Pyelonephritis (acute):

antimicrobial prescribing

NICE guideline
Published: 31 October 2018
www.nice.org.uk/guidance/ng111

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Pyelonephritis (acute): antimicrobial prescribing (NG111)

Your responsibility
The recommendations in this guideline represent the view of NICE, arrived at after careful
consideration of the evidence available. When exercising their judgement, professionals and
practitioners are expected to take this guideline fully into account, alongside the individual needs,
preferences and values of their patients or the people using their service. It is not mandatory to
apply the recommendations, and the guideline does not override the responsibility to make
decisions appropriate to the circumstances of the individual, in consultation with them and their
families and carers or guardian.

Local commissioners and providers of healthcare have a responsibility to enable the guideline to be
applied when individual professionals and people using services wish to use it. They should do so in
the context of local and national priorities for funding and developing services, and in light of their
duties to have due regard to the need to eliminate unlawful discrimination, to advance equality of
opportunity and to reduce health inequalities. Nothing in this guideline should be interpreted in a
way that would be inconsistent with complying with those duties.

Commissioners and providers have a responsibility to promote an environmentally sustainable

health and care system and should assess and reduce the environmental impact of implementing
NICE recommendations wherever possible.

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Pyelonephritis (acute): antimicrobial prescribing (NG111)

Contents
Overview ...................................................................................................................................................................... 4

Who is it for? ............................................................................................................................................................................ 4

Recommendations .................................................................................................................................................... 5

1.1 Managing acute pyelonephritis................................................................................................................................. 5

1.2 Self-care ............................................................................................................................................................................. 7

1.3 Choice of antibiotic ........................................................................................................................................................ 7

Summary of the evidence ....................................................................................................................................... 13

Self-care ..................................................................................................................................................................................... 13

Antibiotics ................................................................................................................................................................................. 13

Choice of antibiotic ............................................................................................................................................................... 14

Antibiotic course length ...................................................................................................................................................... 21

Antibiotic dose frequency .................................................................................................................................................. 23

Antibiotic route of administration .................................................................................................................................. 23

Other considerations ............................................................................................................................................... 25

Medicines adherence ........................................................................................................................................................... 25

Resource implications .......................................................................................................................................................... 25

Update information .................................................................................................................................................. 26

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Pyelonephritis (acute): antimicrobial prescribing (NG111)

This guideline should be read in conjunction with NG109, NG112 and CG54.

Overview
This guideline sets out an antimicrobial prescribing strategy for acute pyelonephritis (upper urinary
tract infection) in children, young people and adults who do not have a catheter. It aims to optimise
antibiotic use and reduce antibiotic resistance.

See a 3-page visual summary of the recommendations, including a table to support prescribing
decisions.

NICE has also produced a guideline on antimicrobial stewardship: systems and processes for
effective antimicrobial medicine use.

Who is it for?
• Health professionals

• People with acute pyelonephritis, their families and carers

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Pyelonephritis (acute): antimicrobial prescribing (NG111)

Recommendations
1.1 Managing acute pyelonephritis
1.1.1 Be aware that acute pyelonephritis is an infection of one or both kidneys usually
caused by bacteria travelling up from the bladder.

Treatment
1.1.2 In people aged 16 years and over with acute pyelonephritis, obtain a midstream
urine sample before antibiotics are taken and send for culture and susceptibility
testing.

1.1.3 In children and young people under 16 years with acute pyelonephritis, obtain a
urine sample before antibiotics are taken and send for culture and susceptibility
testing in line with the NICE guideline on urinary tract infection in under 16s.

1.1.4 Assess and manage children under 5 with acute pyelonephritis who present
with fever as outlined in the NICE guideline on fever in under 5s.

1.1.5 Offer an antibiotic (see the recommendations on choice of antibiotic) to people

with acute pyelonephritis. Take account of:

• 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.

1.1.6 When results of urine cultures are available:

• review the choice of antibiotic and

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Pyelonephritis (acute): antimicrobial prescribing (NG111)

• change the antibiotic according to susceptibility results if the bacteria are resistant,
using a narrow spectrum antibiotic wherever possible.

Advice when an antibiotic prescription is given

1.1.7 When an antibiotic is given, as well as the general advice on self-care, give
advice about:

• possible adverse effects of the antibiotic, particularly diarrhoea and nausea

• nausea with vomiting also being a possible indication of worsening pyelonephritis

• seeking medical help if:

－ symptoms worsen at any time or

－ symptoms do not start to improve within 48 hours of taking the antibiotic or

－ the person becomes systemically very unwell.

Reassessment
1.1.8 Reassess 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

• previous antibiotic use, which may have led to resistant bacteria.

Referral and seeking specialist advice

1.1.9 Refer people aged 16 years and over with acute pyelonephritis to hospital if
they have any symptoms or signs suggesting a more serious illness or condition
(for example, sepsis).

1.1.10 Consider referring or seeking specialist advice for people aged 16 years and
over with acute pyelonephritis if they:

• are significantly dehydrated or unable to take oral fluids and medicines or

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Pyelonephritis (acute): antimicrobial prescribing (NG111)

• are pregnant or

• 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]).

1.1.11 Refer children and young people with acute pyelonephritis to hospital in line
with the NICE guideline on urinary tract infection in under 16s.

See the evidence and committee discussion on choice of antibiotic.

1.2 Self-care
1.2.1 Advise people with acute pyelonephritis about using paracetamol for pain, with
the possible addition of a low-dose weak opioid such as codeine for people over
12 years.

1.2.2 Advise people with acute pyelonephritis about drinking enough fluids to avoid
dehydration.

See the evidence and committee discussion on self-care.

1.3 Choice of antibiotic

1.3.1 When prescribing an antibiotic for acute pyelonephritis, take account of local
antimicrobial resistance data and follow:

• table 1 for non-pregnant women and men aged 16 years and over

• table 2 for pregnant women aged 12 years and over

• table 3 for children and young people under 16 years.

1.3.2 Give oral antibiotics first line if the person can take oral medicines, and the
severity of their condition does not require intravenous antibiotics.

1.3.3 Review intravenous antibiotics by 48 hours and consider stepping down to oral
antibiotics where possible.

Table 1 Antibiotics for non-pregnant women and men aged

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Pyelonephritis (acute): antimicrobial prescribing (NG111)

16 years and over

Antibiotic1 Dosage and course length

First-choice oral antibiotics2

Cefalexin 500 mg twice or three times a day (up to 1 to 1.5 g three or four
times a day for severe infections) for 7 to 10 days

Co-amoxiclav (only if culture 500/125 mg three times a day for 7 to 10 days

results available and
susceptible)

Trimethoprim (only if culture 200 mg twice a day for 14 days

results available and
susceptible)

Ciprofloxacin (consider safety 500 mg twice a day for 7 days

issues3)

First-choice intravenous antibiotics (if vomiting, unable to take oral antibiotics, or severely
unwell). Antibiotics may be combined if susceptibility or sepsis a concern2,4

Co-amoxiclav (only in 1.2 g three times a day

combination or if culture
results available and
susceptible)

Cefuroxime 750 mg to 1.5 g three or four times a day

Ceftriaxone 1 to 2 g once a day

Ciprofloxacin (consider safety 400 mg twice or three times a day

issues3)

Gentamicin Initially 5 to 7 mg/kg once a day, subsequent doses adjusted

according to serum gentamicin concentration5

Amikacin Initially 15 mg/kg once a day (maximum per dose 1.5 g once a
day), subsequent doses adjusted according to serum amikacin
concentration (maximum 15 g per course)5

Second-choice intravenous antibiotics

Consult local microbiologist

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Pyelonephritis (acute): antimicrobial prescribing (NG111)

1
See British national formulary (BNF) for appropriate use and dosing in specific populations, for
example, hepatic impairment, renal impairment and breastfeeding, and administering
intravenous antibiotics.
2
Check any previous urine culture and susceptibility results and antibiotic prescribing and
choose antibiotics accordingly.
3
See MHRA advice for restrictions and precautions for using fluoroquinolone antibiotics due to
very rare reports of disabling and potentially long-lasting or irreversible side effects affecting
musculoskeletal and nervous systems. Warnings include: stopping treatment at first signs of a
serious adverse reaction (such as tendonitis), prescribing with special caution in people over 60
years and avoiding coadministration with a corticosteroid (March 2019).
4
Review intravenous antibiotics by 48 hours and consider stepping down to oral antibiotics
where possible.
5
Therapeutic drug monitoring and assessment of renal function is required (BNF, August 2018).

Table 2 Antibiotics for pregnant women aged 12 years and over

Antibiotic1 Dosage and course length

First-choice oral antibiotic2

Cefalexin 500 mg twice or three times a day (up to 1 to 1.5 g three or four times a day for
severe infections) for 7 to 10 days

First-choice intravenous antibiotic (if vomiting, unable to take oral antibiotics, or severely
unwell)2,3

Cefuroxime 750 mg to 1.5 g three or four times a day

Second-choice antibiotics or combining antibiotics if susceptibility or sepsis a concern

Consult local microbiologist

1
See British national formulary (BNF) for appropriate use and dosing in specific populations, for
example, hepatic impairment and renal impairment, and administering intravenous antibiotics.
2
Check any previous urine culture and susceptibility results and antibiotic prescribing and
choose antibiotics accordingly.
3
Review intravenous antibiotics by 48 hours and consider stepping down to oral antibiotics
where possible.

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Pyelonephritis (acute): antimicrobial prescribing (NG111)

Table 3 Antibiotics for children and young people under 16 years

Antibiotic1 Dosage and course length2

Children under 3 months

Refer to paediatric specialist and treat with intravenous antibiotics in line with the NICE
guideline on fever in under 5s.

Children aged 3 months and over

First-choice oral antibiotic3

Cefalexin 3 to 11 months, 12.5 mg/kg or 125 mg twice a day for

7 to 10 days (25 mg/kg two to four times a day [maximum 1 g per
dose four times a day] for severe infections)
1 to 4 years, 12.5 mg/kg twice a day or 125 mg three times a day
for 7 to 10 days (25 mg/kg two to four times a day [maximum 1 g
per dose four times a day] for severe infections)
5 to 11 years, 12.5 mg/kg twice a day or 250 mg three times a day
for 7 to 10 days (25 mg/kg two to four times a day [maximum 1 g
per dose four times a day] for severe infections)
12 to 15 years, 500 mg twice or three times a day (up to 1 to 1.5 g
three or four times a day for severe infections) for 7 to 10 days

Co-amoxiclav (only if culture 3 to 11 months, 0.25 ml/kg of 125/31 suspension three times a
results available and day for 7 to 10 days (dose doubled in severe infection)
susceptible) 1 to 5 years, 0.25 ml/kg of 125/31 suspension or 5 ml of 125/
31 suspension three times a day for 7 to 10 days (dose doubled in
severe infection)
6 to 11 years, 0.15 ml/kg of 250/62 suspension or 5 ml of 250/
62 suspension three times a day for 7 to 10 days (dose doubled in
severe infection)
12 to 15 years, 250/125 mg or 500/125 mg three times a day for
7 to 10 days

First-choice intravenous antibiotics (if vomiting, unable to take oral antibiotics or severely
unwell). Antibiotics may be combined if susceptibility or sepsis a concern3, 4, 5

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Pyelonephritis (acute): antimicrobial prescribing (NG111)

Co-amoxiclav (only in 3 months to 15 years, 30 mg/kg three times a day (maximum 1.2 g
combination or if culture three times a day)
results available and
susceptible)

Cefuroxime 3 months to 15 years, 20 mg/kg three times a day (maximum

750 mg per dose), increased to 50 to 60 mg/kg three or four times
a day (maximum 1.5 g per dose) for severe infections

Ceftriaxone 3 months to 11 years (up to 50 kg), 50 to 80 mg/kg once a day

(maximum 4 g per day)
9 to 11 years (50 kg and above), 1 to 2 g once a day
12 to 15 years, 1 to 2 g once a day

Gentamicin Initially 7 mg/kg once a day, subsequent doses adjusted according

to serum gentamicin concentration6

Amikacin Initially 15 mg/kg once a day, subsequent doses adjusted

according to serum amikacin concentration6

Second-choice intravenous antibiotic

Consult local microbiologist

1
See British national formulary for children (BNFC) for appropriate use and dosing in specific
populations, for example, hepatic and renal impairment, and administering intravenous
antibiotics. See table 2 if a young woman is pregnant.
2
The age bands apply to children of average size and, in practice, the prescriber will use the age
bands in conjunction with other factors such as the severity of the condition being treated and
the child's size in relation to the average size of children of the same age.
3
Check any previous urine culture and susceptibility results and antibiotic prescribing, and
choose antibiotics accordingly. Where a child or young person is receiving prophylactic
antibiotics, treatment should be with a different antibiotic, not a higher dose of the same
antibiotic.
4
Review intravenous antibiotics by 48 hours and consider stepping down to oral antibiotics
where possible for a total of 10 days.
5
If intravenous treatment is not possible, consider intramuscular treatment if suitable.
6
Therapeutic drug monitoring and assessment of renal function is required (BNFC, August
2018).

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Pyelonephritis (acute): antimicrobial prescribing (NG111)

See the evidence and committee discussion on choice of antibiotic, antibiotic course length and
antibiotic route of administration.

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Pyelonephritis (acute): antimicrobial prescribing (NG111)

Summary of the evidence

The recommendations in this guideline are based on the evidence identified, which was mainly for
people with acute pyelonephritis. Some studies also included people with a complicated urinary
tract infection, or UTI (associated with a structural or functional abnormality, or underlying disease,
which increases the risk of a more serious outcome or treatment failure) or urosepsis (a systemic
response to a UTI).

Self-care
• No systematic reviews or randomised controlled trials (RCTs) of any non-antimicrobial
treatments were identified that met the inclusion criteria.

Committee discussion on self-care

• There was no evidence for the use of oral analgesia in acute pyelonephritis. However,
paracetamol has a well-established efficacy and safety profile for managing pain. The
committee agreed that it was reasonable to advise people about paracetamol for self-
management of pain. A low-dose weak opioid, such as codeine, could be taken with
paracetamol by adults and young people over 12 years for more severe pain.

• Non-steroidal anti-inflammatory drugs, such as ibuprofen, are generally not recommended

for people with acute pyelonephritis because of concerns about renal safety.

• The committee discussed the need for an adequate intake of fluids to ensure a high urine
output, which is believed to help resolve acute pyelonephritis through a mechanical flushing
of bacteria from the kidney. No evidence was found for this and there was no evidence of
what constitutes adequate hydration. However, based on committee experience that
dehydration is often cited as a cause of UTIs, the committee agreed that people should be
advised about drinking enough fluids to avoid dehydration.

Antibiotics
• Acute pyelonephritis is a bacterial infection needing treatment with an antibiotic that reaches
therapeutic concentrations in the kidney.

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Pyelonephritis (acute): antimicrobial prescribing (NG111)

• Gram-negative bacteria are the most common causative pathogens in acute pyelonephritis,
with Escherichia coli (E. coli) causing 60 to 80% of uncomplicated infections. Other gram-
negative pathogens include Proteus mirabilis (responsible for about 15% of infections) as well as
Klebsiella (approximately 20%), Enterobacter and Pseudomonas species. Less commonly, gram-
positive bacteria such as Enterococcus faecalis, Staphylococcus saprophyticus and Staphylococcus
aureus may be seen.

• Complications of acute pyelonephritis include impaired renal function or renal failure, sepsis
and preterm labour in pregnancy.

Choice of antibiotic
Efficacy of antibiotics
• An intravenous cephalosporin (ceftolozane/tazobactam or ceftazidime) was compared with an
intravenous fluoroquinolone (levofloxacin or ciprofloxacin) in 2 RCTs (Wagenlehner et al. 2015
and Pasiechnikov et al. 2015) in adults with acute pyelonephritis, acute obstructive
pyelonephritis or complicated UTI. Moderate quality evidence found that ceftolozane/
tazobactam was significantly more effective than levofloxacin for improving composite cure
(clinical cure and microbiological eradication and microbiological cure; 76.9% versus 68.4%,
number needed to treat [NNT] 12 [range 7 to 43]) but there was no significant difference
between antibiotics for clinical cure. Ceftazidime had a significantly higher rate of clinical cure
compared with ciprofloxacin (88.9% versus 73.8%; NNT 7 [range 4 to 62]; very low quality
evidence).

• An intravenous cephalosporin (ceftriaxone or ceftazidime/avibactam) was compared with an

intravenous carbapenem (ertapenem or imipenem/cilastatin) in 2 RCTs (Park et al. 2012 and
Vazquez et al. 2012) in adults with acute pyelonephritis or complicated UTI. Very low to high
quality evidence found that these cephalosporins and carbapenems were equally effective.

• Very low quality evidence from a small single RCT (Moramezi et al. 2008) in pregnant women
with acute pyelonephritis found no significant difference between intravenous cephalothin
and intravenous ampicillin plus gentamicin in the duration of lower UTI symptoms or
costovertebral angle pain. The mean time to end of fever was reduced with ampicillin plus
gentamicin compared with cephalothin (mean 11 hours lower, p=0.01; very low quality
evidence).

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Pyelonephritis (acute): antimicrobial prescribing (NG111)

• One RCT (Peterson et al. 2008) compared different fluoroquinolones (levofloxacin and
ciprofloxacin: intravenous or oral) for acute pyelonephritis and complicated UTI in adults and
found no significant differences in clinical or microbiological outcomes at follow-up (high
quality evidence).

• One RCT (Talan et al. 2000) compared oral ciprofloxacin with oral co-trimoxazole for acute
pyelonephritis in adult women. Low to moderate quality evidence found that ciprofloxacin was
significantly more effective for clinical cure (96.5% versus 82.9%; NNT 8 [range 5 to 18]) and
microbiological cure (99.1% versus 89.1%; NNT 10 [range 7 to 28]) than co-trimoxazole.

• Low quality evidence from 2 RCTs (Wagenlehner et al. 2015 and Park et al. 2012) found no
difference between antibiotics (ceftolozane/tazobactam versus levofloxacin, and ertapenem
versus ceftriaxone) for treating bacteraemia secondary to complicated UTI or acute
pyelonephritis in adults.

• The evidence for children is based on 1 systematic review (Strohmeier et al. 2014) in acute
pyelonephritis. No evidence from systematic reviews or RCTs was identified for children with
complicated UTI. This systematic review did not find major differences in clinical effectiveness
between different antibiotics compared in the studies (third- and fourth-generation
cephalosporins, aminoglycosides, co-amoxiclav and co-trimoxazole; very low to moderate
quality evidence).

Safety of antibiotics
• Antibiotic-associated diarrhoea occurs in 2 to 25% of people taking antibiotics, depending on
the antibiotic used (NICE clinical knowledge summary on diarrhoea – antibiotic associated).

• About 10% of the general population claim to have a penicillin allergy; this is often because of a
skin rash that occurred while taking a course of penicillin as a child. Fewer than 10% of people
who think they are allergic to penicillin are truly allergic. See the NICE guideline on drug
allergy for more information.

• People with a history of immediate hypersensitivity to penicillins may also react to

cephalosporins and other beta-lactam antibiotics (BNF, August 2018).

• Trimethoprim has a teratogenic risk in the first trimester of pregnancy (folate antagonist; BNF,
August 2018). The manufacturers advise that it is contraindicated in pregnancy (trimethoprim
summary of product characteristics).

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Pyelonephritis (acute): antimicrobial prescribing (NG111)

• Fluoroquinolones are generally not recommended in children or young people who are still
growing (BNF, August 2018). The manufacturers advise to avoid in pregnancy (ciprofloxacin
summary of product characteristics). Tendon damage (including rupture) has been reported
rarely in people receiving fluoroquinolones (BNF, August 2018), and the European Medicines
Agency's Pharmacovigilance Risk Assessment Committee (press release October 2018) has
recommended restricting the use of these antibiotics following a review of disabling and
potentially long-lasting side effects mainly involving muscles, tendons and bones and the
nervous system. Fluoroquinolones remain an option in acute pyelonephritis, which is a severe
infection.

• Aminoglycoside doses are based on weight and renal function, and whenever possible
treatment should not exceed 7 days (BNF, August 2018).

• Overall there did not appear to be major differences in adverse effects between antibiotics
based on the included studies, although these were not well reported (very low to low quality
evidence).

• See the summaries of product characteristics for information on contraindications, cautions

and adverse effects of individual medicines.

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Committee discussion on choice of antibiotic

• Based on evidence and experience, the committee agreed that acute pyelonephritis is a
bacterial infection needing treatment with antibiotics that reach therapeutic concentrations
in the kidney. Antibiotics that don't achieve adequate levels in renal tissue, such as
nitrofurantoin, fosfomycin and pivmecillinam, are to be avoided.

• A urine sample should be sent for culture to confirm susceptibility of the bacteria and inform
treatment choice.

• The committee reviewed the available evidence comparing different antibiotics in adults and
children and agreed that it was limited by its setting (most studies in adults were undertaken
in a hospital, and in children the setting of the studies was not reported). The studies included
various different antibiotics, which may not reflect those chosen in UK practice. The
committee discussed the evidence for a benefit of the intravenous third-generation
cephalosporins, ceftolozane/tazobactam or ceftazidime, over an intravenous
fluoroquinolone, but this was mainly limited to a benefit for composite cure (which included
clinical cure, microbiological eradication and microbiological cure) and the absolute benefits
were small.

• The committee agreed, based on experience, that several oral and intravenous antibiotics
should be available for people with acute pyelonephritis. This enables antibiotics to be
selected based on the severity of illness, antibiotic susceptibilities from culture results when
available, local resistance patterns, risk of resistant bacteria, the setting, and known patient
factors (such as whether the person has a higher risk of developing complications). In line
with antimicrobial stewardship, narrower-spectrum antibiotics should be used wherever
possible.

• Nationally for England, resistance of E. coli (the main causative organism of acute
pyelonephritis) in laboratory-processed urine specimens to the following antibiotics is:

－ cefalexin: 9.9% (varies by area from 8.1 to 11.4%)

－ ciprofloxacin: 10.6% (varies by area from 7.8 to 13.7%)

－ co-amoxiclav: 19.8% (varies by area from 10.8 to 30.7%)

－ trimethoprim: 30.3% (varies by area from 27.1 to 33.4%).

(Public Health England. Antimicrobial resistance quarterly surveillance: March 2018)

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Pyelonephritis (acute): antimicrobial prescribing (NG111)

• The committee also discussed that prescribers should be aware of their local antimicrobial
prescribing data, because resistance rates do vary by area.

• The committee agreed that any recent previous urine culture and susceptibility results, and
antibiotic prescribing, should be reviewed before choosing an antibiotic.

• Based on experience, the committee agreed that if the results of urine culture suggest the
bacteria are resistant to the antibiotic given, people with acute pyelonephritis should be
contacted and the antibiotic changed regardless of whether symptoms are improving or not.
The committee agreed that acute pyelonephritis is a serious infection and antibiotics should
be changed to ensure cure.

Non-pregnant women and men with acute pyelonephritis

• Based on evidence, their experience and resistance data, the committee agreed to
recommend a choice of first-line oral antibiotics
antibiotics, at usual doses for acute pyelonephritis.
These are:

－ cefalexin (a first-generation cephalosporin); based on its broad spectrum of activity and

acceptable levels of resistance

－ co-amoxiclav (a penicillin with a beta-lactamase inhibitor); which is only suitable if

culture results are available and bacteria are susceptible, because resistance rates are
high

－ trimethoprim; which is only suitable if culture results are available and bacteria are
susceptible, because resistance rates are high

－ ciprofloxacin (a fluoroquinolone); based on its broad spectrum of activity and acceptable

levels of resistance (particularly for people who have had previous treatment with
penicillins, or cannot tolerate or are allergic to penicillins).

• The committee noted that use of broad-spectrum antibiotics, such as later-generation

cephalosporins, fluoroquinolones or co-amoxiclav, can create a selective advantage for
bacteria resistant to these second-line broad-spectrum agents, allowing such strains to
proliferate and spread. And, by disrupting normal flora, broad-spectrum antibiotics can leave
people susceptible to harmful bacteria such as Clostridium difficile in community settings.
However, these antibiotics are appropriate for the empirical treatment of acute
pyelonephritis, where coverage of more resistant strains of common bacterial pathogens is
required.

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Pyelonephritis (acute): antimicrobial prescribing (NG111)

• The committee was aware of the European Medicines Agency's Pharmacovigilance Risk
Assessment Committee recommendation to restrict the use of fluoroquinolone antibiotics
following a review of disabling and potentially long-lasting side effects mainly involving
muscles, tendons and bones and the nervous system. However, they discussed that
fluoroquinolone antibiotics are a valuable option for the treatment of acute pyelonephritis,
which is a severe infection, and it is appropriate to reserve fluoroquinolone use for such
conditions. Resistant gram-negative organisms are a particular concern in acute
pyelonephritis, and the committee agreed that ciprofloxacin should remain a first-choice
option to cover what can be a complex infection. The committee was keen to point out,
however, that cefalexin, co-amoxiclav and trimethoprim are also first-choice options, and
antibiotics should be chosen on an individual patient basis, taking fluoroquinolone safety
concerns, as well as susceptibility and resistance, into account.

• Based on evidence, experience and resistance data, the committee agreed to recommend a
choice of first-line intravenous antibiotics
antibiotics, at usual doses, for people with acute
pyelonephritis who are unable to take oral antibiotics due to vomiting, or are more severely
unwell. These are:

－ co-amoxiclav (only in combination or if culture results are available and bacteria are
susceptible)

－ cefuroxime (a second-generation cephalosporin) or ceftriaxone (a third-generation

cephalosporin)

－ ciprofloxacin (taking safety concerns into account)

－ gentamicin or amikacin (aminoglycosides); which may be appropriate for some people

with acute pyelonephritis, particularly those with severe infection or sepsis, but that
efforts should be made to identify the causal bacteria and use reviewed at 48 hours.
Gentamicin is the preferred aminoglycoside in the UK, but shortages of certain
antibiotics may result in the use of alternatives; for example, amikacin in place of
gentamicin.

• The committee agreed, based on experience, that it may be necessary to combine antibiotics
in the care of people with suspected sepsis. This should be done according to local policy or
on the advice of a microbiologist, taking into account local antimicrobial resistance data.

Pregnant women with acute pyelonephritis

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• Based on experience and resistance data, the committee agreed to recommend cefalexin (a
first-generation cephalosporin) as the first-choice oral antibiotic for pregnant women who
don't require intravenous antibiotics, and cefuroxime (a second-generation cephalosporin) as
the first-choice intravenous antibiotic.

• Ciprofloxacin and trimethoprim are not recommended because they should be avoided in
pregnancy. Co-amoxiclav was not recommended because of high resistance levels nationally
and the risks of treatment failure in pregnancy.

• The committee agreed, based on experience, that local microbiologists should be consulted
for advice on second-choice antibiotics, or combining antibiotics if susceptibility or sepsis is a
concern.

Children and young people with acute pyelonephritis

• The committee was aware that the NICE guideline on urinary tract infection in under 16s
makes recommendations on diagnosing acute pyelonephritis and considering referral to a
paediatric specialist.

• Based on evidence, their experience and resistance data, the committee agreed to
recommend cefalexin or co-amoxiclav (only if culture results are available and bacteria are
susceptible) at usual doses for acute pyelonephritis, as first-choice oral antibiotics
antibiotics.

• Based on evidence, experience and resistance data, the committee agreed to recommend a
choice of first-line intravenous antibiotics
antibiotics, at usual doses, for children and young people who
are unable to take oral antibiotics due to vomiting, or are more severely unwell. These are:

－ co-amoxiclav (only in combination or if culture results are available and bacteria are
susceptible); which can be given intravenously

－ cefuroxime (a second-generation cephalosporin) or ceftriaxone (a third-generation

cephalosporin); which would be suitable alternatives to co-amoxiclav

－ gentamicin or amikacin (aminoglycosides); which may be appropriate for some children

and young people with acute pyelonephritis, particularly those with severe infection or
sepsis, but that efforts should be made to identify the causal bacteria and use reviewed
at 48 hours.

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• The committee agreed, based on experience, that it may be necessary to combine antibiotics
in the care of children and young people with suspected sepsis. This should be done
according to local policy or on the advice of a microbiologist, taking into account local
antimicrobial resistance data.

Antibiotic course length

• The evidence for antibiotic course length in the treatment of acute pyelonephritis in adults
comes from 2 systematic reviews (Eliakim-Raz et al. 2013 and Kyriakidou et al. 2008) and
1 RCT (Ren et al. 2017). No significant differences were found for clinical, microbiological or
safety and tolerability outcomes between short courses and longer courses of antibiotics
(7 days or fewer compared with 10 days to 6 weeks in 1 systematic review, and 7 to 14 days
compared with 14 to 42 days in the other systematic review [very low to moderate quality
evidence]). There were no significant differences between a short course (5 days) of
intravenous levofloxacin (750 mg once daily) and a longer course (7 to 14 days) of intravenous
and then oral levofloxacin (500 mg once daily; moderate quality evidence).

• There were some significant differences in clinical effectiveness between different antibiotic
course lengths in 1 systematic review in children with acute pyelonephritis (Strohmeier et al.
2014). However, this was limited to 1 RCT comparing 10 days of oral sulfafurazole with
42 days (moderate quality evidence), with other studies in the review finding no differences in
outcomes (very low quality evidence). Safety and tolerability outcomes were not reported.

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Committee discussions on antibiotic course length

• The committee agreed that the shortest course that is likely to be effective should be
prescribed to reduce the risk of antimicrobial resistance and minimise the risk of adverse
effects.

• Based on evidence, the committee agreed that a short course of antibiotics was generally as
effective as a long course of antibiotics for acute pyelonephritis, but the definition of short
and long course differed depending on the clinical trial definition and the antibiotic used.

• In line with the NICE guideline on antimicrobial stewardship and Public Health England's
Start smart – then focus, the committee agreed that the use of intravenous antibiotics should
be reviewed by 48 hours (taking into account the person's response to treatment and
susceptibility results from urine culture) and switched to oral treatment where possible.

Non-pregnant women and men with acute pyelonephritis

• Based on evidence, experience and resistance data, the committee agreed that, for oral
treatment, a 7-day course of ciprofloxacin was sufficient to treat acute pyelonephritis in non-
pregnant women and men. However, because there was no evidence for 7-day courses of
cefalexin or co-amoxiclax, a range of 7 to 10 days was recommended for these antibiotics.
For trimethoprim, a 14-day course was recommended because there was no evidence for
course lengths shorter than 14 days.

• For intravenous treatment, antibiotics should be reviewed by 48 hours and stepped down to
oral antibiotics where possible, for a total of 7 days.

Pregnant women with acute pyelonephritis

• Based on evidence, experience and resistance data, the committee agreed that, for oral
treatment, a 7- to 10-day course of cefalexin was required to treat acute pyelonephritis in
pregnant women. For intravenous treatment, antibiotics should be reviewed by 48 hours and
stepped down to oral antibiotics where possible, for a total of 7 days.

Children and young people with acute pyelonephritis

• Based on evidence, experience and resistance data, the committee agreed that a 7- to 10-day
course of oral antibiotics was required to treat acute pyelonephritis in children and young
people. For intravenous treatment, antibiotics should be reviewed by 48 hours and stepped
down to oral antibiotics where possible, for a total of 10 days.

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Antibiotic dose frequency

• No systematic reviews or RCTs that compared the frequency of antibiotic dosing in adults
were identified that met the inclusion criteria.

• Evidence from 1 systematic review in children with acute pyelonephritis (Strohmeier et al.
2014) found no significant difference in the clinical effectiveness of aminoglycosides with
once-daily administration compared with 8-hourly administration (moderate quality evidence).
There were no significant differences in the number of children with hearing impairment or
kidney dysfunction (very low quality evidence).

Antibiotic route of administration

• The evidence for route of antibiotic administration in acute pyelonephritis is based on
1 systematic review of 15 RCTs in adults and children (Pohl 2007). This review addressed
different modes of administration of antibiotics, which cover:

－ sequential intravenous then oral treatment compared with intravenous or intramuscular

treatment

－ sequential intravenous then oral treatment compared with oral treatment

－ oral treatment compared with intravenous or intramuscular treatment

－ single-dose intravenous or intramuscular treatment then oral treatment compared with

sequential intravenous then oral treatment.

• Overall, this review found that oral antibiotics were as effective as other routes of
administration in treating symptomatic severe UTI (including pyelonephritis) in both adults
and children. Intravenous or intramuscular antibiotics were significantly better for
bacteriological cure than oral antibiotics at the end of treatment, but this is based on 1 small
RCT (NNT 4 [range 3 to 15]; low quality evidence).

• There were no significant differences in adverse effects between different routes of

administration of antibiotics (very low quality evidence).

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• Further evidence is available from 1 systematic review in children with acute pyelonephritis
(Strohmeier et al. 2014), which compared different routes of administration, which cover:

－ oral treatment compared with sequential intravenous then oral treatment

－ sequential intravenous then oral treatment (short course of 3 to 4 days) compared with
intravenous treatment (longer course of 7 to 14 days)

－ single-dose intramuscular then oral treatment compared with oral treatment

－ oral treatment compared with rectal treatment.

• Overall, this review found no significant differences in the clinical effectiveness of oral
antibiotics (cephalosporins or co-amoxiclav) in children with acute pyelonephritis compared
with other routes of administration (very low to moderate quality evidence).

• Safety and tolerability outcomes were poorly reported in the RCTs included in Strohmeier et
al. (2014), but there did not appear to be any significant differences between different routes
of administration of antibiotics (very low quality evidence).

Committee discussions on antibiotic route of administration

• Based on evidence, the committee agreed that, overall, oral antibiotics were as effective as
other routes of administration for treating acute pyelonephritis in adults and children.

• The committee agreed, based on evidence and experience, that oral antibiotics should be
given first line when people can take oral medicines and the severity of their condition does
not require intravenous antibiotics.

• The committee agreed, based on evidence and experience, that intravenous antibiotics can
be used for people who are unable to take oral antibiotics due to vomiting, or are more
severely unwell, in line with Public Health England's Start smart – then focus.

See the full evidence review for more information.

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Other considerations
Medicines adherence
Medicines adherence may be a problem for some people with medicines that require frequent
dosing (for example, some antibiotics) or longer treatment duration (see the NICE guideline on
medicines adherence).

Resource implications
• One small randomised controlled trial (RCT; Moramezi et al. 2008) in pregnant women with
acute pyelonephritis found no significant difference in length of hospital stay in women taking
a cephalosporin compared with ampicillin plus gentamicin (p=0.22; very low quality evidence).

• One RCT (Talan et al. 2000), which compared ciprofloxacin with co-trimoxazole in adult
women with acute pyelonephritis, found that resource use (hospital stay, visits and telephone
contacts, laboratory tests and prescription costs) was higher in the co-trimoxazole group (no
analysis reported). The only exception was for radiological procedures, which was slightly
higher in the ciprofloxacin group (no analysis reported). One systematic review (Eliakim-Raz et
al. 2013), which compared antibiotic course lengths in adults with acute pyelonephritis and
included the Talan et al. (2000) study, noted a shorter duration of hospital stay with a short
course of antibiotics (7 days or fewer) compared with a longer course (10 days to 6 weeks).

• One RCT in the systematic review by Strohmeier et al. (2014) in children with acute
pyelonephritis found that giving sequential intravenous then oral antibiotics reduced the
duration of hospital stay compared with a longer duration of intravenous antibiotics (4.9 days
compared with 9.8 days).

• Recommended antibiotics are available as generic formulations, see Drug Tariff for costs.

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Update information
Minor changes since publication

September 2019: Minor wording changes were made and a footnote was updated in table 1 to
reflect new restrictions and precautions for the use of fluoroquinolone antibiotics.

ISBN: 978-1-4731-3124-8

Accreditation

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