Uncomplicated Uti

8/8/2019 Uncomplicated Uti

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MANAGEMENT ofUNCOMPLICATED

URINARY TRACT

INFECTION


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U N C O M P L I C A T E D

U R I N A R Y T R A C T I N F E C T I O N

Upper vs. Lower


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U N C O M P L I C A T E D

U R I N A R Y T R A C T I N F E C T I O N

Complicated vs. Uncomplicated

> complicated : increased risk for acquiring

infections, failing therapy, increased morbidity


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RISK FACTORS for DEVELOPING COMPLICATED UTI

Anatomic/obstructionBladder diverticuliNephrolithiasisPolycystic kidney diseaseUrethral/ureteric stricture

Epidemiologic

Age >55 yearsChildhood UTI (>12 years)HospitalizationMalePregnancy

FunctionalIncontinenceNeurogenic bladderUrinary retention/increased

postvoid residual

ImmunosuppressionChronic renal failureDiabetes mellitusDrug or alcohol abuseHIV/AIDSOrgan transplantation

InstrumentationIndwelling catheterIntermittent catheterizationUreteric stent

Other

Prolonged symptoms priorto treatment (>7 days)

Resistant etiologicorganisms

Treatment failure


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E T I O L O G Y

Escherichia coli accounts for ~80% of

uncomplicated UTI

Staphylococcus saprophyticus -- 5-20% of

the reported cases

Klebsiella pneumoniae and Proteus mirabilis


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DRUG

TREATMENT


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D R U G T R E A T M E N T

Combination drug trimethoprim and

Sulfamethoxazole Co-trimoxazole

Fluoroquinolones - ciprofloxacin, norfloxacin

nitrofurantoin


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TRIMETOPHRIM-SULFAMETHOXAZOLE

resulting combination of these two

drugs shows greater antimicrobial activity

considered the standard of

therapy for acute and recurrent UTI

problem of resistance


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TRIMETOPHRIM-SULFAMETHOXAZOLE

Figure 1. Synergism between

trimetophrim and sulfamethoxazole on

inhibition ofE.coli


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MECHANISM of ACTION

SULFAMETHOXAZOLE, a structural analog acting as a

competitive antagonist of para-aminobenzoic acid (PABA) ,

inhibits difydropteroate synthase

TRIMETOPHRIM , prevents the reduction of dihydrofolate

to tetrahydrofolate


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Both have similar antibacterial spectrum but

trimetophrim is far more potent , 20 to 100

times, than sulfamethoxazole

ANTIBACTERIAL SPECTRUM


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Administration

- 1 part trimethoprim and 5 part

sulfamethoxazole plasma concentration of 20

parts sulfamethoxazole and 1 part trimethoprim

PHARMACOKINETICS


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PHARMACOKINETICS

TRIMETOPHRIM SULFAMETHOXAZOLE

Peak bloodconcentration

2 hrs 4 hrs

Half-life 11 hrs 10 hrs.

Excretion(urine)

60% 20-25%


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Urinary Tract Infection-- Trimethoprim concentrates in prostate and

vaginal fluids

Respiratory infection-- chronic bronchitis

-- effective against H. Influenza and S. pneumoniae

CLINICAL USE


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GI Infection-- second line drug for typhoid fever

-- treatment of acute diarrhea against sensitive

strains of eneteropathogenic E. coli.

CLINICAL USE


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ADVERSE DRUG REACTION

DERMATOLOGIC

exfoliative dermatitis, steven- Johnson syndrome

GASTROINTESTINAL

Nausea, vomiting Glossitis and stomatitis

HEMATOLOGIC

Megaloblastic anemia, leucopenia and thrombocytopenia


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Intake with warfarin increses Prothrombin

time

Increase phenytoin levels

Increase hypoglycemic response to

sulfonyureas

DRUG INTERACTIONS


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CONTRAINDICATIONS

Documented hypersensitivity; megaloblastic

anemia due to folate deficiency


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broad antimicrobial activity

commonly employed to treat UTI

few side affects

microbial resistance due to overuse

FLUOROQUINOLONE


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target the bacterial DNA gyrase and

topoisomerase IV

gram positive inhibits topoisomerase IV

responsible for separation of DNA

during cell division.

gram negative - inhibit DNA gyrase preventing

the relaxation of positively supercoiled DNA

MECHANISM of ACTION


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bactericidal and effective against gram

negative organisms

poor anaerobic activity

ANTIMICROBIAL SPECTRUM


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chromosomal mutations

Altered target

Decreased accumulation

RESISTANCE


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ABSORPTION

bioavailability of 80 to 95%

does not impair oral absorption but may

delay the time to peak serum concentrations

antacids containing magnesium or dietary

supplements containing iron or zinc caninterfere with the absorption of the drug

PHARMACOKINETICS


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PHARMACOKINETICS

Table 1. . Pharmacokinetic properties of fluoroquinolones.

Drug

Half-

Life

(h)

Oral

Bioavailability

(%)

Peak Serum

Concentration

(ug/mL)

Oral

Dose

(mg)

Primary Route of

Excretion

Ciprofloxacin 3-5 70 2.4 500 Renal

Gatifloxacin 8 98 3.4 400 RenalGemifloxacin 8 70 1.6 320 Renal & nonrenal

Levofloxacin 5-7 95 5.7 500 Renal

Lomefloxacin 8 95 2.8 400 Renal

Moxifloxacin 9-10 > 85 3.1 400 Nonrenal

Norfloxacin 3.5-5 80 1.5 400 Renal

Ofloxacin 5-7 95 2.9 400 Renal


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Urinary Tract Infection-- fluroquinolones significantly more potent and

efficacious than trimethoprim

-- ciprofloxacin is the most potent of the

fuoroquinolones; useful for treating

infections caused by many Enterobacteraceae and other

gram negative bacilli

CLINICAL USE


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Not all fluoroquinolones can be used for UTI-- Sparfloxacin and moxifloxacin >> lower

concentrations in the urine are not approved for thisindication

CLINICAL USE


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STIs

-- no activity against Treponema pallidum

-- effective treatment against for sensitive strains

of gonorrhea

GI Infections

-- effective for bacterial diarrhea caused by

shigella, salmonella, toxigenic E coli, andcampylobacter

CLINICAL USE


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Respiratory Tract Infection

-- Levofloxacin, gatifloxacin, gemifloxacin, and

moxifloxacin, so-called respiratoryFluoroquinolones >> enhanced gram-positive activity

and activity against atypical pneumonia agents

CLINICAL USE


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Bones, Joint and Soft Tissue Infection

-- Fluoroquinolones (except norfloxacin) have been

used in infections of soft tissues, bones, and joints .

-- Treatment of chronic osteomyelitis

CLINICAL USE


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Ciprofloxacin -- prophylaxis and treatment of anthraxEffective treatment for tularemia

CLINICAL USE


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ADVERSE DRUG REACTION

CNS probelms

Mild headache and dizzines

intake with theophylline -- hallucinations and delirium as well

as seizuresNephrotoxicity

Cystallurias

Photosensitivity

avoid excessive sunlight


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Antacids and cations impair the absorption ofthese drugs.Ciprofloxacin, ofloxacin increase serum levels of thetheophylline by inhibiting its metabolism.Raise the levels of warfarin, caffeine andcyclosporine.Cimetideine interferes with the elimination of thefluroquinolones

DRUG INTERACTIONS


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contraindicated among pregnant women , nursingmothers and children under 18 years of age becauseof the possible danger of articular cartilage erosion

CONTRAINDICATIONS


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drugs are concentrated in the renal tubules hence

they proved to be an effective treatment in urinary

tract infections

URINARY TRACT ANTISEPTICS


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Sensitive bacteria reduce the drug to an active agent inhibit bacterial enzymes involved inmetabolism damage DNA inhibit cell wall synthesis

MECHANISM OF ACTION


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absorbed rapidly and completely from the GItract does not achieve antibacterial concentration inplasma because it is eliminated rapidly plasma half life is 0.3 to 1 hour and about 40% isexcreted unchanged in the urine

PHARMACOKINETICS


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Sensitive bacteria reduce the drug to an active agent inhibit bacterial enzymes involved inmetabolism damage DNA inhibit cell wall synthesis

MECHANISM OF ACTION

Documents

Uncomplicated Uti