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Treatment of Urinary Tract Infections
PROF.
AZZA
El-Medany
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Classification of urinary tract infections
1- Symptomatic infections
Uncomplicated UTI (mainly in women) acute cystitis Acute urethritis recurrent cystitis
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Acute pyelonephritis
Complicated UTI
Acute and chronic prostatitis
2- Asymptomatic bacteriuria
Urinary tract infections(UTI’s)
It is the 2nd most common infection ( after RTI’s).
It is often associated with some obstruction of the flow of urine.
It is more common in women more than men
Incidence of UTI increases in old age(10%
of men & 20% of women).
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Normally urine is sterile. Bacteria comes from digestive tract to opening of the urethra.
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What are the causes of UTI’s
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•Obstruction of the flow of urine (e.g. kidney stone)
• Enlargement of prostate gland in men (common cause)• Catheters placed in urethra and 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).
Organisms Causing urinary tract infections Gm negative bacteria (most common):
•E.coli (approx. 80% of cases)•Proteus•Klebsiella•Pseudomonas
Gm positive bacteria ( less common):• Staphylococcus species
•Chlamydia trachomatis ,Mycoplasma & N. gonorrhea
Treatment of uncomplicated and complicated UTI’s
Antimicrobial agents:TMP or TMP/SMX (co-trimoxazole) Nitrofurantoin Quinolones Tetracyclines Aminoglycosides
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β-Lactam antibiotics
Extended spectrum penicillins
Cephalosporins ( 3rd G. )
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Sulfamethoxazole / Trimethoprim (SMX) (TMP)
Co-trimoxazole ( Bactrim, Septra )
each agent alone is bacteriostatic
Together they are bactericidal (synergism)
MECHANISM OF ACTION
P-Aminobenzoic Acid
Dihydropteroate Sulfonamides synthetase DihydrofolateDihydrofolatereductase Tetrahydrofolate Nucleic acid synthesis
TrimethoprimTrimethoprim
PHARMACOKINETICS
Sulfonamides given orallyRapidly absorbed from stomach and small intestine.Widely distributed to tissues and body fluids & crossing the placenta . bind to serum protein.Metabolized in the liver by the process of acetylation.Eliminated in the urine, partly as such and partly as acetylated derivative.
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Trimethoprim ( TMP )
given orallyWell absorbed from the gutWidely distributed in body fluids & tissuesMore lipid soluble than SMXProtein bound 60% of TMP or its metabolite is excreted in the
urineTMP concentrates in the prostatic fluid.
Clinical uses
Acute urinary tract infections Complicated urinary tract infections Recurrent urinary tract infections
especially in females Prostatitis ( acute/ chronic )
ADVERSE EFFECTS
Gastrointestinal ( Nausea, vomiting) Allergy
Hematologic 1) Acute hemolytic anemia a) hypersensitvity b) G6PD deficiency 2) Megaloblastic anemia due to TMP.
Kernicterus ( Jaundice due to Displace
bilirubin )
CONTRAINDICATIONS
Pregnancy Nursing mother Infants under 6 weeks Renal or hepatic failure Blood disorders
Nitrofurantoin
Effective against E. coli
Gram positive cocci are susceptible
Not effective against P- aeruginosa
Mechanism of action
Changed by bacteria to an active agent
that inhibits various enzymes and damages
bacterial DNA
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Pharmacokinetics • •Absorbed orally
•Well concentrated in the urine
•75%of the dose is rapidly metabolized by the liver , 25% is excreted in the urine unchanged .
• Drug & its metabolites are excreted in the urine• Turns urine to a dark orange- brown.
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Given with food
Keep urinary pH below 5.5 ( acidic urine
augment drug antibacterial activity )
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Adverse effects of nitrofurantoin
GIT disturbances: nausea, vomiting, diarrhea & gastric bleeding ( must be taken with food ).
Headache and nystagmus.
Hemolytic anemia
Pulmonary fibrosis ( on chronic use )
Contraindications
Patients with G 6PD deficiency
Neonates ( babies up to the age of one month )
Pregnant women ( after 38 weeks of pregnancy )
Therapeutic Uses
Used as urinary antiseptics but has little or no systemic antibacterial effect.
Its usefulness is limited to lower UTI’s.
Dose: 50-100 mg ( orally four times daily ) for 7 days
Tetracyclines
Doxycycline
Tetracycline
Tetracyclines
Broad spectrum antibiotic
Bacteriostatic
Mechanism of action
Inhibit protein synthesis by binding reversibly to 30 s ribosomal subunit
DOXYCYCLINE
Pharmacokinetics
Long acting tetracycline
Usually given orally once daily
Absorption is 90-100 %
Absorption in the upper s. intestine
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Absorption is impaired by
1- divalent cations ( Ca, Mg, Fe )
2- milk and its products
3- antacids ( aluminium hydroxide gel, sodium bicarbonate)
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Protein binding 40-80 %
Distributed well, including prostatic tissues
Cross placenta and excreted in milk
Metabolized in liver
Excreted through non renal route
Adverse effects
Nausea, vomiting, epigastric pain and diarrhea
Thrombophlebitis ( i.v route )
Hepatic toxicity ( prolonged therapy with high dose ) Brown discoloration & deformity of teeth ( children) Deformity or growth inhibition of bones( children) Vertigo Superinfections
Therapeutic Uses
Treatment of UTI’s due to Mycoplasma & Chlamydia.
Prostatitis
Contraindications
Pregnancy
Breast feeding
Children ( below 10 years )
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Aminoglycosides (Gentamicin )
Bactericidal antibiotics Inhibits protein synthesis by binding to
30S ribosomal subunits. Active against gram negative aerobic
organisms. Poorly absorbed orally Given I.M, I.V., cross placenta
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Excreted unchanged in urine More active in alkaline medium
Adverse effects : Ototoxicity Nephrotoxicity Neuromuscular blocking effect
Therapeutic uses of Gentamicin
Severe UTIs caused by gram negative aerobic organisms (pseudomonas ) .
Contraindications
Renal dysfunction Pregnancy Patients with hearing problem (Diminished
(hearing Myasthenia gravis
( A) Extended- spectrum penicillins
Amoxicillin / clavulanic acid
piperacillin or piperacillin /
tazobactam
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β-Lactam antibiotics
Mechanism of actions
Inhibit bacterial cell wall synthesis
Bactericidal
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Piperacillin
Effective against pseudomonas aeruginosa & Enterobacter.
Penicillinase sensitive
Can be given in combination with β-lactamase inhibitors as clavulanic acid ,
sulbactam, tazobactam.
(B) 3rd generation cephalosporins
Ceftriaxone & Ceftazidime
Mainly effective against gm negative bacteria.
They are given parenterally
Given in severe / complicated UTIs
& acute prostatitis
Fluroquinolones
Ciprofloxacin , levofloxacin
Inhibits DNA gyrase enzyme
Clinical uses
UTIs caused by multidrug resistance organisms as pseudomonas.
Prostatitis
PROSTATITIS
A ) Acute prostatitis:Non- catheter- or catheter associated usually due to gm- (E.coli or Klebsiella)
b) Chronic prostatitis due to E.coli, Klebsiella & Proteus
Antibiotics used for treatment of prostatitis
TMP/SMX 3rd Generation cephalosporins
(ceftriaxone) Quinolones ( ciprofloxacin , levofloxacin ) Tetracyclines ( Doxycycline)
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