Urinary Tract Infections in Women

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Professor Bernard Haylen
MB BS (SYD) MD (L’POOL) FRCOG FRANZCOG CU
Consultant Urogynaecologist, St Vincent’s and Mater Clinics; Prince of Wales Private Hospitals
Conjoint Professor, University of NSW, Sydney, NSW
bladder.com.au

A: Introduction – Types of Urinary Tract Infections (UTI)

Around 50% of women will have a urinary tract infection (UTI) sometime in their life1. Most of these will be uncomplicated, i.e. there is no structural or functional abnormality of the genitourinary tract, particularly those abnormalities interfering with normal voiding and flushing of any bacteria from the urine.

Examples of a complicated UTI include a wide range of causes of urinary tract obstruction or impaired voiding, urogenital surgery/instrumentation, renal impairment or immune-compromise.

Recurrent urinary tract infections in women involve the determination of the occurrence of at least three symptomatic and medically diagnosed UTIs over the preceding 12 months2. Recurrent UTI is of the six “most common”2 diagnoses in female pelvic floor dysfunction (PFD).
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B: Epidemiology

The majority of recurrent UTIs are believed to be re-infection from extraurinary sources such as the rectum or vagina. However, uropathogenic E. coli, which cause the vast majority (around 80%) of UTI, are known to invade urothelial cells and form quiescent intracellular bacterial reservoirs (QIRS).

It is thought QIRS may provide a source for bacterial persistence and recurrence3,4. Other causative pathogens are Klebsiella, Enterobacter, Proteus, Pseudomonas, Staphylococcus and Enterococcus.
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C: Clinical Presentations

Acute or recurrent presentations will note the typical symptoms of dysuria, pain, suprapubic cramping, frequency, nocturia, cloudy urine or haematuria, and urgency.

Pyrexia, flank and/or back pain, in addition to lower urinary tract symptoms may indicate involvement of the upper urinary tract (pyelonephritis).

Older patients may present with delirium, confusion, falls or immobility.

The presence of nitrites, with or without leucocyte esterase, in dipstick analysis, indicates a likely UTI. Mid-stream urine with bacteriuria greater than 105 colony forming units (CFU)/mL is sufficient for diagnosis of a UTI.

Acute antimicrobial treatments may be based on practitioner preference and prior experience, culture sensitivities and case complexity.

A history of three symptomatic and medically proven UTIs is needed to absolutely confirm the diagnosis of recurrent UTI. Appropriate microbiological evidence should be sought, if available.
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D: Investigation of Recurrent UTI

A renal tract ultrasound is an eminently reasonable investigation, looking for (i) high post-void residual (PVR); (ii) calculi; (iii) other urinary tract abnormality or pathology.

Specialist or subspecialist assessment, including cystoscopy, will depend on the complexity of the UTI history and/or treatment difficulty. Pain or haematuria with infections would definitely lower the threshold for this assessment.

A “functional study of the lower urinary tract”, urodynamics, may be required if other symptoms of pelvic floor dysfunction, including symptoms and/or signs of pelvic organ prolapse (POP) which can create voiding dysfunction, are present.
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E: Management of Recurrent UTI

Medical management of recurrent UTI (and voiding dysfunction if present), in most cases, involves effective UTI prophylaxis, not only to prevent infections, but to improve inflammatory contributions to abnormal voiding parameters, in particular, a raised PVR.

Surgical management may be at times necessary for both if the recurrent UTI is deemed to be due to a high PVR — in turn, the result of a surgically relievable cause (more in older women), such as urethral stenosis (urethral dilatation) or POP repair.

Outcomes of management for the majority of cases of both diagnoses are effective with symptomatic and objective control. Different medical and surgical factors, however, can certainly increase the complexity of their diagnosis and the efficacy of treatment.
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F: UTI Prophylaxis

In terms of non-antibiotic UTI prophylaxis, there is Cochrane evidence supporting the use of methenamine (hexamine) hippurate5, which requires acidic urine (pH<5.5) and there is limited evidence for the role of Vitamin C6 in acidifying urine; and vaginal (though not oral) oestrogen in postmenopausal women7.

As a Category A medication, the use of methenamine hippurate (Hiprex™) can be used in pregnancy and breastfeeding though it is contraindicated in cases of renal or hepatic impairment, gout or dehydration.

Long-term use has demonstrated a favourable safety profile. The use of cranberry products (tablets or juices) to prevent UTI has not been supported by updated Cochrane reviews8. Insufficient evidence is available to make a recommendation on D-Mannose or Probiotics.

In terms of antibiotic UTI prophylaxis, there is evidence for the efficacy in sexually active women, of a single postcoital dose of antibiotic to prevent recurrent UTI, if it was established the UTIs were definitely postcoital.

Studies have involved trimethoprim-sulfamethazole9 or ciprofloxacin10; the latter study showing no difference in efficacy between postcoital and daily use.

Other postcoital antibiotics used are nitrofurantoin, cephalexin and norfloxacin; however, the latter is generally reserved for treatment-resistant organisms.

There is Cochrane evidence11 for the efficacy of continuous low-dose antibiotics. The same range and dose of antibiotics has been used as for the above postcoital antibiotics. The severe side-effect profile was low with less severe side effects, including vaginal and oral candidiasis and gastrointestinal symptoms.

Caution needs to be taken when using nitrofurantoin where there are the risks of hepatotoxicity, pneumonitis and some neurological symptoms11,12.

 References

1: Geerlings SE, Beerepoot MAJ, Prins JM (2014) Prevention of Recurrent urinary tract infections in women antimicrobial and nonantimicrobial strategies. Infect Dis Clin Am 28:135-147 .

2: Haylen BT, Freeman RM, de Ridder D, Swift SE, Berghmans B, Lee J, Monga A, Petri E, Rizk D, Sand P, Schaer G (2010) An International Urogynecological Association (IUGA) – International Continence Society (ICS) Joint Report into the Terminology for Female Pelvic Floor Dysfunction. Neurourology & Urodynamics, 29:4-20. International Urogynecology J, 21:5-26.

3: Mulvey MA, Schilling JD, Hultgren SJ (2001) Establishment of a persistent Escherichia coli reservoir during the acute phase of a bladder infection. Infect Immun 69:4572-4579.

4: Berry RE, Klumpp DJ, Schaeffer AJ. (2009) Urothelial cultures support intracellular bacterial community formation by uropathogenic Escherichia Coli. Infect immune 77:2762-2772.

5: Lee BB, Simpson JM, Craig JC, Bhuta T (2012) Methanamine hippurate for preventing urinary tract infections. Cochrane Database Syst Rev Oct 17;(4)CD003265

6: Carlsson S, Govoni M, Wiklund NP et al. (2003) In vitro evaluation of a new treatment for urinary tract infections caused by nitrate-reducing bacteria. Antimicrob Agents Chemothera. 47:3713-3718.

7: Perrotta C, Aznar M, Mejia R, Albert X, Ng CW (2008) Oestrogens for preventing recurrent urinary tract infections in postmenopausal women. Obstet Gynecol 112:689-690.

8: Jepson RG, Williams G, Craig JC (2012) Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev Oct 17, CD001321

9: Stapleton A, Latham RH, Johnson, Stamm WE. (1990) Postcoital antimicrobial prophylaxis for recurrent urinary tract infection. A randomized, double-blind, placebo-controlled trial. JAMA 264:703-706.

10: Melekos MD, Asbach HW, Gerharz E et al. (1997) Post-intercourse versus daily ciproxin prophylaxis for recurrent urinary tract infections in premenopausal women. J Urol, 157:935-939.

11: Albert X, Huertas I, Pereiro II, et al. (2004) Antibiotics for preventing recurrent urinary tract infections in non-pregnant women. Cochrane Database Syst Rev CD001209

12: Cetti RJ, Venn S, Woodhouse CR. (2009) The risks of long-term nitrofurantoin prophylaxis in patients with recurrent urinary tract infections: a recent medico-legal case. BJU Int 103:567-569.