Previous changes

March 2025 — minor update. Information has been added to the Basis for recommendation of the Management section to clarify that for men, and trans women and non-binary people with a male genitourinary system a trial of daily antibiotic prophylaxis can be considered, and that for women, and trans men and non-binary people with a female urinary system, who are not pregnant, single-dose antibiotic prophylaxis or a trial of daily antibiotic prophylaxis can be considered. Also added ketamine-induced uropathy to the list of potential differential diagnoses. 

December 2024 — minor update. The recommendations on referral and seeking specialist advice have been updated, and recommendations on considering methenamine hippurate for prophylaxis of recurrent UTI has been added to the section on recurrent UTI in line with the updated NICE guideline Urinary tract infection (recurrent): antimicrobial prescribing. 

May 2024 — minor update. Severe cutaneous adverse reactions (SCAR) added as an adverse effect of pivmecillinam, as per the manufacturer's updated SPC.

August 2023 — reviewed. A literature search was conducted in August 2023 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. 

February 2023 — minor update. The NICE quality standards have been updated.

July 2022 — minor update. Some minor text changes were made to this topic in line with the Public Health England (PHE) guideline Diagnosis of urinary tract infections. Quick reference tool for primary care for consultation and local adaption, but no changes were made to recommendations, and a referral recommendation has been removed as the guideline has been withdrawn.  

June 2022 — minor update. The 2012 SIGN Guideline Management of suspected bacterial infection in adults has been replaced with a guideline which solely applies to women. 

November 2018 — reviewed. A literature search was conducted in November 2018 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of this topic. 

July to October 2014 — reviewed. A literature search was conducted in June 2014 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of this topic. No major changes to the recommendations have been made.

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

October 2012 — minor update. The 2012 QIPP options for local implementation have been added to this topic.

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

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

March 2011 — minor update. Minor clarification to the text. 

December 2010 — minor update. Nitrofurantoin capsules have been added as an alternative option to nitrofurantoin tablets in the Prescriptions section. 

May 2010 — minor update. The advice regarding when prophylactic antibiotics should be used when changing an indwelling catheter has been corrected. 

August 2009 to January 2010 — 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. There have been no major changes to the recommendations.

September 2008 — minor correction to the Changes section. 

May 2008 — minor update. Guidance updated to be in line with the SIGN guideline on the Management of Suspected Bacterial Urinary Tract Infection in Adults. 

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. Validated in March 2002 and issued in April 2002.

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 August 2023.

HTAs (Health Technology Assessments)

No new HTAs since 1 August 2023.

Economic appraisals

No new economic appraisals relevant to England since 1 August 2023.

Systematic reviews and meta-analyses

• Williams, G., Stothart, C.I., Hahn, D., et al. (2023) Cranberries for preventing urinary tract infections. Cochrane Database of Systematic Reviews. https://www.cochranelibrary.com/ [Free Full-text]

Primary evidence

No new primary evidence published since 1 August 2023.

New policies

No new national policies or guidelines since 1 August 2023.

New safety alerts

No new safety alerts since 1 August 2023.

Changes in product availability

• New product EXBLIFEP 2 g/0.5 g powder is indicated for the treatment of complicated urinary tract infections (cUTI), including pyelonephritis. See more here.
• 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 UK Health Security Agency (UKHSA) guide Diagnosis of urinary tract infections. Quick reference tool for primary care [UKHSA, 2020], the European Association of Urology (EAU) guideline Urological infections [EAU, 2023], and the British Medical Journal (BMJ) Best Practice guide Urinary tract infections in men [BMJ Best Practice, 2022].  

UTI presenting with atypical symptoms

• The recommendation to be aware of atypical presentations in men aged 65 years or over is based on UKHSA guidance and on what CKS considers good clinical practice [UKHSA, 2020]. 
  • The UKHSA advises that its guidance for diagnosing UTI in people aged over 65 years may also be suitable for some younger people in care homes or who have a long-term urinary catheter.

Collection and storage of urine samples

• Common specimen collection methods include:   
  • Mid-stream urine (MSU) — this is the routine, recommended method. The first part of the voided urine is discarded and without interrupting the flow, 10 mL of urine is collected into a specimen container. 
    • In the elderly and frail who are incontinent, condom catheters may be an option. 
  • Clean-catch urine sample (CCU) — periurethral cleaning is recommended. The whole specimen is collected and an aliquot sent for examination. 
  • Catheter urine sample (CSU) — if the man has a long-term indwelling urinary catheter, drain and discard a few millilitres of urine from the catheter or sampling port, and then collect the urine sample using an aseptic technique. Do not take the specimen from the collection bag, as this is more likely to be contaminated. 
    • If the catheter has been changed, collect from the newly placed catheter. 
    • If the catheter has been removed, obtain a midstream specimen of urine. 
• Specimens should be transported and processed within 4 hours unless boric acid preservative is used — if this is not possible it should be refrigerated at 4°C. 
  • Urine that has been refrigerated at 4°C for 48 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 on sample volume in boric acid containers. 

Interpreting urine culture results

• Generally, the threshold for reporting significant bacteriuria is 10⁵ colony-forming units (CFU)/mL — counts below this are indicative of contamination. 
• In men with urinary symptoms, UTI is usually indicated by at least: 
  • 10³ CFU/mL of a pure or predominant organism (responsible for 80% of the growth).  
  • 10³ CFU/mL of Escherichia coli or Staphylococcus saprophyticus. 
  • 10⁴ CFU/mL of any single organism.
  • 10⁵ CFU/mL mixed growth with one dominant organism. 
• Clinical judgement is required to assess the clinical significance of urine culture results for men with a long-term indwelling urinary catheter, as urine culture may not reflect bladder bacteria.
  • Antibiotic treatment is not routinely needed for asymptomatic bacteriuria in people with a catheter. 
• False-positive culture results can be caused by:
  • Contamination of the urine.
  • Delays and storage at room temperature, which allow organisms to multiply.  
• False-negative culture results can be caused by: 
  • Starting antibiotic treatment before the urine sample is collected.  
  • Boric acid (specimen container preservative) — when the volume of urine is small compared with that of the preservative, boric acid can be bactericidal. 
    • Specimen containers should be filled to the correct mark on the specimen bottle. 

Basis for recommendation

These recommendations are based on the UK Health Security Agency (UKHSA) guide Diagnosis of urinary tract infections. Quick reference tool for primary care [UKHSA, 2020], the UKHSA UK Standards for microbiology investigations. Investigation of urine [UKHSA, 2019], and the National Institute for Health and Care Excellence (NICE) guideline Urinary tract infection (catheter-associated): antimicrobial prescribing [NICE, 2018d]. 

Diagnosis and dipstick testing [UKHSA, 2020]

• No individual or combination of symptoms and dipstick results are completely reliable in diagnosing UTI, therefore, the severity of symptoms and safety-netting are important in all people.
• Dipstick testing should not be used in men aged over 65 years as they become more unreliable with increasing age over 65 years. Up to half of older adults, and most with a urinary catheter, will have bacteria present in the bladder/urine without an infection. 

Culture results

• In men with urinary symptoms, a colony count of at least 10³ CFU/mL of a pure or predominant organism, or 103 CFU/mL of Escherichia coli or Staphylococcus saprophyticus usually indicates UTI. However, routine culture methods may not be sensitive enough to detect low levels of bacteria (less than 10⁴ CFU/mL) so an increased inoculum size may be required [UKHSA, 2019]. 
• UKHSA advises that if a man presents with recurrent pyuria with UTI symptoms, this should be discussed with a local microbiologist as lower counts down to 10² CFU/mL may be significant and a higher volume of urine may need to be cultured, including for fastidious organisms [UKHSA, 2020].

Culture in men with indwelling catheters 

• In people with indwelling catheters, samples may not accurately reflect the true bladder pathogen, and the criteria have not been established for differentiating asymptomatic colonisation of the urinary tract from symptomatic infection [UKHSA, 2019].
  • The quality of the specimen collected and clinical circumstances in the individual patient are critical in the interpretation of bacterial counts. In carefully collected specimens, taken under controlled study conditions in short-term catheterized people, counts of less than 10⁵ colony-forming units (CFU)/mL have been shown to be significant. 

Basis for recommendation

This information is based on the British Medical Journal (BMJ) Best Practice Guide Urinary tract infections in men [BMJ Best Practice, 2022], the European Association of Urology (EAU) guideline Urological infections [EAU, 2023], and the UK Health Security Agency (UKHSA) guide Diagnosis of urinary tract infections. Quick reference tool for primary care [UKHSA, 2020].

When should I refer men with a lower urinary tract infection?

• Admit men to hospital if they develop systemic symptoms such as fever, rigors, chills, vomiting or confusion. 
• Referral to urology is not routinely required for men who have had one uncomplicated lower urinary tract infection (UTI). 
• Refer men to urology who:
  • Have ongoing symptoms despite appropriate antibiotic treatment. 
  • May have an underlying cause or risk factor for the UTI (such as suspected urinary tract obstruction, a history of pyelonephritis, urinary calculi, or previous genitourinary tract surgery). 
  • Have recurrent episodes of UTI (for example, two or more episodes in a 6-month period). 
• Consider referral to urology for men with a suspected upper UTI — for more information, see the CKS topic on Pyelonephritis - acute. 
• Refer urgently using a suspected cancer pathway referral for an appointment within 2 weeks for men:  
  • Aged 45 years and over who have unexplained visible haematuria without UTI, or visible haematuria that persists or recurs after successful treatment of UTI. 
  • Aged 60 years and over who have unexplained non-visible haematuria and either dysuria or a raised white cell count on a blood test. 
• Consider non-urgent referral for bladder cancer in men aged 60 years and over with recurrent or persistent UTI. 
• For more information on when to suspect a urological cancer, see the CKS topic on Urological cancers - recognition and referral.

How should I manage lower urinary tract infection in men?

• Arrange emergency admission to hospital if he is severely unwell with symptoms or signs suggestive of urosepsis (for example, nausea and vomiting, confusion, tachypnoea, tachycardia, or hypotension). 
• If hospital admission is not needed offer an antibiotic, taking into account:  
  • Previous urine culture and susceptibility results. 
  • Previous antibiotic use, which may have led to resistant bacteria. 
• Start empirical antibiotic drug treatment with trimethoprim or nitrofurantoin (if eGFR [estimated glomerular filtration rate] is 45 mL/min/1.73m² or more), taking into account local antimicrobial resistance data. Prescribe: 
  • Trimethoprim 200 mg twice daily for 7 days.
  • Nitrofurantoin 100 mg modified-release twice daily (or if unavailable 50 mg four times daily) for 7 days.
    • Nitrofurantoin is not recommended for men with prostate involvement as it is unlikely to reach therapeutic levels in the prostate. If acute prostatitis is suspected, quinolones are the first-choice antibiotic. For more information, see the CKS topic on Prostatitis - acute. 
  • Provide appropriate information and advice. 
• Arrange follow-up, for example, after 48 hours, depending on clinical judgement, to check the man's response to treatment and the urine culture results.
  • Review the choice of antibiotic. 
  • Change the antibiotic according to susceptibility results. If the bacteria are resistant and symptoms are not already improving, use a narrow-spectrum antibiotic wherever possible. 
• Reassess if symptoms worsen rapidly or significantly at any time, or do not start to improve within 48 hours of starting antibiotic treatment, and consider: 
  • Other possible diagnoses. 
  • Any symptoms or signs suggesting a more serious illness or condition, such as pyelonephritis. For more information, see the CKS topic on Pyelonephritis - acute. 
  • Whether previous antibiotic use may have led to resistant bacteria. 
  • Whether referral for specialist urological assessment is needed. 

How should I manage recurrent urinary tract infection in men?

If a man presents with recurrent episodes of lower urinary tract infection (UTI), for example, two or more episodes in the last 6 months: 

• Treat each episode as acute lower UTI, and ensure urine culture is arranged on each occasion. 
• Advise the man about behavioural and personal hygiene measures that may help to reduce the risk of UTI, for example: 
  • Drinking enough fluids to avoid dehydration. 
  • Not delaying habitual and post-coital urination.
• Refer or seek specialist advice on further investigation and management for:
  • Men, trans women and non-binary people with a male genitourinary system, aged 16 years and over.
  • Pregnant trans men and non-binary people.
  • Anyone who has had gender reassignment surgery that involved structural alteration of the urethra. 
• Ensure that any current UTI has been adequately treated, then consider a trial of daily antibiotic prophylaxis if behavioural and personal hygiene measures alone are not effective or not appropriate. Take into account: 
  • Any further investigations (for example, ultrasound) that may be needed to identify an underlying cause.
  • 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. 
  • The person's preferences for antibiotic use.
• Seek specialist advice if considering methenamine hippurate (1 g twice daily) as an alternative to daily antibiotic prophylaxis for recurrent UTI in men, and trans women and non-binary people with a male genitourinary system.
• If discussing methenamine hippurate as a preventative treatment, explain that:
  • Over-the-counter sachets that make urine more alkaline (such as sachets used to relieve UTI symptoms that contain potassium citrate or sodium citrate) should not be used while taking methenamine hippurate because these can make the medicine less effective.
  • Medical help should be sought for acute UTI symptoms. 
• Review treatment with methenamine hippurate within 6 months, and then every 12 months, or earlier if agreed with the person.
• Refer urgently, using a suspected cancer pathway referral for an appointment within 2 weeks, for men:   
  • Aged 45 years and over who have unexplained visible haematuria without urinary tract infection, or visible haematuria that persists or recurs after successful treatment of urinary tract infection.
  • Aged 60 years and over who have unexplained non-visible haematuria and either dysuria or a raised white cell count on a blood test.
• Consider non-urgent referral for bladder cancer in men aged 60 years and over with recurrent or persistent unexplained UTI. 
• For more information on when to suspect urological cancer, see the CKS topic on Urological cancers - recognition and referral.

When should I refer men who have a urinary tract infection and an indwelling catheter?

• Admit men to hospital if they have any symptoms or signs suggesting a more serious illness or condition (for example, sepsis). 
• Consider referring or seeking specialist advice for men with catheter-associated urinary tract infection (UTI) if they: 
  • Are significantly dehydrated or unable to take oral fluids and medicines.
  • Have a higher risk of developing complications (for example, people with known or suspected structural or functional abnormality of the genitourinary tract, or underlying disease [such as diabetes or immunosuppression]).
  • Have recurrent episodes of UTI (for example, two or more episodes in a 6-month period). 
  • Have bacteria that are resistant to oral antibiotics.
• Consider referral to urology for men with a suspected upper UTI — for more information, see the CKS topic on Pyelonephritis - acute. 
• Refer urgently using a suspected cancer pathway referral for an appointment within 2 weeks for men:   
  • Aged 45 years and over who have unexplained visible haematuria without urinary tract infection, or visible haematuria that persists or recurs after successful treatment of urinary tract infection.
  • Aged 60 years and over who have unexplained non-visible haematuria and either dysuria or a raised white cell count on a blood test.
• Consider non-urgent referral for bladder cancer in men aged 60 years and over with recurrent or persistent unexplained UTI. 
• For more information on when to suspect urological cancer, see the CKS topic on Urological cancers - recognition and referral.

How should I manage urinary tract infection in men with an indwelling catheter?

• Arrange emergency admission to hospital if the patient is severely unwell with symptoms or signs suggestive of urosepsis (for example nausea and vomiting, confusion, tachypnoea, tachycardia, or hypotension). 
• If hospital admission is not needed:
  • Check that the catheter is correctly positioned, drains correctly, and is not blocked.
  • Consider removing or, if this cannot be done, changing the catheter as soon as possible if it has been in place for more than 7 days.  
    • Do not allow catheter removal or change to delay antibiotic treatment. 
    • Do not give antibiotic prophylaxis for catheter changes unless the man has a history of symptomatic UTIs due to catheter change. 
  • Offer an antibiotic, taking into account: 
    • The severity of symptoms.
    • The risk of developing complications, which is higher in people with known or suspected structural or functional abnormality of the genitourinary tract or immunosuppression.
    • Previous urine culture and susceptibility results.
    • Previous antibiotic use, which may have led to resistant bacteria.
  • Start empirical antibiotic drug treatment with nitrofurantoin (if eGFR [estimated glomerular filtration rate] is 45 ml/min/1.73m² or more), trimethoprim (if low risk of resistance), or amoxicillin (if culture shows susceptibility) taking into account local antimicrobial resistance data. Prescribe: 
    • Nitrofurantoin 100 mg modified-release twice daily (or if unavailable 50 mg four times daily) for 7 days.
    • Trimethoprim 200 mg twice daily for 7 days.
    • Amoxicillin 500 mg three times daily for 7 days. 
  • If these are unsuitable, prescribe pivmecillinam — an initial dose of 400 mg, then 200 mg three times a day for a total of 7 days.  
  • If acute prostatitis is suspected, quinolones are the first-choice antibiotic. For more information, see the CKS topic on Prostatitis - acute. 
  • Provide information and advice. 
• Review culture and sensitivity results when they become available.   
  • Review the choice of antibiotic.
  • Change the antibiotic according to susceptibility results if the bacteria are resistant, using narrow-spectrum antibiotics wherever possible.
• Reassess people with catheter-associated UTI if symptoms worsen at any time or do not start to improve within 48 hours of taking the antibiotic, taking account of: 
  • Other possible diagnoses.  
  • Any symptoms or signs suggesting a more serious illness or condition, such as sepsis or pyelonephritis. For more information, see the CKS topics on Sepsis and Pyelonephritis - acute. 
  • Previous antibiotic use, which may have led to resistant bacteria. 
  • Any measures that may help prevent further UTI. 
  • Whether referral for specialist urological assessment is needed. 

What measures can be taken to help prevent urinary tract infection in men with an indwelling catheter?

• Do not offer antibiotic prophylaxis to prevent catheter-associated urinary tract infections (UTIs). 
• Do not routinely offer antibiotic prophylaxis when changing an indwelling urinary catheter. 
• Consider antibiotic prophylaxis for men who: 
  • Have a history of symptomatic UTI after catheter change.
  • Experience trauma during catheterization.
• Ensure an indwelling urinary catheter is appropriate for the man. 
  • Regularly review the clinical need for catheterization and remove the catheter as soon as possible. 
    • The duration of catheterization should be minimal. 
  • Use intermittent catheterization or condom drainage systems in preference to an indwelling catheter, if this is clinically appropriate and practical. 
• Measures that are recommended to prevent the introduction of infection include:
  • Ensuring healthcare professionals are trained and assessed in their competency to perform urethral catheterization using an aseptic technique. 
  • Always keeping the urinary drainage bag below the level of the bladder and the connecting tube, and ensuring there is no contact with the floor. 
  • Emptying the urinary drainage bag frequently enough to maintain urine flow and prevent reflux, and changing it when clinically indicated. 
  • Changing catheters only when clinically necessary (for example, to prevent blockage), or according to the manufacturer's recommendations. 
    • Do not change at fixed intervals. 
• Measures that are not routinely recommended to prevent UTI include:
  • Bladder instillations or washouts. 
  • Applying topical antiseptics or antibiotics to the catheter, urethra, or meatus. 

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.  

[BNF, 2023; EMC, 2023a]

Adverse effects

• Gastrointestinal — nausea and diarrhoea (common), vomiting (uncommon).
  • Very rarely: antibiotic-associated colitis.
• 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, and drug reaction with eosinophilia and systemic symptoms (DRESS).
• Other very rare adverse effects include: 
  • Hepatitis and cholestatic jaundice.
  • Hyperkinesia, dizziness, and convulsions.
  • Interstitial nephritis.
  • Leukopenia, thrombocytopenia, and haemolytic anaemia.
  • Severe allergic reactions.

[BNF, 2023; EMC, 2023a]

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. 
• Coumarin anticoagulants (warfarin and phenindione) — INR may be increased. Monitor INR within 3 days of starting or stopping amoxicillin. 
• Live cholera vaccine — vaccine efficacy may be reduced. Avoid concurrent use and for 14 days before and 10 days after vaccine administration.
• Live oral typhoid vaccine — the immune response may be reduced. Avoid concurrent use and for 3 days before to 3 days after receiving the live vaccine. 

[Preston, 2023]

Contraindications and cautions

• Do not prescribe trimethoprim in people with:
  • Blood dyscrasias. 
• Prescribe trimethoprim with caution in the elderly and 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 predisposion to folate deficiency — administration of a folate supplement should be considered. 

[BNF, 2023; MHRA, 2023a]

Adverse effects

• Blood disorders — leukopenia, megaloblastic anaemia, thrombocytopenia, agranulocytosis, methaemoglobinaemia.
• Gastrointestinal — nausea, diarrhoea, vomiting (common).
• Nervous system — headache (common), dyskinesias, tremor, ataxia, dizziness, syncope, vertigo, tinnitus, 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, angioedema.
• Other adverse effects include:
  • Anaphylaxis.
  • Hyperkalaemia (very common, particularly in the elderly and in HIV patients), hypoglycaemia, hyponatraemia (very rare). 
  • Liver enzyme disturbances, cholestatic jaundice.
  • Myalgia, arthralgia.
  • Raised serum creatinine.
  • Uveitis.

[BNF, 2023; MHRA, 2023a]

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, particularly in the elderly. Monitor for digoxin adverse effects, and adjust 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 dose accordingly. 
• Repaglinide — exposure to repaglinide is slightly increased. The manufacturer advises against concurrent use. 
• Live cholera vaccine — vaccine efficacy may be reduced. Avoid concurrent use, and for 14 days before and 10 days after vaccine administration. 
• Live oral typhoid vaccine — the immune response may be reduced. Avoid concurrent use and for 3 days before to 3 days after receiving the live vaccine. 

[Preston, 2023]

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. 
  • Peripheral neuropathy or susceptibility to peripheral neuropathy — treatment should be stopped at the first signs of neural involvement (paraesthesia).
  • Vitamin B (particularly folate) deficiency. 

[BNF, 2023; EMC, 2023b]

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, 2023b]: 
  • 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, especially if elderly.
  • 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.

[BNF, 2023; EMC, 2023b]

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 vaccine — vaccine efficacy may be reduced. Avoid concurrent use and for 14 days before and 10 days after vaccine administration. 
• Live oral typhoid vaccine — the immune response may be reduced. Avoid concurrent use and for 3 days before to 3 days after receiving the live vaccine. 

[Preston, 2023]

Contraindications and cautions

• Do not prescribe pivmecillinam 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.
  • Hypersensitivity to cephalosporins. 
  • Acute porphyrias. 
  • Carnitine deficiency or concurrent treatment with valproic acid, valproate, or any other medication liberating pivalic acid due to increased risk of carnitine depletion.
  • Gastrointestinal obstruction.
  • Oesophageal strictures. 

[BNF, 2023; EMC, 2023c]

Adverse effects

• Gastrointestinal — diarrhoea, nausea (common), vomiting, abdominal pain, dyspepsia, oesophageal ulcer, oesophagitis, and mouth ulceration (uncommon). 
• Other uncommon adverse effects include:
  • Abnormal hepatic function. 
  • Carnitine reduced. 
  • Fatigue.
  • Headache, dizziness. 
  • Rash, urticaria, pruritus. 
  • Severe cutaneous adverse reactions (SCAR)
  • Thrombocytopenia. 
  • Vertigo.
  • Vulvovaginal fungal infection. 

[BNF, 2023; EMC, 2024]

Drug interactions

• Methotrexate — pivmecillinam may reduce methotrexate clearance, causing an increased risk of toxicity.
  • Monitor methotrexate according to local guidelines and protocols.
• Coumarin anticoagulants (warfarin and phenindione) — the effects of coumarins are not normally altered. However, it may be prudent to monitor INR within 3 days of starting or stopping a penicillin. 
• Valproate — concurrent treatment with valproic acid, valproate, or other medication liberating pivalic acid increases the risk of carnitine depletion. Avoid concurrent use. If this is not possible, monitor closely.
• Live cholera vaccine — vaccine efficacy may be reduced. Avoid concurrent use and for 14 days before and 10 days after vaccine administration. 
• Live oral typhoid vaccine — the immune response may be reduced. Avoid concurrent use and for 3 days before to 3 days after receiving the live vaccine. 

[Preston, 2023]