Urinary tract infection
Mr. Chandrajeet Kumar Yadav
Assoc. Professor
Department Of Pharmacology
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Urinary tract infections (UTIs)
1. Upper urinary tract (kidney & ureters) infections:
pyelonephritis
2. Lower urinary tract (bladder, urethra & prostate): cystitis,
urethritis & prostatitis (more common).
** Upper urinary tract infections are more serious.
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UTI
• It is the 2nd most common infection (after RTIs)
• It is often associated with some obstruction of the
flow of urine
• It is more common in women more than men
30:1 (Why ?)
• Incidence of UTI increases in old age (10% of men
& 20% of women). 4
What are the causes of UTI
Normally urine is sterile. Bacteria comes from digestive
tract to opening of the urethra.
• Obstruction of the flow of urine (e.g. kidney stone)
• Enlargement of prostate gland in men (common cause)
• Catheters placed in urethra & bladder
• Not drinking enough fluids
• Waiting too long to urinate
• Large uterus in pregnant women
• Poor toilet habits (wiping back to front for women)
• Disorders that suppress the immune system (diabetes &
cancer chemotherapy).
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Bacteria responsible of UTIs
Gm-ve bacteria (most common):
• E. coli (approx. 80% of cases)
• Proteus mirabilis
• Klebsiella
• Pseudomonas aeruginosa
Gm+ve bacteria (less common):
• Staphylococcus saprophyticus (Approx. 20%)
• Mycoplasma, Chlamydia trachomatis & Neisseria gonorrhea (limited
to urethra, unlike E. coli may be sexually transmitted). 6
UTI can be:
• Simple:
Infections do not spread to other parts of the body & go away
readily with treatment (Due to E. coli in most cases).
• Complicated:
Infections spread to other parts of the body & resistant to
many antibiotics, thus more difficult to cure. {Due to hospital-
acquired bacteria (E. coli, Klebsiella, Proteus, Pseudomonas,
enterococci, staphylococci)}. 7
Treatment of UTI
Antibiotics:
1- Co-trimoxazole (SMX + TMP), p.o.
2- Nitrofurantoin, p.o.
3- Tetracyclines, e.g. Doxycycline, p.o.
4- Aminoglycosides, e.g. Gentamicin
5- Cephalosporins (e.g. Ceftriaxone & Ceftazidime)
6- Quinolones, e.g. Ciprofloxacin, p.o. 8
Co-trimoxazole (Bactrim, Septra)
Sulfamethoxazole-Trimethoprim
(SMX) (TMP)
Alone, each agent is bacteriostatic
Together they are bactericidals (synergism)
The optimal ratio of TMP to SMX in vivo is 1:20.
(formulated 1(TMP): 5(SMX); 160 mg TMP + 800 mg SMX;
80 mg TMP + 400 mg SMX; 8 mg TMP + 40 mg SMX).
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MECHANISM OF ACTION
P-Aminobenzoic Acid (PABA)
Dihydropteroate Sulfonamides*
synthetase
Dihydrofolate
Dihydrofolate
reductase Trimethoprim*
Tetrahydrofolate
Purines & DNA synthesis
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* Inhibit gm-ve & gm+ve bacteria
Absorption, metabolism & Excretion
(PK):
Sulfonamides
- Mainly given po/ (or IV)
- Rapidly absorbed from stomach & small intestine
- Widely distributed to tissues & body fluids (including CNS, CSF),
placenta & fetus
- Absorbed sulfonamides bind to serum protein (approx. 70% )
- Metabolized in the liver by the process of acetylation
- Eliminated in the urine, partly as such & partly as acetylated
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PK
TMP
• Usually given orally/ IV, alone or in combination with SMX
• Well absorbed from the gut
• Widely distributed in body fluids & tissues (including CSF)
• More lipid soluble than SMX
• Protein bound (approx. 40 %)
• 60% of TMP or its metabolite is excreted in the urine
• It’s a weak base, concentrates in the prostatic & vaginal fluids
(> acidic than plasma). 12
ADVERSE EFFECTS (TMP+SMX)
1. GIT- Nausea, vomiting
2. Allergy
3. Hematologic
a) Acute hemolytic anemia
a. hypersensitivity b. G6PD deficiency
b) Megaloblastic anemia due to TMP.
Drug interactions
Displace bilirubin- if severe – kernicterus
Potentiate warfarin, oral sulfonylurea hypoglycemics. 13
CONTRAINDICATIONS (TMP+SMX)
1. Pregnancy
2. Nursing mother
3. Infants under 6 weeks
4. Renal or hepatic failure
5. Blood disorders.
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Nitrofurantoin
Antibacterial Spectrum:
- Bactericidal for gm-ve & gm+ve bacteria
- Effective against E. coli & Staph. saprophyticus,
but other common UT gm-ve bacteria may be
resistant.
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Mechanism of action of nitrofurantoin
Sensitive bacteria reduce the drug to an active
agent (by bacterial reductase) that inhibits various
enzymes & damages DNA.
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PK of nitrofurantoin
• Absorption is complete after oral use
• Metabolized (75%) & excreted so rapidly that no
systemic antibacterial action is achieved
• Concentrated in the urine (25% of the dose
excreted unchanged)
• Urinary pH is kept < 5.5 (acidic) to enhance drug
activity
• It turns urine to a dark orange-brown (harmless). 17
Adverse effects of nitrofurantoin
• GI disturbances: bleeding of the stomach, nausea,
vomiting & diarrhea (must be taken with food)
• Headache and nystagmus
• Hemolysis in patients with G6PD deficiency
Contraindications:
• Patients with G6PD deficiency >>> anemia
• Neonates
• Pregnant women (after 38 wks of pregnancy). 18
Therapeutic Uses of nitrofurantoin
It is used as urinary antiseptic.
Its usefulness is limited to lower uncomplicated UTI’s
& cannot be used for upper UT or systemic
infections.
Dose: 50-100 mg, po q 6h/7 days
Long acting: 100 mg twice daily.
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Tetracyclines
(e.g. Doxycycline)
It is a long-acting tetracycline
Mechanism of action
Bacteriostatic, Inhibits protein synthesis by binding
reversibly to bacterial 30S ribosomal subunits.
Against gm+ve & gm-ve bacteria.
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Doxycycline (Cont.’)
PK
• Usually given po
• Absorption is 90-100%
• Absorbed in the upper s. intestine & best in absence of food
• Food & di & tri-valent cations (Ca2+, Mg2+, Fe2+, AL3+) impair drug
absorption & reduce its effectiveness
• Protein binding 40-80 %
• Distributed well, including CSF
• Cross placenta & excreted in milk
• Largely metabolized in the liver. 21
Doxycycline (Cont’.)
Side effects
1. GIT: nausea, vomiting , diarrhea & epigastric pain (give with food)
2. Thrombophlebitis – i.v
3. Hepatic toxicity (prolonged therapy with high dose)
4. Brown discolouration of teeth – children
5. Deformity or growth inhibition of bones – children
6. Phototoxicity (sensitivity to sunlight)
7. Vertigo
8. Superinfections (alter the intestinal flora due to broad spectrum
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activity).
Contraindications of doxycycline
• Pregnancy
• Breast feeding
• Children (below 10 yrs).
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Therapeutic Uses of Doxycycline
• Treatment of UTI’s due to many gm-ve & gm+ve
bacteria including Mycoplasma & Chlamydia, 100
mg p.o bid for 7 days
• Prostatitis.
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Aminoglycosides
e.g. GENTAMICIN, i.m, i.v.
• Bactericidal antibiotics
• Inhibits protein synthesis by binding to 30S
bacterial ribosomal subunits
• Active against gm-ve aerobic organisms
• Poorly absorbed orally
• Cross placenta.
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Gentamicin (CONT’)
• Excreted unchanged in urine
• More active in alkaline medium
Adverse effects :
• Ototoxicity
• Nerve damage (e.g. vestibular nerve)
• Nephrotoxicity
• Neuromuscular blocking effect. 26
Gentamicin (CONT’)
Therapeutic uses in UTI’s
Severe infections caused by gm-ve organisms
(pseudomonas or enterobacter) infection.
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Cephalosporins, (Detail was explained in respiratory lec.)
3rd generation cephalosporins
Ceftriaxone & Ceftazidime
• Mainly effective against gm-ve bacteria
• Acts by inhibition of cell wall synthesis
• Bactericidal
• They are given parenterally
• Given in severe / complicated UTIs
• & acute prostatitis. 28
Fluoroquinolones
(Detail was explained in respiratory lec.)
e.g. Ciprofloxacin
Active against gm-ve aerobic organisms
Mechanism of action
Inhibits bacterial DNA gyrase enzyme & cell division resulting in
bacterial cell death
Clinical use
• UTI caused by multidrug resistance organisms as
pseudomonas
• Prostatitis (acute/ chronic). 29
Ciprofloxacin ….Adverse effects
GIT: Nausea, vomiting, diarrhea
CNS effects: confusion, insomnia, headache, anxiety
Damage of growing cartilage (reversible arthropathy)
Photosensitivity (avoid excessive sunlight).
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