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Treatment of Urinary Tract Infections

Prof.

Mohammed Saad Al-Humayyd

Prof.

Azza Hafiz

El-Medany

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Classification of urinary tract infections

Symptomatic infections

Uncomplicated acute cystitis Acute urethritis recurrent cystitis

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Acute pyelonephritis

Complicated

Acute and chronic prostatitis

Asymptomatic

bacteriuria

Urinary tract infections

It is the 2nd most common infection ( after RTI’s).

More common in women

Incidence increases in old age

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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 • 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•PseudomonasGm+ bacteria • Staphylococcus species

•Chlamydia trachomatis ,Mycoplasma & N. gonorrhea

Treatment of uncomplicated and complicated UTI’s

Antibiotics:TMP/SMX complex (co-trimoxazole)NitrofurantoinQuinolones : ciprofloxacin, levofloxacin Tetracyclines (Doxycycline , tetracycline)

Aminoglycosides ( gentamicin )

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β-Lactam antibiotics Extended spectrum penicillins Amoxicillin/clavulanic acid combination Piperacillin / tazobactam combination

Cephalosporines ( 3rd G. ceftriaxone,

ceftazidime)

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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 DihydrofolateDihydrofolatereductase Tetrahydrofolate Nucleic acid synthesis

TrimethoprimTrimethoprim

PHARMACOKINETICS

Sulfamethoxazole given orallyRapidly absorbed from stomach and small intestine.Widely distributed to tissues and body fluids , cross

placenta Bind to serum proteinMetabolized in the liver .Eliminated in the urine

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Trimehoprim ( TMP )

orally, alone or in combination with SMX Well absorbed from the gut Widely distributed in body fluids & tissues More lipid soluble than SMX Protein bound Excreted in the urine 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.

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Must be given with food or milk

Keep urinary pH below 5.5 ( acidic ) to enhance drug activity

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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

Given orally Absorption is 90-100%

di & tri-valent cations ( Ca, Mg, Fe, AL) impair absorption Protein binding 40-80 % Distributed well, including , prostatic tissues Cross placenta and excreted in milk Excreted through non-renal route

Adverse effects

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

Therapeutic Uses

UTI’s due to Mycoplasma & Chlamydia

Prostatitis

Contraindications

Pregnancy

Breast feeding

Children

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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

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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

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β-Lactam antibiotics

Piperacillin

Effective against pseudomonas aeruginosa

Penicillinase sensitive Given in combination with β-lactamase

inhibitors as tazobactam.

3rd 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

Due 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 3rd Generation cephalosporines

Quinolones Tetracyclines

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