This document discusses urinary tract infections (UTIs). It notes that UTIs are very common, especially in women, and outlines the symptoms, types, causes, and treatment of UTIs. The main types discussed are uncomplicated UTIs, complicated UTIs, and catheter-associated UTIs. It provides details on the classes of antibiotics used to treat UTIs, particularly quinolones and nitrofurantoin. It also explains the mechanisms of action and structures of common quinolone antibiotics like nalidixic acid, norfloxacin, and ciprofloxacin.

1. URINARY TRACT INFECTION
Dr. Akhil Nagar
RCP-IPER
Shirpur

2. • UTIs are the most common bacterial infection requiring
medical care.
• Catheter-associated UTIs (CA-UTIs) are the most common
type of health care–associate
• The symptoms of UTIs are generally mild, and inappropriate
use of antibiotics can lead to antibiotic resistance infections.
• Epidemiology: 60% of women have at least one
symptomatic UTI during their lifetime.
• 10% of women have one or more episodes of symptomatic
UTIs each year.
• Young, sexually active women 18–24 years of age have the
highest incidence of UTIs.
• 25% of these women have spontaneous resolution of
symptoms.

3. • Pathophysiology: Lower UTIs, also known as cystitis,
more prevalent in women than in men.
• Primarily because of anatomic differences, including
shorter urethral length and moist periurethral
environment.
• It start with contamination by pathogen residing in the
gut, followed by colonization of the urethra and, finally,
migration by the flagella of the pathogen to the bladder
or kidney.
• Upper UTIs, also known as pyelonephritis, develop
when uropathogens ascend to the kidneys by the
ureters.
• In severe cases of pyelonephritis, the affected kidney
may be enlarged.

4. • In the non-pregnant adult woman with a normal urinary
tract, bacteriuria infrequently progresses to
symptomatic cystitis or pyelonephritis..
• The urethra is usually colonized with bacteria, and
sexual intercourse can force bacteria into the female
bladder.
• spermicides can also increase colonization.
• TYPES OF UTI:
1. Uncomplicated UTI
2. Complicated UTI
3. catheter-associated UTI.

5. 1. Uncomplicated UTI: Lower urinary symptoms,
dysuria, frequency, and urgency.
2. Complicated UTI: Pregnant women, men, obstruction,
immunosuppression, renal failure, renal
transplantation.
3. Catheter-associated UTI: Presence of indwelling
urinary catheters with signs and symptoms of UTI and
no other source of infection.

6. Classification:
1. Quinolones: Nalidixic Acid, Norfloxacin,
Enoxacin, Ciprofloxacin, Ofloxacin,
Lomefloxacin, Sparfloxacin, Gatifloxacin,
Moxifloxacin.
2. Nitrofurans (Nitrofurantoin)
3. Misc.
a. Methamines
b. Furazolidine.

7. The antibacterial quinolones can be divided into two
classes on the basis of their dissociation properties in
physiologically relevant conditions.
The first class, represented by nalidixic acid, oxolinic
acid, and cinoxacin, possesses only the 3-carboxylic acid
group as an ionizable functionality
The second class of antibacterial quinolones embraces the
broad-spectrum fluoroquinolones (namely, norfloxacin,
enoxacin, ciprofloxacin, ofloxacin, lomefloxacin, and
sparfloxacin), all of which possess, in addition to the 3-
carboxylic acid group, a basic piperazino functionality at
the 7- position and a 6-fluoro substituent.

8. Nalidixic Acid - 1, 8-
naphthyridine-3-
carboxylic acid
Norfloxacin –
(1-piperazinyl) –
3-quinolinecarboxylic
acid

9. Enoxacin
Ciprofloxacin-
1-Cyclopropyl-6-fluoro-
1,4-dihydro-4-oxo-7-(1-
piperazinyl)-3-quinoline
carboxylic acid

10. Ofloxacin –
1,4,-benzoxazine-6-
carboxylic
acid
Lomefloxacin

11. Sparfloxacin
Gatifloxacin

12. Moxifloxacin
Quinolones:
• The quinolones comprise a series of synthetic antibacterial
agents patterned after nalidixic acid, a naphthyridine
derivative introduced for the treatment of urinary tract
infections.
• Isosteric heterocyclic groupings in this class include the
quinolones (e.g., norfloxacin, ciprofloxacin, lomefloxacin),
the naphthyridines (e.g., nalidixic acid, enoxacin), and the
cinnolines (e.g., cinoxacin).

13. • For urinary tract infections, good oral absorption,
activity against common Gram-negative urinary
pathogens, and comparatively higher urinary
(compared with plasma and tissue) concentrations are
the key useful properties.
• These more potent analogs are sometimes classified
separately (from the urinary tract-specific agents) as the
fluoroquinolones, because all members of the group
have a 6-fluoro substituent in common.
• The highly polar quinolones are believed to enter
bacterial cells through densely charged porin channels
in the outer bacterial membrane.

14. Mechanism of Nalidixic acid
• The bactericidal action of nalidixic acid and its
congeners is known to result from the inhibition
of DNA synthesis.
• They cause the inhibition of bacterial DNA
gyrase (topoisomerase II), an enzyme
responsible for introducing negative supercoils
into circular duplex DNA.
• Although nalidixic acid inhibits gyrase activity,
it binds only to single-stranded DNA and not to
either the enzyme or double-helical DNA.

15. Furazolidine
Methanamine
hexamethylenetetramine
Nitrofurantoin
1-(5-nitro-2-
furfurylidene)-1-
aminohydantoin

16. • Structure–activity:
• 1,4-dihydro-4-oxo-3-pyridinecarboxylic acid moiety is
essential for antibacterial activity.
• The pyridone system must be annulated with an aromatic
ring. Isosteric replacements of nitrogen for carbon atoms
at positions 2 (cinnolines), 5 (1,5 napthyridines), 6 (1,6-
naphthyridines), and 8 (1,8-naphthyridines) are consistent
with retention of antibacterial activity.
• Although the introduction of substituents at position 2
greatly reduces or abolishes activity, positions 5, 6, 7
(especially), and 8 of the
• Fluorine atom substitution at position 6 is also associated
with significantly enhanced antibacterial
activityannulated ring may be substituted with good
effects.

17. • Alkyl substitution at the 1-position is essential for
activity, with lower alkyl (methyl, ethyl, cyclopropyl)
compounds generally having progressively greater
potency.
• Aryl substitution at the 1-position is also consistent with
antibacterial activity, with a 2,4-difluorophenyl group
providing optimal potency. Ring condensations at the
1,8-,5,6-, 6,7-, and 7,8-positions also lead to active
compounds.
• Newer members of the class possessing 6-fluoro and 7-
piperazinyl substituents exhibit an extended spectrum of
activity that includes effectiveness against additional
Gram-negative pathogens

18. • Another property of the quinolone class is
phototoxicity, extreme sensitivity to sunlight.
Quinolones possessing a halogen atom at the
8-position (e.g., lomefloxacin) have the highest
incidence of phototoxicity, whereas those
having an amino (e.g., sparfloxacin) or
methoxy group at either the 5 -or 8-position
have the lowest incidence