Volume 22 Issue 2 April 2020
Introduction
• Worldwide: >150 million UTIs diagnosed annually UTI→ most common infection in women
• In UK UTI responsible for:1-3% primary care consultations 15% of primary care antibiotic prescription
• Diagnosis:
presence of clinical symptoms (dysuria, suprapubic tenderness, urinary urgency and frequency)
and presence of bacteria in urine culture (>10 5 Cfu/ml)
• Most common bacterium:
Escherichia coli (E. coli).
• Can swiftly invade susceptible urothelial cells in lower urinary tract & rapidly multiply.
• 1 bacterium can produce 10 000-100 000 daughter bacteria within 24 hrs
• Main Risk factors: being female, spermicide use, sexual intercourse and renal tract anomalies
• Treatment:
Antibiotics 1st line: Trimethoprim or Nitrofurantoin
2nd line: Gentamicin
• Uncomplicated UTI→ oral Complicated→ admission & IV
• UTI is an acute event
• Recurrent UTI: 3 UTIs per year or 2 UTIs in 6 months
• Challenging due to antibiotic resistance
• Conditions that can arise from UTI include abscess, preterm birth in pregnancy & repeat infections
• Recurrent UTIs can result in renal scarring, which may precede hypertension & even renal failure
• Micro biologically cultural-able bacteriuria: 2-3% in age 15-24 yrs 20% in 65-80 yrs
• Each episode of UTI: average 6.1 days of disability & 2.4 days of school/work absence in USA
• Hospital Anxiety and Depression Scale (HADS):
can be used to assess psychological impact.
• Simple, reliable and extensively investigated method
• LUTI has significantly ↑ scores for both anxiety & depression
• Mean HADS scores can ↓ by 32% after treatment.
Low-dose antibiotic prophylaxis
• Decision to start any treatment to be taken with care
• Treatment to be started on correlation of symptoms & urine culture
• 1/3 E.Coli related UTIs are resistant to usual 1st-line antibiotics
• Aim of treatment:
swift assessment and prevention of uncomplicated lower UTI ascending into ureters &
kidneys or systemic infection
• Delay in prescription of antibiotic: 2x ↑ chance of needing hospital admission.
• Antibiotics vs placebo:
• Antibiotics more effective in eradicating bacteriuria & relieving symptoms
• Rate of microbiological recurrence of UTI per patient per year: 0-0.9 with antibiotics vs 0.8-3.6 with
placebo
• NNT 1.85 RR 0.21 in favor of antibiotics
• Adverse effects:
alteration of balance of natural flora of urinary tract (which is protective)
• Significant ↑ oral/vaginal candidiasis (if treated with nitrofurantoin vs placebo)
• ↑ in GI symptoms
• Liver toxicity→ liver failure
• Acute/Chronic pulmonary toxicity→ pulmonary fibrosis
• Long-term antibiotic use→ antibiotic resistance
Chinese herbal medicine(CHM)
• Mechanism of action:
Unclear Lack of robust data to support it use
• CHM vs placebo:
favorable for CHM but overall poor quality studies. RCTs are needed
Methenamine
• Methenamine inactive weak base slowly hydrolysis in urine to ammonia & formaldehyde
• Formaldehyde has antimicrobial properties which denatures protein structure of bacteria
• Neither bactericidal nor biostatic but nonspecific action makes most organism susceptible & no organisms
are resistant
• 76% less likely to have UTIs as compared to placebo
Cranberries and D-mannose
Cranberry juice: previously recommended
• Mode of Action is aggregation of cranberry parts on surface pili of bacteria & ↓ its ability to adhere /
penetrate the urothelial cells.
Bacteria clumped together and excreted in urine
• Cranberries vs antibiotics:
superior to standard management but inferior to antibiotics
• NICE & RCOG recommend against the use of cranberry
D-mannose:
sugar derived form cranberry.
• Same mechanism of action as cranberry
• D-mannose vs nitrofurantoin vs no t/m:
no difference in UTIs recurrence rates. More data needed
• NICE recommends non-pregnant may wish to try D-mannose as self-care treatment
Lactobacilli
• Genus of bacterium found in intestine and produces lactic acid
• Used as Probiotic
• Compared to antibiotics: in favor of antibiotics (less UTIs, longer recurrence time but resistance)
• Although safe & effective, further data needed
Urethral dilatation
• Urethral dilation or cystoscopy alone:
no significant difference in number of UTIs at 6 months
• Women assigned to urethral dilation group: 30% had subjectively complete resolution of symptoms
Estrogens
• Estrogen receptors are in vagina, urethra, trigone of bladder & pelvic floor musculature
• Menopause: ↓ estrogen level→ ↑ pH→ more alkaline environment detrimental to natural
flora(lactobacillus)
• Exogenous vaginal estrogens: ↓ vaginal atrophy & ↑ lactobacillus
• NICE: in postmenopausal vaginal estrogens are effective in preventing rUTI but systemic estrogens are not
Glycosaminoglycans (GAG)
• Bladder urothelial has 3 distinct layers — Basal, Intermediate & Surface (from deep to superficial)
• Surface layer covered by GAG of disaccharide, which is hydrophilic with strong negative charge. GAG easily
binds water molecules & results in well-hydrated/non-adhesive bladder surface
Function of GAG layer:
antibacterial coating of bladder to prevent bacterial adherence
• Removal of GAG layer: 100-fold ↑ in bacterial adherence
• GAG layer deficiency: ↑ rate of UTI
• Replacement of GAG layer: with synthetic hyaluronic acid (HA) effective, tolerable & used in rUTI
prophylaxis
Sublingual vaccination
• Sublingual therapeutic vaccination now developed against UTI
• Contains mixture of equal amounts of selected strains of E.Coli, Klebsiella Pneumoniae, Proteus Vulgaris &
Enterococcus Faecalis
• Highly effective in reducing rUTI
• Standard antibiotic treatment compared with vaccination: at 12-months follow-up
• 100% UTI in antibiotic group vs 35% in vaccination group
• UK study: with Uromune 78% had no UTIs in 12-months (100% women had at-least 3 UTIs in 12-month prior
to treatment)
• Vaccination not yet licensed / not funded by NHS in UK
• Further research needed.
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