Clinical Topic A-Z Clinical Speciality

Pyelonephritis - acute

Pyelonephritis - acute
D011704Pyelonephritis
Infections and infestationsKidney disease and urology
2013-06-01Last revised in June 2013

Pyelonephritis - acute - Summary

Acute pyelonephritis is caused by infection within the renal pelvis, with or without active infection of the renal parenchyma. In most people, it is caused by bacteria ascending from the lower urinary tract.

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

Acute pyelonephritis is diagnosed in a person with a proven urinary tract infection (UTI) who has loin pain and/or fever. There are no clinical features or routine investigations that conclusively distinguish acute pyelonephritis from cystitis.

Acute pyelonephritis should be suspected in people with loin pain and/or fever.

A dipstick test should be performed on the urine for leucocyte esterase and nitrite for evidence of a UTI. In addition, a midstream or catheter specimen of urine should be sent for culture and sensitivity.

A final diagnosis of acute pyelonephritis is made in people with loin pain and/or fever if a UTI is confirmed by culturing a urinary pathogen from the urine, and other causes for symptoms (such as pelvic inflammatory disease, appendicitis, and renal calculi) have been excluded.

Whether or not a person with acute pyelonephritis should be admitted to hospital depends on a number of factors including the severity of their symptoms, their general state of health, comorbidities, and age.

If admission to hospital is not required the person can be managed in primary care.

An antibiotic can be started once a midstream or catheter specimen of urine has been obtained for culture and sensitivity. Once the result is obtained the initial antibiotic can be changed if necessary.

For women who are not pregnant, men, and people with indwelling catheters, ciprofloxacin can be used. Co-amoxiclav is an alternative.

For pregnant women who do not require admission, cefalexin can be used.

Pain and fever should be treated with paracetamol.

Sufficient fluid intake to maintain hydration should be advised.

A review should be carried out after 24 hours to assess response to treatment.

Some groups of people will require referral for investigation of an underlying abnormality of the renal tract.

Have I got the right topic?

192months3060monthsBoth

This CKS topic covers the diagnosis and management of adults with suspected acute pyelonephritis.

This CKS topic does not cover the diagnosis and management of lower urinary tract infection.

There are separate CKS topics on Renal colic - acute, Urinary tract infection - children, Urinary tract infection (lower) - men, and Urinary tract infection (lower) - women.

The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary health care.

How up-to-date is this topic?

How up-to-date is this topic?

Changes

Last revised in June 2013

June 2013 — reviewed. A literature search was conducted in June 2013 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of this topic. No major changes to recommendations have been made.

Previous changes

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

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

May 2011 — minor update. The 2010/2011 QIPP options for local implementation have been added to this topic [NPC, 2011]. Issued in June 2011.

October 2008 to March 2009 — 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 are no major changes to the recommendations.

May 2005 — reviewed. Validated in September 2005 and issued in November 2005.

December 2001 — reviewed. Validated in March 2002 and issued in April 2002.

December 1998 — written, replacing guidance on Acute pyelonephritis. Validated in March 1999 and issued in May 1999.

Update

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 June 2013.

HTAs (Health Technology Assessments)

No new HTAs since 1 June 2013.

Economic appraisals

No new economic appraisals relevant to England since 1 June 2013.

Systematic reviews and meta-analyses

No new systematic review or meta-analyses since 1 June 2013.

Primary evidence

No new randomized controlled trials published in the major journals since 1 June 2013.

New policies

No new national policies or guidelines since 1 June 2013.

New safety alerts

No new safety alerts since 1 June 2013.

Changes in product availability

No changes in product availability since 1 June 2013.

Goals and outcome measures

Goals

To make an accurate diagnosis of pyelonephritis

To assess someone with pyelonephritis, and decide who should be admitted to hospital and who can be managed at home

To provide appropriate treatment for people managed in primary care

To appropriately refer for investigation of an underlying abnormality of the renal tract

QIPP — Options for local implementation

QIPP — Options for local implementation

Antibiotic prescribing — especially quinolones and cephalosporins

Review and, where appropriate, revise current prescribing practice and use implementation techniques to ensure prescribing is in line with Health Protection Agency (HPA) guidance.

Review the total volume of antibiotic prescribing against local and national data.

Review the use of quinolones and cephalosporin prescribing against local and national data.

[NICE, 2013]

Background information

Causes

What causes it?

Acute pyelonephritis is caused by infection within the renal pelvis, with or without active infection of the renal parenchyma [Tomson and Armitage, 2010]. In most people, it is caused by bacteria ascending from the lower urinary tract. The most common pathogens are:

Escherichia coli.

Klebsiella pneumoniae.

Proteus species.

Pseudomonas species.

Enterococcus species.

Complications

What are the complications?

Complications of acute pyelonephritis include [Grabe et al, 2013]:

Impaired renal function or renal failure, due to bacterial damage to the renal parenchyma.

Septicaemia.

Preterm labour in pregnancy.

The risk of developing a complication is increased in people with [Efstathiou et al, 2003; Grabe et al, 2013]:

Severe illness, including hypotension, tachycardia, reduced levels of consciousness, or dehydration.

Age over 65 years.

Abnormalities of renal tract anatomy and function (such as vesico-ureteric reflux and polycystic kidney disease).

Foreign body within the renal tract, including renal stones and urinary, ureteric, or nephrostomy catheters.

Immunocompromise, for example due to immunosuppressant drug use, cancer, cancer therapies, or AIDS.

Diabetes mellitus.

Pregnancy.

Persistent pyelonephritis despite treatment.

Renal impairment.

Diagnosis

Diagnosis of acute pyelonephritis

Diagnosis

How do I diagnose acute pyelonephritis?

Acute pyelonephritis is diagnosed in a person with a proven urinary tract infection (UTI) who has loin pain and/or fever. There are no clinical features or routine investigations that conclusively distinguish acute pyelonephritis from cystitis.

Suspect acute pyelonephritis in people with loin pain and/or fever.

Dipstick test the urine for leucocyte esterase and nitrite for evidence of a UTI. For further information, see Dipstick testing.

If both dipstick tests are negative, a UTI is unlikely.

If the leucocyte esterase test alone is positive, a UTI is moderately likely.

If the nitrite test is positive, with or without a positive leucocyte esterase test, a UTI is highly likely.

Consider and exclude other causes of loin pain and/or fever (particularly if both dipstick tests are negative), including:

Pelvic inflammatory disease.

Appendicitis.

Renal calculi.

Send a midstream (or catheter) specimen of urine for culture and sensitivity.

A final diagnosis of acute pyelonephritis is made in people with loin pain and/or fever if:

A UTI is confirmed by culturing a urinary pathogen from the urine, and

Other causes for symptoms have been excluded.

Dipstick testing

Dipstick testing

Urinary nitrite and leucocyte esterase

People with acute pyelonephritis have increased numbers of white blood cells and bacteria in their urine.

Nitrite is produced by most urinary pathogens in contact with urine. A positive nitrite test is strongly suggestive of a urinary tract infection (UTI). A negative result occurs when:

No pathogens are present.

Pathogens are present but were not in contact with urine long enough to produce detectable levels of nitrite.

Pathogens that do not produce nitrite are present.

Leucocyte esterase is present in white blood cells.

A positive leucocyte esterase test occurs when sufficiently high levels of white blood cells are present in urine as a response to either infection or contamination.

A negative leucocyte esterase test occurs either because there is no infection present or because infection is present but the numbers of white blood cells are insufficient to produce a positive result.

Interpretation of urine dipstick tests in people with urinary tract symptoms

Nitrite positive, and leucocyte esterase positive or negative — over 90% will have a UTI.

Nitrite negative and leucocyte positive — 50% will have a UTI.

Nitrite negative and leucocyte negative — 5% will have a UTI.

[Ramakrishnan and Scheid, 2005; COMPASS, 2012]

Basis for recommendation

Basis for recommendation

Clinical features suggestive of infection localized to the upper urinary tract

In the absence of more sensitive clinical features or practical clinical tests, experts recommend diagnosing acute pyelonephritis based on evidence of a UTI in a person with loin pain or a temperature over 38°C [Tomson and Armitage, 2010].

Dipstick tests for nitrite and leucocyte esterase

Experts recommend urinary dipstick tests to detect nitrite and leucocyte esterase to help distinguish people with acute pyelonephritis from those with similar symptoms and signs who do not have a urinary tract infection (UTI) [COMPASS, 2012; SIGN, 2012;].

Although dipstick tests are neither highly sensitive nor specific, they help support decisions to either start immediate treatment for pyelonephritis or investigate for other causes of symptoms and signs.

Microbiological examination of urine for all people with suspected pyelonephritis

Experts recommend sending a midstream or catheter specimen of urine for culture and sensitivity in all people with suspected acute pyelonephritis to [SIGN, 2012; HPA and British Infection Association, 2013]:

Confirm the diagnosis.

Guide an appropriate change of treatment if the infection is not sensitive to empirical antibiotics.

Management

Management

Scenario: Management : covers management of people with acute pyelonephritis, including the decision to treat in primary care or admit to secondary care.

Scenario: Management

Scenario: Management of acute pyelonephritis

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Admission or treatment

When should I arrange admission for a person with acute pyelonephritis?

Admit people who:

Are significantly dehydrated or who are unable to take oral fluids and medications.

Have signs of sepsis, including:

A temperature greater than 38°C or less than 36°C, and

Marked signs of illness (such as impaired level of consciousness, perfuse sweating, rigors, pallor, significantly reduced mobility), or

Significant tachycardia, hypotension, or breathlessness.

Are pregnant and pyrexial.

Are frail, elderly residents in care homes who have recently been hospitalized or who have had recurrent urinary tract infection.

Fail to improve significantly within 24 hours of starting antibiotics.

Consider admitting people who are able to take oral fluids and medications if they are pyrexial and have a risk factor for developing a complication. In the absence of any widely accepted admission criteria, clinical judgement on when to admit is required. A low threshold is required for people with:

Immunocompromise, for example due to immunosuppressant drug use, cancer, cancer therapies, or AIDS.

A foreign body within the renal tract, including renal stones and ureteric or nephrostomy catheters.

Abnormalities of renal tract anatomy or function, including vesico–ureteric reflux and polycystic kidney disease.

Diabetes mellitus.

Renal impairment.

Advanced age.

Manage in primary care those people with acute pyelonephritis who are:

Pyrexial but have no risk factors for developing a complication from acute pyelonephritis.

Apyrexial, with or without risk factors for developing a complication.

Basis for recommendation

Basis for recommendation

These recommendations are largely based on expert opinion and limited evidence of the risk factors for developing complications from acute pyelonephritis.

Absolute indications for hospital admission

There is expert consensus to arrange admission for people with acute pyelonephritis who:

Are unable to take fluid and medications [Neumann and Moore, 2011].

Have signs of sepsis [Neumann and Moore, 2011].

Fail to improve within 24 hours of starting antibiotics in primary care [HPA and British Infection Association, 2013].

A number of experts recommend arranging admission for all pregnant women with acute pyelonephritis, for at least a short observation period, because of the risk of preterm labour and maternal renal complications [Ramakrishnan and Scheid, 2005; COMPASS, 2012].

Experts from the Health Protection Agency recommend treatment with ertapenem, or other carbapenem, for frail, elderly residents from care homes who have been recently hospitalized or who have had recurrent urinary tract infection, because they are at increased risk of having a pathogen resistant to ciprofloxacin and cephalosporins [Livermore, Personal Communication, 2009].

Treatment requires hospital admission because carbapenems are only available in an intravenous form and no suitable oral alternative exists.

Relative indications for hospital admission

Although experts recommend considering admission for people with a risk factor for developing a complication from acute pyelonephritis, CKS could find no specific criteria as to when to arrange admission for those with:

Immunocompromise.

A foreign body within the renal tract.

Abnormalities of renal tract anatomy or function.

Diabetes mellitus.

Renal impairment.

Advanced age.

Serious complications from acute pyelonephritis can develop rapidly. It is therefore recommended that there should be a low threshold for arranging admission for people with the above risk factors.

Treatment in primary care

People without signs of sepsis or risk factors for developing a complication of acute pyelonephritis have a good prognosis. Experts widely recommend treatment of these people in primary care [Ramakrishnan and Scheid, 2005].

In the absence of any trial evidence, experts agree that people who are apyrexial and appear otherwise well can be considered to be at low risk for developing a serious complication from acute pyelonephritis, whether they have a risk factor or not [Solomon, Personal Communication, 2009; Wullt, Personal Communication, 2009].

Management

How do I manage a person with suspected acute pyelonephritis in primary care?

Arrange admission, if this is indicated. See Admission or treatment for further information.

Obtain a midstream (or catheter specimen) of urine for culture and sensitivity testing before starting empirical antibiotics.

Prescribe an antibiotic.

For women who are not pregnant, men, and people with indwelling catheters:

Treat with ciprofloxacin 500 mg twice daily for 7 days.

Co-amoxiclav 500/125 mg three times a day for 14 days is an alternative.

For pregnant women who do not require admission:

Treat with cefalexin 500 mg twice daily for 10 to 14 days.

Treat pain and fever with paracetamol.

Maintain full hydration — advise sufficient fluid intake to ensure frequent passage of pale-coloured urine.

Review 24 hours after starting treatment and arrange admission if there is any clinical deterioration or the person does not respond to treatment.

Review culture and sensitivity results when they become available, and change the antibiotic if indicated.

Consider referral for investigation of an underlying abnormality of the renal tract, for:

Men, following their first episode of acute pyelonephritis.

Women, following two or more episodes of acute pyelonephritis.

All people with a urinary tract infection caused by Proteus species.

Basis for recommendation

Basis for recommendation

Antibiotics

These recommendations conform with advice issued by the Health Protection Agency (HPA) [HPA and British Infection Association, 2013].

The HPA recommend ciprofloxacin and co-amoxiclav for the empirical treatment of acute pyelonephritis. This is based on the need to cover the broad spectrum of pathogens that cause acute pyelonephritis, and their excellent kidney penetration. Cefalexin has a reduced spectrum of activity, but is considered to have a better safety profile in pregnant women.

Although ciprofloxacin, cefalexin, and co-amoxiclav are associated with an increased risk of Clostridium difficile, meticillin-resistant Staphylococcus aureus (MRSA), and other antibiotic-resistant infections, this has to be balanced against the risk of treatment failure and consequent serious complications with the use of narrow spectrum antibiotics.

Treatment of pain and fever

Paracetamol is recommended by experts, based on the extrapolation of the effectiveness of paracetamol in the treatment of pain and fever in other conditions [COMPASS, 2012].

Nonsteroidal anti-inflammatory drugs are generally not recommended by experts because they are thought to increase the risk of renal impairment in people with acute pyelonephritis [COMPASS, 2012].

Maintenance of full hydration

This is recommended by experts to maintain a high urine output [COMPASS, 2012], which is believed to help resolve acute pyelonephritis by mechanically flushing the bacteria from the kidney.

Referral criteria for investigation of an underlying risk factor

In the opinion of experts, these criteria identify most people who are likely to have an underlying abnormality of the renal tract and are based on evidence that [Zandi-Nejad and Brown, 2001]:

Men with acute pyelonephritis are more likely to have an underlying abnormality of renal function or anatomy.

People with recurrent acute pyelonephritis are more likely to have an underlying abnormality of renal function or anatomy.

Proteus species is much more common in people with renal calculi.

Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (http://medicines.org.uk/emc), or the British National Formulary (BNF) (www.bnf.org).

Ciprofloxacin

Ciprofloxacin

Contraindications and cautions

What are the contraindications and cautions for ciprofloxacin?

Do not prescribe ciprofloxacin to people with a history of tendon disorders related to quinolone use.

Tendon damage has been reported rarely in people taking quinolone antibiotics. It may occur within 48 hours of starting treatment and up to several months after stopping treatment.

People over 60 years of age and people also taking corticosteroids are at an increased risk of tendon damage.

If tendinitis is suspected, stop the quinolone immediately.

Prescribe ciprofloxacin with caution in:

People with:

Epilepsy or conditions that predispose to seizures.

Glucose-6-phosphate dehydrogenase deficiency — if ciprofloxacin is clinically indicated in these group of people, monitor them closely for potential occurrence of haemolysis.

Myasthenia gravis — ciprofloxacin may exacerbate the symptoms of myasthenia gravis.

Conditions which predispose to QT interval prolongation such as electrolyte disturbances.

Moderate or severe renal impairment — prescribe half of the recommended ciprofloxacin dose.

People taking drugs that may prolong QT interval, for example amiodarone, sotalol, terfenadine, and amisulpride — quinolones can also prolong the QT interval, increasing the risk of Torsades de pointes arrhythmias.

Children and adolescents — possible adverse effects related to joints or surrounding tissues.

[ABPI Medicines Compendium, 2012a; BNF 65, 2013]

Adverse effects

What key adverse effects are associated with ciprofloxacin and how do I manage them?

The key adverse effects of ciprofloxacin include:

Nausea and vomiting.

Diarrhoea — consider pseudomembranous colitis if a person develops severe diarrhoea during or after treatment with ciprofloxacin. If pseudomembranous colitis is suspected, stop treatment and admit the person (or seek specialist advice).

Headache and abdominal pain — consider prescribing a suitable analgesic. See the CKS topic on Analgesia - mild-to-moderate pain.

Hypersensitivity reaction — life-threatening allergic reactions (anaphylaxis and anaphylactoid reactions) are rare but could occur after a single dose of ciprofloxacin.

If this occurs, stop ciprofloxacin and give adequate medical treatment. See the CKS topic on Angio-oedema and anaphylaxis.

Musculoskeletal adverse effects — tendinitis and tendon rupture (especially the Achilles tendon) is rare but can occur within 48 hours of taking ciprofloxacin. This is usually seen in elderly people or people on corticosteroid treatment.

Discontinue ciprofloxacin if any signs of tendinitis (for example painful swelling or inflammation) are reported.

Advise the person to rest the affected limb.

[ABPI Medicines Compendium, 2012a; BNF 65, 2013]

Pseudomembranous colitis

Pseudomembranous colitis

Severe diarrhoea during or after treatment with antibiotics may be a sign of pseudomembranous colitis.

Pseudomembranous colitis is an acute, exudative colitis caused by Clostridium difficile, a Gram-positive toxin-releasing bacillus. It often follows antibiotic treatment and is usually of acute onset, but may become chronic.

It is a particular hazard of ampicillin, amoxicillin, co-amoxiclav, second- and third-generation cephalosporins, clindamycin, and quinolones.

[Bartlett, 2010]

Interactions

What interactions are associated with ciprofloxacin?

Methotrexate — avoid concomitant use with ciprofloxacin.

Renal tubular transport of methotrexate may be inhibited by ciprofloxacin, leading to increased plasma levels of methotrexate and increased risk of methotrexate toxicity.

Theophylline — check serum theophylline levels on day 2 of ciprofloxacin treatment and reduce theophylline dose if necessary.

Concurrent administration of ciprofloxacin and theophylline can cause an increase in serum theophylline levels, leading to theophylline-induced adverse effects.

Phenytoin — monitor phenytoin levels in people taking ciprofloxacin.

Simultaneous administration of phenytoin and ciprofloxacin may increase or decrease serum phenytoin levels.

Ciprofloxacin has also been reported to cause seizures so it should be used with caution in people with epilepsy.

Oral anticoagulants — monitor the international normalized ratio (INR) frequently during, and shortly after, co-administration of ciprofloxacin with an oral anticoagulant.

Increased anticoagulant effects and bleeding has been reported in a few people taking anticoagulants and ciprofloxacin.

Ropinirole — monitor for ropinirole-related adverse effects during, and shortly after, co-administration with ciprofloxacin, and adjust the dose of ropinirole if necessary.

Concomitant use of ropinirole with ciprofloxacin may increase the concentration of ropinirole.

Triptans — manufacturers recommend a maximum zolmitriptan dose of 5 mg in 24 hours in people taking ciprofloxacin.

Zolmitriptan levels may be increased by ciprofloxacin.

Food and dairy products — advise the person to avoid dairy products within 1–2 hours of taking ciprofloxacin.

Absorption of ciprofloxacin may be reduced by dairy products or mineral-fortified drinks, such as milk and yogurt drinks.

Supplements and over-the-counter medications — advise that due to the risk of chelation complex formation, leading to decreased absorption of ciprofloxacin, ciprofloxacin should be taken either 12 hours before, or at least 4 hours after, the following preparations:

Multivalent cation-containing drugs and mineral supplements, such as calcium, magnesium, aluminium, and iron.

Polymeric phosphate binders (such as sevelamer).

Sucralfate.

Antacids (but not histamine (H2)-receptor antagonist).

Highly buffered drugs (such as didanosine tablets) containing magnesium, aluminium, or calcium.

Oral hormonal contraception — additional contraceptive precautions are not required during or after courses of ciprofloxacin.

However, advise women about the importance of correct contraceptive practice if they experience vomiting or diarrhoea. For further information, see the section on Antibiotics in the CKS topic on Contraception - assessment.

[ABPI Medicines Compendium, 2012a; Baxter and Preston, 2013; BNF 65, 2013]

Breastfeeding

Can I prescribe ciprofloxacin to a woman who is breastfeeding?

Avoid ciprofloxacin in breastfeeding women.

Ciprofloxacin should be avoided in breastfeeding women because it can be excreted into breast milk and in animal studies they have been shown to irreversibly damage growing cartilage. However, if a complicated infection (such as a urinary tract or pseudomonas infection) really requires a quinolone, whenever possible ciprofloxacin should be used and breastfeeding continued [Schaefer et al, 2007].

The amount of ciprofloxacin excreted in breast milk is too small to be harmful but the manufacturer advises that it should be avoided in breastfeeding women where possible [BNF 65, 2013].

Co-amoxiclav

Co-amoxiclav

Contraindications and cautions

What are the contraindications and cautions for co-amoxiclav?

Do not prescribe co-amoxiclav to people with:

A true penicillin hypersensitivity. Gastrointestinal adverse effects alone (such as nausea, vomiting, or diarrhoea) do not constitute an allergy to penicillin.

History of penicillin-associated hepatic dysfunction.

Prescribe co-amoxiclav with caution in people with:

A history of allergic reaction to penicillins.

Hypersensitivity to cephalosporins.

Mononucleosis — use is not recommended due to increased risk of erythematous skin rash.

Cytomegalovirus infections.

Acute or chronic lymphocytic leukaemia.

Hepatic impairment.

Renal impairment:

Reduce the dose of co-amoxiclav if creatinine clearance is 30 mL/min or less.

[ABPI Medicines Compendium, 2012b; BNF 65, 2013]

Adverse effects

What key adverse effects are associated with co-amoxiclav and how do I manage them?

Anaphylaxis (delayed or immediate) is a serious but rare adverse effects of co-amoxiclav. If this occurs, stop co-amoxiclav and give adequate medical treatment. See the CKS topic on Angio-oedema and anaphylaxis.

The most common adverse effects of co-amoxiclav include:

Diarrhoea — suspect pseudomembranous colitis if a person develops severe diarrhoea during or after treatment with co-amoxiclav. If pseudomembranous colitis is suspected, stop treatment and consider arranging admission or seeking specialist advice.

Nausea.

Vomiting.

Skin rash.

Mucocutaneous candidosis.

[ABPI Medicines Compendium, 2012b; BNF 65, 2013]

Pseudomembranous colitis

Pseudomembranous colitis

Severe diarrhoea during or after treatment with antibiotics may be a sign of pseudomembranous colitis.

Pseudomembranous colitis is an acute, exudative colitis caused by Clostridium difficile, a Gram-positive toxin-releasing bacillus. It often follows antibiotic treatment and is usually of acute onset, but may become chronic.

It is a particular hazard of ampicillin, amoxicillin, co-amoxiclav, second- and third-generation cephalosporins, clindamycin, and quinolones.

[Bartlett, 2010]

Interactions

What key interactions are associated with co-amoxiclav?

Allopurinol — be aware that concomitant use of allopurinol and amoxicillin may increase the incidence of skin rashes. Concomitant use need not be avoided for this reason.

Anticoagulants (for example warfarin) — monitor the prothrombin time or international normalised ratio more closely with the addition or withdrawal of a penicillin, as adjustment of the anticoagulant dose may be necessary.

Prolongation of prothrombin time has been reported in people taking penicillins and warfarin concurrently.

Methotrexate — monitor methotrexate levels more closely. One recommendation is to carry out twice weekly platelet and white cell counts for 2 weeks initially, with the measurement of methotrexate levels if toxicity is suspected.

Penicillins may reduce the excretion of methotrexate. This interaction is not usually serious and risk factors are unknown (even people on low doses of methotrexate have been affected).

Probenecid — be aware that probenecid reduces the excretion of penicillin antibiotics, and may raise their serum levels. This may be a beneficial adverse effect but consider any possible detrimental effects of raised levels of penicillin antibiotics.

Oral hormonal contraception — additional contraceptive precautions are not required during or after courses of penicillins.

However, advise women about the importance of correct contraceptive practice if they experience vomiting or diarrhoea. For further information, see the section on Antibiotics in the CKS topic on Contraception - assessment.

[ABPI Medicines Compendium, 2012b; Baxter and Preston, 2013; BNF 65, 2013]

Breastfeeding

Can I prescribe co-amoxiclav to a woman who is breastfeeding?

Co-amoxiclav can be used by breastfeeding women.

Penicillin antibiotics and cephalosporins are the antibiotics of choice in breastfeeding women. When necessary, other beta-lactam antibiotics and clavulanic acid can also be used [Schaefer et al, 2007]

Cefalexin

Cefalexin

Use in pregnancy

Cefalexin can be used at any stage in pregnancy.

Available data show no evidence of teratogenicity, although the manufacturer advises caution when prescribing cefalexin in pregnancy.

Contraindications and cautions

Do not prescribe cefalexin to people with:

Known allergy to the cephalosporin group of antibiotics.

Acute porphyria.

Prescribe cefalexin with caution to penicillin-sensitive people.

The British National Formulary states that about 0.5 to 6.5% of penicillin-sensitive people will also be allergic to cephalosporins.

Key adverse effects

Gastrointestinal adverse effects (such as nausea, vomiting, and diarrhoea) are commonly reported.

The manufacturer of cefalexin advises that pseudomembranous colitis should be considered in people who develop antibiotic-associated diarrhoea. It can be mild, or can be life threatening. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone.

[ABPI Medicines Compendium, 2012c; UKTIS, 2012; BNF 65, 2013]

Evidence

Evidence

Supporting evidence

Risk factors for complications

Evidence on risk factors for developing a complication of acute pyelonephritis

Risk factors for the development of a serious complication of acute pyelonephritis have been identified in an observational study using multi-variant analysis [Efstathiou et al, 2003]. This study, however, did not quantify the level of risk from each factor. An individual's risk will vary according to their overall state of health and age. Clinical judgement must be used to estimate the risk for each person.

The study included 225 people diagnosed with acute pyelonephritis. Data were collected on:

Thirteen variables that were thought to be risk factors for the development of a serious complication of acute pyelonephritis.

Serious complications included death, treatment failure, and prolonged duration of stay in hospital.

The increased risk of a serious complication was calculated for each variable using multi-variant analysis.

Results:

Increased risk of death from acute pyelonephritis was associated with:

People older than 65 years of age.

Bedridden status.

Septic shock.

Recurrent acute pyelonephritis.

Diabetes.

Renal calculi.

Immunosuppression.

Prolonged hospitalization was associated with:

Diabetes.

Long-term catheterization.

People older than 65 years of age.

Treatment failure was associated with:

Recent hospitalization.

Recent use of antibiotics.

Search strategy

Scope of search

A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on the primary care management of acute pyelonephritis.

Search dates

September 2008 - June 2013

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline and these were adapted for other databases. Further details are available on request.

exp Pyelonephritis/, pyelonephritis.tw., upper urinary tract infection$.tw., upper UTI.tw.

Table 1 . Key to search terms.
Search commands Explanation
/ indicates a MeSH subject heading with all subheadings selected
.tw indicates a search for a term in the title or abstract
exp indicates that the MeSH subject heading was exploded to include the narrower, more specific terms beneath it in the MeSH tree
$ indicates that the search term was truncated (e.g. wart$ searches for wart and warts)
Topic specific literature search sources

European Association of Urology

Infectious Diseases Society of North America

Sources of guidelines

National Institute for Health and Care Excellence (NICE)

Scottish Intercollegiate Guidelines Network (SIGN)

Royal College of Physicians

Royal College of General Practitioners

Royal College of Nursing

NICE Evidence

Health Protection Agency

World Health Organization

National Guidelines Clearinghouse

Guidelines International Network

TRIP database

GAIN

NHS Scotland National Patient Pathways

New Zealand Guidelines Group

Agency for Healthcare Research and Quality

Institute for Clinical Systems Improvement

National Health and Medical Research Council (Australia)

Royal Australian College of General Practitioners

British Columbia Medical Association

Canadian Medical Association

Alberta Medical Association

University of Michigan Medical School

Michigan Quality Improvement Consortium

Singapore Ministry of Health

National Resource for Infection Control

Patient UK Guideline links

UK Ambulance Service Clinical Practice Guidelines

RefHELP NHS Lothian Referral Guidelines

Medline (with guideline filter)

Driver and Vehicle Licensing Agency

NHS Health at Work (occupational health practice)

Sources of systematic reviews and meta-analyses

The Cochrane Library :

Systematic reviews

Protocols

Database of Abstracts of Reviews of Effects

Medline (with systematic review filter)

EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

NIHR Health Technology Assessment programme

The Cochrane Library :

NHS Economic Evaluations

Health Technology Assessments

Canadian Agency for Drugs and Technologies in Health

International Network of Agencies for Health Technology Assessment

Sources of randomized controlled trials

The Cochrane Library :

Central Register of Controlled Trials

Medline (with randomized controlled trial filter)

EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

Drug & Therapeutics Bulletin

TRIP database

Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

Department of Health

Health Management Information Consortium (HMIC)

Patient experiences

Healthtalkonline

BMJ - Patient Journeys

Patient.co.uk - Patient Support Groups

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

British National Formulary (BNF)

electronic Medicines Compendium (eMC)

European Medicines Agency (EMEA)

LactMed

Medicines and Healthcare products Regulatory Agency (MHRA)

REPROTOX

Scottish Medicines Consortium

Stockley's Drug Interactions

TERIS

TOXBASE

Micromedex

UK Medicines Information

References

ABPI Medicines Compendium (2012a) Summary of product characteristics for Ciproxin tablets 500mg. Electronic Medicines Compendium..Datapharm Communications Ltd.www.medicines.org.uk [Free Full-text]

ABPI Medicines Compendium (2012b) Summary of product characteristics for Co-amoxiclav 500 mg/125 mg film-coated tablets. Electronic Medicines Compendium..Datapharm Communications Ltd.www.medicines.org.uk [Free Full-text]

ABPI Medicines Compendium (2012c) Summary of product characteristics for Cefalexin 500mg Capsules. Electronic Medicines Compendium..Datapharm Communications Ltd.www.medicines.org.uk [Free Full-text]

Bartlett, J.G. (2010) Clostridium difficile. In: Warrell, D.A., Cox, T.M. and Firth, J.D. (Eds.) Oxford textbook of medicine. 5th edn. Oxford: Oxford University Press. 800-803.

Baxter, K. and Preston, C.L. (Eds.) (2013) Stockley's drug interactions 2013: pocket companion. London: Pharmaceutical Press.

BNF 65 (2013) British National Formulary. 65th edn. London: British Medical Association and Royal Pharmaceutical Society of Great Britain.

COMPASS (2012) COMPASS therapeutic notes on the management of bacterial urinary tract infections in primary care. ..Northern Ireland Health and Social Care Board.www.medicinesni.com [Free Full-text]

Efstathiou, S.P., Pefanis, A.V., Tsioulos, D.I. et al. (2003) Acute pyelonephritis in adults: prediction of mortality and failure of treatment. Archives of Internal Medicine 163(10), 1206-1212. [Abstract] [Free Full-text]

Grabe, M., Bjerklund-Johansen, T.E., Botto, H. et al. (2013) Guidelines on urological infections. ..European Association of Urology.www.uroweb.org [Free Full-text]

HPA and British Infection Association (2013) Management of infection guidance for primary care for consultation and local adaptation. ..Health Protection Agency.www.hpa.org.uk [Free Full-text]

Livermore, D. (2009) Personal communication. Director, Antibiotic Resistance Monitoring and Reference Laboratory, Health Protection Agency: London.

Neumann, I. and Moore, P. (2011) Pyelonephritis (acute) in non-pregnant women. Clinical Evidence..BMJ Publishing Ltd.www.clinicalevidence.com [Free Full-text]

NICE (2013) Key therapeutic topics - medicines management options for local implementation. ..National Institute for Health and Care Excellence.www.nice.org.uk [Free Full-text]

NPC (2011) Key therapeutic topics 2010/11 - Medicines management options for local implementation. ..National Prescribing Centre.www.npc.nhs.uk [Free Full-text]

NPC (2012) Key therapeutic topics - medicines management options for local implementation. ..National Prescribing Centre.www.npc.nhs.uk [Free Full-text]

Ramakrishnan, K. and Scheid, D.C. (2005) Diagnosis and management of acute pyelonephritis in adults. American Family Physician 71(5), 933-942. [Abstract] [Free Full-text]

Schaefer, C., Peters, P. and Miller, R.K. (Eds.) (2007) Drugs during pregnancy and lactation: treatment options and risk assessment. 2nd edn. Oxford: Academic Press.

SIGN (2012) Management of suspected bacterial urinary tract infection in adults: a national clinical guideline. ..Scottish Intercollegiate Guidelines Network.www.sign.ac.uk [Free Full-text]

Solomon, L. (2009) Personal communication. Consultant in General Medicine, Royal Preston Hospital: Preston.

Tomson, C. and Armitage, A. (2010) Urinary tract infection. In: Warrell, D.A., Cox, T.M. and Firth, J.D. (Eds.) Oxford textbook of medicine. 5th edn. Oxford: Oxford University Press. 4103-4122.

UKTIS (2012) Use of cephalosporins in pregnancy. TOXBASE..UK Teratology Information Service.www.toxbase.org

Wullt, B. (2009) Personal communication. Consultant in Urology, Gainsborough NHS Treatment Centre: Gainsborough.

Zandi-Nejad, K. and Brown, P.D. (2001) Diagnostic investigation of pyelonephritis. Current Infectious Diseases Reports 3(6), 529-533. [Abstract]