Urinary Tract Infection Workshop

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1 Urinary Tract Infection Workshop Diagnosis, sampling, antibiotic selection, recurrence, prophylaxis Nick Francis, Robin Howe, Harry Ahmed

2 Outline Diagnosis and sampling Nick 10 min Choice of antibiotic Robin 10 min Prophylaxis in recurrent UTI Harry 10 min Discussion and questions All 30 min

3 Mrs. Jones 60 yo woman 3 day h/o dysuria and frequency

4 Urine sample

Urine transparency as an index of absence of infection.

5 Prospective cohort of urine samples from 363 adults attending a nephrology clinic over a 6- month period. A clear urine sample had a negative predictive value of 97%. PhillipsG, FlemingLW, KhanIand, Stewart WK. Urine transparency as an index of absence of infection. British Journal of Urology 1992;70: children presenting to an emergency department with possible UTI. The finding of clear urine (from MSU or catheter) on visual inspection had a negative predictive value of 97.3%. A clear urine sample from 418 elderly people admitted to hospital for any reason had a negative predictive value of 91.2%.

9 Recommends MSU and cleansing with water. Only reference is for not using antiseptic.

11 The first portion of urine is not collected, because it is always contaminated by commensal urethral flora in both sexes. It is important to wash the introitus around the urethra in females, and the glans penis in males with water only, before micturition. This reduces false-positive urine cultures by 20% or more [24]. The use of antiseptics and soaps is not recommended as this may affect bacterial viability.

13 Sexual intercourse should be avoided for 1 day before specimen collection because of the resulting increased amounts of proteins and cells. To demonstrate reliable bacterial growth, classical microbiological advice has been to allow bacteria a log phase of growth by incubating the urine in the bladder for 4-8 h.

14 242 women symptoms suggestive of UTI Not mid-stream, no cleansing N=77 Mid-stream, perineal cleansing, spreading labia N=81 Mid-stream, perineal cleansing, vaginal tampon N=84 29% 32% 31% Lifshitz E and Kramer L. Outpatient urine culture: does collection technique matter? Archives of Internal Medicine 2000;150:

15 Prospective study obtained a new urine sample each day for 8 days (using a different set of instructions each day) from 111 healthy young women. There was no statistically significant difference in contamination rates between the following techniques: no precautions (31%) midstream sample (23.9%) midstream sample with perineal cleansing (20.4%) midstream and holding labia apart (21.1%) holding the labia apart as the sole technique was associated with a lower contamination rate (13%). Baerheim A, Digraines A, Hunsakaar S. Evaluation of urine sampling technique: bacterial contamination of samples from women students. Br J Gen Pract 1992;42: Leisure MA, Dudley SM, Donowitz LG. Does a clean catch sample reduce bacterial contamination? New England Journal of Medicine. 1993;328: A midstream urine specimen and a midstream urine specimen with prior cleansing were obtained during consecutive urinations in a series of 105 asymptomatic female health care workers. Sixty four percent of samples obtained by each method were found to be contaminated.

19 Antibiotic Choice

Antimicrobial Usage in Primary Care in Wales (2005-2015)

20 Antimicrobial Usage in Primary Care in Wales ( ) Trimethoprim Nitrofurantoin Co-amoxiclav Cefalexin Ciprofloxacin

21 Antibiotic Choice

22 Effectiveness of the antimicrobial agent Trimethoprim = Nitrofurantoin (only lower UTI) = Ciprofloxacin = Fosfomycin = Pivmecillinam > Cefalexin = Amoxicillin > Methenamine

23 All but 1 E. coli sensitive to Cefalexin. All patients sterile urine during treatment

24 Effectiveness of the antimicrobial agent Pathogen spectrum and antibiotic sensitivity

25 Antimicrobial resistance: community urinary coliforms

if organism resistant to 3GC UHW resistance rates

26 Antimicrobial resistance: community urinary coliforms Fosfomycin/ Pivmecillinam Tested if organism resistant to 3GC UHW resistance rates (2015): Fosfomycin: 27/ % Pivmecillinam: 44/ %

27 Impact of resistance on outcome Outcome at 5-9 days Infection with TMP-SMXsusceptible pathogen Infection with TMP- SMX-resistant pathogen p Microbiological cure 288/353 (82%) 64/151 (42%) < Clinical cure 293/333 (88%) 81/151 (54%) < Raz et al. (2002) CID 34: 1165

28 Estimated impact of TMP-SMX resistance in patients given TMP-SMX for acute uncomplicated UTI Gupta et al. (2001) Ann Intern Med 135: 41

29 Effectiveness of the antimicrobial agent Pathogen spectrum and antibiotic sensitivity Patient s individual risk and previous antibiotic treatment

30 Trimethoprim resistance rate in community urinary coliforms by age group

31 E. coli bacteraemias in Wales by age

32 Prior TMP and the likelihood of TMP resistance Hiller S et al (2007) JAC 60: 92-99

33 Effectiveness of the antimicrobial agent Pathogen spectrum and antibiotic sensitivity Patient s individual risk and previous antibiotic treatment Effects on the resistance situation in the patient and/or ecological effects (collateral damage)

34 Owens RC et al (2008) CID 46: S19 Risk of C. difficile

35 Risk of C. difficile Gut disruption minimal with Nitrofurantion/ Fosfomycin/ Pivmecillinam Owens RC et al (2008) CID 46: S19

Effectiveness of the antimicrobial agent Pathogen spectrum and antibiotic sensitivity Patient s individual risk and previous antibiotic treatment Effects on the resistance situation in

36 Effectiveness of the antimicrobial agent Pathogen spectrum and antibiotic sensitivity Patient s individual risk and previous antibiotic treatment Effects on the resistance situation in the patient and/or ecological effects (collateral damage) Patient physiological factors Nitrofurantoin: egfr<45 avoid egfr use with caution (risk of toxicity/ failure of treatment)

37 Effectiveness of the antimicrobial agent Pathogen spectrum and antibiotic sensitivity Patient s individual risk and previous antibiotic treatment Effects on the resistance situation in the patient and/or ecological effects (collateral damage) Patient physiological factors Undesired drug effects. Agents generally safe Nitrofurantoin: lung fibrosis (usually only after >6 months) Co-amoxiclav: cholestatic jaundice commoner in elderly

38 Mrs Jones 60 yo woman Antibiotic selection Trimethoprim May be resistant (age, prior treatment) Nitrofurantoin Good option (only for lower UTI) Fosfomycin Good option Pivmecillinam Good option

39 Prophylaxis in Recurrent UTI

40 Initiating prophylactic antibiotic in women with recurrent UTI 10 RCTs 430 women aged Antibiotic versus placebo Proportion of women in each arm experiencing a microbiologically confirmed UTI during the prophylaxis period Antibiotic arm Placebo arm 24/ /177 RR 0.21 (0.13, 0.34) ARR 54% NNT 1.85 Albert X, Huertas I, Pereiro, II, et al. Antibiotics for preventing recurrent urinary tract infection in non-pregnant women. Cochrane Database Syst Rev 2004(3):Cd doi: /

41 What about women over 65?

42 930,000 people aged >=65 between 2004 and ,714 (21%) had at least one UTI 15,561 / 196,714 had recurrent UTI (8%) About 5% of 15,561 prescribed > 6/12 of Nitrofurantoin / Trimethoprim / Cefalexin, presumably for prophylaxis

43 Are the episodes true UTIs?

44 Cohort study 550 Nursing Home Residents followed up for 1 year When UTI is clinically suspected, what signs/symptoms are most predictive of bacteriuria and pyuria? Juthani-Mehta M, Quagliarello V, Perrelli E, et al. Clinical features to identify urinary tract infection in nursing home residents: a cohort study. J Am Geriatr Soc 2009;57(6):963-70

45 Non-antibiotic prophylaxis

46 Vaginal oestrogens Vs placebo Perrotta C, Aznar M, Mejia R, et al. Oestrogens for preventing recurrent urinary tract infection in postmenopausal women. Cochrane Database Syst Rev 2008(2):Cd doi: /

47 Cranberry 24 studies No statistically significant decrease in UTI rates in cranberry arm vs control arm High drop out rates in cranberry arms suggesting poorly tolerated Details of potency of different cranberry products poorly reported Jepson RG, Williams G, Craig JC. Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev 2012;10:Cd doi: / CD001321

48 Antibiotic prophylaxis Initiation

50 Number of women with at least one UTI during prophylaxis period Number of women with at least one UTI post prophylaxis Raz 2003 Beerepoot 2012 Kranjcec 2014 YES YES YES NO YES NO Time to first recurrence NO YES YES Mean number of UTIs during prophylaxis Mean number of UTIs after prophylaxis YES YES NO NO YES NO Adverse events YES YES YES Antibiotic resistance NO YES NO

51 Number of women with at least one UTI during prophylaxis period Number of women with at least one UTI post prophylaxis Raz 2003 Beerepoot 2012 Kranjcec 2014 YES YES YES NO YES NO Time to first recurrence NO YES YES Mean number of UTIs during prophylaxis Mean number of UTIs after prophylaxis YES YES NO NO YES NO Adverse events YES YES YES Antibiotic resistance NO YES NO

52 Antibiotic versus control (Oestrogen, Lactobacilli, placebo) Proportion of women in each arm experiencing a microbiologically confirmed UTI during prophylaxis ARR 13% NNT 7.7

53 Antibiotic prophylaxis On-going management

1. The preferred treatment option for an initial UTI episode in a 22-year-old female patient

1 Chapter 79, Self-Assessment Questions 1. The preferred treatment option for an initial UTI episode in a 22-year-old female patient with normal renal function is: A. Trimethoprim-sulfamethoxazole B. Cefuroxime