advise the parents/carers that bronchiolitis is usually a self-limiting illness and that symptoms tend to peak between three and five days of onset.
  • Provide self-care advice:
    • Advise the parents/carers to use either paracetamol or ibuprofen to treat a child who is distressed due to fever. Antipyretic medications should not be used with the sole aim of reducing body temperature and should be continued for only as long as the child appears distressed.
    • Advise the parents/carers to consider changing to the other medication if the child's distress is not alleviated, but not to give both medications simultaneously, and to only alternate the medication if the distress persists, or recurs before the next dose is due.
    • Advise them not attempt to reduce fever by under-dressing the child or with use of tepid sponging.
    • Advise them to encourage the child to take fluids regularly. For infants that are breastfed, advise continued breastfeeding.
  • Advise parents/ carers to check on the child regularly, including through the night, and to seek medical advice if they are unable to cope, or if the child deteriorates, particularly if:
    • Breathing rate increases or there are any episodes of apnoea, signs of cyanosis, or increased effort of breathing (such as grunting, nasal flaring, or marked chest recession).
    • The child's fluid intake is reduced to 50–75% of normal, or there are signs of dehydration such as dry mouth or no wet nappy for 12 hours.
    • The child becomes less responsive or difficult to rouse.
    • There is persistent worsening of fever.
  • Advise the child's parents/carers not smoke in the home as this increases the risk of more severe symptoms of bronchiolitis
  • Use clinical judgement to determine whether follow-up is necessary, and if so, arrange at an appropriate interval.

How should I manage community-acquired pneumonia in children?

• Determine the severity of the child's condition:
  • Measure the child's temperature.
  • Examine the child's chest, and record their respiratory rate, pulse, and blood pressure. 
  • Measure the child's oxygen saturation in room air using pulse oximetry (if available). 
  • Note the degree of agitation and consciousness. Agitation and behavioural changes in a child may be a sign of hypoxia. 
  • Look for signs of exhaustion, cyanosis (bluish lips or extremities), and use of accessory muscles while the child is at rest.
  • Assess the child's hydration status by measuring capillary refill time, examining skin turgor and dryness of mucous membranes, and ascertaining urine output.
• Immediately refer children for emergency hospital care (usually by 999 ambulance) if there are any of the following:
  • Persistent oxygen saturation of less than 92% when breathing air.
  • Grunting, marked chest recession, or a respiratory rate of over 60 breaths/minute.
  • Cyanosis (indicated by pale/mottled/ashen/blue skin, lips or tongue).
    • Note: auscultation revealing absent breath sounds with a dull percussion note should raise the possibility of a pneumonia complicated by effusion and should trigger a referral to hospital.
  • Child looks seriously unwell, does not wake, or if roused does not stay awake, or does not respond to normal social cues.
  • A temperature of 38°C or higher in a child aged three months or less.
• Consider referral for children with any of the following:
  • A temperature of 39°C or higher in a child aged 3–6 months.
  • Tachycardia (more than 160 beats/minute in a child aged less than 1 year, more than 150 beats/minute in a child aged one to two years, and more than 140 beats/minute in a child aged two to five years).
  • Inadequate oral fluid intake (50–75% of usual volume).
  • Pallor of skin, lips or tongue reported by parent or carer.
  • Abnormal response to social cues.
  • Waking only with prolonged stimulation.
  • Decreased activity.
  • Nasal flaring.
  • Clinical dehydration (indicated by reduced skin turgor and/or a capillary refill time of more than three seconds, and/or dry mucous membranes, and/or reduced urine output).
  • Factors that should lower the threshold for hospital admission include:
    • Chronic lung disease (including bronchopulmonary dysplasia).
    • Haemodynamically significant congenital heart disease.
    • Neuromuscular disorders.
    • Immunodeficiency.
    • Age under three months.
    • The infant having been born prematurely, particularly before 32 gestational weeks.
    • Factors that might affect a carer's ability to look after a child with bronchiolitis, such as adverse social circumstances, or concerns about the skill and confidence of the carer in looking after a child with community-acquired pneumonia at home, or the carer being able to spot red flag symptoms.
    • Longer distance to healthcare in case of deterioration.
• While awaiting admission to hospital, give controlled supplementary oxygen to all children whose oxygen saturation is persistently less than 92%.
• If the child does not require hospital admission:
  • Prescribe antibiotics. All children with a clinical diagnosis of pneumonia should receive antibiotics, as bacterial and viral pneumonia cannot reliably be distinguished from each other.
    • Children aged less than two years presenting with mild symptoms of lower respiratory tract infection do not usually have pneumonia, and need not be treated with antibiotics, but should be reviewed if symptoms persist. A history of conjugate pneumococcal vaccination gives greater confidence to this decision.
    • Amoxicillin is recommended as first choice for oral antibiotic therapy. Alternatives are erythromycin, doxycycline, or clarithromycin. Macrolide antibiotics may be added at any age if there is no response to first-line empirical therapy. 
    • Offer a 5 day course of antibiotics for babies aged 1 to 2 months, and those aged over 12 years with non-severe community-acquired pneumonia without complications or underlying disease.. For doses, see the section on Prescribing information.
    • Offer a 3-day course of antibiotics for babies and children aged 3 months (corrected gestational age) to 11 years with non-severe community-acquired pneumonia without complications or underlying disease. For doses, see the section on Prescribing information.
      • Consider extending use of antibiotics beyond 3 days if the child is not clinically stable, for example, if they are in respiratory distress or their oxygen saturation levels have not improved as expected.
    • For all children and young people with community-acquired pneumonia, stop antibiotic treatment after 5 days unless microbiological results suggest a longer course is needed or the child or young person is not clinically stable.
  • Provide self-care advice:
    • Advise the parents/carers to use either paracetamol or ibuprofen to treat a child who is distressed due to fever. Antipyretic medications should not be used with the sole aim of reducing body temperature and should be continued for only as long as the child appears distressed.
    • Advise the parents/carers to consider changing to the other medication if the child's distress is not alleviated, but not to give both medications simultaneously, and to only alternate the medications if the distress persists, or recurs before the next dose is due.
    • Advise them not attempt to reduce fever by under-dressing the child or with use of tepid sponging.
    • Advise them to encourage the child to take fluids regularly. For infants that are breastfed, advise continued breastfeeding.
  • Advise the child's parents/carers not smoke in the home.
  • For children managed at home, advise parents/ carers to check on the child regularly, including through the night, and to seek medical advice if they are unable to cope, or if the child deteriorates, particularly if:
    • Breathing rate increases or there are any episodes of apnoea, signs of cyanosis, or increased effort of breathing (such as grunting, nasal flaring, or marked chest recession).
    • The child's fluid intake is reduced to 50–75% of normal, or there are signs of dehydration such as dry mouth or no wet nappy for 12 hours.
    • The child becomes less responsive or difficult to rouse.
    • There is persistent worsening of fever, or if fever does not settle within 48 hours of initiation of antibiotic treatment.
  • Arrange follow-up at an appropriate interval using clinical judgement.

Contraindications and cautions

• Do not prescribe amoxicillin to people with:
  • History of penicillin-associated hepatic dysfunction.
  • A true penicillin hypersensitivity. Gastrointestinal adverse effects alone (such as nausea, vomiting, or diarrhoea) do not constitute an allergy to penicillin.
• Prescribe amoxicillin with caution to people with:
  • Hypersensitivity to cephalosporins.
  • Chronic kidney disease (CKD) — reduce the dose if the estimated glomerular filtration rate (eGFR) is less than 10 mL/min/1.73 m².

[ABPI, 2020a; BNF for Children, 2021]

Adverse effects

• The most common adverse effects of amoxicillin includes nausea, vomiting, skin rash, and diarrhoea.
• Consider pseudomembranous colitis if a person develops severe diarrhoea during or after treatment with amoxicillin.
  • Pseudomembranous colitis is an acute, exudative colitis caused by Clostridioides difficile, a Gram-positive toxin-releasing bacillus. It often follows antibiotic treatment. For more information, see the CKS topic on Diarrhoea - antibiotic associated.
• Amoxicillin can also cause fungal infection and vaginitis.
• Anaphylaxis (delayed or immediate) is a serious but rare adverse effect of treatment with amoxicillin. For more information, see the CKS topic on Angio-oedema and anaphylaxis.
• Other potential adverse effects of co-amoxiclav 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). 

[ABPI, 2020a; BNF for Children, 2021; EMC, 2024a]

Drug interactions

Possible drug interactions with amoxicillin include:

• Allopurinol — be aware of the increased risk of rash when allopurinol is given with amoxicillin. It is not necessary to stop either drug if this occurs.
• Warfarin — monitor the international normalized ratio (INR) closely during concomitant use. Any significant changes seem to occur after 4 days of concurrent use. Adjust the warfarin dose as necessary according to the INR.
• Methotrexate — consider measuring platelet and white cell counts twice weekly for 2 weeks initially, and measure methotrexate levels if toxicity is suspected.

Dosing information

• Amoxicillin:
  
  • Age 1 month to 2 months — 125 mg 3 times daily, for 5 days. Dose can be increased if necessary up to 30 mg/kg 3 times a day.
  • 3 months to 11 months — 125 mg three times a day for 3 days. Dose can be increased if necessary up to 30 mg/kg 3 times a day.
  • 1 year to 4 years — 250 mg three times a day for 3 days. Dose can be increased if necessary up to 30 mg/kg 3 times a day.
  • 5 years to 11 years — 500 mg three times a day for 3 days. Dose can be increased if necessary up to 30 mg/kg 3 times a day (max per dose 1 g).
  • 12 years to 17 years — 500 mg three times a day for 5 days. Dose can be increased if necessary up to 1 g 3 times a day.

[BNFC, 2025; NICE, 2025]

Contraindications and cautions

• Do not prescribe cefaclor to people with:
  • Cefalosporin hypersensitivity.
• Prescribe cefaclor with caution to people with:
  • Sensitivity to beta-lactam antibacterials 
  • Chronic kidney disease (CKD) — manufacturer advises that dosage adjustments for patients with moderate or severe renal impairment are not usually required.

[BNF for Children, 2021]

Adverse effects

• The most common adverse effects of cefaclor include diarrhoea, nausea, and vomiting.
• Consider pseudomembranous colitis if a person develops severe diarrhoea during or after treatment with cefaclor.
  • Pseudomembranous colitis is an acute, exudative colitis caused by Clostridium difficile, a Gram-positive toxin-releasing bacillus. It often follows antibiotic treatment. For more information, see the CKS topic on Diarrhoea - antibiotic associated.
• Other reported adverse reactions include headache; allergic reactions including rashes, pruritus, urticaria, serum sickness-like reactions with rashes, fever and arthralgia, and anaphylaxis; Stevens-Johnson syndrome, toxic epidermal necrolysis; disturbances in liver enzymes, transient hepatitis and cholestatic jaundice; eosinophilia and blood disorders (including thrombocytopenia, leucopenia, agranulocytosis, aplastic anaemia and haemolytic anaemia); reversible interstitial nephritis, hyperactivity, nervousness, sleep disturbances, hallucinations, confusion, hypertonia, and dizziness.
• Neurotoxicity — reports have been identified in association with cephalosporin treatment. Symptoms may include encephalopathy, myoclonus and seizures. If cefaclor-associated neurotoxicity is suspected, consider discontinuing treatment.

[ABPI, 2015; BNF for Children, 2021]

Drug interactions

Possible drug interactions with cefaclor include:

• Warfarin — monitor the international normalized ratio (INR) closely during concomitant use. Adjust the warfarin dose as necessary according to the INR.
• Probenecid — The renal excretion of cefaclor is inhibited by probenecid.

[ABPI, 2015]

Dosing information

• Age 1 month to 1 year – 62.5 mg every 8 hours; doses doubled for severe infections.
• Age 1 to 5 years – 125 mg every 8 hours; doses doubled for severe infections.
• Age over 5 years – 250 mg every 8 hours; doses doubled for severe infections

[BNF for Children, 2021]

Contraindications and cautions

Do not prescribe doxycycline to:

• Children under 12 years of age.
• Girls who are pregnant or breastfeeding.
• People with:
  • Liver disease.
  • Systemic lupus erythematosus.
  • Myasthenia gravis.
  • Porphyria.

[ABPI, 2021a; BNF for Children, 2021]

Adverse effects

• Blood disorders — haemolytic anaemia, thrombocytopenia, neutropenia, eosinophilia (rare).
• Gastrointestinal — nausea, vomiting, diarrhoea (common), dyspepsia (uncommon). Abdominal discomfort, tooth discolouration, and enamel hypoplasia in children (frequency unknown).
  • Rarely: dysphagia, oesophagitis, oesophageal irritation, pseudomembranous colitis. For more information, see the CKS topic on Diarrhoea - antibiotic associated. (Advice to swallow the capsules with plenty of water, in an upright position, and well before going to bed helps to reduce the frequency of oesophagitis and oesophageal ulceration.)
• Immune system disorders – hypersensitivity common (including anaphylaxis, angioedema, exacerbation of systemic lupus erythematosus, Henoch-Schonlein purpura). Rarely drug reaction with eosinophilia and systemic symptoms (DRESS).
• Hepatic disorders – hepatotoxicity, hepatitis, jaundice, hepatic failure (frequency unknown).
• Renal disorders — blood urea increased.
• Skin — photosensitivity, rash (common).
  • Rarely: toxic epidermal necrolysis, Stevens–Johnson syndrome, erythema multiforme, exfoliative dermatitis, and fixed eruption.
• Other rare adverse effects include:
  
  • Arthralgia, myalgia.
  • Flushing.
  • Severe headache and/or visual disturbances — may be an early symptom of benign intracranial hypertension, a rare but serious adverse effect. Headache is a relatively common side effect.
  • Tinnitus.

 [BNFC, 2024; EMC, 2024b]

Drug interactions

Possible drug interactions with doxycycline include:

• Phenobarbital, carbamazepine, phenytoin, and primidone — metabolism of doxycycline may be accelerated by these drugs, leading to a reduced plasma concentration.
  • Monitor the therapeutic effect of doxycyline, as a dose increase may be necessary.
• Rifampicin — may cause a reduction in doxycycline levels, leading to undertreatment.
  • Monitor the effects of concurrent use and increase the doxycycline dosage as necessary.
• Sucralfate and antacids — can reduce the absorption of tetracyclines.
  • Advise the person taking a tetracycline to wait at least 2 hours before taking sucralfate or antacids.

[ABPI, 2021a; BNF for Children, 2021] 

Dosing information

• Age 12 to 16 years – 200 mg on first day, then 100 mg daily; severe infections, 200 mg daily.

[BNF for Children, 2021]

Contraindications and cautions

Clarithromycin

• Do not prescribe clarithromycin to people:
  • With severe hepatic impairment in combination with renal impairment.
  • Taking drugs that prolong the QT interval (for example haloperidol, sotalol, amisulpride, terfenadine, and pimozide) — macrolides can also prolong the QT interval, which is a risk factor for Torsades de pointes.
  • With hypokalaemia — due to the risk of prolongation of the QT interval.
  • With a history of QT prolongation or ventricular cardiac arrhythmia, including Torsades de pointes.
• Prescribe clarithromycin with caution to people with:
  • Hepatic impairment (or people concomitantly receiving potentially hepatotoxic drugs) — clarithromycin is mainly excreted by the liver.
  • Moderate to severe renal impairment.
    • Use half the normal dose in severe renal impairment (eGFR less than 30 mL/min). Avoid Klaricid XL^® (clarithromycin prolonged-release once daily tablets) in people with eGFR less than 30 mL/min, as the dose cannot be reduced.
  • Myasthenia gravis — macrolides may aggravate weakness symptoms.
  • Severe cardiac insufficiency, or bradycardia (less than 50 beats per minute) — increased risk of QT prolongation.

Erythromycin

• Do not prescribe erythromycin to people with
  • Porphyria.
  • A history of QT interval prolongation or ventricular cardiac arrhythmia.
  • Conditions that predispose to QT interval prolongation such as electrolyte disturbances and people taking drugs that prolong the QT interval.
• Prescribe erythromycin with caution to people with:
  • Neonate under 2 weeks (risk of hypertrophic pyloric stenosis)
  • Hepatic impairment (or people concomitantly receiving potentially hepatotoxic drugs) — erythromycin is mainly excreted by the liver.
  • Taking drugs that prolong the QT interval (for example haloperidol, sotalol, amisulpride, terfenadine [avoid use with terfenadine], and pimozide) — macrolides can also prolong the QT interval, which is a risk factor for Torsades de pointes.
  • Moderate to severe renal impairment:
    • Give a maximum dose for erythromycin of 1.5 g a day in severe renal impairment due to the risk of ototoxicity.
  • Myasthenia gravis — macrolides may aggravate weakness symptoms.
  • Conditions that predispose to QT interval prolongation.

Azithromycin

• Do not prescribe azithromycin to people:
  • With severe hepatic impairment.
  • Taking drugs that prolong the QT interval (for example haloperidol, sotalol, amisulpride, terfenadine, and pimozide) — macrolides can also prolong the QT interval, which is a risk factor for Torsades de pointes.
  • With hypokalaemia, due to the risk of prolongation of the QT interval.
  • With a history of QT prolongation or ventricular cardiac arrhythmia, including Torsades de pointes.
• Prescribe azithromycin with caution to people with:
  • Mild to moderate hepatic impairment.
  • Moderate to severe renal impairment.
  • Myasthenia gravis — macrolides may aggravate weakness symptoms.

[ABPI, 2017; ABPI, 2020b; ABPI, 2021b; MHRA, 2020; BNF for Children, 2021]

Adverse effects

• Nausea, vomiting, abdominal discomfort, and diarrhoea are the most common adverse effects of macrolides, and are milder and less frequent with clarithromycin and azithromycin than with erythromycin.
• Consider pseudomembranous colitis if a person develops severe diarrhoea during or after treatment with a macrolide.
  • Pseudomembranous colitis is an acute, exudative colitis caused by Clostridium difficile, a Gram-positive toxin-releasing bacillus. It often follows antibiotic treatment. For more information, see the CKS topic on Diarrhoea - antibiotic associated.
• Anaphylaxis is rarely associated with macrolide treatment.
• Hepatotoxicity (including cholestatic jaundice) and rash have been reported following treatment with macrolides.
• Reversible hearing loss (sometimes with tinnitus) can occur after large doses of clarithromycin (1–2 g) and erythromycin (4 g).
• Other adverse effects reported rarely or very rarely include pancreatitis, QT interval prolongation, arrhythmias, Stevens-Johnson syndrome, and toxic epidermal necrolysis.

[ABPI, 2017; ABPI, 2020b; ABPI, 2021b; MHRA, 2020; BNF for Children, 2021]

Drug interactions

Drug interactions with macrolides include:

• Carbamazepine — macrolides inhibit the cytochrome P450 enzyme CYP3A4, resulting in reduced carbamazepine metabolism.
  • Reduce the dose of carbamazepine by 30–50% during treatment with macrolides.
  • Advise the person to report symptoms of carbamazepine toxicity (such as dizziness, diplopia, ataxia, or confusion).
• Rivaroxaban — erythromycin may increase levels of rivaroxaban, increasing the risk of bleeding. 
• 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.
• Calcium channel blockers (CCB's) — due to an increased risk of hypotension, caution is advised with the concurrent use of macrolides and CCB's metabolised by CYP3A4 (such as verapamil, amlodipine, and diltiazem).
• Drugs that prolong the QT interval (such as haloperidol, sotalol, terfenadine, and pimozide) — 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 beta₂-agonists) — hypokalaemia is a risk factor for QT prolongation.
  • Seek advice from a microbiologist regarding a suitable alternative antibiotic.
• Ciclosporin — azithromycin can affect clearance of ciclosporin. If co-administration of these drugs is necessary, ciclosporin levels should be monitored and the dose adjusted accordingly.
• 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.
• Oral hypoglycaemic drugs and insulin — the concomitant use of clarithromycin and oral hypoglycaemic drugs (such as sulphonylureas) and/or insulin can result in significant hypoglycaemia. Careful monitoring of glucose levels is recommended.
• 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.
• Lomitapide — concurrent use with erythromycin increases transaminase levels and is contraindicated.
• Corticosteroids — levels of corticosteroids may be increased with erythromycin use. Monitor for corticosteroid adverse effects (such as moon face, weight gain, hyperglycaemia), and adjust the corticosteroid dose or stop the macrolide as appropriate. 

[ABPI, 2017; ABPI, 2021b; MHRA, 2020; BNF for Children, 2021; EMC, 2024c]

Dose

Clarithromycin

• Body weight under 8 kg: 7.5 mg/kg twice a day.
• Body weight 8–11 kg: 62.5 mg twice a day.
• Body weight 12–19 kg: 125 mg twice a day.
• Body weight 20–29 kg: 187.5 mg twice a day.
• Body weight 30–40 kg: 250 mg twice a day.
• Child 12–16 years: 250 mg twice daily, increased if necessary in severe infections to 500 mg twice a day.

Erythromycin

• Neonate: 3 mg/kg 4 times daily.
• Child 1 month –16 years: 3 mg/kg 4 times daily

Azithromycin

• Child over 6 months: 10 mg/kg once daily (max. 500 mg once daily), or
• Body-weight 15–25 kg: 200 mg once daily.
• Body-weight 26–35 kg: 300 mg once daily.
• Body-weight 36–45 kg: 400 mg once daily.
• Body-weight over 45 kg: 500 mg once daily.

[BNF for Children, 2021]

Contraindications and cautions

• Beta-₂ agonists should be used with caution in people with:
  • Hyperthyroidism — beta-₂ agonists may stimulate thyroid activity.
  • Diabetes mellitus — there is a rare risk of ketoacidosis (especially after intravenous beta-₂ agonist administration). Additional blood glucose measurements are recommended when treatment with a beta-₂ agonist is commenced.
  • Cardiovascular disease (including hypertension) — beta-₂ agonists may cause an increased risk of arrhythmias and significant changes to blood pressure and heart rate.
  • Susceptibility to QT-interval prolongation.
  • Hypokalaemia — plasma potassium concentration may be reduced by beta-₂ agonists (particularly high doses).
  • Convulsive disorders.

[BNF for Children, 2021]

Adverse effects

• Adverse effects of short-acting beta-₂ agonists are usually dose related and include:
  • Fine tremor — occurs particularly in the hands and is usually worse in the first few days of treatment.
  • Palpitations.
  • Headache.
  • Seizure.
  • Anxiety.
  • Hypokalaemia.
  • Cardiac arrhythmia and paradoxical bronchospasm (rare).
• Advise people who are using terbutaline turbohaler to rinse their mouth with water after each use. A fraction of the dose will always be deposited in the mouth and rinsing will minimize the amount of drug that is absorbed systemically.
• The risk of adverse events may be higher in children with a predisposition to arrhythmias and in children with pre-existing cardiovascular disease, or hypertension.

[ABPI, 2018a; ABPI, 2018b; BNF for Children, 2021]

Drug interactions

Drug interactions with short-acting beta-2 agonists include:

• Corticosteroids, diuretics, and xanthine derivatives such as theophylline — monitor potassium levels.
  • Beta-₂ agonists can cause hypokalaemia (particularly at high doses), and this can be increased by other potassium-depleting drugs, such as corticosteroids, loop diuretics, and xanthine derivatives.
• Digoxin — monitor potassium levels and be alert to signs of digoxin toxicity, such as loss of appetite, nausea, vomiting, bradycardia, visual disturbance, and drowsiness.

[ABPI, 2018a; ABPI, 2018b; BNF for Children, 2021]

Dosing information

• Short-acting beta-₂ agonists (SABAs), such as salbutamol and terbutaline, have a rapid onset of action (5 minutes) and their effects last for up to 4 hours.
  • Doses vary depending on the child's age, response to treatment and the preparation prescribed. For more details, see the British National Formulary and the manufacturers' Summaries of Product Characteristics.
  • Use of a SABA as required is at least as effective as regular (four times daily) use. 

[BNF for Children, 2021]