Urinary Tract Infections Myths and Reality

1. Urinary Tract InfectionsMyths and Reality Dr Steve Holden Consultant Microbiologist and NUH Lead for Antimicrobial Stewardship Declaration of interest: Consultancy with Profile Pharma Dr Annie Joseph Microbiology Registrar and Co-author of Nottinghamshire Primary Care Antibiotic Guidelines

2. Session overview • What are the key issues? • UTI diagnosis in the elderly • Laboratory processing of samples • Management of UTIs • Asymptomatic bacteriuria • Local susceptibility data and guidelines • Special circumstances • Future local work

4. Recent publications • Health & Social Care Act 2008 Code of Practice on the prevention and control of infections • New Criterion 3: antimicrobial stewardship • NICE Antimicrobial Stewardship Guideline (NG15) • Recommendations for prescribers, providers & commissioners • Patient Safety Alert (NHSE, HEEM and PHE) • TARGET (Treat Antibiotics Responsibly, Guidance, Education, Tools)

5. The Key Issues • Increasing bacterial resistance (locally and globally) • Emergence of pan-resistant coliform bacteria. • Diagnosing UTI in the elderly • Unnecessary treatment of asymptomatic bacteriuria. • Joined up approach for sending samples, processing and interpretation of results needed. • New guideline on management of UTI.

6. UTI diagnosis in elderly • Considerations: • Catheterised vs Non-catheterised • Lower vs Upper UTI • Complicated vs Uncomplicated UTI • Structural e.g. obstruction, calculi. • Neurogenic bladder • Diabetes, immunosuppression • Alterative diagnoses

7. National Guidance: PHE • SIGN:

8. National Guidance: SIGN

9. Catheter-associated UTI (CAUTI) • Urinalysis and culture positivity not helpful unless symptoms or signs of CAUTI • The following do not predict infection: • Odorous or cloudy urine • Positive dipstick for LE/nitrites; presence of pyuria.

10. Sample processing overview • Dipstick? • Dipstick screen useful as a negative (but not positive) predictor in those with equivocal symptoms. • Poor evidence to support use of dipsticks in the elderly. • Sample sent to lab for MC&S • All samples have automated microscopy performed by flow cytometry. • Samples flagged by flow cytometer that require culture & sensitivities.

11. Microscopy and culture • Flow cytometers set up for sensitivity, not specificity • Very high negative predictive value (99% in women) • Positive microscopy indicates need to culture sample. • Negative = immediate result. • Presence of excess epithelial cells indicates poorly obtained sample. • Evaluation for microscopic haematuria should be done by dipstick. • Culture and direct sensitivities now performed giving 24hr result. • Amoxicillin removed from testing • Current agents: co-amoxiclav, cefalexin, ciprofloxacin, pivmecillinam, nitrofurantoin, trimethoprim and piptazobactam.

12. Asymptomatic bacteriuria (ASB) • Presence of bacteria in the urine without clinical evidence of urinary tract infection • Different from perineal or other contamination i.e. when the bugs cultured were not in the patient’s urine at all. • Presence of pyuria does not indicate infection • Odorous or cloudy urine does not indicate infection • Common in the elderly and catheterised

13. Source: Infectious Diseases Society of America, CID 2005;40:643-54

14. ASB: What’s the problem? • Treatment is not indicated. • Does not reduce frequency of symptomatic infection or prevent further episodes of ASB • Contributes to increasing antimicrobial resistance; risk of side effects including C.diff. • Number Needed to Harm = 3 • Probably the most significant contributor to inappropriate antimicrobial use. • Therefore looking for it should be avoided. • Exceptions are pregnancy (UK guidance to confirm with second sample) and prior to invasive urologic procedures e.g. TURP

15. Experience at NUH and elsewhere • Audit on admissions wards at QMC showed >40% of patients treated for UTI actually had ASB. • ED audit showed 15% of patients treated for LE +/- nitrite positive dips with no evidence of infection. • Sample sent “routinely”  clinician reviewing result does not know why sample sent and treats out of caution. • Toronto: 48% of patients with ASB treated unnecessarily vs. 12% after lab withheld antibiotic susceptibility results (CID 2014:58)

16. Requests and sample labelling • Type of urine e.g. MSU, CSU • Affects processing and reporting • Clinical details: • Difficult or multi-resistant isolates are reviewed by medical microbiologist • We can release certain sensitivities or provide extra interpretative comments. • Many studies estimate over 60% of urine samples are unnecessarily sent for MC&S. • Education of nursing staff and anyone who can send urine samples • “Let’s send it, just in case…..”

17. Genuine UTI… what to treat with?

18. Resistance in urinary pathogens • Multiple mechanisms • No longer test or report “ESBLs” as one of many types of betalactam resistance and does not help to know clinically. • Resistance to betalactam agents e.g. co-amoxiclav often accompanied by resistance to certain others e.g. trimethoprim. • Drivers of resistance • Individual patients: Antibiotic exposure over time, broad-spectrum agents with effects on flora, cross-infection in hospital/care facilities. • Global: Injudicious (and valid) use of antimicrobials; international spread. • Concerning emergence of carbapenem-resistant coliforms (CRE). Becoming endemic in certain countries and UK centres. Few or even no therapeutic options.

19. 20% cut-off for empirical use recommended by IDSA guidelines

22. Updated UTI guidance June 2015

23. CAUTI management & prevention • Treatment of CA-UTI and removal of catheter if inserted for >2 weeks. • Treatment duration poorly defined • IDSA suggest 7 days • What doesn’t work: • Antibiotic prophylaxis or treatment of CA-ASB • Adding antimicrobials to catheter drainage bags • Routine use of antibiotic prophylaxis for catheter change

24. What are the ideal agents? • What do we need? • Low rate of resistance • Unique mode of action • Highly concentrated in the urine • Minimal impact of normal flora • Low rate of allergy, intolerance and contra-indications • Cheap and easily available • Easy to test in the laboratory for sensitivity

25. Nitrofurantoin • Remains very active against coliforms except Proteus spp. • Concerns about use in elderly / renal impairment • Possible pulmonary and hepatotoxicity • Failure to concentrate in renal tract • MHRA has recently updated guidance: • Avoid if eGFR <45 unless no alternatives (CI if <30) • Not suitable for pyelonephritis or systemic symptoms eg. fever

26. Pivmecillinam • Betalactam drug • Low rate of resistance – Europe 4.2% resistance • Now testing first line for all urine isolates at NUH • Minimal effect on GI flora • CI in penicillin allergy • Unique mode of action • Highly concentrated in the urine • Cost comparable with nitrofurantoin • Safe in pregnancy and children

27. Others • Trimethoprim resistance now unacceptably high for empirical use in the elderly • Amoxicillin and co-amoxiclav similar • Major drivers of resistance and C.diff • Cephalosporins • Acceptable resistance rates but again major drivers of resistance • Ciprofloxacin • Surely not…?? • Currently the third line option for empirical therapy and first-line for pyelonephritis

28. Ciprofloxacin • Highly effective drug for treating most types of UTI • Concerns about selecting MRSA and C.diff • Prevalence of MRSA now very low • Main problem with quinolones is selection of 027 strain (of Stoke Mandeville fame). This is now rarely seen. • Prior to this has been relatively C.diffsparing. • Should not be used empirically for other conditions outside of the guideline indication • However, can also select more resistant coliforms and should be avoided if we can find a more suitable alternative.

29. Fosfomycin • >90% of multi-resistant coliforms susceptible • Currently unlicensed in UK but widely used in some other European countries • UK licensed product likely by end of 2015 (Profile Pharma) • Single 3g sachet for uncomplicated UTI • Well tolerated • Minimal impact on GI flora • Safe in penicillin allergy • Can be used currently unlicensed to avoid admission • Under microbiology/ID advice (Amber 2 indication) • Available via wholesalers • If likely delay >24hrs then community script to QMC or KMH pharmacy

30. Unusual problems • Pseudomonas: Genuine uncomplicated infection very rare • Only susceptible to ciprofloxacin. Resistance develops after exposure. Urology referral may be indicated if genuine recurrent infection. • Staphylococcus aureus: Very rare cause of uncomplicated UTI • In a woman could reflect perineal flora • Repeated isolation from male MSU could indicate extra-renal systemic infection with excretion in urine. This is well described and requires investigation. • Common catheter coloniser that may cause ascending infection. MRSA can be troublesome although often trimethoprim susceptible. • Candida spp.: Most likely commensal or thrush but genuine urinary tract infection requires investigation with imaging. Only likely if predisposing factors e.g. severe immunosuppression or renal tract abnormality

31. Pre-surgical screening • No evidence that this is useful or that treating ASB prior to most surgery including prosthetic joint insertion reduces post-op infection. • Exception is for urological procedures where mucosa will be breached • Risk of ascending infection and sepsis • Use sensitivities to guide peri-op prophylaxis • This should be organised or advised by urologists.

32. Recurrent UTIs • ≥ 3 symptomatic UTIs in one year • Microbiological confirmation should be obtained prior to considering antibiotic prophylaxis • Indications for referral to Urology (NICE CKS) • Review prophylaxis after 6 months • Evidence for long-term prophylaxis: • In women <65 years • Combined data for all agents studied (including quinolones and beta-lactams) • Long-term efficacy not studied • Side-effects in about 20% of patients

33. Recurrent UTIs • Choice based on prior sensitivity results • Breakthrough resistant UTIs – indication to stop • No evidence for drug holidays or rotational antibiotics • Pivmecillinam not advised as prophylaxis • Failure of trial of prophylaxis Urology referral

34. Take home messages • Antibiotic resistance rising dramatically. • Treatment of asymptomatic bacteriuria is a global medical error that needs work. • New guidelines now in place. • We are here to help. QMC extension 61163 between 9am to 5.30pm– there is a medical microbiologist available or one who will shortly get back to you.

35. Future work • Newly formed Antimicrobial Stewardship Committee at NUH with Primary Care representation • Integrated Fellowship in Clinical Microbiology and Antimicrobial Stewardship starting in May 2016 • Interested in getting involved? • Please leave contact details today • Or contact: amelia.joseph@nuh.nhs.uk

36. Questions?