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Treatment of Urinary Tract Infections

Treatment of Urinary Tract Infections. PROF. AZZA El-Medany. Classification of urinary tract infections. 1- Symptomatic infections Uncomplicated UTI (mainly in women) acute cystitis Acute urethritis recurrent cystitis. Acute pyelonephritis Complicated UTI

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Treatment of Urinary Tract Infections

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  1. Treatment of Urinary Tract Infections

  2. PROF. AZZA El-Medany

  3. Classification of urinary tract infections 1- Symptomatic infections Uncomplicated UTI (mainly in women) • acute cystitis • Acute urethritis • recurrent cystitis

  4. Acute pyelonephritis Complicated UTI Acute and chronic prostatitis 2- Asymptomatic bacteriuria

  5. 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).

  6. Continue • Normally urine is sterile. Bacteria comes from digestive tract to opening of the urethra.

  7. What are the causes of UTI’s . 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).

  8. 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

  9. Treatment of uncomplicated and complicated UTI’s Antimicrobial agents: TMP or TMP/SMX (co-trimoxazole) Nitrofurantoin Quinolones Tetracyclines Aminoglycosides

  10. Continue β-Lactam antibiotics Extended spectrum penicillins Cephalosporins ( 1st & 3rd G. )

  11. Sulfamethoxazole / Trimethoprim (SMX) (TMP) Co-trimoxazole ( Bactrim, Septra ) each agent alone is bacteriostatic Together they are bactericidal (synergism)

  12. MECHANISM OF ACTION P-Aminobenzoic Acid Dihydropteroate Sulfonamides synthetase Dihydrofolate Dihydrofolate reductase Tetrahydrofolate Nucleic acid synthesis Trimethoprim

  13. PHARMACOKINETICS Sulfonamides given orally Rapidly 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.

  14. Continue Trimethoprim ( TMP ) given orally Well absorbed from the gut Widely distributed in body fluids & tissues More lipid soluble than SMX Protein bound 60% of TMP or its metabolite is excreted in the urine TMP concentrates in the prostatic fluid.

  15. Clinical uses • Acute urinary tract infections • Complicated urinary tract infections • Recurrent urinary tract infections especially in females • Prostatitis ( acute/ chronic )

  16. ADVERSE EFFECTS • Gastrointestinal ( Nausea, vomiting) • Hematologic 1) Acute hemolytic anemia a) hypersensitvity b) G6PD deficiency 2) Megaloblastic anemia due to TMP. • Kernicterus ( bilirubin –induced brain dysfunction )

  17. Continue adverse effects • Crystalluria • Hypersensitivity reactions • Neonatal jaundice

  18. CONTRAINDICATIONS • Pregnancy ( cross placenta) • Nursing mother ( secreted in milk) • Newborn Infants ( encephalopathy) • Renal or hepatic failure • Blood disorders

  19. Nitrofurantoin Effective against E. coli Gram positive cocci are susceptible Not effective against P- aeruginosa

  20. Mechanism of action • Changed by bacteria to an active agent that inhibits various enzymes and damages bacterial DNA

  21. Pharmacokinetics Absorbed rapidly and completely from GIT Well concentrated in the urine Rapidly metabolized by the liver , 40 % is excreted unchanged into the urine. Turns urine to a dark orange- brown.

  22. Continue • Given with food • The antibacterial activity is higher in an acidic urine

  23. Adverse effects of nitrofurantoin GIT disturbances: nausea, vomiting, diarrhea & gastric bleeding . Headache and nystagmus. Hemolytic anemia ( glucose-6-phosphate dehydrogenase deficiency) Pulmonary fibrosis ( on chronic use )

  24. Contraindications Patients with G 6PD deficiency Neonates (babies up the age of one month) Pregnant women ( after 38 weeks of pregnancy{ late pregnancy} ) Patients with decreased renal function

  25. Therapeutic Uses Used as urinary antiseptics . Prophylaxis of recurrent urinary tract infections Not effective in systemic UTI as pyelonephritis Dose: 50-100 mg ( orally four times daily ) for 7 days

  26. Tetracyclines Doxycycline Minocycline

  27. Tetracyclines Broad spectrum antibiotic Bacteriostatic Mechanism of action Inhibit protein synthesis by binding reversibly to 30 s ribosomal subunit

  28. DOXYCYCLINE & Minocycline Pharmacokinetics Long acting tetracyclines Usually given orally once daily Absorption is 90-100 % Absorption in the upper s. intestine

  29. Continue • Absorptionis impaired by 1- divalent cations ( Ca, Mg, Fe ) 2- milk and its products 3- antacids ( aluminium hydroxide gel, sodium bicarbonate)

  30. Continue Protein binding 40-80 % Distributed well, including prostatic tissues Cross placenta and excreted in milk Metabolized in liver Doxycycline is excreted through non renal route , minocycline is excreted through kidney

  31. & deformity of teeth ( children) Deformity 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

  32. Therapeutic Uses Treatment of UTI’s & chronic prostatitis due to Mycoplasma & Chlamydia.

  33. Contraindications • Pregnancy • Breast feeding • Children ( up to 12 years )

  34. Aminoglycosides (Gentamicin,tobramycin) • 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

  35. CONTINUE • Excreted unchanged in urine • More active in alkaline medium • Adverse effects : • Ototoxicity • Nephrotoxicity • Neuromuscular blocking effect

  36. Therapeutic uses • Severe UTIs caused by gram negative aerobic organisms , gentamicin is effective in treating pseudomonal infections .

  37. Contraindications • Renal dysfunction • Pregnancy • Patients with hearing problem (Diminished (hearing • Myasthenia gravis

  38. β-Lactam antibiotics ( A) Extended- spectrum penicillins Amoxicillin / clavulanic acid piperacillin / tazobactam

  39. Mechanism of actions • Inhibit bacterial cell wall synthesis • Bactericidal

  40. Piperacillin • Effective against pseudomonas aeruginosa & Enterobacter. • Penicillinase sensitive Can be given in combination with β-lactamase inhibitors as clavulanic acid , sulbactam, tazobactam.

  41. (B) Cephalosporins 3rd generation : Ceftriaxone & Ceftazidime Mainly effective against gm- bacteria. They are given parenterally Given in severe / complicated UTIs & acute prostatitis 1st generation , Cephalexin

  42. Fluroquinolones • Ciprofloxacin , levofloxacin • Inhibits DNA gyrase enzyme

  43. Clinical uses • UTIscaused by multidrug resistance organisms as pseudomonas. • Prostatitis

  44. Contraindications • Adolescent under 18 years • Pregnancy • Breast feeding mothers

  45. PROSTATITIS A ) Acute prostatitis: Non- catheter- or catheter associated usually due to gm- (E.coli or Klebsiella) b) Chronic prostatitisdue to E.coli, Klebsiella & Proteus

  46. Antibiotics used for treatment of prostatitis • TMP/SMX • Ceftriaxone • Ciprofloxacin , levofloxacin • Doxycycline in chronic prostatitis especially in trachomatis & chlamydia infections

  47. Antibiotics used in tratment of UTI in children • Cephalosprins • Penicillins • Aminoglycosides ( with precaution )

  48. Antibiotics not recommended in children • Tetracyclines • Quinolones

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