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Urinary tract infection upper urinary tract infection and lower urinary tract infection
This document discusses urinary tract infections (UTIs), their types, causes, and treatment options. Key bacteria such as E. coli are primarily responsible for UTIs, with treatment often involving antibiotics like TMP/SMX and nitrofurantoin. The document also outlines the mechanisms of action, pharmacokinetics, and adverse effects of various antibiotics used in treating these infections.
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Urinary tract infection upper urinary tract infection and lower urinary tract infection
- 1. Prof. Mohammad Alhumayyd Departmentof Pharmacology
- 3. Urinary tract infections(UTI’s) 1.Upper urinary tract (kidney &ureters) infections: pyelonephritis 1. Lower urinary tract (bladder, urethra & prostate): cystitis , urethritis & prostatitis. ** Upper urinary tract infections are more serious.
- 4. 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 30:1 (Why?). • Incidence of UTI increases in old age(10% of men & 20% of women).
- 5. What are thecauses of UTI’s 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 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).
- 6. Bacteria responsible ofurinary tract infections Gm- bacteria (most common): •E.coli (approx. 80% of cases) •Proteus •Klebsiella •Pseudomonas Gm+ bacteria : •Staphylococcus Saprophyticus •Chlamydia trachomatis ,Mycoplasma & N. gonorrhea (limited to urethra, unlike E.coli may be sexually transmitted)
- 7. Urinary tract infectionscan be: •Simple: Non-catheter associated(community-acquired). Do not spread to other parts of the body and go away readily with treatment ( Due to E.coli in most cases). •Complicated:Catheter- associated(nosocomial) , immunosuppression,stones,renal disease, diabetes) Spread to other parts of the body and resistant to many antibiotics and more difficult to treat.{Due to hospital- acquired bacteria(E.coli, Klebsiella,, Proteus, Pseudomonas, enterococci, staphylococci)}
- 8. Treatment of simpleand complicated UTI’s Antibiotics: TMP, TMP/SMX (co-trimoxazole),p.o. Nitrofurantoin,p.o. Tetracyclines, e.g. Doxycycline,p.o. Aminoglycosides, e.g. gentamicin Β-lactam antibiotics: extended – spectrum penicillins(e.g.piperacillin) 3rd generation cephalosporins (e.g.ceftriaxone&ceftazidime) Quinolones, e.g. ciprofloxacin,p.o.
- 9. Sulfamethoxazole- Trimethoprim (SMX) (TMP) Co-trimoxazole( Bactrim, Septra ) Alone, each agent is bacteriostatic Together they are bactericidals(synergism) The optimal ratio of TMP to SMX in vivo is 1:20 (formulated 5(SMX):1(TMP); 800mg SMX+160mg TMP; 400 mg SMX+ 80 mg TMP; 40 mg SMX+8 mg TMP).
- 10. MECHANISM OF ACTION P-AminobenzoicAcid Dihydropteroate Sulfonamides synthetase Dihydrofolate Dihydrofolate reductase Tetrahydrofolate Nucleic acid synthesis Trimethoprim Trimethoprim
- 11. Absorption,metabolism&Excetion Sulfonamides Mainly given orally Rapidlyabsorbed from stomach and small intestine. Widely distributed to tissues and body fluids ( including CNS, CSF ), placenta and 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 and partly as acetylated derivative.
- 12. Trimehoprim ( TMP) Usually given orally, 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 TMP concentrates in the prostatic fluid.
- 13. ADVERSE EFFECTS 1.Gastrointestinal- Nausea,vomiting 2. Allergy 3. Hematologic a) Acute hemolytic anemia a) hypersensitvity b) G6PD deficiency b) Megaloblastic anemia due to TMP. 4. Drug interactions Displace bilirubin- if severe – kernicterus Potentiate warfarin, oral hypoglycemics.
- 14. CONTRAINDICATIONS 1. Pregnancy 2. Nursingmother 3. Infants under 6 weeks 4. Renal or hepatic failure 5. Blood disorders
- 15. Nitrofurantoin Antibacterial Spectrum: Effective againstE. coli or Staph. saprophyticus , but other common UT gm- bacteria may be resistant.
- 16. Mechanism of actionof nitrofurantoin Sensitive bacteria reduce the drug to an active agent that inhibits various enzymes and damages DNA.
- 17. Pharmacokinetics 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.
- 18. Adverse effects of nitrofurantoin GIdisturbances: bleeding of the stomach,nausea, vomiting and diarrhea(must be taken with food). Pulmonary fibrosis. Headache and nystagmus. Containdications: Pts with G6PD deficiency(haemolytic anaemia) Neonates Pregnant women(after 38 wks of pregnancy)
- 19. Therapeutic Uses ofnitrofurantoin It is used as urinary antiseptics . Its usefulness is limited to lower UTI’s & cannot be used for upper UT or systemic infections. Dose: 50-100 mg, po q 6h/7 days. Long acting: 100mg twice daily.
- 20. Tetracyclines (e.g. Doxycycline) It isa long acting tetracycline Mechanism of action Inhibit protein synthesis by binding reversibly to 30 s subunit
- 21. Doxycycline ( Cont.) Pharmacokinetics Usually given orally Absorption is 90-100% Absorbed in the upper s. intestine & best in absence of food Food & di & tri-valent cations ( Ca, Mg, Fe, AL) impair absorption Protein binding 40-80 % Distributed well, including CSF Cross placenta and excreted in milk Largely metabolized in the liver
- 22. Doxycycline ( Cont.) Side effects 1. 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. Vertigo 7. Superinfections.
- 23. Contraindications • Pregnancy • Breastfeeding • Children(below 10 yrs) 23
- 24. Therapeutic Uses ofDoxycycline •Treatment of UTI’s due to Mycoplasma & Chlamydia, 100 mg p.o bid for 7 days. • Prostatitis
- 25. Aminoglycosides e.g. GENTAMICIN,i.m,i.v. • Bactericidalantibiotics • Inhibits protein synthesis by binding to 30S ribosomal subunits. • Active against gram negative aerobic organisms. • Poorly absorbed orally(highly charged). • cross placenta.
- 26. Gentamicin(CONT) • Excreted unchangedin urine • More active in alkaline medium • Adverse effects : • Ototoxicity • Nephrotoxicity • Neuromuscular blocking effect
- 27. Therapeutic uses ofGentamicin in UTI’s • Severe infections caused by gram negative organisms (pseudomonas or enterobacter).
- 28.
- 29. Piperacillin • Effective againstpseudomonas aeruginosa & Enterobacter. • Penicillinase sensitive • Can be given in combination with β-lactamase inhibitors as clavulanic acid ,sulbactam, tazobactam.
- 30. 3rd generation cephalosporins Ceftriaxone &Ceftazidime Mainly effective against gm- bacteria. Acts by inhibition of cell wall synthesis Bactericidal They are given parenterally Given in severe / complicated UTIs & acute prostatitis
- 31. Fluroquinolones e.g. ciprofloxacin Mechanism ofaction • Inhibits DNA gyrase enzyme
- 32. Clinical uses • UTI,s causedby multidrug resistance organisms as pseudomonas. • Prostatitis ( acute / chronic )
- 33. PROSTATITIS ETIOLOGY: a) Acute prostatitis: Non-catheter- usually due to gm- bacteria(E.coli or Klebsiella) Antibiotics used:TMP/SMX,IV(160/800mg bid), a cephalosporin or ciprofloxacin. Catheter associated due to gm- or enterococci. Antibiotics used: ciprofloxacin or ceftriaxone. b) Chronic prostatitis due to E.coli, Klebsiella & Proteus Antibiotics used: ciprofloxacin,500mg bid for at least 12 wks