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Treatment of Urinary Tract Infections

PROF.

AZZA

El-Medany

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Classification of urinary tract infections

1- Symptomatic infections

Uncomplicated UTI (mainly in women) acute cystitis Acute urethritis recurrent cystitis

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Acute pyelonephritis

Complicated UTI

Acute and chronic prostatitis

2- Asymptomatic bacteriuria

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).

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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 (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).

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

Treatment of uncomplicated and complicated UTI’s

Antimicrobial agents:TMP or TMP/SMX (co-trimoxazole) Nitrofurantoin Quinolones Tetracyclines Aminoglycosides

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β-Lactam antibiotics

Extended spectrum penicillins

Cephalosporins ( 3rd G. )

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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 DihydrofolateDihydrofolatereductase Tetrahydrofolate Nucleic acid synthesis

TrimethoprimTrimethoprim

PHARMACOKINETICS

Sulfonamides given orallyRapidly 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.

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Trimethoprim ( TMP )

given orallyWell absorbed from the gutWidely distributed in body fluids & tissuesMore lipid soluble than SMXProtein bound 60% of TMP or its metabolite is excreted in the

urineTMP 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) Allergy

Hematologic 1) Acute hemolytic anemia a) hypersensitvity b) G6PD deficiency 2) Megaloblastic anemia due to TMP.

Kernicterus ( Jaundice due to Displace

bilirubin )

CONTRAINDICATIONS

Pregnancy Nursing mother Infants under 6 weeks 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

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Pharmacokinetics • •Absorbed orally

•Well concentrated in the urine

•75%of the dose is rapidly metabolized by the liver , 25% is excreted in the urine unchanged .

• Drug & its metabolites are excreted in the urine• Turns urine to a dark orange- brown.

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Given with food

Keep urinary pH below 5.5 ( acidic urine

augment drug antibacterial activity )

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Adverse effects of nitrofurantoin

GIT disturbances: nausea, vomiting, diarrhea & gastric bleeding ( must be taken with food ).

Headache and nystagmus.

Hemolytic anemia

Pulmonary fibrosis ( on chronic use )

Contraindications

Patients with G 6PD deficiency

Neonates ( babies up to the age of one month )

Pregnant women ( after 38 weeks of pregnancy )

Therapeutic Uses

Used as urinary antiseptics but has little or no systemic antibacterial effect.

Its usefulness is limited to lower UTI’s.

Dose: 50-100 mg ( orally four times daily ) for 7 days

Tetracyclines

Doxycycline

Tetracycline

Tetracyclines

Broad spectrum antibiotic

Bacteriostatic

Mechanism of action

Inhibit protein synthesis by binding reversibly to 30 s ribosomal subunit

DOXYCYCLINE

Pharmacokinetics

Long acting tetracycline

Usually given orally once daily

Absorption is 90-100 %

Absorption in the upper s. intestine

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Absorption is impaired by

1- divalent cations ( Ca, Mg, Fe )

2- milk and its products

3- antacids ( aluminium hydroxide gel, sodium bicarbonate)

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Protein binding 40-80 %

Distributed well, including prostatic tissues

Cross placenta and excreted in milk

Metabolized in liver

Excreted through non renal route

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

Therapeutic Uses

Treatment of UTI’s due to Mycoplasma & Chlamydia.

Prostatitis

Contraindications

Pregnancy

Breast feeding

Children ( below 10 years )

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Aminoglycosides (Gentamicin )

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

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Excreted unchanged in urine More active in alkaline medium

Adverse effects : Ototoxicity Nephrotoxicity Neuromuscular blocking effect

Therapeutic uses of Gentamicin

Severe UTIs caused by gram negative aerobic organisms (pseudomonas ) .

Contraindications

Renal dysfunction Pregnancy Patients with hearing problem (Diminished

(hearing Myasthenia gravis

( A) Extended- spectrum penicillins

Amoxicillin / clavulanic acid

piperacillin or piperacillin /

tazobactam

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β-Lactam antibiotics

Mechanism of actions

Inhibit bacterial cell wall synthesis

Bactericidal

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Piperacillin

Effective against pseudomonas aeruginosa & Enterobacter.

Penicillinase sensitive

Can be given in combination with β-lactamase inhibitors as clavulanic acid ,

sulbactam, tazobactam.

(B) 3rd generation cephalosporins

Ceftriaxone & Ceftazidime

Mainly effective against gm negative bacteria.

They are given parenterally

Given in severe / complicated UTIs

& acute prostatitis

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 3rd Generation cephalosporins

(ceftriaxone) Quinolones ( ciprofloxacin , levofloxacin ) Tetracyclines ( Doxycycline)

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