Upper urinary tract infections (U-UTI) and urosepsis in non-pregnant adults

Upper urinary tract infections (U-UTI) and urosepsis in non-pregnant adults - secondary care

Publication: 22/10/2013

Next review: 17/02/2025

Clinical Guideline

CURRENT

ID: 3501

Approved By: Improving Antimicrobial Prescribing Group

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.

UPPER URINARY TRACT INFECTIONS (U-UTI) AND UROSEPSIS IN NON-PREGNANT ADULTS

Diagnostics
Assessment
Empirical Treatment
Review by 72
Directed Therapy
Empirical switch from IV
Appendix 1 - Susceptibility data

Signs and symptoms of upper UTI include acute dysuria, frequency and fever (>38C) with systemic signs of infection, such as rigors and back/loin pain.

Any patient with a suspected or proven upper urinary tract source of infection should be treated as per this guideline.

This guideline should also be used for patient with a suspected or proven urinary tract source of severe sepsis or who are nil by mouth at the time of initiating antibiotics.

If your patient has signs of signs and symptoms of Lower UTI without signs of severe sepsis, please see the Lower UTI guideline.
Please see separate guidance for UTI in pregnancy and prostatitis.

Antibiotics are not routinely required following urinary tract instrumentation (see Urinary procedures prophylaxis guidance), and should only be initiated if there are clinical signs and symptoms of urinary sepsis, when this guidance should be followed.

UTI should not be diagnosed purely on the basis of bacteriuria or pyuria in a urine sample.

DIAGNOSTICS

Whilst upper UTI or Urosepsis is ultimately a clinical diagnosis, appropriate sampling allows appropriately directed treatment.

All patients	Blood culture (prior to starting antibacterials)
	MSU (or CSU if catheterised) should be sent from all symptomatic patients, prior to antibacterials (do not delay antibacterials with severe sepsis)
	Renal tract imaging is required
All patients	Do not perform urine dipsticks

ASSESSMENT: Complicated or uncomplicated upper UTI

All UTIs should be classified as either complicated or uncomplicated as per the table below:

Uncomplicated upper UTIs	Acute, sporadic or recurrent upper UTI, limited to non-pregnant women with no known relevant anatomical or functional abnormalities within the urinary tract or comorbidities
Complicated upper UTIs	These are UTIs with an increased chance of a complicated course (e.g. persistent infection, treatment failure, recurrence): i.e. men, pregnant women, relevant anatomical or functional abnormalities of the urinary tract, indwelling urinary tract prosthetic material including catheters, renal diseases, immunocompromise, diabetes mellitus

EMPIRICAL TREATMENT (renal dose adjustment may be required)

If your patient has had a positive urine or blood culture with a coliform (e.g. E.coli, Klebsiella spp, Enterobacter spp in the past, please:
- Check previous results for evidence of multi resistant coliforms (e.g. ESBL, AMP-C, CPE)
- Check for resistance to empirical treatment options below.
- Discuss with microbiology if resistance has been previously reported.
Ensure adequate fluids and offer appropriate (simple) analgesia
Please use the DIRECTED TREATMENT section if your patient has a current blood culture or urine culture result available at the time of initiating antibiotics.
Notes on empirical options:
- Doses assume normal renal and hepatic function

Severity classification	Recommended treatment	2nd line
Duration: Patients with no sepsis and uncomplicated UTI: 7 days Patients with sepsis: see directed therapy for durations
No sepsis	Ciprofloxacin ¹ PO 500mg 12-hourly If unable to take orally, then give Ciprofloxacin IV 400mg 12-hourly.
Sepsis	Age <65 Cefuroxime IV 1.5g 8-hourly^2,3	Age <65 with allergy to penicillins and not able to tolerate cephalosporins Ciprofloxacin ¹ PO 500mg 12-hourly (give IV if unable to absorb) +/- a stat dose of Gentamicin³
	Age ≥65 Piperacillin/tazobactam IV 4.5g 8-hourly	Age ≥65 AND allergy to penicillins/cephalosporins Aztreonam IV 1g 8-hourly
Severe sepsis	Age <65 Cefuroxime IV 1.5g 8-hourly +/- a stat dose of Gentamicin⁴	Age <65 with allergy to penicillins and not able to tolerate cephalosporins Ciprofloxacin ¹ IV 400mg 12-hourly +/- a stat dose of Gentamicin⁴
	Age ≥65 Piperacillin/tazobactam IV 4.5g 8-hourly +/- a stat dose of Gentamicin⁴	Age ≥65 with allergy to Penicillins/Cephalosporins Aztreonam IV 1g 8-hourly +/- a stat dose of Gentamicin⁴
	*‘+/- a stat dose of gentamicin’: A stat dose of Gentamicin4 can be given empirically whilst awaiting culture results if the patient does not initially respond to single agent therapy. Gentamicin prescribing guidance* can be found here. LTHT uses once daily dosing with 7mg/kg IBW (ideal body weight) and the Yorkshire Hartford Nomogram for monitoring and dosing frequency. A level should be taken following all treatment doses of gentamicin in case continuation is required.
Previous resistant organism5 (MR-GNB, e.g. ESBL, AMP-C or CPE) in any sample	Refer to susceptibility results. If resistant (or not detailed on the report) to the severity/age appropriate choice(s) listed above, please discuss with Microbiology.
*Previous Pseudomonas aeruginosa* from the urinary tract (including swabs of sites of entry to the urinary tract)**	Refer to susceptibility results and the DIRECTED TREATMENT table below. Discuss with Microbiology if required.

REVIEW BY 72 HOURS

By 72 hours of antibiotic treatment, diagnostics should have proven your initial diagnosis or guided to a new diagnosis. If your patient is prescribed IV antibiotics then they should be reviewed daily.

The review, outcome and future plans (where appropriate) should be documented in the medical notes.

IVOS (IV to Oral Switch)	If your initial diagnosis is correct and the patient is prescribed IV antibiotics, review whether an oral switch is appropriate using the ACED criteria (see below). If they meet all 4 criteria consider switching using the oral options listed in the table above. A - Afebrile for 24 hours C - Clinically improving E - Eating and drinking D - not Deep seated infection
Stop	If no signs of infection and diagnostics support this decision.
Change	If the patient is not clinically responding, check microbiology results to see if directed therapy is required or you may need to consider an alternative diagnosis (including renal calculi, obstruction, abscess, etc). If your patient does not meet the ACED criteria yet, please de-escalate to an appropriate IV option as per table 1 below and plan for the appropriate PO option from table 2 once the ACED criteria are met.
Continue	If the patient is improving but does not fully meet ACED criteria. Review daily until ready to switch.

DIRECTED THERAPY

The tables below are in order of preference based on culture results. Please select the first appropriate agent for your patient.

Doses assume normal renal and hepatic function.

Directed IV options: for use with culture results available prior to starting treatment, or with culture results and an oral switch is not yet appropriate. Please switch to PO (table 2) at the first appropriate opportunity.

	Treatment	Notes
Duration: 7-14 days including appropriate oral step-down, agent dependent; please see table 2 for more details. Courses may need to be extended from the durations stated in table 2 if there are complicating factors, such as renal abscess, infected calculi/stents in situ - please discuss with Microbiology
1	Co-amoxiclav IV 1.2 g 8-hourly	Avoid in penicillin allergy
2	Cefuroxime IV 1.5g 8-hourly	Avoid in penicillin allergy unless known to tolerate cephalosporins (since allergy identified). Avoid in ≥65 year olds if possible.
3	Aztreonam IV 1g 8-hourly	During shortages this should not be used if there is an appropriate alternative option (incl. lower in the table)
4	Piperacillin/tazobactam IV 4.5g 8-hourly Increased to IV 4.5g 6-hourly for Pseudomonas aeruginosa	Avoid in penicillin allergy
5	Uncomplicated uUTI: Fosfomycin IV 6g 12-hourly Complicated uUTI: Fosfomcyin IV 8g 12-hourly
If susceptible to either Co-trimoxazole or Ciprofloxacin consider earlier switch to PO due to excellent oral bioavailability, see table below for doses. The IV dosing given below should be used only where the patient has inadequate enteral absorption.
	Co-trimoxazole IV 960mg 12-hourly	Avoid in trimethoprim OR sulphonamide allergy
	Ciprofloxacin IV 400mg 12-hourly (preference is PO if possible) Increased to IV 400mg 8-hourly for Pseudomonas aeruginosa	MHRA warning¹

Directed Oral options: for use with culture results prior to starting treatment where IVs are not required, or as IVOS step-down option.

Doses assume normal renal function

	Treatment		Duration	Notes
Duration of treatment: 7-14 days in total (including IV), agent dependent Courses may need to be extended from the durations below if there are complicating factors, such as renal abscess, infected calculi/stents in situ - please discuss with Microbiology
1	Age <65 Cefalexin 1.5g PO 6-hourly Note: this is 12 tablets daily, consider alternative option if there is a concern about adherence.		7 to 10 days	Do not use cefuroxime in immediate (IgE mediated) reaction to Penicillin2, unless known to tolerate cephalosporins (since time of allergy).
2	Co-amoxiclav PO 625mg 8-hourly PLUS Amoxicillin PO 500mg 8-hourly		7 to 10 days	Do not use in penicillin allergy
3	Trimethoprim PO 200mg 12-hourly		14 days
4	Co-trimoxazole PO 960mg 12-hourly		10-14 days	Do not use in trimethoprim or sulphonamide allergy
5	Ciprofloxacin PO 500mg 12-hourly Increased to 750mg 12-hourly for Pseudomonas aeruginosa		7 days	MHRA warning1
6	Amoxicillin PO 1g 8-hourly		14 days	Do not use in penicillin allergy
Antibiotics that must NOT be used for upper UTIs or Urosepsis
Nitrofurantoin		It only achieves high concentration in urine, making it suitable for lower urinary tract infections (cystitis) only.
Pivmecillinam		No evidence supports its use in upper UTI
Oral Fosfomycin		No evidence supports its use in upper UTI

Empirical oral switch from IV

Where the diagnosis is confirmed, but cultures have failed to isolate the pathogen and there are no recent results to guide directed therapy, there can be a need for an empirical oral switch from IV. This table should NOT be used if culture results are available.

Doses assume normal renal and hepatic function.

IV treatment given	Empirical Oral switch	Total duration	Notes
Courses may need to be extended from the durations below if there are complicating factors, such as renal abscess, infected calculi/stents in situ - please discuss with Microbiology
Ciprofloxacin	Ciprofloxacin ¹ PO 500mg 12-hourly	7 days	MHRA warning¹
Cefuroxime	Co-amoxiclav PO 625mg 8-hourly PLUS Amoxicillin PO 500mg 8-hourly	7-10 days	Different spectrum of activity between IV and oral option. Monitor for continued improvement.
Piperacillin/tazobactam	Co-amoxiclav PO 625mg 8-hourly PLUS Amoxicillin PO 500mg 8-hourly OR Ciprofloxacin ¹ PO 500mg 12-hourly	7-10 days 7 days
Aztreonam	Ciprofloxacin PO 500mg 12-hourly¹	7 days

Footnotes

	Treatment		Duration	Notes
Duration of treatment: 7-14 days in total (including IV), agent dependent Courses may need to be extended from the durations below if there are complicating factors, such as renal abscess, infected calculi/stents in situ - please discuss with Microbiology
1	Age <65 Cefalexin 1.5g PO 6-hourly Note: this is 12 tablets daily, consider alternative option if there is a concern about adherence.		7 to 10 days	Do not use cefuroxime in immediate (IgE mediated) reaction to Penicillin2, unless known to tolerate cephalosporins (since time of allergy).
2	Co-amoxiclav PO 625mg 8-hourly PLUS Amoxicillin PO 500mg 8-hourly		7 to 10 days	Do not use in penicillin allergy
3	Trimethoprim PO 200mg 12-hourly		14 days
4	Co-trimoxazole PO 960mg 12-hourly		10-14 days	Do not use in trimethoprim or sulphonamide allergy
5	Ciprofloxacin PO 500mg 12-hourly Increased to 750mg 12-hourly for Pseudomonas aeruginosa		7 days	MHRA warning¹
6	Amoxicillin PO 1g 8-hourly		14 days	Do not use in penicillin allergy
Antibiotics that must NOT be used for upper UTIs or Urosepsis
Nitrofurantoin		It only achieves high concentration in urine, making it suitable for lower urinary tract infections (cystitis) only.
Pivmecillinam		No evidence supports its use in upper UTI
Oral Fosfomycin		No evidence supports its use in upper UTI

Provenance

Record:	3501
Objective:
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

NICE guideline NG111: Pyelonephritis (acute): antimicrobial prescribing https://www.nice.org.uk/guidance/ng111/resources/visual-summary-pdf-6544161037
Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, Hooton TM. Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis. 2005 Mar 1;40(5):643-54
SIGN 88: Management of suspected bacterial urinary tract infection in adults (accessed April 2020)
Johansen TE, Botto H, Cek M, Grabe M, Tenke P, Wagenlehner FM, Naber KG. Critical review of current definitions of urinary tract infections and proposal of an EAU/ESIU classification system. Int J Antimicrob Agents. 2011 Dec;38 Suppl:64-70.
Oral Antibiotics in pyleonephritis: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858297/pdf/10096_2019_Article_3679.pdf
NICE upper UTI guidance. https://www.nice.org.uk/guidance/ng111/resources/visual-summary-pdf-6544161037
NICE Clinical Knowledge Summary - Pyelonephritis - acute. Complications | Background information | Pyelonephritis - acute | CKS | NICE Last revision date at time of access, March 2021.
European Association of Urology Infection guidelines: EAU Guidelines: Urological Infections | Uroweb

Approved By

Improving Antimicrobial Prescribing Group

Document history

LHP version 2.1

Related information

APPENDIX 1

Local susceptibility data for E coli isolated from blood cultures (BC) and Urine samples in the year 2019-2020 (1/5/19-30/4/20). As the most common causative pathogen for UTIs, E coli resistance rates are monitoring to influence empirical treatment choices

Antibiotic tested	Amoxicillin	Co-amoxiclav	Ciprofloxacin	Trimethoprim	Cotrimoxazole	Cephalexin	Cefuroxime	Aztreonam	Piperacillin-tazobactam	Gentamicin
Number of blood culture isolates tested	821	820	821		821		820	820	821	821
Number of urine isolates tested	7739	1263	7741	7737		7742

For urine isolates identified as ESBL or AMPC+ that were tested for susceptibility to gentamicin 73.1% were sensitive (231 of 316), with 0.6% (2 isolates) Intermediate, with the remaining 26.3% resistant. There were 1288 isolates identified as ESBL or AMPC, of which 1117 were E colis (mainly ESBLs).

In blood cultures there were 191 ESBL/AMPC isolates with 138 sensitive to Gent (72.3%) and 53 resistant (27.7%)

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