Download - 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