Contenu connexe


Plus de Lifecare Centre(20)


ABC of Uncomplicated Lower Urinary Tract Infection in women (PART -1 ) Dr Sharda Jain Dr Jyoti Agarwal

  1. ABC of Lower in women Urinary Tract Infection Dr. Sharda Jain Dr Jyoti Agarwal Uncomplicated
  2. 3rd most common infection after respiratory and gastrointestinal.  Annually 150 million people develop UTI worldwide.  Grossly under-reported  10 % in general population  65 years=20 %  50-60 % have UTI in their Life Time.  Urinary tract infection (UTI) is a collective term that describes any infection involving any part of the urinary tract, namely the kidneys, ureters, bladder and urethra.  Upper UTI (kidneys and ureters) and lower UTI (bladder and urethra).  UTIs are caused by bacteria commonly, fungi and viruses occasionally Urinary Tract Infections
  3. Urinary Tract Infections  Significant bacteriuria is defined as the presence of 105 or more colony forming units (CFU) per ml of urine or 102 organism per ml when accompanied by pyuria (>10 wbc/mm3) IDSA (Inf disease society of America ) defines UTI as requiring 103 organisms per ml to diagnose cystitis and 104 per ml for pyelonephritis.
  4. URINARY TRACT INFECTIONS Females are more prone to get urinary tract infections than males due to:  Shorter urethra which opens nearer to the vagina  At the time of pregnancy due to reduced immunity  Easy contamination of the urinary tract with faecal flora because of proximity to anus
  5. Asymptomatic bacteriuria/UTI  Asymptomatic bacteriuria (ABU) is present if a patient does not exhibit the clinical signs of UTI and the upper limit of ≥ 105 CFU/mL is exceeded in two consecutive properly collected samples of midstream urine (from women).  A single detection is adequate for men.  Screening and treatment of asymptomatic bacteriuria is only necessary in : • Pregnant women • Before a urological operation • Renal transplant recipients
  6. Why it is important to treat asymptomatic bacteriuria in pregnancy?  Prevalence of 45%. Thus, the routine screening is advocated.  If left untreated, it may progress from lower urinary tract and can reach kidneys to cause pyelonephritis.  This effects UTI on baby in utero are like  Low birth weight of baby  Higher incidence of fetal deaths The American College of Obstetrics and Gynaecology recommends that a urine culture be obtained at the first prenatal visit and a repeat urine culture should be obtained during the third trimester
  7. Symptoms of Cystitis: • Lower pelvic pain • Dysuria (painful urination) • Polyuria (frequent urination) • Urinary urgency • Nocturia ( urination during night) • Haematuria (urine with traces of blood) Symptoms of Pyelonephritis: All symptoms of cystitis and additional: • Fever • Flank pain Symptomatic UTI:
  8. TRIAD :dysuria, frequency, and Urgency in otherwise healthy non-pregnant women. UTI occurring in: o Pregnant women o Men o Obstruction o Immunosuppression o Renal failure o Renal transplantation o Urinary retention from neurologic disease o Individuals with risk factors that predispose to persistent or relapsing infection (e.g., Calculi, indwelling catheters or other drainage devices) Uncomplicated UTI: Complicated UTI:
  9. UTI is termed as recurrent when it develops again after the complete resolution from previous UTI ( 3 Negative C/S ) When a patient develop UTI at following frequencies, the condition falls in the category of recurrent UTI 3 episodes of UTI in last 12 months 2 UTI in last 6 months Recurrent UTI:
  10. 11 • 70 - 95% cases are caused by E.coli • 5 -15% cases are attributed to: Staphylococcus saprophyticus Klebsiella species Proteus mirabilis
  11.  E. coli is commonly present in the intestine and its easy to get transferred from anal region to urethra region specially in women due to close proximity of these two opening.  E. coli has particular ability to adhere to the urinary epithelium with its fimbriae (hair like structures). Why E. Coli causes majority of Urinary Tract Infections (UTIs)?  E. coli forms a biofilm (a slimy film) on bladder surface which increases its adhesiveness and also offers resistance to antibiotic penetration.
  12. Routes of Urinary Tract Infection Ascending route: Uropathogens originate from rectal flora and enter the urinary tract via the urethra into the bladder. Uropathogens initially adhere to and colonise urothelium of the distal urethra. Haematogenous route: Renal parenchyma may be breeched in patients with Staph aureus or Candida that originate from oral sources in immunosuppressed patients Lymphatic route: In retroperitoneal abscesses and severe bowel infections.
  13. DIAGNOSIS OF UTI 1. Urine dipsticks: Detection of blood, leukocytes, and nitrite independently increases the likelihood of the presence of a UTI. The combination of the positive findings further increases the likelihood of the diagnosis. 2. Urine microscopy: Important diagnostic test to rule out UTI Leukocytes, detection of blood, nitrite helps in diagnosis of UTI. 3. Urine culture: Colony counts of up to 103–104 CFU/ml of typical uropathogens is clinically relevant for diagnosis.
  14. Management of UTI • Classify the type of infection, such as acute uncomplicated cystitis or pyelonephritis, acute complicated cystitis or pyelonephritis or asymptomatic bacteriuria (ASB). • Antibiotics remains the main stay of treatment along with symptomatic therapies. • IDSA recommends that empiric regimens for uncomplicated UTI particularly susceptible to E. coli like Fosfomycin ,Trometamol. • Antibiotics with a lower potential for collateral damage are preferred for uncomplicated cystitis like Fosfomycin.
  15.  Low fluid intake or chronic under hydration is a common risk factor for UTI.  Inadequate fluid intake leads to concentrated, high osmolality urine and infrequent voiding, both of which encourages bacterial growth.  Larger fluid volumes cause increased bladder activity overall as the bladder fills more rapidly and fully, resulting mechanical ‘flushing’ of the urinary tract, with larger voided volumes at a potentially faster flow rate, will reduce the bacterial load.  Regular and frequent voiding will reduce urinary stasis and proliferation of bacteria in the residual urine in the bladder. Role of Hydration in UTI:
  16. Non microbial therapies for UTI 1. Cranberry: Cranberry inhibits adhesions to uroepithelial cells. As a result, cranberry products including juice, tablets, or capsules may reduce the frequency of recurrent UTIs in women. 2. D-mannose: D mannose, adhesion blocker, used by women to prevent cystitis, but data to support their use are limited.
  17. Non Microbial Therapies for UTI 5. Urine Alkalinisation: Urinary alkalisers are salts that produce alkaline aqueous solutions. When suspended in water agents such as sodium bicarbonate and sodium citrate react to produce hydroxide ions, which are basic anions capable of accepting and neutralising protons like hydrogen ions. , The purpose of alkalinisation is to neutralise acidic urine and thereby interfere with the genesis of pain induced by a low pH environment. Currently there is insu!icient evidence to support the use of urinary alkalisers for symptoms in acute uncomplicated UTI. Cochrane Database of Systematic Reviews 2016, Issue 4. Art. No.: CD010745.
  18. Non microbial therapies for UTI 3. Topical estrogen therapy: In postmenopausal women, replacement with topical estrogen therapy normalizes the vaginal flora and has been shown to reduce the risk of recurrent UTI. Use of 0.5 mg of estriol vaginal cream at night for 2 weeks followed by twice-weekly administration for 8 months significantly reduced the incidence of UTIs compared with placebo. N Engl J Med 1993;11:753-6.
  19. 4. Probiotics: Probiotics protect the vagina from bacterial colonization by blocking attachment and producing hydrogen peroxide that is microbicidal to E. coli and other uropathogens. Lactobacillus appears to be promising as an antibiotic-sparing agent. Non microbial therapies for UTI
  20. Antimicrobial therapy for UTI  Most uncomplicated UTIs are treated in the outpatient setting.  Patients who present with fever or systemic symptoms should be hospitalized and treated with parenteral antibiotics.  Initial therapy is based on the local susceptibility patterns of E. coli and other uropathogens.  For the treatment of cystitis, an adequate urinary antibiotic concentration is important to ensure response to therapy.
  21. Uncomplicated UTI responds to short therapy, while upper tract infection requires longer treatment Antimicrobial therapy for UTI:
  22. ANTIBIOTIC ADMINISTRATION PATTERN 1. AMOXICILLIN CLAVULANATE Standard (5-7 days) 2. CEPHALOSPORINS (Cefuroxime, Cefixime, Ceftibuten) Standard (5-7 days) 3. NITROFURANTOIN Standard (7 days) 4. COTRIMOXAZOL (trimethoprim + sulfamethoxazole) Standard (7 days) 6. NORFLOXACIN Short (3-5 days) 7. CIPROFLOXACIN Short (3-5 days) 8. FOSFOMYCIN TROMETAMOL Single dose - short (1-3 days) commonly used antibiotics for uncomplicated UTI.
  23. 2022 RECOMMENDATIONS Treatment of UTI Antibiotics Nitrofurans - Nitrofurantoin Fluoroquinolones - Norfloxacin Cephalosporins - Cefixime Penicillins - Amoxyclav Phosphonic acid derivative - Fosfomycin GROWING RESISTANCE  INEFFECTIVE  OUTDATED  OUTDATED  HIGHLY EFFECTIVE AGAINST E.COLI & SHOWS LEAST RESISTANCE 
  24. The First Line Antimicrobial in Urinary Tract Infection 2022 Dr Sharda Jain FOSFOMYCINE
  25. 27 • Discovered in 1969 in Spain • A phosphonic acid derivative • Broad spectrum bactericidal antibiotic with activity against both Gram +ve and Gram –ve uropathogens • Features in the WHO list of essential medicines Basics of Fosfomycin
  26. 28 Mode of action of Fosfomycin
  27. 29 Mode of action of Fosfomycin  Fosfomycin inhibits the cell wall synthesis of bacteria. 1. Fosfomycin interferes with the first committed step in peptidoglycan biosynthesis. 2. It inactivates enzyme UDP-N Acetyl Glucosamine Enolpyruvyl transferase (MurA)  Fosfomycin also reduces adherence of bacteria to uroepithelial cells
  28. 30 • Absorption Rapidly absorbed following oral administration and converted to the free acid, fosfomycin. Absolute oral bioavailability under fasting conditions is 40% • Distribution Not bound to plasma proteins. Distributed in the kidneys, bladder wall, prostate and seminal vesicles • Excretion Unchanged in both urine and faeces • Half-life 5.7 (+_2.8) hours. Urinary concentrations equal to or greater than 100 µg/mL were maintained for 26-48 hours. Pharmacokinetics
  29.  Gram Negative uropathogens Escherichia coli (E.coli) Klebsiella pneumoniae Proteus mirabilis Pseudomonas aeruginosa 31 Spectrum of Coverage  Gram Positive uropathogens Enterococcus faecalis Staphylococcus saprophyticus
  30. 32 • High susceptibility against E.coli • Optimum urinary concentration allows once daily dosing • Lowest resistance rates compared to other antimicrobials • Established efficacy and safety with single dose therapy • Better patient compliance Salient features
  31. 33 Highest efficacy against E.coli J Clin Diagn Res. 2017 Feb
  32. Shows least resistance Ind J of Med Res 2019, 149
  33. 35 • Unique antibiotic that is chemically unrelated to any other known antibiotic • No cross resistance with other antibiotics because of its unique structure and mechanism • Ability to penetrate into biofilms. Not only eradicates clinically significant bacteria but also modify biofilm structure • Low rates of drug interactions with other agents Why fosfomycin shows least resistance ?
  34. 36 International recommendations
  35. 37 The forgotten antibiotic for MDR Gram negative bacteria A first line oral therapy for Acute Uncomplicated Cystitis Testimonials from leading journals Brazilian Journal of Infectious Disease 2015
  36. Dosage
  37. Take Home Points Canadian Journal of Infectious disease & Medical Microbiology, 2016
  38. Summary • UTI is the common infection occurring in young women. • The most common pathogen causing UTI is E.coli. • The most common presentation in young non pregnant women is acute uncomplicated cystitis. • The recommended treatment for acute uncomplicated cystitis is short course with antimicrobials like Fosfomycin, nitrofurantoin, and quinolones. • Fosfomycin is a broad spectrum bactericidal antibiotic which is active against both gram positive and gram negative bacteria.
  39. Summary • Fosfomycin should be considered as first line treatment of acute uncomplicated cystitis due to the following unique features:  High susceptibility against E.coli.  Optimal urinary concentration  Least resistance even after long term use  Established efficacy and safety  Single dose therapy with better patient compliance • Single dose Fosfomycin had similar clinical and bacteriological efficacy to 3-7 day regimens of quinolones, nitrofurantoin, co-trimoxazole and amoxicillin in women with uncomplicated lower UTIs. • The recommended dose of Fosfomycin is single 3 g dose.
  40. • . 42 Dr. Sharda Jain Fosfomycin