Upper Urinary Tract Infection ( UTI ) ( pyelonephritis/urosepsis ) in Adults ( ≥ 16 years of age ) - Guideline for the management of in secondary care

Publication: 22/10/2013  
Last review: 22/08/2018  
Next review: 22/08/2021  
Clinical Guideline
CURRENT 
ID: 3501 
Approved By: Improving Antimicrobial Prescribing Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2018  

 

This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

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Update October 2018: Table 1 and reference to aztreonam under Directed therapy have been updated to reflect Aztreonam dose change as 1g vials are now available.

Guideline for Management of Upper Urinary Tract Infection (pyelonephritis/urosepsis) in Adults (≥ 16 years of age)

Summary
Upper Urinary Tract Infection ( UTI ) ( pyelonephritis/urosepsis ) in Adults ( ≥ 16 years of age )

Clinical diagnosis

  • The diagnosis of upper urinary tract infection (upper UTI) is primarily based on symptoms and signs.
  • Upper UTI symptoms/signs include: Dysuria, frequency and fever (≥ 37.7°C) with other features including rigors, back pain, costovertebral angle (loin) pain.
  • In a patient with a urinary tract infection who is sufficiently unwell as to require blood cultures collecting, their UTI should be considered an upper UTI.

Investigations required

  • A urine dipstick test should be performed on a mid-stream or “single pass catheter” urine sample from any hospital patient in whom upper UTI is being considered.
  • Urine dipstick results:
    • A positive nitrite test is good evidence of a UTI when combined with symptoms of a UTI.
    • If negative (for nitrite, leukocyte esterase, protein and blood), then a urinary tract infection is unlikely, with a negative predictive value ≥ 95%.
  • All patients with suspected upper UTI should have a urine sample sent for microbiological analysis.
  • Patients with a suspected upper UTI and systemic inflammatory response syndrome (SIRS) or signs of severe sepsis should have a blood culture taken before antibiotics are started.
  • Ultrasound: All patients with a diagnosis of upper UTI should have a renal ultrasound.

Non-Antimicrobial Management
Supportive therapy includes management of severe sepsis (see severe sepsis bundle) and sepsis. This includes:

  • IV fluids
  • Oxygen therapy
  • Discussion with the ICU outreach.

Empirical (initial) antimicrobial treatment
Empirical treatment depends upon:

  • Severity of infection
  • Previous microbiological results.

Therefore, before treating:

  • Define the severity of infection
  • Check the patient’s previous susceptibility testing results.

Table 1. Empirical Antimicrobial therapy for upper UTI.

Severity Classification

Recommended Treatment          

Suitable in penicillin allergy:

No sepsis

Ciprofloxacin Description: electronic Medicines Compendium information on Ciprofloxacin PO 500mg 12-hourly1

Ciprofloxacin Description: electronic Medicines Compendium information on Ciprofloxacin PO 500mg 12-hourly1

Sepsis

Age <65
Cefuroxime Description: electronic Medicines Compendium information on Cefuroxime IV 1.5g 8-hourly
Age >65
Aztreonam Description: electronic Medicines Compendium information on Aztreonam 3IV 1g 8-hourly

Aztreonam Description: electronic Medicines Compendium information on Aztreonam 3IV 1g 8-hourly

Severe sepsis

 

Age <65
Cefuroxime Description: electronic Medicines Compendium information on Cefuroxime IV 1.5g 8-hourly +/- Gentamicin. Refer to LTHT Gentamicin prescribing guidance
Age >65
Aztreonam Description: electronic Medicines Compendium information on Aztreonam 3IV 1g 8-hourly +/- Gentamicin2
Refer to LTHT Gentamicin prescribing guidance

Aztreonam Description: electronic Medicines Compendium information on Aztreonam 3IV 1g 8-hourly +/- Gentamicin2
Refer to LTHT Gentamicin prescribing guidance

In Pregnancy
(No sepsis, sepsis and severe sepsis)

Cefuroxime Description: electronic Medicines Compendium information on Cefuroxime IV 1.5g 8-hourly

Aztreonam Description: electronic Medicines Compendium information on Aztreonam 3 IV 1g 8-hourly
Mild allergy to penicillin only: Cefuroxime Description: electronic Medicines Compendium information on Cefuroxime IV 1.5g 8-hourly.

1 -If unable to tolerate oral Ciprofloxacin Description: electronic Medicines Compendium information on Ciprofloxacin replace with IV Ciprofloxacin Description: electronic Medicines Compendium information on Ciprofloxacin 400mg 12-hourly
2 - See text below for advice on gentamicin prescribing.
3_ This is an alternative in beta lactam allergy as recommended by microbiology. Use in pregnancy is against Summary of Product Characteristics (SPC) recommendation.

See also;

Referral criteria for specialist input
Consider a urological referral in patients with

  • Recurrent UTIs: ≥1 year for men or ≥ 3 per year (or ≥ 2 per 6 months) for women or who persistently fail to respond to appropriate treatment
  • Persistent haematuria
  • Features of urinary obstruction
  • Renal calculi
  • History of upper UTIs or previous genito-urinary tract surgery.

Abnormality seen on ultrasound imaging.

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Background

The distal urethra is exposed to bacteria from the environment and from a patient’s normal bowel flora (e.g. Escherichia coli). These bacteria can ascend the urethra to the bladder and from there ascend the ureters to the kidneys. This may result in an upper urinary tract infection (upper UTI). Occasionally bacteria in the blood or from adjacent structures in the pelvis/abdomen can enter the kidneys and cause upper UTI. [Evidence level B]

Risk Factors

Risk factors for upper UTI in non-pregnant women include sexual intercourse three or more times per week during the previous 30 days, UTIs in the previous 12 months, diabetes, stress incontinence in the previous 30 days, a new sex partner in the previous year, recent spermicide use, and a history of UTIs in the patient's mother. Older women, women who are menopausal or pregnant, and women who have preexisting urinary tract structural abnormalities or obstructions have a higher risk of UTI, but not necessarily of acute upper UTI.1 [Evidence level B]

Epidemiology

Among the female population, annual rates of outpatient and inpatient upper UTI have been estimated at 12–13 cases per 10,000 population and 3–4 cases per 10,000 population, respectively; among the male population, the rates were 2–3 cases per 10,000 population and 1–2 cases per 10,000 population, respectively. Incidence was highest among young women, followed by infants and the elderly population. The ratio of outpatient to inpatient cases was highest among young women (ranging from 5:1 to 6:1). Escherichia coli causes 80% of cases of acute upper UTI in women and 70% of cases in men but is less dominant in older age groups. 2 [Evidence level B]

Bacterial aetiology

  • Over 95% of UTIs are caused by a single bacterial species.
  • The frequency of different species involved varies with clinical setting, e.g. community or hospital acquisition.
  • The predominant organism in acute infection is E. coli (75-85%).
  • Other relatively common pathogens include Proteus species (which can be associated with renal stone formation), Klebsiella spp, and Enterococcus spp (which are often associated with renal tract instrumentation).
  • Staphylococcus aureus is an uncommon cause of upper UTI. In the kidney it is an occasional cause of renal abscess. This is most commonly seen in intravenous drug users who commonly have S. aureus infections which can metastasise to the kidneys. 2 [Evidence level B]

Complications

Complications include renal abscess and death but estimates of their frequency are poorly documented. [Evidence level D]

Terminology

Upper Urinary tract infection is often called pyelonephritis. This name derives from the Greek words pyelum (renal pelvis which is formed by the proximal dilated ureter) and nephron (kidney) and itis (inflammation). Inflammation in the case of pyelonephritis is caused by infection.

Urosepsis refers to a urinary tract infection associated with sepsis. Most Urosepsis is related to the upper urinary tract and this term is used by some as an equivalent term to upper UTI/pyelonephritis.

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Clinical Diagnosis

Recommendation: The diagnosis of the upper urinary tract infection is primarily based on symptoms and signs.

Symptoms and signs to classify a UTI: 3
Lower UTI: Dysuria and frequency without other features e.g. fever, back pain, loin pain or systemic features of infection.
Upper UTI: Dysuria, frequency and fever with other features including rigors, back pain, costovertebral angle (loin) pain which is usually unilateral and may worsen on micturition, nausea, vomiting and diarrhoea. Dysuria and frequency are not present in all cases of upper UTI. [Evidence level C]

In a patient with a urinary tract infection who is sufficiently unwell as to require blood cultures collecting their UTI should be considered an upper UTI

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Severity Assessment

Recommendation: The severity of infection is classified as upper UTI without sepsis, with sepsis and with severe sepsis.
The severity of infection is classified as:

  • Upper UTI without sepsis: Upper UTI without SIRS.
  • Upper UTI with sepsis: Upper UTI with SIRS. SIRS definition: 2 or more of the following: Body temperature < 36°C or > 38°C , Heart rate > 90 bpm, Respiratory rate > 20 breaths per minute or, on blood gas, a PaCO2 less than 32 mm Hg (4.3 kPa). White blood cell count 4 × 109 or > 12 × 109 cells/L
  • Upper UTI with severe sepsis. Severe sepsis definition: sepsis with organ dysfunction e.g. hypotension, poor urine output, hypoxaemia, metabolic acidosis, clotting abnormalities or new confusion/altered mental status.

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Investigation

Recommendations:

  • A urine dipstick test should be performed on a mid-stream or “single pass catheter” urine sample from any hospital patient in whom upper UTI is being considered. 4/5 [Evidence level B]
  • Urine dipstick test should not be used on urine samples collected from indwelling catheters because bacteria colonising the catheter and the inflammation caused by the catheter, will give falsely positive nitrite and leucocyte esterase results respectively. 4/5 [Evidence level B]
  • On a urine dipstick test:4/5
    • A positive nitrite test is good evidence of a UTI when combined with symptoms of a UTI.
    • If negative (for nitrite, leukocyte esterase, protein and blood), then a urinary tract infection is unlikely, with a negative predictive value ≥ 95%. [Evidence level B]
  • All patients with suspected upper UTI should have a urine sample sent for microbiological analysis. Urine samples may be one of:
    • A midstream urine (MSU)
    • A catheter specimen urine (CSU)
    • A “post insertion of catheter” urine
    • An ileal conduit/urostomy sample
  • The method of urine collection should always be stated on the request form.
  • Patients with a suspected upper UTI and a systemic inflammatory response or signs of severe sepsis should have a blood culture taken before antibiotics are started.
  • Note: where a diagnosis of upper UTI is very likely, and the patient has provided an MSU; and sepsis/severe sepsis are absent blood cultures are not mandatory. This is because most of these patients will have the bacterial cause identified in the MSU sample. 6[Evidence level B]
  • Recommended imaging is:
  • Ultrasound: All patients with a diagnosis of upper UTI should have a renal ultrasound.
  • CT scan: All patients with a diagnosis of upper UTI and features/history of renal stones should have a renal CT scan.

Evidence review/justification for recommendations

Interpretation of microbiology results
The interpretation of microbiology investigations for UTIs is heavily dependent upon the pre-test probability i.e. the probability of infection based on the clinical examination and history. For example, where there is a high probability of infection based on the clinical history negative microbiology results do not exclude a diagnosis of urinary tract infection.

Urine dipstick testing.4/5[Evidence level B]
Near patient testing using a commercially available dipstick test is rapid and reliable. It has a good negative predictive value i.e. if all the results are negative it is unlikely a patient has a UTI.

Dipstick results that have been used in the assessment of UTI include nitrite, leukocyte esterase, blood and protein.

  • Nitrite is produced by the action of the bacterial enzyme nitrite reductase. If this test is positive it is good evidence of a UTI. This enzyme is not present in all bacteria therefore a negative result does not exclude a UTI.
  • Leucocyte esterase is detected if intact and lysed leucocytes are present. This enzyme indicates inflammation but inflammation may or may not be caused by infection. If this test is positive it is suggestive of, but does not confirm a UTI.
  • Blood and protein: haematuria and proteinuria can occur with UTIs, but are also present in many other conditions. Their presence in urine is not well associated with UTIs.

Interpreting the urine dipstick result4/5
Urine samples can be easily contaminated at the time of sampling. It is not possible to know this at the time of sampling although it may be suggested by the patient’s ability to provide a clean catch MSU. Contamination may be indicated when the sample is analysed in the laboratory, by a mixed growth and/or the presence of epithelial cells. [Evidence level B]

Nitrite positive: Evidence of UTI when combined with symptoms of a UTI.
Leucocyte esterase positive: Possible UTI though other causes of inflammation equally as likely.
Blood and/or protein positive: Not diagnostic of a UTI.
If negative (for nitrite, leukocyte esterase, protein and blood), then a urinary tract infection is unlikely, with a negative predictive value ≥ 95%. If negative, urine sample should only be sent for microbiological investigations if there is high clinical suspicion of urinary tract infection, or from patients at particular risk of urinary tract infection/asymptomatic bacteriuria.

The dipstick test should not be used to exclude bacteriuria in pregnancy.

Laboratory urinary analysis4/5 (including culture) [Evidence level B]
The interpretation of urine samples is heavily dependent upon the clinical details and the method of urine collection. For example, in the absence of urinary symptoms any growth of bacteria is likely to represent asymptomatic bacteruria or contamination. Asymptomatic bacteriuria is not a disease entity outside pregnancy and normally requires no treatment. Urinary catheters inevitably become colonised with bacteria so the growth of bacteria from urine collected via an indwelling catheter cannot be used alone as evidence of a urinary tract infection.
In the microbiology laboratory urine samples may undergo the following tests:

  • White cell count
  • Red cell count
  • Epithelial cell count
  • Bacterial culture and identification
  • Antibiotic susceptibility testing

White cell count

  • A raised white cell count in urine is called a pyuria.
  • At LTHT we define pyuria as ≥ 104 leukocytes/mL of urine (>40 leukocytes/microlitre).
  • Pyuria can be present without UTI, but its presence does increase the probability that a UTI is present.
  • Causes of pyuria in the absence of detectable bacteriuria (“sterile pyuria”) commonly include concurrent antibiotics, the presence of a foreign body (e.g. catheter), urinary calculus or neoplasm, lower genital tract infections (including urethritis, such as caused by Chlamydia). Renal tract tuberculosis is a rare cause. Early morning urine specimen(s) for acid fast bacilli (AFB) investigations should NOT be sent solely on the basis of one urine sample with “sterile” pyuria.

Red cell count

  • A raised red cell count is called haematuria
  • At LTHT we define haematuria as >140 red cells/microliter.
  • There are many causes of haematuria one of which includes infection. Haematuria is a poor indicator of bacterial infection.

Epithelial cells

  • Epithelial cells are found on the surface of internal and external body surfaces.
  • Types of epithelial cells found in urine samples include vaginal epithelial cells, urethral epithelial cells and bladder epithelial cells.
  • Epithelial cells from these different sites have different physical appearances. When microscopy of urine sample was performed manually it was possible to report the cell type.
  • If vaginal epithelial cells were seen this indicated the urine sample was contaminated by vaginal contents and so the results of the test were unreliable. This is because vaginal contents may contain white cells, red cells and bacteria.
  • Microscopy is now automated i.e. completed by machine. Automated microscopy cannot differentiate between the different types of epithelial cell. Therefore, when epithelial cells are reported it suggests there may be vaginal contamination but does not confirm it.

Bacterial count and culture

  • An estimate of the quantity of bacteria is made based on the number of bacteria growing on urine culture.
  • At LTHT we define a significant growth of bacteria as ≥105 colony forming units of pure growth/mL mid-stream specimen of urine (MSU). Urinary tract infections, principally lower UTIs, may be associated with lower bacterial counts.
  • Mixed growth from a midstream urine sample can occur e.g. E. coli and Enterococcus spp. This increases the probability that the sample is contaminated.
  • Patients with upper UTI normally have a significant growth of bacteria. Bacterial counts below this level do not exclude the diagnosis of upper UTI.
  • Rapid transport and culture, or special measures to assure preservation of the sample are essential for reliable laboratory diagnosis.
  • Delays and storage at room temperature allow organisms to multiply which generates results that do not reflect the true clinical situation. Where delays in processing are unavoidable, refrigeration at 4°C or the use of a boric acid preservative is essential.

Bacteria which are recognised as a cause of upper UTI are:

  • E. coli
  • Other coliforms including Klebsiella spp, Enterobacter spp and Proteus spp.
  • Enterococcus: antimicrobial therapy of enterococci can be difficult as they are only reliably sensitive to Amoxicillin Description: electronic Medicines Compendium information on Amoxicillin and Vancomycin Description: electronic Medicines Compendium information on Vancomycin.
  • Pseudomonas can cause upper UTI, it is most commonly seen when a urinary catheter is in situ. Pseudomonas is only sensitive to Ciprofloxacin Description: electronic Medicines Compendium information on Ciprofloxacin, Ceftazidime Description: electronic Medicines Compendium information on Ceftazidime, piperacillin/ tazobactam, and Meropenem Description: electronic Medicines Compendium information on Meropenem.

Antibacterial susceptibility testing7
Routine susceptibility testing of urines is standardised i.e. it is not different depending upon if a patient has upper or lower tract infection. Therefore not all antibiotics reported on urine culture results are suitable for the treatment of upper UTI. For example, nitrofurantoin is suitable for the treatment of lower UTI but not upper UTI. The susceptibility testing completed and reported may be modified if clinical details provided by the requester indicate upper tract infection.

Collecting urine sample(s) for Microbiology

  • Urine cultures are positive in around 90% of cases of acute upper UTI
  • Therefore for all suspected UTIs, if possible, a urine sample should be collected prior to starting empiric antimicrobial therapy.
  • The preferred sample is the mid-stream urine. This should be collected half way through urination preferably without interruption of flow to reduce contamination with urethral or peri-urethral flora.
  • Prior cleansing with water does not reduce contamination rates; and use of an antiseptic may lead to a false negative culture result.
  • For patients from whom a mid-stream urine specimen cannot be obtained, a clean-catch urine sample should be taken. After peri-urethral cleaning, the whole voided urine is collected into a sterile container; and a sample for examination is then taken from this.
  • For catheterised patients, the specimen should be obtained aseptically from a sample port in the catheter tubing. The specimen should not be taken from the collection bag.
  • The urine sample for Microbiology should normally be sent in a red-topped (boric acid containing) sterile universal container. Boric acid inhibits bacterial growth in the container post sample collection. The container should ideally be filled to the line as directed – a false negative culture result can occur with a small urine volume.

blood cultures [Evidence level B]
Both upper and lower tract UTI are likely to have urinalysis which suggests UTI. A positive blood culture suggests upper urinary tract infection is more likely than lower UTI.

In a hospital study of patients aged 5-62 years old (median 27 years) admitted with a primary discharge diagnosis of upper UTI blood cultures contributed little to clinical management. Therefore where the diagnosis of upper UTI is very likely and a good quality MSU is collected blood cultures are not mandatory.6

Non microbiological investigation

Blood tests

  • A neutrophilia is consistent with a bacterial infection and correlated with clinical findings will support the diagnosis of upper UTI.
  • C-reactive protein testing is not routinely required in patients unless the diagnosis of upper UTI is uncertain e.g. renal stones. In most patients response to therapy can be assessed by monitoring clinical signs and symptoms and the neutrophil count. In selected patients the CRP may be useful to assess response to therapy.

Radiological imaging

Recommended imaging is:

  • Ultrasound: All patients with a diagnosis of upper UTI should have a renal ultrasound.
  • CT scan: All patients with a diagnosis of upper UTI and features/history of renal stones should have a renal CT scan.
  • The sensitivity/specificity of radiological tests (ultrasound & CT) for upper UTI are ill defined.
  • Most commonly the kidneys will appear normal on radiological imaging in a patient with upper UTI.
  • The radiological abnormalities most commonly associated with upper UTI are a swollen kidney (>2cm difference in size between kidneys) and loss of cortical-medullary differentiation.
  • These radiological findings are non-specific, and may represent any causes of acute kidney injury e.g. acute glomerulonephritis.
  • Always exclude pregnancy before requesting a CT scan, and report that pregnancy has been excluded when requesting a CT scan.
  • Radiological imaging of the urinary tract may demonstrate anatomical or physical abnormalities e.g. renal stones and renal abscess. Their identification may modify the antimicrobial management of patients. If renal stones or abscess are suspected renal imaging should be completed.
  • Cancer risk from CT scans for pyelonephritis: The typical scan dose length product is 910mGycm which gives an effective dose of 13.7mSv. The risk of fatal cancer associated with this is approximately 1 in 1450. These estimates are based on a risk coefficient of 1 in 20000 per mSv and apply to a person of working age, 18-65.

Urine appearance: Production of turbid urine is reported to have a sensitivity of 90% and a specificity of 66% for the presence of symptomatic bacteriuria. This means if a patient has clear urine it is unlikely they have a UTI, but does not exclude it. It also means many patients with turbid urine do not have a UTI. Turbid urine should not in itself be used to diagnose a UTI. 5[Evidence level B]

Referral imaging
Patients meeting the criteria for urological referral should have urinary tract investigations completed prior to their specialist review. For women this normally includes a renal ultrasound. For men this normally includes a renal ultrasound and urinary flow studies. [Evidence level C]

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Treatment
Non-Antimicrobial Treatment

Supportive therapy includes management of severe sepsis and sepsis. This includes:

  • IV fluids
  • Oxygen therapy
  • Discussion with the ICU outreach.

If catheterised

  • If the catheter is no longer indicated consider catheter removal at the earliest possibility.
  • If the catheter is still indicated consider:
    • Early catheter exchange if clinically indicated with antimicrobial prophylaxis (Urinary Catheterisation Prophylaxis in Adults) or,
    • Catheter exchange when the urinary tract is considered to be sterile (>48 hours after treatment initiated) and the patient is still on antibiotics. [Evidence level D]

Consider a urological referral in patients with

  • Recurrent UTIs (≥1 year for men or ≥4 year for women) or who persistently fail to respond to appropriate treatment
  • Persistent haematuria
  • Features of urinary obstruction
  • Calculi
  • History of upper UTIs or previous genito-urinary tract surgery.
  • Abnormality seen on ultrasound imaging.

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Empirical Antimicrobial Treatment

Recommendation: Empirical treatment depends upon the severity of infection and previous microbiological results. Therefore, before treating define the severity of infection and check the patient’s previous susceptibility testing results. Modify the following guidance if antimicrobial resistance has been previously identified. [Evidence level B]

Empirical Antimicrobial [Evidence level A-D]
First define severity and previous microbiology before moving to Table 1 below.

  • Upper UTI without sepsis: Upper UTI without SIRS.
  • Upper UTI with sepsis: Upper UTI with SIRS. SIRS definition: 2 or more of the following: Body temperature < 36°C or > 38°C , Heart rate > 90 bpm, Respiratory rate > 20 breaths per minute or, on blood gas, a PaCO2 less than 32 mm Hg (4.3 kPa). White blood cell count 4 × 109 or > 12 × 109 cells/L
  • Upper UTI with severe sepsis. Severe sepsis definition: sepsis with organ dysfunction e.g. hypotension, poor urine output, hypoxaemia, metabolic acidosis, clotting abnormalities or new confusion/altered mental status
  • If there are previous microbiology results e.g. GP MSU samples to guide antibiotic therapy.
    • In certain individual cases, including if recent antimicrobial therapy &/or previous bacteriology results available, an alternative empiric antimicrobial may be more suitable (consider discussing with Microbiology).

Table 1. Empirical Antimicrobial therapy for upper UTI.

Severity Classification

Recommended Treatment          

Suitable in penicillin allergy:

No sepsis

Ciprofloxacin Description: electronic Medicines Compendium information on Ciprofloxacin PO 500mg 12-hourly1

Ciprofloxacin Description: electronic Medicines Compendium information on Ciprofloxacin PO 500mg 12-hourly1

Sepsis

Age <65
Cefuroxime Description: electronic Medicines Compendium information on Cefuroxime IV 1.5g 8-hourly
Age >65
Aztreonam Description: electronic Medicines Compendium information on Aztreonam 3IV 1g 8-hourly

Aztreonam Description: electronic Medicines Compendium information on Aztreonam 3IV 1g 8-hourly

Severe sepsis

 

Age <65
Cefuroxime Description: electronic Medicines Compendium information on Cefuroxime IV 1.5g 8-hourly +/- Gentamicin. Refer to LTHT Gentamicin prescribing guidance.
Age >65
Aztreonam Description: electronic Medicines Compendium information on Aztreonam 3IV 1g 8-hourly +/- Gentamicin2
Refer to LTHT Gentamicin prescribing guidance

Aztreonam Description: electronic Medicines Compendium information on Aztreonam 3IV 1g 8-hourly +/- Gentamicin2
Refer to LTHT Gentamicin prescribing guidance

In Pregnancy
(No sepsis, sepsis and severe sepsis)

Cefuroxime Description: electronic Medicines Compendium information on Cefuroxime IV 1.5g 8-hourly

Aztreonam Description: electronic Medicines Compendium information on Aztreonam 3 IV 1g 8-hourly
Mild allergy to penicillin only: Cefuroxime Description: electronic Medicines Compendium information on Cefuroxime IV 1.5g 8-hourly.

1 -If unable to tolerate oral Ciprofloxacin Description: electronic Medicines Compendium information on Ciprofloxacin replace with IV Ciprofloxacin Description: electronic Medicines Compendium information on Ciprofloxacin 400mg 12-hourly
2 - See text below for advice on gentamicin prescribing.
3_ This is an alternative in beta lactam allergy as recommended by microbiology. Use in pregnancy is against Summary of Product Characteristics (SPC) recommendation.

Justification/evidence review

Antimicrobial resistance
Empirical antibiotics have been chosen from those antibiotics with a high level of susceptibility in E. coli, as shown in Table 2.

Table 2. Antimicrobial resistance rates in E. coli from blood cultures- All LTHT samples 2011-12

Organism

Antibiotic

% Sensitive

E. coli

Amoxicillin Description: electronic Medicines Compendium information on Amoxicillin

32%

 

Trimethoprim3

59%

 

Co-Amoxiclav (Amoxicillin-Clavulanate) Description: electronic Medicines Compendium information on Co-Amoxiclav (Amoxicillin-Clavulanate)

65%

 

Ciprofloxacin Description: electronic Medicines Compendium information on Ciprofloxacin

83%

 

Gentamicin

92%

 

Cefuroxime Description: electronic Medicines Compendium information on Cefuroxime

92%

 

Aztreonam Description: electronic Medicines Compendium information on Aztreonam

92%

 

Piperacillin/tazobactam Description: electronic Medicines Compendium information on Piperacillin/tazobactam

92%

3 -Trimethoprim can normally be replaced by PO Co-trimoxazole (contains trimethoprim and suxamethoxazole) Description: electronic Medicines Compendium information on Co-trimoxazole <sup>(contains trimethoprim and suxamethoxazole)</sup> at 960mg 12-hourly.

Advice on the use of gentamicin

Gentamicin for synergy
Gentamicin has been shown to be synergistic with other antibiotics when tested in the laboratory. This led to regimes for treating infections that involved the use of Gentamicin in combination with other antibiotics. Analysis of trials with Gentamicin combination therapy has NOT shown any clinical advantage of combination therapy over monotherapy. Gentamicin should NOT therefore be added for synergy.8 [Evidence level A]

Gentamicin to cover for resistant bacteria
Delayed appropriate therapy affects outcome in patients with severe sepsis, therefore consider adding Gentamicin to provide effective antibiotic therapy for resistant bacterial pathogens.

Antibiotic resistance is increasing. When considering all bacteraemias from LTHT there is resistance to commonly used antibiotics e.g. Co-Amoxiclav (Amoxicillin-Clavulanate) Description: electronic Medicines Compendium information on Co-Amoxiclav (Amoxicillin-Clavulanate)(35%) Ciprofloxacin Description: electronic Medicines Compendium information on Ciprofloxacin(17%), Cefuroxime Description: electronic Medicines Compendium information on Cefuroxime(9%), piperacillin-tazobactam (9%), Aztreonam Description: electronic Medicines Compendium information on Aztreonam(8%). These figures are likely to represent an artificially high rate of resistance compared to all E. coli causing upper UTI. Gentamicin is sometimes used to cover for resistance until the infecting organism is known and susceptibility results are available, or the patient has clinically improved. For example, of Ciprofloxacin Description: electronic Medicines Compendium information on Ciprofloxacin/Cefuroxime Description: electronic Medicines Compendium information on Cefuroxime/piperacillin-tazobatam resistant E. coli approximately 70% are sensitive to Gentamicin. The rationale for gentamicin’s use is based on evidence that early treatment of infections with an antibiotic the bacteria is sensitive to is associated with a reduced mortality. 9 There is though no evidence that this strategy is associated with a reduced mortality in upper UTI. The decision to use Gentamicin is therefore a risk-benefit decision. The risk of using Gentamicin is that there is an increased risk of nephrotoxicity and ototoxicity, the benefit is that there is an increased chance the patient will receive an antibiotic the bacteria is sensitive to. [Evidence level D]

Gentamicin when a patient has renal impairment/transplant
Gentamicin can cause renal toxicity; the consequences of this toxicity are greater in patients with pre-existing renal impairment and renal transplants. The risk/benefit assessment before the use of Gentamicin should account for this. [Evidence level D]

Daily review of gentamicin
Gentamicin use should be reviewed daily, it can be stopped when a patient has clinically improved or when susceptibility testing confirms the susceptibility the other prescribed antibiotic. Often only a single dose of Gentamicin is prescribed on admission and stopped before a second dose following a patient’s clinical response. [Evidence level D]

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Directed Antimicrobial Treatment (when microbiology results are known)

Recommendation: Antimicrobial susceptibility results should be reviewed 48-72 hours after sending a urine result to microbiology. [Evidence level B]

Recommendation: Where susceptibility results are available these should guide antimicrobial prescription. [Evidence level B]

Review urine culture results at 48-72hours

Antibiotics to be avoided in upper UTI 10 (despite being suitable for lower UTI) [Evidence level B-C]

  • Nitrofurantoin: is an ineffective treatment for upper UTI because it doesn’t achieve effective concentrations in renal/prostatic tissue. It only achieves high concentration in urine, making it suitable for lower urinary tract infections only.
  • Pivmecillinam: No evidence supports its use in upper urinary tract infections.
  • Oral Fosfomycin : No evidence supports its use in upper urinary tract infection.

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Duration of Treatment

Recommendations [Evidence level B]

Uncomplicated upper UTI

Complicated upper UTI*

The duration of therapy should take account of both IV and PO regimes. For example, a patient receiving 48 hours of iv Cefuroxime Description: electronic Medicines Compendium information on Cefuroximerequires only 5 days of Ciprofloxacin Description: electronic Medicines Compendium information on Ciprofloxacin therapy

*Complicated upper UTI: LTHT defines this as upper UTI in the presence of functional or structural abnormalities of the genitourinary tract. These include the presence of a calculus, vesicoureteric reflux, reflux nephropathy, indwelling catheter, urinary obstruction, a urinary stent; or recent instrumentation. It also includes infection in a patient with certain underlying host factors, such as immune system compromise or impaired renal function. Hospital admission does not equate to complicated upper UTI. [Evidence level B]

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Switch to oral agent(s)

Recommendation: Oral antimicrobials are indicated when clinical assessment indicates oral therapy is suitable and when susceptibility testing results are available. 48-72 hours after starting therapy is good time to assess if oral antibiotics are suitable as susceptibility testing results should be available.

Recommendation: If microbiology results are not available a decision must be made about switching to an oral antibiotic. Without microbiology results there is an increased risk an antibiotic without activity against the infecting bacteria will be prescribed. This may lead to a relapse. In some instances e.g. elderly, there may be a high risk from the oral antibiotics e.g. Co-Amoxiclav (Amoxicillin-Clavulanate) Description: electronic Medicines Compendium information on Co-Amoxiclav (Amoxicillin-Clavulanate), for Clostridium difficile infection. Consideration can therefore be given to completing a course of IV therapy with an antimicrobial with a low risk of C. difficile infection (piperacillin-tazobactam or Aztreonam Description: electronic Medicines Compendium information on Aztreonam).

Oral antimicrobial options are shown in Table 3 and Table 4.

Table 3: Oral antimicrobial therapy-microbiology susceptibility results available.

Drug

Notes

Ciprofloxacin Description: electronic Medicines Compendium information on Ciprofloxacin500mg 12-hourly

Avoid in pregnancy

Trimethoprim 200mg 12-hourly3

Avoid in first trimester of pregnancy

Co-Amoxiclav (Amoxicillin-Clavulanate) Description: electronic Medicines Compendium information on Co-Amoxiclav (Amoxicillin-Clavulanate)625mg 8-hourly

Risk of Clostridium difficile
Not suitable in penicillin allergy

Cefalexin Description: electronic Medicines Compendium information on Cefalexin500mg 8-hourly

Risk of Clostridium difficile
Not suitable in severe penicillin allergy

Amoxicillin Description: electronic Medicines Compendium information on Amoxicillin500mg 8-hourly

Not suitable in penicillin allergy

3 No published criteria are available to test if Trimethoprim is likely to be effective for upper UTIs and some Gram positive bacteria. We therefore report Co-trimoxazole (contains trimethoprim and suxamethoxazole)Description: electronic Medicines Compendium information on Co-trimoxazole <sup>(contains trimethoprim and suxamethoxazole)</sup> susceptibility results in some patients.

Co-trimoxazole (contains trimethoprim and suxamethoxazole) Description: electronic Medicines Compendium information on Co-trimoxazole <sup>(contains trimethoprim and suxamethoxazole)</sup> sensitivity can normally be used to infer Trimethoprim sensitivity.

Trimethoprim can be replaced by PO Co-trimoxazole (contains trimethoprim and suxamethoxazole) Description: electronic Medicines Compendium information on Co-trimoxazole <sup>(contains trimethoprim and suxamethoxazole)</sup> at 960mg 12-hourly which is recommended in a number of international guidelines10.

Prescribers of Co-trimoxazole (contains trimethoprim and suxamethoxazole) Description: electronic Medicines Compendium information on Co-trimoxazole <sup>(contains trimethoprim and suxamethoxazole)</sup> should note that Co-trimoxazole (contains trimethoprim and suxamethoxazole) Description: electronic Medicines Compendium information on Co-trimoxazole <sup>(contains trimethoprim and suxamethoxazole)</sup> is associated with rare but serious side-effects (e.g. Stevens-Johnson syndrome and blood dyscrasias, notably bone marrow depression and agranulocytosis) especially in the elderly.

Table 4 Oral antimicrobial therapy- without microbiology results to guide choice

Empirical IV therapy

Oral suggestion

Notes

Ciprofloxacin Description: electronic Medicines Compendium information on Ciprofloxacin

Ciprofloxacin Description: electronic Medicines Compendium information on Ciprofloxacin500mg 12-hourly PO

Risk of Clostridium difficile

Piperacillin/tazobactam Description: electronic Medicines Compendium information on Piperacillin/tazobactam

Ciprofloxacin Description: electronic Medicines Compendium information on Ciprofloxacin500mg PO 12-hourly
or
Co-Amoxiclav (Amoxicillin-Clavulanate) Description: electronic Medicines Compendium information on Co-Amoxiclav (Amoxicillin-Clavulanate)625mg PO 8-hourly

Risk of Clostridium difficile with Ciprofloxacin Description: electronic Medicines Compendium information on Ciprofloxacin and Co-Amoxiclav (Amoxicillin-Clavulanate) Description: electronic Medicines Compendium information on Co-Amoxiclav (Amoxicillin-Clavulanate).
Piperacillin/tazobactam Description: electronic Medicines Compendium information on Piperacillin/tazobactam and
Co-Amoxiclav (Amoxicillin-Clavulanate) Description: electronic Medicines Compendium information on Co-Amoxiclav (Amoxicillin-Clavulanate) are not suitable in penicillin allergy

Cefuroxime Description: electronic Medicines Compendium information on Cefuroxime

Co-Amoxiclav (Amoxicillin-Clavulanate) Description: electronic Medicines Compendium information on Co-Amoxiclav (Amoxicillin-Clavulanate)625mg PO 8-hourly

Risk of Clostridium difficile
Co-Amoxiclav (Amoxicillin-Clavulanate) Description: electronic Medicines Compendium information on Co-Amoxiclav (Amoxicillin-Clavulanate) is not suitable in penicillin allergy.
Cefuroxime Description: electronic Medicines Compendium information on Cefuroxime is not suitable in severe penicillin allergy

Aztreonam Description: electronic Medicines Compendium information on Aztreonam

Ciprofloxacin Description: electronic Medicines Compendium information on Ciprofloxacin500mg PO 12-hourly

Risk of Clostridium difficile

Justification/evidence review
Where possible empirical oral antibiotics have been chosen from those antibiotics with a high level of susceptibility in E. coli, as shown in Table 5.

Table 5: Antimicrobial susceptibility rates E. coli in MSU samples- All LTHT samples 2011-12.

Organism

Antibiotic

% Sensitive

E. coli

Amoxicillin Description: electronic Medicines Compendium information on Amoxicillin

46%

 

Trimethoprim

63%

 

Ciprofloxacin Description: electronic Medicines Compendium information on Ciprofloxacin

91%

 

Co-Amoxiclav (Amoxicillin-Clavulanate) Description: electronic Medicines Compendium information on Co-Amoxiclav (Amoxicillin-Clavulanate)

Not known

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Treatment Failure
Please discuss these patients with microbiology for a full review of their diagnosis and previous microbiology results.

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Provenance

Record: 3501
Objective:

Aims

  • To standardise and improve the diagnosis and management of upper urinary tract infections in adults (≥ 16 years of age).

Objectives

  • To provide evidence-based recommendations for the diagnosis, appropriate investigation and antimicrobial therapy of upper urinary tract infections in adults (≥ 16 years of age).
  • To advise in the event of antimicrobial allergy.
  • To set-out criteria for referral to specialists.
Clinical condition:

Upper Urinary Tract Infection (pyelonephritis/urosepsis)

Target patient group: Adults (≥ 16 years of age)
Target professional group(s): Secondary Care Doctors
Pharmacists
Adapted from:

Evidence base

Evidence base

  1. Diagnosis and treatment of acute upper UTI in women. Colgan R, Williams M, Johnson JR. Am Fam Physician. 2011 Sep 1; 84(5):519-26.
  2. Population-based epidemiologic analysis of acute pyelonephritis. Czaja CA, Scholes D, Hooton TM, Stamm WE. Clin Infect Dis. 2007 Aug 1; 45(3):273-80.
  3. Sobel J D and Kaye D. Urinary tract infections. In: Mandell GL, Bennett JE, Dolin R. (eds) Principles and Practice of Infectious Diseases 7th Edn 2009 875-905.
  4. http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1194947404720
  5. SIGN Management of suspected bacterial urinary tract infection in adults A national clinical guideline July 2006
  6. McMurray BR, Wrenn KD, Wright SW.Usefulness of blood cultures in pyelonephritis. Am J Emerg Med. 1997 Mar; 15(2):137-40.
  7. A. Kucers, N. McK. Bennett, and R. J. Kemp, The Use of Antibiotics: A Comprehensive Review with Clinical Emphasis, Lippincott Williams & Wilkins, Philadelphia, Pa, USA, 4th edition, 1987.
  8. Beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy for sepsis in immunocompetent patients: systematic review and meta-analysis of randomised trials. BMJ. 2004 Mar 20; 328(7441):668.
  9. Paul M, Benuri-Silbiger I, Soares-Weiser K, Leibovici L. (Liebovici).
  10. IDSA Guidelines for Antimicrobial Treatment of Uncomplicated Acute Bacterial Cystitis and Acute Pyelonephritis in Women. Clinical Infectious Diseases 1999; 29:745-758.

Evidence levels:
A. Meta-analyses, randomised controlled trials/systematic reviews of RCTs
B. Robust experimental or observational studies
C. Expert consensus.
D. Leeds consensus. (where no national guidance exists or there is wide disagreement with a level C recommendation or where national guidance documents contradict each other)

Approved By

Improving Antimicrobial Prescribing Group

Document history

LHP version 1.0

Related information

Not supplied

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