1 Treatment of Urinary Tract Infections

Prof. Mohammed Saad Al-Humayyd Prof. Azza Hafiz El-Medany

4 Classification of urinary tract infections Symptomatic infections Uncomplicated acute cystitis Acute urethritis recurrent cystitis

5 Acute pyelonephritis Complicated Acute and chronic prostatitis Asymptomatic bacteriuria

Urinary tract infections It is the 2 nd most common infection ( after RTI’s). More common in women Incidence increases in old age

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 Enlargement of prostatic gland Catheters placed in urethra and bladder. Not drinking enough fluids. Waiting too long to urinate. Pregnancy Poor toilet habits(wiping back to front for women) Suppress the immune system

Microorganisms causes urinary tract infections Gm- bacteria E.coli Proteus Klebsiella Pseudomonas Gm+ bacteria Staphylococcus species Chlamydia trachomatis,Mycoplasma & N. gonorrhea

Treatment of uncomplicated and complicated UTI’s Antibiotics:  TMP/SMX complex (co-trimoxazole)  Nitrofurantoin  Quinolones : ciprofloxacin, levofloxacin  Tetracyclines (Doxycycline, tetracycline) Aminoglycosides ( gentamicin )

Continue β-Lactam antibiotics  Extended spectrum penicillins Amoxicillin/clavulanic acid combination Piperacillin / tazobactam combination  Cephalosporines ( 3 rd G. ceftriaxone, ceftazidime) 11

Sulfamethoxazole- Trimethoprim (SMX) (TMP) Co-trimoxazole each agent alone is bacteriostatic Together they are bacteriocidal (synergism)

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

PHARMACOKINETICS Sulfamethoxazole given orally Rapidly absorbed from stomach and small intestine. Widely distributed to tissues and body fluids, cross placenta Bind to serum protein Metabolized in the liver. Eliminated in the urine

Continue Trimehoprim ( TMP )  orally, alone or in combination with SMX WWell absorbed from the gut WWidely distributed in body fluids & tissues MMore lipid soluble than SMX PProtein bound EExcreted in the urine TTMP concentrates in the prostatic fluid.

Clinical uses Acute urinary tract infections Complicated urinary tract infections Recurrent urinary tract infections Upper respiratory tract infections Pneumocystis carinii pneumonia 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)

CONTRAINDICATIONS  Pregnancy  Nursing mother  Infants under 6 weeks  Renal or hepatic failure  Blood disorders

Nitrofurantoin Bacterial Spectrum : E. coli Some Gm+ cocci are susceptible.

Pharmacokinetics  Absorption is complete after oral use  Metabolized & excreted rapidly that has no systemic antibacterial action  Excreted in the urine  It turns urine brown.

Continue Must be given with food or milk Keep urinary pH below 5.5 ( acidic ) to enhance drug activity 21

Adverse effects of nitrofurantoin  GIT disturbances : ( Nausea, vomiting and diarrhea )  Headache and nystagmus.  Hemolytic anemia  Pulmonary toxicity on chronic use (pulmonary fibrosis)

Contraindications Patients with G 6P deficiency Neonates Pregnant women

Therapeutic Uses As urinary antiseptics (little or no systemic antibacterial effect ) Dose: 100 mg ( orally four times daily )

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

Pharmacokinetics  G Given orally AAbsorption is %  di & tri-valent cations ( Ca, Mg, Fe, AL) impair absorption  Protein binding % DDistributed well, including, prostatic tissues CCross placenta and excreted in milk EExcreted through non-renal route

Adverse effects  Nausea, vomiting and diarrhea  Thrombophlebities  Hepatic toxicity  B Brown discoloration & deformity of teeth ( children)  D Deformity of bones ( children)  Vertigo  Superinfections & deformity of teeth ( children) Deformity

Therapeutic Uses UTI’s due to Mycoplasma & Chlamydia Prostatitis

Contraindications Pregnancy Breast feeding Children 29

Aminoglycosides Bactericidal 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 More active in alkaline medium Adverse effects Ototoxicity Nephrotoxicity Neuromuscular blocking effect

e.g. Gentamicin Severe infections caused by gram negative organisms as pseudomonas enterobacter.

Contraindications Renal dysfunction Pregnancy Diminished hearing Myasthenia gravis

1-Extended- spectrum penicillins ( piperacillin) 2- Cephalosporins 34 β-Lactam antibiotics

Piperacillin Effective against pseudomonas aeruginosa Penicillinase sensitive Given in combination with β-lactamase inhibitors as tazobactam.

3 rd generation cephalosporins Ceftriaxone & Ceftazidime  Effective against gm- bacteria.  Inhibit bacterial cell wall synthesis  Bactericidal  Given parenterally  Given in severe / complicated UTIs acute prostatitis

Fluroquinolones Levofloxacin & Ciprofloxacin Inhibits DNA gyrase enzyme

Clinical uses UTI,s caused by multidrug resistance organisms as pseudomonas. Prostatitis ( acute / chronic )

PROSTATITIS A ) Acute prostatitis B) Chronic prostatitis D ue to gram –V organisms as (E.coli, Klebsiella )

Antibiotics used for treatment of prostatitis Acute/ Chronic ( Different in route & duration of treatment ) TMP/SMX complexs 3 rd Generation cephalosporines Quinolones Tetracyclines 40