Recommendations
Urgent
Think ‘Could this be sepsis?’ based on acute deterioration in a patient in whom there is clinical evidence or strong suspicion of infection.[27][28][29][30] See our topic Sepsis in adults.
Use a systematic approach (e.g., National Early Warning Score 2 [NEWS2]), alongside your clinical judgement, to assess the risk of deterioration due to sepsis. Consult local guidelines for the recommended approach at your institution.[28][29][30][31]
In the community: refer for emergency medical care in hospital (usually by blue-light ambulance in the UK) any patient who is acutely ill with a suspected infection and is:[28]
Deemed to be at high risk of deterioration due to organ dysfunction (as measured by risk stratification)
At risk of neutropenic sepsis.
In hospital: urgently consult a senior clinical decision-maker (e.g., ST4 level doctor in the UK) if you suspect sepsis.[28][29][30][32]
Send urine for culture before giving antibiotics if there are signs or symptoms of sepsis in a patient with suspected urinary tract infection.[27]
Treat people with acute pyelonephritis immediately (after taking a urine sample for culture) with empirical antibiotics.[34][36] Follow your local protocol or take advice from microbiology.[27][34][36] Take into consideration:[36]
Severity of symptoms
Risk of developing complications (higher in people with abnormality of the genitourinary tract or immunosuppression)
Previous urine culture and susceptibility results
Previous antibiotic use, which may have led to resistant bacteria.
Consult senior or specialist colleagues for patients with prostatitis, patients with signs or symptoms of a urological cancer or obstruction, patients who are pregnant, and any other patients at risk of complications.
Key Recommendations
Patients with uncomplicated acute pyelonephritis can usually be treated in the community with oral antibiotics.
Consider for hospital treatment patients who seem unwell as they may have severe pyelonephritis, a urinary obstruction, or complications of pyelonephritis.
Assess patients individually to decide on the need for hospital treatment. Consider the patient’s ability to cope as well as the clinical severity.
When urine culture results are available, review the empirical antibiotic and change according to susceptibility results if the bacteria are resistant. Use a narrow-spectrum antibiotic where possible.[36]
If symptoms worsen, or do not start to improve within 48 hours of starting the antibiotic, consider other possible diagnoses and reassess any signs or symptoms suggesting a more serious condition, such as sepsis. Consider any previous antibiotic use, which may have led to resistant bacteria.[36]
Consider treating patients with acute pyelonephritis without complications in the community.[33]
Consider for hospital treatment patients who seem unwell as they may have severe pyelonephritis, a urinary obstruction, or complications of pyelonephritis.
Assess patients individually to decide on the need for hospital treatment. Consider the patient’s ability to cope as well as the clinical severity.
Refer to hospital urgently any patient who is haemodynamically unstable or has any other signs or symptoms of sepsis.[36] See our topic Sepsis in adults.
Practical tip
Think ‘Could this be sepsis?’ based on acute deterioration in a patient in whom there is clinical evidence or strong suspicion of infection.[27][28][29][30] See our topic Sepsis in adults.
Use a systematic approach (e.g., National Early Warning Score 2 [NEWS2]), alongside your clinical judgement, to assess the risk of deterioration due to sepsis. Consult local guidelines for the recommended approach at your institution.[28][29][30][31]
In the community: refer for emergency medical care in hospital (usually by blue-light ambulance in the UK) any patient who is acutely ill with a suspected infection and is:[28]
Deemed to be at high risk of deterioration due to organ dysfunction (as measured by risk stratification)
At risk of neutropenic sepsis.
In hospital: urgently consult a senior clinical decision-maker (e.g., ST4 level doctor in the UK) if you suspect sepsis.[28][29][30][32]
Send urine for culture before giving antibiotics if there are signs or symptoms of sepsis in a patient with suspected urinary tract infection.[27]
Consider referring to hospital a patient who:[33][36]
Has comorbidities, such as reduced kidney function (acute kidney injury or chronic kidney disease) or diabetes
Is at higher risk of developing complications (such as patients with underlying diseases, immunosuppression, or an abnormality of the genitourinary tract)
Has a metabolic derangement
Has severe flank or abdominal pain
Has a high fever (>39.4°C)
Is pregnant
Has significant dehydration
Is unable to take oral fluids or medicine.
In practice, consider also referring men with acute pyelonephritis because of the risk of complications or alternative diagnoses, such as prostatitis.
Consider acute pyelonephritis to be uncomplicated if it is limited to non-pregnant, pre-menopausal women with no known relevant urological abnormalities or comorbidities.[34]
Patients with uncomplicated acute pyelonephritis can usually be treated in the community with oral antibiotics.
Patients with uncomplicated pyelonephritis may occasionally require hospital admission.[34] For example, patients may need to be treated with intravenous antibiotics due to vomiting or if they are otherwise unable to tolerate oral antibiotics.
Give intravenous antibiotics to patients who require hospitalisation and are severely unwell, or who are unable to tolerate oral antibiotics.[36] See Complicated acute pyelonephritis below.
Antibiotic therapy
Treat people with uncomplicated acute pyelonephritis immediately with oral antibiotics (after taking a midstream urine sample for culture and susceptibility testing).[34][36]
Escherichia coli is the main causative organism of acute pyelonephritis, accounting for 60% to 80% of uncomplicated infections.[36]
Consider local antimicrobial resistance data.[36] When selecting an antibiotic take into account:[36]
Severity of symptoms
Risk of developing complications (higher in people with abnormality of the genitourinary tract or immunosuppression)
Previous urine culture and susceptibility results
Previous antibiotic use, which may have led to resistant bacteria.
Follow your local protocol or take advice from microbiology. However, in the UK, the National Institute for Health and Care Excellence (NICE) recommends the following.[36]
Empirical antibiotics
For men and non-pregnant women, NICE recommends the following oral antibiotics first-line:[36]
Cefalexin for 7 to 10 days
Amoxicillin/clavulanate (if culture results are available due to high resistance rates) for 7 to 10 days
Trimethoprim (if culture results are available due to to high resistance rates) for 14 days
This course is recommended due to a lack of evidence for shorter courses
Ciprofloxacin for 7 days (see Drug safety alert for fluoroquinolones below).
The European Association of Urology recommends treating men with pyelonephritis for a minimum of 14 days, preferably with a fluoroquinolone (consider safety issues), because prostatic involvement is frequent.[34]
Consider safety issues with fluoroquinolones such as ciprofloxacin (see Drug safety alert below).
Drug safety alert: EMA and MHRA restrictions on the use of fluoroquinolone antibiotics
In November 2018, the European Medicines Agency (EMA) completed a review of serious, disabling, and potentially irreversible adverse effects associated with systemic and inhaled fluoroquinolone antibiotics. These adverse effects include tendonitis, tendon rupture, arthralgia, neuropathies, and other musculoskeletal or nervous system effects.
As a consequence of this review, the EMA now recommends that fluoroquinolone antibiotics be restricted for use in serious, life-threatening bacterial infections only. Furthermore, it recommends that fluoroquinolones should not be used for mild to moderate infections unless other appropriate antibiotics for the specific infection cannot be used, and should not be used in non-severe, non-bacterial, or self-limiting infections. Patients who are older, have renal impairment, or have had a solid organ transplant, and those being treated with a corticosteroid are at a higher risk of tendon damage. Co-administration of a fluoroquinolone and a corticosteroid should be avoided.[45] The UK-based Medicines and Healthcare products Regulatory Agency (MHRA) supports these recommendations.[46]
Consult with a microbiologist about whether a fluoroquinolone is an appropriate option for your patient.
Avoid antibiotics that don’t achieve adequate levels in renal tissue, such as nitrofurantoin, fosfomycin, and pivmecillinam.[36]
Evidence: Choice of antibiotic
There is very little evidence to guide choice of antibiotic for adults with acute pyelonephritis, with most studies finding no difference in effectiveness. Narrower-spectrum antibiotics should be used wherever possible and resistance rates need to be taken into account.
The UK National Institute for Health and Care Excellence (NICE) in its 2018 guideline on antimicrobial prescribing in acute pyelonephritis identified seven randomised controlled trials (RCTs) that compared different antibiotics in adults. Most of the studies were in hospital inpatients.[36]
Two RCTs found intravenous cephalosporins (ceftolozane/tazobactam or ceftazidime) may be more effective than intravenous fluoroquinolones (levofloxacin or ciprofloxacin) in adults with acute pyelonephritis, acute obstructive pyelonephritis, or complicated urinary tract infection (UTI).[47][48]
Ceftolozane/tazobactam was more effective than levofloxacin for improving composite cure (clinical cure and microbiological eradication and microbiological cure: 76.9% vs. 68.4%, number needed to treat [NNT] 12, quality of evidence as assessed by GRADE moderate), but there was no difference for clinical cure.
Ceftazidime was more effective than ciprofloxacin for clinical cure (88.9% vs. 73.8%, NNT 7, GRADE very low).
Two RCTs found an intravenous cephalosporin versus an intravenous carbapenem equally effective in adults with acute pyelonephritis or complicated UTI (GRADE very low to high).[49][50]
One RCT compared different fluoroquinolones in adults with acute pyelonephritis and complicated UTI and found no difference in clinical or microbiological outcomes at follow-up (GRADE high).[51]
One RCT found oral ciprofloxacin was more effective than oral trimethoprim/sulfamethoxazole for the treatment of acute pyelonephritis in women (clinical cure 96.5% vs. 82.9%, NNT 8; microbiological cure 99.1% vs. 89.1%, NNT 10; GRADE low to moderate).[52]
The NICE guideline committee highlighted that wherever possible narrower-spectrum antibiotics should be used in accordance with antimicrobial stewardship. While it recommended a range of antibiotics it agreed that individual factors (including recent previous urine culture and susceptibility results), fluoroquinolone safety concerns, and local information on susceptibility and resistance should all be taken into account when choosing which antibiotic to prescribe.[36]
When providing a prescription for antibiotics in the community, give advice about possible adverse effects (particularly diarrhoea and nausea) and response to treatment.
Advise that nausea and vomiting may be an indication of worsening pyelonephritis.
Ask the patient to seek medical help if the symptoms worsen or do not begin to improve within 48 hours of starting the antibiotic, or if the patient becomes systemically very unwell.[36]
If symptoms worsen, or do not start to improve within 48 hours of starting the antibiotic, consider other possible diagnoses and reassess any signs or symptoms suggesting a more serious condition, such as sepsis. See our topic Sepsis in adults. Consider any previous antibiotic use, which may have led to resistant bacteria.[36]
Pathogen-targeted antibiotics
When results of urine culture and sensitivity testing are available:[36]
Review the choice of antibiotic based on the microbiological results
Change the antibiotic according to susceptibility results if bacteria are resistant and symptoms are not improving, selecting a narrow-spectrum antibiotic where possible.
Duration of treatment
Prescribe the shortest course that is likely to be effective to reduce the risk of antimicrobial resistance and minimise the risk of adverse effects.[36] See durations stated for each drug above.
The NICE antimicrobial prescribing guideline committee agreed, based on evidence, that a short course of antibiotics was as effective as a long course for acute pyelonephritis, but the exact duration of a ‘short’ or ‘long’ course differs depending on the clinical trial definition and the antibiotic used.[36]
Guidance from the American College of Physicians recommends short-course (5-7 days) antibiotic treatment with a fluoroquinolone in men or women with uncomplicated pyelonephritis, or 14 days of trimethoprim/sulfamethoxazole, depending on antibiotic susceptibility.[53]
The European Association of Urology recommends treating men with pyelonephritis for a minimum of 14 days, because prostatic involvement is frequent.[34]
Evidence: Duration of antibiotic treatment
Shorter courses of antibiotics seem to be as effective as longer courses for the treatment of adults with acute pyelonephritis, and use of shorter courses represents better antimicrobial stewardship.
The UK National Institute for Health and Care Excellence (NICE) in its 2018 guideline on antimicrobial prescribing in acute pyelonephritis recommends using the shortest course possible for first-line treatment, although the actual duration varies between 7, 7 to 10, and 14 days depending on choice of antibiotic.[36] The evidence underpinning this came from two systematic reviews and one randomised controlled trial (RCT).[54][55][56]
The first systematic review (search date up to August 2012) compared ≤7 days treatment with a longer course.[54] It included RCTs of women and men (>16 years) treated as inpatients or outpatients for pyelonephritis or urinary tract infection (UTI) with sepsis.
The authors found eight RCTs (n=2515; four compared fluoroquinolones, three compared beta-lactams, and one compared a fluoroquinolone with trimethoprim/sulfamethoxazole).
Five RCTs made comparisons using the same antibiotic, and three RCTs made comparisons using different antibiotics.
There was no difference in clinical failure at the end of the long-treatment arm (per protocol analysis, five RCTs, n=1076, relative risk [RR] 0.63, 95% CI 0.33 to 1.18), and no difference in clinical failure or microbiological failure at the end of follow-up even in people with bacteraemia.
In a subgroup analysis of studies with >20% people with urogenital abnormalities, microbiological failure at end of follow-up was more likely with shorter treatment (three RCTs, n=287, RR 1.78, 95% CI 1.02 to 3.10).
Only two studies reported on mortality; in one, there was one death in each study arm, and in the other there were no deaths.
Development of resistance at the end of follow-up was rare and there was no significant difference between shorter and longer duration.
One RCT reported length of hospital stay, which was shorter in the short-treatment arm. Readmission was not reported by any of the included RCTs.
Adverse events were similar between the arms, although no trial specifically reported Clostridium difficile-associated diarrhoea.
The second systematic review (search date March 2008) included four RCTs and did not find any differences in effectiveness, adverse events, or withdrawal from treatment with shorter (7- to 14-day) versus longer (14- to 42-day) treatment with the same antibiotic regimen.[55]
The RCT (n=330) compared a short course (5 days of intravenous levofloxacin) with a longer course (7-14 days of intravenous levofloxacin followed by oral levofloxacin) in adults (≥18 years old) diagnosed with complicated UTI or acute pyelonephritis.[56]
It found 45.7% of the shorter-course group and 43.4% of the longer-course group had acute pyelonephritis.
Clinical and microbiological effectiveness, clinical and microbiological recurrence rates, and adverse effects were all similar between groups.
The guideline committee agreed that, based on UK antimicrobial stewardship guidance, when prescribing intravenous antibiotics these should be reviewed by 48 hours and if possible switched to the oral route.[36][57][58]
Self-care advice
Advise patients about supportive self-care and when to seek further help:[27][36]
Advise patients to drink enough fluids to avoid dehydration (recommendation based on NICE guideline committee experience)[36]
For analgesia, recommend patients take paracetamol and add a weak opioid, such as codeine, if needed (recommendation based on NICE guideline committee opinion).[36] Avoid non-steroidal anti-inflammatory drugs due to the potential risk of acute kidney injury.[36]
Consider acute pyelonephritis to be complicated if the patient has a structural or functional abnormality, an underlying disease that increases the risk of a more serious outcome or has treatment failure, or sepsis. Examples include an obstruction requiring catheterisation, acute kidney injury, abscess formation, and antibiotic failure.
Consider all urinary tract infections in men, including acute pyelonephritis, to be complicated.[34]
See the Urgent section above and our topic Sepsis in adults for more information on managing sepsis.
See Pregnant women below for management of acute pyelonephritis during pregnancy.
Patients with complicated acute pyelonephritis should be admitted to hospital for treatment with intravenous antibiotics and with supportive care.[36]
Antibiotic therapy
Treat people with complicated acute pyelonephritis immediately with intravenous antibiotics (after taking a midstream urine sample for culture and susceptibility testing).[34][36]
Consider local antimicrobial resistance data.[36] When selecting an antibiotic take into consideration:[36]
Severity of symptoms
Risk of developing complications (higher in people with abnormality of the genitourinary tract or immunosuppression)
Previous urine culture and susceptibility results
Previous antibiotic use, which may have led to resistant bacteria.
Follow your local protocol or take advice from microbiology. However, in the UK, the National Institute for Health and Care Excellence (NICE) recommends the following.[36]
Empirical antibiotics
For men and non-pregnant women, NICE recommends the following intravenous antibiotics first-line:[36]
Amoxicillin/clavulanate (if culture results are available due to high resistance rates)
Cefuroxime
Ceftriaxone
Ciprofloxacin (see Drug safety alert for fluoroquinolones below)
Gentamicin or amikacin, particularly for those with severe infection or sepsis (take caution in those with reduced kidney function)
Therapeutic drug monitoring and assessment of renal function is required with gentamicin and amikacin.
Treat men with complicated acute pyelonephritis with antibiotics for a minimum duration of 14 days, preferably with a fluoroquinolone (see Drug safety alert below) because prostatic involvement is frequent.[34]
Drug safety alert: EMA and MHRA restrictions on the use of fluoroquinolone antibiotics
In November 2018, the European Medicines Agency (EMA) completed a review of serious, disabling, and potentially irreversible adverse effects associated with systemic and inhaled fluoroquinolone antibiotics. These adverse effects include tendonitis, tendon rupture, arthralgia, neuropathies, and other musculoskeletal or nervous system effects.
As a consequence of this review, the EMA now recommends that fluoroquinolone antibiotics be restricted for use in serious, life-threatening bacterial infections only. Furthermore, it recommends that fluoroquinolones should not be used for mild to moderate infections unless other appropriate antibiotics for the specific infection cannot be used, and should not be used in non-severe, non-bacterial, or self-limiting infections. Patients who are older, have renal impairment, or have had a solid organ transplant, and those being treated with a corticosteroid are at a higher risk of tendon damage. Co-administration of a fluoroquinolone and a corticosteroid should be avoided.[45] The UK-based Medicines and Healthcare products Regulatory Agency (MHRA) supports these recommendations.[46]
Consult with a microbiologist about whether a fluoroquinolone is an appropriate option for your patient.
Consult a microbiologist if second-choice antibiotics are required, if you need to combine antibiotics, or if sepsis is a concern.[36]
Pathogen-targeted antibiotics
When results of urine culture and sensitivity testing are available:[36]
Review the choice of antibiotic based on the microbiological results
Change the antibiotic according to susceptibility results if bacteria are resistant and symptoms are not improving, selecting a narrow-spectrum antibiotic where possible.
Duration of treatment
Prescribe the shortest course that is likely to be effective to reduce the risk of antimicrobial resistance and minimise the risk of adverse effects.[36]
The NICE antimicrobial prescribing guideline committee agreed, based on evidence, that a short course of antibiotics was as effective as a long course for acute pyelonephritis, but the exact duration of a ‘short’ or ‘long' course differs depending on the clinical trial definition and the antibiotic used.[36]
Review the use of intravenous antibiotics within 48 hours and switch to oral treatment when possible. Take into account the patient’s response to treatment and urine culture and susceptibility results.[36]
Treat men with complicated acute pyelonephritis for a minimum duration of 14 days, because prostatic involvement is frequent.[34]
Supportive care
Provide fluids and analgesia, as necessary.
For analgesia, give paracetamol and add a weak opioid, such as codeine, if needed (recommendation based on NICE guideline committee opinion).[36] Avoid non-steroidal anti-inflammatory drugs due to the potential risk of acute kidney injury.[36]
In pregnant women, acute pyelonephritis may have adverse effects on the mother, such as anaemia, renal insufficiency, and respiratory insufficiency, and also on the unborn child, causing preterm labour and birth.[59]
Consider outpatient management if the symptoms are mild and close follow-up of the patient is possible.[33][36]
Give oral cefalexin for 7 to 10 days as the first choice of antibiotic in pregnant women.[36]
Avoid ciprofloxacin and trimethoprim in pregnancy.[36]
When providing a prescription for antibiotics in the community, give advice about possible adverse effects (particularly diarrhoea and nausea) and response to treatment.
Advise that nausea and vomiting may be an indication of worsening pyelonephritis.
Ask the patient to seek medical help if the symptoms worsen or do not begin to improve within 48 hours of starting the antibiotic, or if the patient becomes systemically very unwell.[36]
Closely monitor and follow up pregnant patients being treated in the community.[34]
Refer or admit to hospital pregnant women with severe pyelonephritis for treatment and supportive care.[33][36]
If the patient needs intravenous antibiotics (because they are vomiting, severely unwell, or unable to take oral antibiotics), give cefuroxime as the first-line treatment.[36]
Review the intravenous antibiotics after 48 hours and step down to oral antibiotics where possible, for a total treatment duration of 7 days.[36]
Consult a microbiologist if second-choice antibiotics are required, if you need to combine antibiotics, or if sepsis is a concern.[36] See our topic Sepsis in adults.
Treat asymptomatic bacteriuria in pregnant women to ensure eradication of the bacteria.[34]
[ 
]
[Evidence C]
Supportive care
In the community, advise patients about supportive self-care and when to seek further help:[27][36]
Advise patients to drink enough fluids to avoid dehydration (recommendation based on National Institute for Health and Care Excellence [NICE] guideline committee experience)[36]
For analgesia, recommend patients take paracetamol, if needed (recommendation based on NICE guideline committee opinion).[36] A weak opioid, such as codeine, may be an option in pregnant women under specialist guidance, provided it is not used near term.
In hospital, provide fluids and analgesia, as necessary.
For analgesia, give paracetamol, if needed (recommendation based on NICE guideline committee opinion).[36] A weak opioid, such as codeine, may be an option in pregnant women under specialist guidance, provided it is not used near term.
Pathogen-targeted antibiotics
When results of urine culture and sensitivity testing are available:[36]
Review the choice of antibiotic based on the microbiological results
Change the antibiotic according to susceptibility results if bacteria are resistant and symptoms are not improving, selecting a narrow-spectrum antibiotic where possible.
Reassess the patient if symptoms worsen rapidly or significantly at any time or do not start to improve within 48 hours of taking an antibiotic.[27]
Take account of:[27]
Other possible diagnoses. See the Differentials section
Any symptoms or signs suggesting a more serious illness or condition (e.g., sepsis. See Sepsis in adults)
Previous antibiotic use, which may have led to resistant bacteria.
Send a urine sample for culture and susceptibility testing if this has not already been done and review treatment when results are available.[27]
Do not request routine post-treatment urine cultures or urinalysis in asymptomatic patients.[34]
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