Previous changes

December 2023 — minor update. Information on possible neurological adverse effects of cefalexin added in line with updated SPC.

April 2023 — minor update. Typographical error corrected in the section on prophylaxis treatment for amoxicillin age range. 

August 2022 — minor update. This topic has been updated with the NICE quality standards covering Urinary tract infection in children and young people.

July 2022 — minor update. The section on diagnosis has been updated in line with the updated NICE guideline Urinary tract infection in under 16s: diagnosis and management.

February 2019 — reviewed. A literature search was conducted in February 2019 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. Some minor structural changes have been made, and management recommendations have been updated in line with the latest NICE guidelines. 

October to November 2017 — reviewed and updated. A literature search was conducted in October 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.

September 2017 — minor update. Recommendations to delay the decision to treat children aged between 3 months and 3 years until the results of urine culture and routine microscopy are available removed according to updates to the NICE guideline. 

July 2015 — minor update. A link to the CKS topic on Analgesia has been added to the Prescribing Information section.

November 2014 — minor update to the contraindication of use of nitrofurantoin in children with an estimated glomerular filtration rate (eGFR) of less than 45 mL/minute/1.73 m².

December 2012 to May 2013 — reviewed. A literature search was conducted in November 2012 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of the topic.

There have been changes to the recommendations on:

• When to send a urine specimen for culture.
• Antibiotic options for treatment of upper UTI.
• Use of prophylactic antibiotics.
• Referral for further investigation.

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. Prescriptions have been updated to reflect the revised dosing. 

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

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

August 2009 — minor update. Advice from the National Institute for Clinical Excellence guideline on when to suspect child maltreatment has been added to this topic. 

January 2009 — minor update to reflect guidance from the Health Protection Agency (HPA) to avoid broad spectrum antibiotics (e.g. co-amoxiclav, quinolones, and cephalosporins) when narrow spectrum antibiotics remain effective, as broad spectrum antibiotics increase the risk of Clostridium difficile, MRSA, and resistant UTIs. 

September 2008 — minor correction to the Changes section. 

December 2007 to April 2008 — converted from CKS guidance to CKS topic structure. The evidence-base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence.

The main changes to the recommendations for managing urinary tract infections in infants and children are:

• Duration of treatment of lower UTI/cystitis is 3 days.
  • However, CKS recommends that nitrofurantoin be prescribed for 7 days as its licence specifies, and the NICE guideline does not specifically recommend prescribing outside the terms of the licence.
• Duration of treatment of upper UTI/acute pyelonephritis is 7–10 days.

In comparison with previously accepted good practice the NICE guidelines recommend considerably narrower indications for imaging investigations and long term prophylactic antibiotics following a UTI. However, as imaging investigations and prophylactic antibiotics would normally be arranged by (or after consultation with) a specialist, their indications are outside the scope of this CKS topic.

January to March 2006 — reviewed. Validated in June 2006 and issued in July 2006.

November 2005 — minor technical update. 

January 2002 — written replacing sections of previous guidance on UTI (lower) — acute and UTI (lower) — recurrent. Issued in April 2002.

New evidence

No new evidence published since 1 March 2024.

Evidence-based guidelines

No new evidence-based guidelines published since 1 March 2024.

HTAs (Health Technology Assessments)

No new HTAs since 1 March 2024.

Economic appraisals

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

Systematic reviews and meta-analyses

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

Primary evidence

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

New policies

No new national policies or guidelines since 1 March 2024.

New safety alerts

No new safety alerts since 1 March 2024.

Changes in product availability

• New Product fomicyt (fosfomycin) 40 mg/ml powder for solution for infusion is licensed in all age groups for the treatment of complicated urinary tract infections. See more here.

Basis for recommendation

These recommendations are based on the National Institute for Health and Care Excellence (NICE) guideline Urinary tract infection in under 16s: diagnosis and management [NICE, 2022b], and the Public Health England (PHE) guideline Diagnosis of urinary tract infections: quick reference tool for primary care [PHE, 2020]. 

Interpreting urine analysis

Table 2. Interpreting microscopy results

Table 3. Urine dipstick testing strategies for children aged over 3 months.

Collection and storage of urine samples

• Collect the urine sample before starting empirical antibiotic treatment [NICE, 2022b]. 
• In infants and toddlers, obtain a clean catch urine (CCU) sample — gentle suprapubic cutaneous stimulation using gauze soaked in cold fluid helps trigger voiding [PHE, 2020; NICE, 2022b]. 
  • Potties cleaned in hot water with washing-up liquid may be used. 
  • Other non-invasive methods include urine collection pads.
  • Do not use cotton wool balls, gauze, or sanitary towels.
• When it is not possible or practical to collect urine by non-invasive methods, catheter samples or suprapubic aspiration (SPA) should be used.
  • Before SPA is attempted, ultrasound guidance should be used to demonstrate the presence of urine in the bladder. 
• Avoid delay when collecting and testing the urine sample — if the sample cannot be collected at the consultation, advise the parents or carers to collect and return the urine sample as soon as possible, ideally within 24 hours.
• Do not delay treatment in a child with a high risk of serious illness if a urine sample cannot be obtained [NICE, 2022b].
• Specimens should be transported and processed with 4 hours unless boric acid preservative is used — if this is not possible it should be refrigerated at 4°C [PHE, 2020; NICE, 2022b]. 
  • Urine that has been refrigerated at 4°C for 24 hours remains suitable for culture.
  • If the sample is preserved with boric acid, it can be stored at room temperature prior to transport. Urine preserved with boric acid remains suitable for culture and microscopy for up to 96 hours.
  • Note: boric acid may be inhibitory to some organisms and may inhibit tests for leukocyte esterase. It is essential to follow the manufacturer’s instructions regarding appropriate sample volumes in boric acid containers.

Basis for recommendation

These recommendations are based on the National Institute for Health and Care Excellence (NICE) guidelines Urinary tract infection in under 16s: diagnosis and management [NICE, 2022b], Fever in under 5s: assessment and initial management [NICE, 2021], and the Public Health England (PHE) guideline Diagnosis of urinary tract infections: quick reference tool for primary care [PHE, 2020].

Basis for recommendation

These recommendations are based on the British Medical Journal (BMJ) best practice guide Urinary tract infections in children [BMJ, 2023], and the National Institute for Health and Care Excellence (NICE) guideline Child maltreatment: when to suspect maltreatment in under 18s [NICE, 2017].

How should I manage non-reccurent urinary tract infection in an infant or child?

• If the child has been assessed at high risk of serious illness, refer urgently to secondary care.
• If UTI is suspected in children aged under 3 months — refer urgently to a paediatric specialist for treatment with parenteral antibiotics. 
• For children aged 3 months or older with acute pyelonephritis/upper UTI: 
  • Consider referral to a paediatric specialist. Use clinical judgement to determine whether this is necessary.
  • Start oral antibiotic treatment with cefalexin or, only if culture results are available and susceptible, co-amoxiclav.
    • If culture results show that the causative organism is resistant to the initially prescribed antibiotic, switch to an alternative.
    • Infants and children who are already receiving prophylactic antibiotics, should be treated with an alternative antibiotic.
  • Reassess if symptoms worsen at any time or do not start to improve within 48 hours of treatment.
    • Consider Differential diagnosis; signs or symptoms suggestive of a more serious illness or condition; and previous antibiotic use, which may have led to resistant bacteria.
    • Arrange an ultrasound of the urinary tract to identify structural abnormalities such as obstruction and to ensure prompt management.
    • Consider referral to a paediatric specialist.
• For all children aged 3 months or older with cystitis/lower UTI: 
  • Start oral antibiotic treatment — first-line options include trimethoprim (if there is a low risk of resistance), or nitrofurantoin (if eGFR is 45ml/minute or more). 
    • If culture results show that the causative organism is resistant to the initially prescribed antibiotic, switch to an alternative.
    • Infants and children who are already receiving prophylactic antibiotics, should be treated with an alternative antibiotic.
  • Second-line options (if there is no improvement in UTI symptoms 48 hours after starting first-line treatment, or first choice is not suitable) include nitrofurantoin (if eGFR is 45ml/minute or more) if it has not been used as a first-line option (see above), amoxicillin (only if culture results available and susceptible), or cefalexin.
  • Reassess if symptoms worsen at any time or do not start to improve within 48 hours of treatment.
    • Consider Differential diagnosis; signs or symptoms suggestive of a more serious illness or condition; and previous antibiotic use, which may have led to resistant bacteria.
    • Arrange an ultrasound of the urinary tract to identify structural abnormalities such as obstruction and to ensure prompt management.
    • Send a urine sample for culture and susceptibility testing if not previously done, and review treatment when results become available.
• Arrange imaging when appropriate, including for atypical UTI.
  • Arrange an ultrasound of the urinary tract:
    • During the acute infection in all children with atypical infection.
    • Within 6 weeks, for all children younger than 6 months of age with first-time UTI that responds to treatment.
    • In babies and children with a non-E. coli UTI that is responding well to antibiotics and has no other features of atypical infection, a non-urgent ultrasound can be requested, to happen within 6 weeks.
    • Infants and children with abnormal imaging results should be assessed by a paediatric specialist.
  • Ensure that a dimercaptosuccinic acid scintigraphy (DMSA) scan to detect renal parenchymal defects is carried out within 4–6 months following the acute infection in all children aged under 3 years with atypical UTI.
    • This investigation should be arranged by paediatric specialists when appropriate. 
    • If the baby or child has a subsequent UTI while waiting for a DMSA scan, review the timing of the scan and consider doing it sooner.
    • Infants and children with abnormal imaging results should be assessed by a paediatric specialist. 
  • Atypical UTI is indicated by: 
    • Poor urine flow.
    • Abdominal or bladder mass.
    • Raised creatinine.
    • Sepsis.
    • Failure to respond to treatment with suitable antibiotics within 48 hours.
    • Infection with non-E. coli organisms.
• If dysfunctional elimination syndromes and/or constipation are suspected, these should be addressed. 
  • For more information, see the CKS topic on Constipation in children. 
• Ensure that all children with UTI with an antenatally diagnosed renal abnormality and/or hypertension have received follow-up with a paediatric nephrologist. 
  • Use clinical judgement to determine whether those with a family history of vesicoureteric reflux or renal disease require secondary care follow-up.
• Provide the child, parents, and carers (as appropriate) with information and advice.

What information and advice should I provide to a child with a UTI?

• Provide the child, parents, and carers (as appropriate) with information and advice.
  • Advise the parents or carers to bring the child for reassessment if they do not respond to treatment within 24–48 hours, symptoms worsen, or they become systemically unwell. 
    • At this follow-up, if an alternative diagnosis is not made, a urine sample should be sent for culture if this has not already been carried out. 
  • Outline the need for treatment, treatment options, the importance of completing any course of treatment, the nature of and reason for any urinary tract investigation, prognosis, and reasons and arrangements for long-term management if required.
  • Advise on the use of paracetamol for pain relief where required. For information on prescribing, see the section on Paracetamol in the CKS topic on Analgesia - mild-to-moderate pain. 
  • Ensure that they are aware of the possibility of a UTI recurring and the need to seek prompt treatment from a healthcare professional should this occur. Advise on preventing and recognizing recurrence.
    • Advise on the prompt recognition of symptoms. 
    • Advise on adequate fluid intake to avoid dehydration. 
    • Advise that children who have had a UTI should have ready access to clean toilets when required and should not be expected to delay voiding. 
  • Advise on possible adverse effects of antibiotics, particularly diarrhoea and nausea.
    • Advise that nausea with vomiting may also be an indication of worsening pyelonephritis.
  • Patient information leaflets on UTI in children are available at NHS.

How should I manage recurrent UTI in children?

• Recurrent urinary tract infection (UTI) is defined as:
  • Two or more episodes of UTI with acute pyelonephritis/upper urinary tract infection, or
  • One episode of UTI with acute pyelonephritis/upper urinary tract infection plus one or more episode of UTI with cystitis/lower urinary tract infection, or
  • Three or more episodes of UTI with cystitis/lower urinary tract infection.
• If the child has been assessed at high risk of serious illness, refer urgently to secondary care.
• Refer all children with recurrent UTI to a paediatric specialist for assessment and investigations.
• For children aged 3 months or over with recurrent UTI, ensure that any current UTI has been adequately treated, then take specialist advice and consider a trial of daily antibiotic prophylaxis, if behavioural and personal hygiene measures alone are not effective or not appropriate. Take account of:
  • Underlying causes following specialist assessment and investigations.
  • The uncertain evidence of the benefit of antibiotic prophylaxis for reducing the risk of recurrent UTI and the rate of deterioration of renal scars.
  • The severity and frequency of previous symptoms.
  • The risks of long-term antibiotic use.
  • The risk of developing complications.
  • Previous urine culture and susceptibility results.
  • Previous antibiotic use, which may have led to resistant bacteria.
  • Preferences for antibiotic use.
• When a trial of daily antibiotic prophylaxis is given, provide advice about:
  • The risk of resistance with long-term antibiotics, which means they may be less effective in the future.
  • Possible adverse effects of long-term antibiotics.
  • Returning for review within 6 months.
  • Seeking medical help if there are symptoms of an acute UTI.
• Arrange an ultrasound of the urinary tract:
  • During the acute infection for children aged under 6 months with recurrent UTI.
  • Within 6 weeks for children aged 6 months and over with recurrent UTI.
• Ensure that a dimercaptosuccinic acid scintigraphy (DMSA) scan to detect renal parenchymal defects is carried out within 4–6 months following the acute infection in all children with recurrent UTI.
  • This investigation should be arranged by paediatric specialists when appropriate. 
•  Some children and young people under 16 years with recurrent UTI may wish to try cranberry products with the advice of a paediatric specialist (evidence of benefit is uncertain). 
  • Advise about the sugar content of cranberries and it should be considered as part of the child's daily sugar intake.

Dose

Treatment

• For the treatment of lower UTI, prescribe trimethoprim at the following doses, for children aged:
  • 3–5 months — 4 mg/kg (maximum 200 mg per dose) or 25 mg twice a day for 3 days.
  • 6 months to 5 years — 4 mg/kg (maximum 200 mg per dose) or 50 mg twice a day for 3 days.
  • 6 –11 years — 4 mg/kg (maximum 200 mg per dose) or 100 mg twice a day for 3 days.
  • 12–15 years — 200 mg twice a day for 3 days.

Prophylaxis

• As a prophylactic, prescribe trimethoprim at the following doses, for children aged:
  • 3–5 months — 2 mg/kg at night (maximum 100 mg per dose) or 12.5 mg at night.
  • 6 months to 5 years — 2 mg/kg at night (maximum 100 mg per dose) or 25 mg at night.
  • 6–11 years — 2 mg/kg at night (maximum 100 mg per dose) or 50 mg at night.
  • 12–15 years — 100 mg at night.

[NICE, 2019b; NICE, 2022c]

Contraindications and cautions

• Do not prescribe trimethoprim to children:
  • With blood dyscrasias.
  • Severe hepatic insufficiency.
  • Under the age of 4 months.
  • Hypersensitivity to trimethoprim or any other constituents of the medication.
• Prescribe trimethoprim with caution in people with: 
  • Impaired renal function. 
    • Prescribe half the normal dose after 3 days if eGFR (estimated glomerular filtration rate) is 15-30 mL/min/1.73m².
    • Prescribe half the normal dose if eGFR is less than 15 mL/min/1.73m².
  • Hyperkalaemia, or taking medication that is known to cause hyperkalaemia — monitor electrolytes closely. 
  • Acute porphyria. 
  • Folate deficiency or predisposition to folate deficiency — administration of a folate supplement should be considered. 

[BNFC, 2024; MHRA, 2024]

Adverse effects

• Blood disorders — leukopenia, megaloblastic anaemia, thrombocytopenia, agranulocytosis, and methaemoglobinaemia.
• Gastrointestinal — nausea, diarrhoea, and vomiting (common).
• Nervous system — headache (common), dyskinesias, tremor, ataxia, dizziness, syncope, vertigo, tinnitus, and aseptic meningitis (very rare),
• Skin and subcutaneous tissue — pruritus and skin rashes (common).
  • Rarely: photosensitivity, exfoliative dermatitis, fixed drug eruption, erythema multiforme, erythema nodosum, Stevens-Johnson Syndrome, toxic epidermal necrolysis, bullous dermatitis, purpura, and angioedema.
• Other adverse effects include:
  • Anaphylaxis.
  • Hyperkalaemia (very common, particularly in HIV patients), hypoglycaemia, and hyponatraemia (very rare). 
  • Liver enzyme disturbances, and cholestatic jaundice.
  • Myalgia and arthralgia.
  • Raised serum creatinine.
  • Uveitis.

[BNFC, 2024; MHRA, 2024]

Drug interactions

• Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-II receptor antagonists (AIIRAs) — there may be an increased risk of hyperkalaemia with the concurrent use of these drugs and trimethoprim. Monitor potassium concentrations. 
• Azathioprine and mercaptopurine — increased risk of haematological toxicity particularly if used for extended periods of time. Monitor the full blood count routinely. 
• Ciclosporin — serum creatinine levels may be increased. Possible increased risk of nephrotoxicity. Monitor ciclosporin concentrations and renal function closely. 
• Clozapine — both clozapine and trimethoprim can cause blood dyscrasias. Concurrent use is contraindicated. 
• Coumarins (warfarin) — the anticoagulant effect of coumarins may be potentiated.
• Digoxin — digoxin levels may be increased if taken with trimethoprim. Monitor for digoxin adverse effects and adjust the dose accordingly. 
• Diuretics — hyperkalaemia may be exacerbated by concomitant administration of diuretics, particularly potassium-sparing diuretics and/or thiazide diuretics and eplerenone.
• Methotrexate — there is an increased risk of haematologic adverse effects. Several cases of bone marrow suppression have been reported (some fatal). Full blood count should be monitored routinely.
• Phenytoin — phenytoin levels may be increased if taken with trimethoprim. Monitor phenytoin levels and adjust the dose accordingly. 
• Repaglinide — exposure to repaglinide is slightly increased. The manufacturer advises against concurrent use. 
• 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 is a teratogenic risk in the first trimester of pregnancy. The manufacturer advises that it should not be used in women who are pregnant.
  • Trimethoprim use during the first trimester may increase the risk of certain congenital malformations due to folate antagonistic effects — where possible, first-trimester use of trimethoprim should be avoided, particularly by those at risk of folic acid deficiency or those who are taking other folate antagonists. There is no evidence that trimethoprim causes harm beyond the first trimester and it may be used where clinically indicated.
  • If trimethoprim is indicated during the first trimester, concomitant folate supplementation (folic acid 5 mg once daily) is recommended. 

Breastfeeding

• Trimethoprim is excreted in breast milk, but is not known to be harmful in short-term use.

[UKTIS, 2024; BNFC, 2024; MHRA, 2024]

Dose

Treatment

• For treatment of lower UTI prescribe nitrofurantoin at the following doses, for children aged: 
  • 3 months to 11 years — 750 micrograms/kg four times a day for 3 days.
  • 12 –15 years — 50 mg four times a day or 100 mg modified-release twice a day for 3 days.

Prophylaxis 

• As a prophylactic, prescribe nitrofurantoin at the following doses, for children aged:
  • 3 months to 11 years — 1 mg/kg at night.

[NICE, 2019b; NICE, 2022c]

Contraindications and cautions

• Do not prescribe nitrofurantoin in people with:
  • Acute porphyria. 
  • Renal impairment — eGFR (estimated glomerular filtration rate) less than 45 mL/minute/1.73 m². 
    • A short course of up to 7 days may be used if the eGFR is 30–44 mL/minute/1.73 m² and a urinary tract infection has suspected or proven multi-drug resistance, when the benefits of nitrofurantoin are considered to outweigh the risks of adverse effects. 
  • Glucose-6-phosphate dehydrogenase deficiency. 
• Prescribe nitrofurantoin with caution in people with: 
  • Anaemia.
  • Debilitating conditions.
  • Diabetes mellitus.
  • Electrolyte imbalance.
  • Hepatic impairment. 
  • Pulmonary disease.
  • Peripheral neuropathy or susceptibility to peripheral neuropathy — treatment should be stopped at the first signs of neural involvement (paraesthesia).
  • Vitamin B (particularly folate) deficiency. 

[EMC, 2023a; BNFC, 2024]

Adverse effects

• Blood and lymphatic system — aplastic anaemia (rare), leukopenia, megaloblastic anaemia, thrombocytopenia, agranulocytosis, and methaemoglobinaemia.
• Gastrointestinal — nausea, diarrhoea, vomiting, and abdominal pain.
• Hepatobiliary disorders — chronic active hepatitis (fatalities have been reported), hepatic necrosis, autoimmune hepatitis, and cholestatic jaundice.
• Nervous system — benign intracranial hypertension, peripheral neuropathy, nystagmus, vertigo, dizziness, headache, and drowsiness. 
• Respiratory, thoracic and mediastinal disorders — pulmonary fibrosis, possible association with lupus-erythematous-like syndrome, acute pulmonary reactions, subacute pulmonary reactions, chronic pulmonary reactions, cough, and dyspnoea.
• Skin and subcutaneous tissue — drug rash with eosinophilia and systemic symptoms (DRESS syndrome), lupus-like syndrome associated with pulmonary reaction, exfoliative dermatitis and erythema multiforme (including Stevens-Johnson Syndrome), maculopapular, erythematous or eczematous eruptions, cutaneous vasculitis, urticaria, rash, and pruritus, and transient alopecia.
• Other adverse effects include:
  • Asthenia, fever, chills, drug fever, and arthralgia.
  • Collapse and cyanosis.
  • Psychotic reactions, depression, and euphoria.
  • Urine discolouration (yellow or brown).
• Note: the Medicines and Healthcare products Regulatory Agency (MHRA) has issued a reminder of the risks of pulmonary and hepatic adverse drug reactions associated with nitrofurantoin. It reminds healthcare professionals to [MHRA, 2023]: 
  • Advise patients and caregivers to be vigilant for new or worsening respiratory symptoms while taking nitrofurantoin, and promptly investigate any symptoms that may indicate a pulmonary adverse reaction.
  • Increase vigilance for acute pulmonary reactions in the first week of treatment.
  • Closely monitor patients on long-term therapy for new or worsening respiratory symptoms.
  • Discontinue treatment immediately if new or worsening symptoms of pulmonary damage occur.
  • Be vigilant for symptoms and signs of liver dysfunction in patients taking nitrofurantoin for any duration, particularly with long-term use, and monitor patients periodically for signs of hepatitis and for changes in biochemical tests that would indicate hepatitis or liver injury.
  • Use caution when prescribing to patients with pulmonary disease that may mask the signs and symptoms of adverse reactions.
  • Advise patients to read carefully the advice in the patient information leaflet about symptoms of possible pulmonary and hepatic reactions and to seek medical advice if they experience these symptoms. 
  • Report suspected adverse drug reactions (ADRs) to the Yellow Card scheme.

[EMC, 2023a; BNFC, 2024]

Drug interactions

• Alkalizing agents (for example, potassium citrate and sodium bicarbonate) — efficacy of nitrofurantoin may be decreased, although there is a lack of evidence to confirm this. Be alert for reduced efficacy. 
• Clozapine — both clozapine and nitrofurantoin may cause blood dyscrasias. If concurrent use is necessary, increase the frequency of full blood count monitoring.
• Magnesium trisilicate — absorption of nitrofurantoin may be reduced. Monitor response. 
• Quinolone antibiotics (for example, ciprofloxacin) — quinolones and nitrofurantoin are antagonists in vitro, but the clinical importance is uncertain.  
• 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

• Nitrofurantoin is not known to be harmful in pregnancy, however, the BNFC recommends that nitrofurantoin should be avoided at term, because of the risk of neonatal haemolysis.

Breastfeeding

• Nitrofurantoin is excreted in small amounts in breastmilk. Avoid breastfeeding during treatment with nitrofurantoin if the newborn is glucose-6-phosphate dehydrogenase deficient.

[EMC, 2023a; BNFC, 2024]

Dose

Treatment

• As a treatment for upper UTI prescribe cefalexin at the following doses, for children aged: 
  • 3–11 months — 12.5 mg/kg or 125 mg twice a day for 7–10 days (25 mg/kg two to four times a day [maximum 1 g four times a day] for severe infections).
  • 1–4 years — 12.5 mg/kg twice a day or 125 mg three times a day for 7–10 days (25 mg/kg two to four times a day [maximum 1 g four times a day] for severe infections).
  • 5 –11 years — 12.5 mg/kg twice a day or 250 mg three times a day for 7–10 days (25 mg/kg two to four times a day [maximum 1 g four times a day] for severe infections).
  • 12–15 years — 500 mg two to three times a day (up to 1 g to 1.5 g three to four times a day for severe infections) for 7–10 days.
• As a treatment for lower UTI prescribe cefalexin at the following doses, for children aged:
  • 3–11 months — 12.5 mg/kg or 125 mg twice a day for 3 days.
  • 1–4 years — 12.5 mg/kg twice a day or 125 mg three times a day for 3 days.
  • 5–11 years — 12.5 mg/kg twice a day or 250 mg three times a day for 3 days.
  • 12–15 years — 500 mg twice a day for 3 days.

Prophylaxis

• As a prophylactic, prescribe cefalexin to children aged 3 months to 15 years — 12.5 mg/kg at night (maximum 125 mg per dose).

 [NICE, 2019a; NICE, 2019b; NICE, 2022c]

Contraindications and cautions

• Do not prescribe cefalexin to women with:
  • A known allergy to the cephalosporin group of antibiotics or a history of immediate hypersensitivity to penicillin and other beta-lactams.
• Prescribe cefalexin with caution to women with:
  • Sensitivity to penicillin and other beta-lactams — up to 10% of penicillin-sensitive people will also be allergic to first- and early second-generation cephalosporins and 2-3% for third-generation cephalosporins. 

[BNFC, 2024]

Adverse effects

• Gastrointestinal — diarrhoea (most common), nausea, vomiting, abdominal pain (common).
• Nervous system — headache and dizziness (common).
  • Tremor, myoclonia, convulsions, and encephalopathy have also been reported — most cases occurred in patients with renal impairment on doses above the recommended maximum and resolved following discontinuation. 
• Psychiatric — hallucinations, confusion, agitation.
• Skin – rash urticaria (common), angioedema, erythema multiforme, severe cutaneous adverse reactions (SCARs), Stevens-Johnson syndrome and toxic epidermal necrolysis (exanthematic necrolysis) (rare).
• Other adverse effects include: 
  • Anaphylaxis (uncommon).
  • Arthralgia and myalgia.
  • Eosinophilia, leucopoenia, neutropenia, thrombocytopenia (common), agranulocytosis, and haemolytic anaemia (rare). 
  • Fatigue. 
  • Genital and anal pruritus.
  • Hepatitis (transient) and cholestatic jaundice.
  • Increased risk of infection.
  • Interstitial nephritis (rarely).
  • Joint disorders.
  • Nephritis tubulointerstitial (rare)
  • Pseudomembranous colitis (for more information, see the CKS topic on Diarrhoea - antibiotic associated).
  • Vaginal discharge.

[BNFC, 2024; EMC, 2024]

Drug interactions

• Aminoglycosides (for example gentamicin) — possible increased risk of nephrotoxicity. Routine renal monitoring for the aminoglycoside is usually adequate.
• Oral anticoagulants (warfarin and phenindione) — cefalexin may enhance the anticoagulant effect. Monitor the international normalized ratio (INR) closely during concomitant use. 
• Probenecid — renal excretion of cefalexin is inhibited. However, no dose adjustment is normally required.
• Voclosporin — possible increased risk of nephrotoxicity. If concurrent use is unavoidable, monitor renal function more frequently.
• 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

• Cefalexin is not known to be harmful in pregnancy.

Breastfeeding

• Cefalexin is present in small amounts in breastmilk, but it is appropriate to use. 

[BNFC, 2024]

Dose

• For upper UTI prescribe co-amoxiclav at the following doses, for children aged: 
  • 3 –11 months — 0.25 mL/kg of 125/31 suspension three times a day for 7–10 days (dose doubled in severe infection).
  • 1–5 years — 0.25 mL/kg of 125/31 suspension or 5 ml of 125/ 31 suspension three times a day for 7–10 days (dose doubled in severe infection).
  • 6 –11 years — 0.15 mL/kg of 250/62 suspension or 5 ml of 250/ 62 suspension three times a day for 7–10 days (dose doubled in severe infection).
  • 12–15 years — 250/125 mg or 500/125 mg three times a day for 7–10 days.

[NICE, 2019a]

Contraindications and cautions

• Do not prescribe co-amoxiclav in people with:
  • A true penicillin allergy — allergic reactions to penicillins occur in 1–10% of exposed individuals; anaphylactic reactions occur in fewer than 0.05% of treated patients.
    • Gastrointestinal adverse effects alone (for example nausea, vomiting, or diarrhoea) do not constitute an allergy to penicillin. See the CKS topic on Angio-oedema and anaphylaxis for more information.
  • A history of co-amoxiclav- or penicillin-associated jaundice or hepatic dysfunction.
  • A history of a severe immediate hypersensitivity reaction (for example, anaphylaxis) to another beta-lactam agent (for example, a cephalosporin).
• Prescribe co-amoxiclav with caution in people with:
  
  • Hepatic impairment — monitor at regular intervals.
  • Chronic kidney disease (CKD) — reduce the dose if the creatinine clearance is 30 mL/minute or less.
  • Acute lymphocytic leukaemia, chronic lymphocytic leukaemia, cytomegalovirus infection, glandular fever — increased risk of erythematous rashes.

[EMC, 2023b; BNFC, 2024]

Adverse effects

• Gastrointestinal — diarrhoea, nausea and vomiting (common), vomiting (very common).
  • Very rarely: antibiotic-associated colitis.
• Nervous system — headache, dizziness (uncommon).
• Skin — skin rash, urticaria and pruritus (uncommon), drug reaction with eosinophilia and systemic symptoms (DRESS) (frequency unknown).
  • Very rarely: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous and exfoliative dermatitis, acute generalised exanthematous pustulosis (AGEP), Drug reaction with eosinophilia and systemic symptoms (DRESS), linear IgA disease.
• Other rare, or very rare adverse effects include:
  • Hepatitis, cholestatic jaundice.
  • Hyperactivity, convulsions.
  • Hypersensitivity reactions (serious and occasionally fatal).  
  • Interstitial nephritis.
  • Kounis syndrome. 
  • Leucopoenia, thrombocytopenia, haemolytic anaemia.

[EMC, 2023b; BNFC, 2024]

Drug interactions

• Allopurinol — concomitant use of allopurinol and amoxicillin may increase the incidence of skin rashes.
• Methotrexate — co-amoxiclav may reduce methotrexate clearance, causing an increased risk of toxicity.
  • For people on high dose methotrexate, standard routine monitoring will identify any decreases in elimination, which should be managed according to local guidelines/protocols.
  • For people on low dose methotrexate, consult local or national guidelines/protocols for recommendations on appropriate monitoring and management.
• Mycophenolate mofetil — reduction in the level of active metabolite may occur when given with co-amoxiclav. Monitor mycophenolate efficacy.
• Oral anticoagulants (warfarin, phenindione) — prolongation of prothrombin time has been reported. 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

• Co-amoxiclav is not known to be harmful in pregnancy.

Breastfeeding

• Trace amounts of co-amoxiclav are found in breastmilk, but it is appropriate for use in women who are breastfeeding. However, the manufacturer advises that co-amoxiclav should only be used during breastfeeding after a benefit/risk assessment.

[EMC, 2023b; BNFC, 2024]

Dose

Treatment

• As a treatment for lower UTI prescribe amoxicillin at the following doses, for children aged: 
  • 1–11 months — 125 mg three times a day for 3 days
  • 1–4 years — 250 mg three times a day for 3 days.
  • 5–15 years — 500 mg three times a day for 3 days.

Prophylaxis

• As a prophylactic, prescribe amoxicillin at the following doses, for children aged:
  • 3 months to 11 months — 62.5 mg at night.
  • 1–4 years — 125 mg at night.
  • 5–15 years — 250 mg at night.

[NICE, 2019b; NICE, 2022c]

Contraindications and cautions

• Do not prescribe amoxicillin in people with:
  • A true penicillin allergy — allergic reactions to penicillins occur in 1–10% of exposed individuals. Anaphylactic reactions occur in fewer than 0.05% of treated people.
  • Hypersensitivity to cephalosporins. 
• Prescribe amoxicillin with caution to people with:
  • Renal impairment — reduce the dose of amoxicillin in severe renal impairment. 
  • Cytomegalovirus — there is an increased risk of erythematous rashes.  
  • Glandular fever (infectious mononucleosis) — erythematous rashes are common following the use of amoxicillin.  
  • Acute lymphocytic leukaemia and chronic lymphocytic leukaemia — increased risk of erythematous rashes.

[EMC, 2023c; BNFC, 2024]

Adverse effects

• Gastrointestinal — nausea and diarrhoea, vomiting (common) antibiotic-associated colitis (uncommon).
• Skin and subcutaneous tissue — skin rash (common), urticaria and pruritus (uncommon).
  • Very rarely: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous and exfoliative dermatitis, acute generalised exanthematous pustulosis, severe cutaneous adverse reactions (SCARs), and drug reaction with eosinophilia and systemic symptoms (DRESS).
• Other very rare adverse effects include:
  • Angioedema (rare)
  • Arthralgia (uncommon).
  • Hepatitis and cholestatic jaundice (rare).
  • Hyperkinesia, dizziness, and convulsions.
  • Interstitial nephritis.
  • Thrombocytopenia (common), leucopoenia (uncommon), agranulocytosis, and haemolytic anaemia (rare).
  • Severe allergic reactions.

[EMC, 2023c; BNFC, 2024]

Drug interactions

• Allopurinol — increased risk of rash when allopurinol is given with amoxicillin. It is not necessary to avoid concurrent use.
• Methotrexate — amoxicillin may reduce methotrexate clearance, causing an increased risk of toxicity. 
  • Standard routine monitoring of high-dose methotrexate will identify any problems, which should be managed according to local guidelines/protocols.
  • Consult local or national guidelines/protocols for people on low-dose methotrexate. 
• Mycophenolate mofetil— amoxicillin reduces exposure to mycophenolate. Monitor for efficacy.
• Coumarin anticoagulants (warfarin and phenindione) — INR may be increased. Monitor INR within 3 days of starting or stopping amoxicillin. 
• 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

• Amoxicillin is not known to be harmful in pregnancy.

Breastfeeding

• Trace amounts of amoxicillin are found in breast milk, but it is appropriate to use in women who are breastfeeding. 
  • Penicillins (and cephalosporins) are the antibiotics of choice in women who are breastfeeding.
  • Although unlikely, the infant could develop gastrointestinal disturbances and oral candida infection, particularly if used for prolonged periods or high doses, and there is a theoretical risk of hypersensitivity. As a precaution, monitor the infant for gastrointestinal disturbances, oral candida infection, hypersensitivity reactions (including rashes or breathing problems), nausea, irritability, and drowsiness.

 [EMC, 2023c; BNFC, 2024; SPS, 2024]