ABC
of
Lower
in women
Urinary Tract Infection
Dr. Sharda Jain
Dr Jyoti Agarwal
Uncomplicated

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

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.

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

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

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

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:

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:

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:

11
• 70 - 95% cases are caused by
E.coli
• 5 -15% cases are attributed to:
Staphylococcus saprophyticus
Klebsiella species
Proteus mirabilis

 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.

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.

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.

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.

 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:

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.

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.

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.

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

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.

Uncomplicated UTI responds to
short therapy,
while upper tract
infection requires
longer treatment
Antimicrobial therapy for UTI:

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.

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 

The First Line Antimicrobial
in Urinary Tract Infection 2022
Dr Sharda Jain
FOSFOMYCINE

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

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Mode of action of Fosfomycin

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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

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• 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

 Gram Negative uropathogens
Escherichia coli (E.coli)
Klebsiella pneumoniae
Proteus mirabilis
Pseudomonas aeruginosa
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Spectrum of Coverage
 Gram Positive uropathogens
Enterococcus faecalis
Staphylococcus saprophyticus

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• 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

33
Highest efficacy against
E.coli
J Clin Diagn Res. 2017 Feb

Shows least resistance
Ind J of Med Res 2019, 149

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 ?

36
International
recommendations

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

Dosage

Take Home Points
Canadian Journal of Infectious disease & Medical Microbiology, 2016

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.

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.

• .
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Dr. Sharda Jain
Fosfomycin