Urology and Urinary Tract Infections in Adults

Urology and Urinary Tract Infections in Adults Full Title of Guideline: Author (include email and role): Division & Speciality: Scope (Target audience, state if Trust wide): Review date (when this version goes out of date): Explicit definition of patient group to which it applies (e.g. inclusion and exclusion criteria, diagnosis): Guideline for the treatment of urinary tract infections in adults Dr A Joseph, SpR Microbiology Mr R Parkinson, Consultant Urologist Annette Clarkson Specialist Pharmacist antimicrobials and Infection Control All adult specialties except Obstetrics Doctors, Pharmacists, Nurses August 2019 Inclusion: Adult patients including Urology Exclusion: Pregnant patients, refer to guideline for antibiotics in obstetrics Changes from previous version (not applicable if this is a new guideline, enter below if extensive): Addition of fosfomycin for first line treatment of lower UTI Changes to UTI diagnostic algorithm Changes to format of antimicrobial treatment regimens. Updated wording and clarification of advice around oral follow on therapy in upper UTI. Updated information on epididymitis/orchitis algorithm 15/12/17 updated frequency of fosfomycin dosing as per PHE Summary of evidence base this IDSA guideline for treatment of uncomplicated cystitis and guideline has been created from: pyelonephritis in women 2010 Local microbiological sensitivity surveillance and local audit of E. coli bacteraemias. Recommended best practice based on clinical experience of guideline developers. Public Health England. Management of infection guidance for primary care for consultation and local adaptation -updated 2016 BASHH Prostatitis 2008 European Association of Urology Guidelines on Urological Infections 2015 BASHH 2010 guidelines epididymitis orchitis GRASP 2013 report: The gonococcal resistance to antimicrobials surveillance program (England & Wales) Cochrane Database of Systematic Reviews: Antibiotic duration for treating uncomplicated, symptomatic lower urinary tract infections in elderly women 2008. Renal Drug Database access 10/07/2017 Diagnosis, Prevention, and Treatment of Catheter-Associated Urinary Tract Infection in Adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America (2010) This guideline has been registered with the trust. However, clinical guidelines are guidelines only. The interpretation and application of clinical guidelines will remain the responsibility of the individual clinician. If in doubt contact a senior colleague or expert. Caution is advised when using guidelines after the review date or outside of the Trust. Nottingham Antibiotic Guidelines Committee Page 1 of 15

Contents Urinary tract infection diagnosis algorithms: - Non-catheterised patient 65 years - Non-catheterised patient <65 years - Catheterised patient Lower urinary tract infection (cystitis) Catheter-associated urinary tract infection Prophylaxis for change of long-term catheters Recurrent urinary tract infections Upper urinary tract infections (pyelonephritis and systemic infection of urinary tract origin) Acute prostatitis Epididymitis and Orchitis Appendix 1: Example fosfomycin prescriptions Page 3 Page 4 Page 5 Page 6 Page 8 Page 9 Page 9 Page 10 Page 13 Page 14 Page 15 Glossary of abbreviations: NPV MSU CSU MC&S WCC CRP ESBL Negative predictive value Mid-stream urine Catheter specimen urine Microscopy, culture and sensitivity test White Cell Count C-reactive protein Extended beta-lactamase Nottingham Antibiotic Guidelines Committee Page 2 of 15

* Urine samples sent in red top containers must have a minimum volume of 20ml to provide sufficient sample for testing. If <20ml urine, please send in a white top container. All samples should be sent to the lab immediately. Nottingham Antibiotic Guidelines Committee Page 3 of 15

Lower Urinary Tract Infection (Cystitis) An infection of the bladder or lower urinary tract; without features of pyelonephritis or high risk of death red sepsis. Clinical practice points: 1. Use algorithm on pages 3-5 to determine if treatment is needed. 2. Review previous cultures prior to prescribing. If a multi-resistant isolate is present or the following choices are unsuitable, discuss with Microbiology regarding other treatment options. 3. For patients with a urinary catheter please see the section on page 5. 4. Antibiotics are not indicated for asymptomatic bacteriuria, unless pregnant or awaiting urology surgery where bleeding is expected. 5. Review antibiotic with culture results at 24-48 hours. 6. Simple lower UTI in women - 3 days oral treatment is usually sufficient (excluding when prescribing fosfomycin single dose) 7. For male patients, diabetics, those with structural or functional abnormality of the urinary tract, or recent urinary surgery/ instrumentation (excluding urinary tract catheterisation) - treat for 5-7 days (or two fosfomycin doses 48 hours apart on day 1 and day 3). Nottingham Antibiotic Guidelines Committee Page 6 of 15

Lower UTI Treatment first-line oral choices These agents are concentrated in the urine so are good options for lower UTI. They all currently have low resistance rates and minimal effect on normal flora (low C. difficile risk). However they are NOT suitable for patients who are systemically unwell or have High risk of death Red Sepsis (see guidelines). These are agents specifically targeting urinary tract infections. They will not offer broad cover for foci of infection outside of the urinary tract. Most multi-resistant isolates including ESBL-producing strains remain sensitive to nitrofurantoin, pivmecillinam and fosfomycin; these options should be used when possible. If these are not suitable, then discuss with Microbiology. Fosfomycin Nitrofurantoin Pivmecillinam Lower UTI in women: 3g as a single dose orally Lower UTI in men, diabetes, those with structural or functional abnormality of the urinary tract, or recent surgery/instrumentation: 3g on day 1 and a second dose of 3g on day 3 (The second dose is off label, though it is recommended practice within the literature and in PHE guidelines) Ensure prescribe on the antibiotic section of the prescription chart, even for single doses- See appendix 1 (page 15) for examples Not recommended when CrCl <10mL/min A 3g dose provides effective therapy for approximately 48 hours Most effective when taken an hour before or two hours after food 100mg MR BD orally Duration: Lower UTI in women: 3 days Lower UTI in men, diabetes, those with structural or functional abnormality of the urinary tract, or recent surgery/instrumentation: 7 days If to be used via an enteral feeding tube prescribe Nitrofurantoin normal release tablets 50mg QDS and see memo on antibiotic website: Not recommended when CrCl <45mL/min Considerations: This is a urinary antiseptic with no activity outside of the bladder Should not be used in systemically unwell patients, or where pyelonephritis is a possibility. Pulmonary reactions are rare (0.001%) but more common in the elderly and those with impaired renal function 400mg immediately, followed by 200mg TDS orally Duration: Lower UTI in women: 3 days Lower UTI in men, diabetes, those with structural or functional abnormality of the urinary tract, or recent surgery/instrumentation: 7 days Not recommended when CrCl <10mL/min Contra-indicated in penicillin allergy Contra-indicated in patients with oesophageal strictures Avoid in patients taking sodium valproate or valproic acid Tablets are film coated and must be swallowed whole with at least half a glass of water whilst upright Nottingham Antibiotic Guidelines Committee Page 7 of 15

Catheter-associated Urinary Tract Infections (CA-UTI): In patients with urinary catheters in situ, bacteriuria is commonly present and treatment is not indicated in the absence of symptoms. Urine dipstick is not clinically useful. Do not send catheter-specimen urine (CSU) for culture as a routine "screen" in the absence of symptoms. Only send a CSU for culture if the patient is symptomatic, or has signs of pyelonephritis or systemic infection The results of CSU samples should always be interpreted in conjunction with clinical parameters. Clinical assessment should be made regarding whether infection is likely to involve only the lower urinary tract, or upper urinary tract (pyelonephritis and systemic infection of urinary tract origin), see the empirical treatment of Sepsis Guideline for further information. http://nuhnet/diagnostics_clinical_support/antibiotics/pages/septicaemia/septicaemi a.aspx The ongoing need for the urinary catheter should be assessed, alternatives considered, and the catheter should be removed if possible. If an indwelling catheter has been in place for longer than 2 weeks at the onset of CA-UTI (and there is ongoing need for a urinary catheter) the catheter should be changed during the treatment course. Treatment Review previous Microbiology results prior to prescribing, send a pretreatment CSU sample. Follow the first-line treatment choices outlined in either the lower or upper urinary tract sections of this guideline (page 7, and page 11) according to the clinical assessment. Duration 7 days. In women who have had the catheter removed, this can be shortened to 3 days if rapid clinical response to antibiotics. Nottingham Antibiotic Guidelines Committee Page 8 of 15

Prophylaxis for change of long-term catheters Routine antibiotic prophylaxis is not recommended and will select for resistant bacteria. Urine dipstick is not clinically useful, only send CSU if the patient has symptoms. Do not send a catheter-specimen urine (CSU) for culture as a routine "screen". Consider prophylaxis for those who have history of recurrent post catheter change infections. The antibiotic choice is as follows: 1st Line: Gentamicin 2mg/kg IV as a single dose. Check for history of Gentamicinresistant organisms before prescribing. 2nd Line: Treat according to previous sensitivities, where possible use PO Nitrofurantoin M/R 100mg BD give two doses only (one dose approx. 4 hours before catheter change and second dose 12 hours after the first dose) Not suitable for patients with CrCl < 45mL/min. MRSA Positive patients: Patients with a catheter and a diagnosis of MRSA in their urine who are at risk of developing a bacteraemia at catheter change because they have traumatic catheter changes or who have had infections following catheter change previously. Gentamicin 2mg/kg IV single dose prior to catheter change. A minority of MRSA strains locally are resistant to Gentamicin so please review the susceptibility results and seek advice if required. Recurrent Urinary Tract Infections Patients with recurrent UTIs may be more likely to have resistant organisms due to repeated exposure to antibiotics. In patients known to have recurrent UTIs, a pretreatment MSU should be sent and previous microbiology results reviewed prior to prescribing. Assessment for possible underlying urinary tract abnormalities should be considered and Urology referral made if appropriate. Prophylaxis for recurrent urinary tract infections should not be routinely started. If considering prophylaxis then discussion with Microbiology and/or Urology is required, with regards to choice of agent, monitoring and follow-up. If a patient is admitted on prophylactic antibiotics for recurrent UTIs, review urine culture results and stop the prophylaxis if resistance is demonstrated on culture. Consider whether ongoing antibiotic prophylaxis is appropriate and discuss with microbiology regarding choice of agent. All changes must be communicated to the GP on discharge. Nottingham Antibiotic Guidelines Committee Page 9 of 15

Upper Urinary Tract Infections: Pyelonephritis and Systemic Infection of Urinary Tract origin Defined as: Patients with pyelonephritis: usually have loin pain, kidney tenderness and signs of systemic infection. Patients with lower urinary tract symptoms and signs of systemic infection. Patients with known or possible structural or functional abnormalities of the urinary tract and signs of systemic infection. Assess patient according to the NUH Sepsis guidelines http://nuhnet/diagnostics_clinical_support/antibiotics/pages/septicaemia/septicaemi a.aspx. Ensure two sets of blood cultures and a urine sample are sent (clearly labelled with the type of specimen e.g. MSU, CSU, nephrostomy urine) Review previous culture results and assess risk of Multi-resistant Gram-negative Organisms (MRGNO) prior to prescribing antibiotic: Risk factors for Multiresistant Gram-negative Organisms (MRGNO) Previous history of isolation of ESBL positive E. coli or multi-resistant gram negative organisms OR Recurrent urinary or biliary tract infections ( 3 in last 12 months) Systemic infection despite current or recent (within last week) treatment with broad-spectrum antibiotics e.g. co-amoxiclav, cefuroxime or quinolones (ciprofloxacin, levofloxacin) Recurrent admissions with neutropenic sepsis requiring treatment with piperacillin-tazobactam. Nottingham Antibiotic Guidelines Committee Page 10 of 15

Treatment If no risk factors for Multiresistant Gram Negative Organism (MRGNO) 1 st line Non-severe penicillin allergy E.g. No anaphylaxis, angioedema or urticarial rash in first 72 hours Severe penicillin allergy Temocillin IV 2 gram BD Note, THIS IS A PENICILLIN Cefuroxime IV 1.5gram TDS If patient is previous C. difficile positive (PCR or toxin), cefuroxime required microbiology approval before use. Ciprofloxacin IV 400mg BD if High risk red sepsis or unable to take orally, converting as soon as possible to: PO Ciprofloxacin 500mg BD If patient is previous C. difficile positive (PCR or toxin), or MRSA colonisation, ciprofloxacin requires microbiology approval before use. If the patient has High risk red sepsis or the blood pressure fails to respond to initial bolus fluids: Consider adding single dose Gentamicin IV 5mg/kg (max 500mg) if normal renal function. For advice on dosing in renal impairment, refer to Trust antibiotic website. http://nuhnet/diagnostics_clinical_support/antibiotics/pages/a-z/gentamicin.aspx If at risk of Multiresistant Gram Negative Organism (MRGNO) Meropenem IV 500mg QDS Review antibiotics with microbiology within 48 hours Not to be used in severe penicillin allergy (i.e. anaphylaxis, angioedema, urticarial rash within 72 hours of starting). Please discuss with microbiology. Further therapy Review need for IV antibiotics at 48 hours with microbiology results using IV-PO switch guideline on antibiotic website. If culture results available to guide therapy, a narrow spectrum agent should be used according to sensitivities. See table below for recommended course lengths Nottingham Antibiotic Guidelines Committee Page 11 of 15

MSU sensitivity No MSU result available Switch to Ciprofloxacin PO 500mg BD Total Course length IV+PO Comments 7 days Micro approval required if previous C. difficile (PCR or toxin) or MRSA colonisation MSU result available and agent chosen based on sensitivities Trimethoprim PO 200mg BD Ciprofloxacin PO 500mg BD Cefalexin PO 500mg TDS 10 days Targeted therapy to be used whenever sensitive Severe drug interaction with methotrexate, avoid concomitant use. 7 days Micro approval required if previous C. difficile (PCR or toxin) or MRSA colonisation 10 days Not in severe penicillin allergy Micro approval required if previous C. difficile (PCR or toxin) If above options not appropriate due to resistance, allergies etc: Discuss with microbiology Pivmecillinam and Fosfomycin little evidence in upper-uti. Discuss with microbiology before prescribing DO NOT USE Nitrofurantoin as an oral stepdown after IV therapy for upper UTI (pyelonephritis or systemic infection of urinary tract origin) as it has insufficient systemic concentrations to be used for this indication. Nottingham Antibiotic Guidelines Committee Page 12 of 15

Acute Prostatitis Acute prostatitis is caused by urinary tract pathogens. Infection may spread from the distal urethra but can also spread from the bladder, blood and lymphatic system. Acute prostatitis is an uncommon complication of UTI, urological instrumentation or catheterisation. Acute prostatitis is an acute severe systemic illness. Symptoms include: symptoms of a urinary tract infection: dysuria, frequency and urgency symptoms of prostatitis: low back pain, perineal, penile and sometimes rectal pain symptoms of bacteraemia: fever and rigors; arthralgia and myalgia; recurrent Gram negative bacteraemia of unknown focus. Signs include: an extremely tender, swollen and tense, smooth textured prostate gland which is warm to the touch Cases of suspected prostatitis should be discussed with Urology, so that appropriate imaging +/- intervention can be arranged. Ensure a urine sample is sent for MC&S (clearly-labelled with the specimen type e.g. MSU), and two sets of blood cultures are taken. First line: PO Ciprofloxacin 500mg bd for 28 days If patient is previous C.difficile positive (PCR or toxin) ciprofloxacin requires Microbiology approval before use If vomiting, concerns about absorption or if High risk red sepsis, give IV ciprofloxacin 400mg BD, converting to oral as soon as oral route available Second line (If ciprofloxacin unsuitable e.g. resistant organism or contra-indicated): PO Trimethoprim 200mg bd for 28 days (off label use) Antibiotic choice should be reviewed at 48 hours with urine MC&S, blood cultures, and imaging results. Nottingham Antibiotic Guidelines Committee Page 13 of 15

MANAGEMENT OF EPIDIDYMITIS AND ORCHITIS Clinical presentation: Pain and swelling of the epididymis +/- testes (Orchitis), pyrexia, with or without urethral discharge (ENSURE TESTICULAR TORSION EXCLUDED). Sexual history: It is important to take a sexual history in ALL cases. Sexually transmitted infections (STIs) may be the underlying cause of epididymitis and orchitis, especially in younger patients (under 35 years). However, patients over 35 years of age without suggestion of sexual contact are more likely to have infections of urological origin. Gram negative enteric organisms are more commonly the cause if recent instrumentation or catheterisation has occurred. Causative agents: Organisms of the urinary tract e.g. Escherichia coli. Sexually transmitted infection (STI) e.g. Chlamydia trachomatis, Neisseria gonorrhoea In non-immunised males born between 1982-1986 mumps orchitis must be considered. Send an inside cheek/throat viral swab for mumps PCR testing. Nottingham Antibiotic Guidelines Committee Page 14 of 15

Appendix 1: Example Prescriptions for Fosfomycin dosing in lower UTI: Nottingham Antibiotic Guidelines Committee Page 15 of 15