1 Treatment of Urinary Tract Infections

PROF. AZZAEl-Medany And Dr Ishfaq Bukhari

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

5 Acute pyelonephritis (infection of the kidney) Complicated UTI Acute and chronic prostatitis 2- Asymptomatic bacteriuria

Urinary tract infections(UTI’s) It is the 2 nd 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).

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. 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 (the most problematic bug) Gm positive bacteria ( less common): Staphylococcus species Other: Chlamydia trachomatis,Mycoplasma & N. gonorrhea

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

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

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 Dihydrofolate Dihydrofolate reductase Tetrahydrofolate Nucleic acid synthesis Trimethoprim

PHARMACOKINETICS Sulfonamides given orally Rapidly absorbed from stomach and small intestine. 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.

Continue Trimethoprim ( TMP ) same as SMX, Well absorbed from the gut More lipid soluble than SMX TMP 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)  Hematologic 1) Acute hemolytic anemia a) hypersensitvity b) G6PD deficiency 2) Megaloblastic anemia due to TMP (Folate defiecency).  Kernicterus ( bilirubin –induced brain dysfunction )

Continue adverse effects Crystalluria Hypersensitivity reactions (skin reaction) Neonatal jaundice 17

CONTRAINDICATIONS  Pregnancy ( cross placenta)  Nursing mother ( secreted in milk)  Newborn Infants ( encephalopathy)  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 20

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.

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

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 )

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

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

Tetracyclines Doxycycline Minocycline

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

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

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

Continue Protein binding % 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

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)  D Deformity or growth inhibition of bones( children)  Vertigo  Superinfections & deformity of teeth ( children) Deformity

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

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

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

CONTINUE Excreted unchanged in urine Adverse effects : Ototoxicity Nephrotoxicity Neuromuscular blocking effect

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

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

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

Mechanism of actions Inhibit bacterial cell wall synthesis Bactericidal 39

Piperacillin Very Effective against pseudomonas aeruginosa & Enterobacter. (remember Piperacillin, remember “p” for pseudomonas) Penicillinase sensitive Can be given in combination with β- lactamase inhibitors as clavulanic acid, sulbactam, tazobactam.

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

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 Ceftriaxone Ciprofloxacin, levofloxacin Doxycycline in chronic prostatitis especially in trachomatis & chlamydia infections 45

Antibiotics used in tratment of UTI in children Cephalosprins (ceftriaxone, ceftazidime) Penicillins (amoxycillin) Aminoglycosides ( with precaution ) 46

Antibiotics not recommended to treat UTI in children Tetracyclines Quinolones 47