Urinary tract infections 2

1. Drug therapy of
Urinary Tract
Infections
Dr. C.Adithan
Professor

2. UTI – Which is which ?
Upper UTI
Lower UTI

3. Risk Factors
1. Aging
 Increased incidence of diabetes mellitus, Risk of
urinary stasis, Impaired immune response
2.Females: short urethra, having sexual intercourse,
use of contraceptives that alter normal bacteria flora of
vagina and perineal tissues; with age increased
incidence of cystocele, rectocele (incomplete emptying)
3.Males: prostatic hypertrophy, bacterial prostatitis,
anal intercourse
4.Urinary tract obstruction: tumor or calculi,
strictures
5.Impaired bladder innervation

4. Organisms implicated in UTI
Mostly gram negative bacteria
• E. coli (80 %)
• In patients with catheters – Serratia,
Pseudomonas
• In patients with stones – Proteus, Klebsiella
Gram positive bacteria - less role
• Staph saprophyticus, Staph aureus, Staph
epidermidis
Other agents
• Chlamydia, gonococci, ureaplasma,
mycoplasma, candida

5. • Symptoms alone are unreliable
• Examination of the urine is the
cornerstone of diagnosis
• Urine C & S testing (2 days)
• In vitro resistance predicts - higher failure
rate
FOR DIAGNOSIS

6. Collection of urine:
• Mid stream clean catch method is
preferred method
• Catheterization for patient who are
uncooperative or unable to void, but
introduction of bacteria in the bladder
occurs at 1-2%
• Suprapubic aspiration bypasses the
contaminating organism in the urethra,
safe and painless.

7. Diagnostic levels
• More than or equal to 105
bacteria/ml
• Suprapubic aspiration/
catheters: 102 - 104 bacteria/ml
• Counts > 105 with multiple
species - contamination

8. Clinical features: URETHRITIS
E. coli: Duration of <3 days with high fever, hematuria and
suprapubic pain
Chlamydia or gonococci: Duration of >7 days with gradual
onset, risky sexual activity, no h/o supra pubic pain,
hematuria
Urethritis – Dysuria,
frequency and pyuria,
with or without
bacterial growth

9. Clinical features: CYSTITIS
Cystitis – Dysuria, frequency, urgency, suprapubic
pain. Cloudy malodorous urine. Bacteriuria,
hematuria and pyuria, with or without fever

10. Clinical features: ACUTE PYELONEPHRITIS
Acute pyelonephritis – above features with rapidly
developing illness, renal angle tenderness or pain on
deep abdominal palpation and high fever (> 38.3O C)

11. Chronic pyelonephritis
a) Involves chronic inflammation and scarring of
tubules and interstitial tissues of kidney
b) Common cause of chronic renal failure
c) May develop from chronic hypertension,
vascular conditions, severe vesicourteteral
reflux, obstruction of urinary tract
d) Behaviors
1.Asymptomatic
2.Mild behaviors: urinary frequency, dysuria, flank pain

12. Clinical features:
Catheter associated UTI
Suspect if, catheterized and…
 Prolonged catheterization
 Severe underlying illness
 Disconnection of catheter and drainage tube
 Faulty catheter care
 Lack of systemic antimicrobial therapy

13. Treatment of UTI - Principles
• Predisposing factors to be corrected
• Lower UTI (uncomplicated) - short courses of
therapy
• Upper UTI - longer therapy
• Relief of symptom does not mean bacteriologic
cure
• CAIs - usually antibiotic-sensitive
• Repeated infections, instrumentation, or recent
hospitalization - antibiotic-resistant strains

14. Treatment regimens for UTI
Acute uncomplicated cystitis
• No other complication
– 3-Day regimens: oral TMP-SMX, TMP, quinolone
– 7-day regimen: nitrofurantoin
• Diabetes, symptoms >7 d, recent UTI, age >65 yrs
– 7-day regimen: oral TMP-SMX, TMP, quinolone

15. Treatment regimens for UTI
Acute uncomplicated cystitis
Pregnancy
–7-day regimen: oral amoxicillin,
nitrofurantoin, cefpodoxime
–Continuous low-dose prophylaxis with
nitrofurantoin for recurrent infection

16. Doses used for acute uncomplicated cystitis
in women
TMP-SMX, 160/800 mg q12h
TMP, 100 mg q12h
Norfloxacin, 400 mg q12h, Ciprofloxacin, 250 mg q12h
Ofloxacin, 200 mg q12h, Levofloxacin, 250 mg/d
Nitrofurantoin, 100 mg qid
Amoxicillin, 250 mg q8h
Cefpodoxime, 100 mg q12h

17. Treatment regimens for UTI
Acute uncomplicated pyelonephritis
Mild to moderate illness, outpatient therapy
– Oral quinolone for 7–14 d (initial dose IV if desired)
– (or) single-dose ceftriaxone IV (1 g)
– (or) Gentamicin (3–5 mg/kg) IV followed by oral TMP-
SMX for 14 d
Severe illness: hospitalization required
– Parenteral quinolone, gentamicin (± ampicillin),
ceftriaxone, or aztreonam until defervescence
– Followed by oral quinolone, cephalosporin, or TMP-SMX
for 14 d

18. Treatment regimens for UTI
COMPLICATED UTI in men and women
Mild to moderate illness, outpatient therapy
– Oral quinolone for 10–14 d
Severe illness: hospitalization required
• Parenteralampicillin and gentamicin, quinolone,
ceftriaxone, aztreonam, ticarcillin/clavulanate, or
Imipenem-cilastatin until defervescence
• Followed by oral quinolone or TMP-SMX for 10–21 d

19. Oral regimens: pyelonephritis
and complicated UTI
• TMP-SMX, 160/800 mg q12h
• Ciprofloxacin, 500 mg q12h
• Ofloxacin, 200–300 mg q12h
• Lomefloxacin, 400 mg/d
• Levofloxacin, 250 mg q12h
• Moxifloxacin, 400 mg/d
• Amoxicillin, 500 mg q8h
• Cefpodoxime, 200 mg q12h
• Ciprofloxacin, 400 mg q12h
• Ofloxacin, 400 mg q12h
• Levofloxacin, 500 mg/d
• Gentamicin, 1 mg/kg q8h
• Ceftriaxone, 1–2 g/d
• Ampicillin, 1 g q6h
• Imipenem-cilastatin, 250–500 mg
q6–8h
• Ticarcillin/clavulanate, 3.2 g q8h
• Aztreonam, 1 g q8–12h
Parenteral regimens:
pyelonephritis and complicated
UTI

20. Asymptomatic bacteriuria
• For a catheterized patient - Remove catheter; short
course of antibiotic therapy
• For a patient without catheter – Usually no antibiotics
• For a patient without catheter – Antibiotic needed for
pregnancy, neutropenia, renal transplants, obstruction
– Usually 7 day oral therapy
– Longer-term therapy (4–6 weeks) - in high-risk
patients with persistent asymptomatic
bacteriuria

21. Salient points on specific drugs
Nitrofurantoin
• Primarily bacteriostatic. Cidal at higher conc;
• Activity more at acidic urine
• Mechanism – bacterial enzymatic reduction to
reactive intermediate – DNA damage
• Gm (-) ve organisms – E.coli; No cross resistance
• Probenecid – inhibit tubular secretion – reduces
activity
• Antagonizes action of nalidixic acid
(urinary antiseptic)

22. Salient points on specific drugs
Nitrofurantoin (contd--)
• Adverse effects – GI intolerance, chills,
fever, leucopenia, peripheral neuritis,
hemolytic anemia in G6PD deficiency
• In patients taking nitrofurantoin - urine
turns dark brown on standing

23. Salient points on specific drugs
Methenamine (urinary antiseptic)
• Decompose in acidic urine to release formaldehyde
• Enteric coated tablets
• Administered with ascorbic acid (pH <5.5)
• No resistance
• Not preferred now – gastritis due to release of
HCHO in stomach, chemical cystitis, hematuria
• C/I in renal failure and liver disease
• Methenamine increased the risk of crystalluria
when sulphonamides are given together

24. Salient points on specific drugs
Phenazopyridine – orange dye
 Urinary analgesic.
 No antiseptic property
 Tab. Pyridium 200 mg t.d.s

25. Salient points on specific drugs
Sulfonamides: use has decreased
Co-trimoxazole: Response and usage reduced,
empirical use in acute UTI, Not used in pregnancy
Ampicillin/Amoxicillin: Higher failure and relapse
rate, Combined with clavulanic acid for better
result
Piperacillin/carbenicillin: Only in serious
pseudomonas infection

26. Salient points on specific drugs
Cephalosporin:
 Used only based on C & S report.
 Increasingly used especially in women with
nosocomial Klebsiella and Proteus infection.
 Cephalexin given OD is for prophylaxis of recurrent
cystitis, especially in women likely to get pregnant
Gentamicin:
 very effective against most pathogens including
Pseudomonas
 Narrow margin of safety

27. Salient points on specific drugs
Nalidixic acid
• First member of quinolone – DNA gyrase inhibitor
• Highly protein bound, One active metabolite
• Spectrum – E.coli, Proteus, Klebsiella, Enterobacter,
Shigella
• Not active against pseudomonas
• Plasma and tissue levels – non therapeutic
• Concentration in urine – bactericidal
• ADRs – GIT upset, rashes, headache, drowsiness,
vertigo, visual disturbances, seizures, hemolysis in
G6PD deficiency
• C/I in infants
• Dose – 0.5 to 1 gm TDS to QID

28. Urinary pH in use of urinary AMA
Acidic pH Alkaline pH Not dependent on pH
Nitrofurantoin Cotrimoxazole Chloramphenicol
Methenamine Aminoglycosides Ampicillin
Tetracycline Cephalosporins Colistin
Cloxacillin Fluoroquinolones

29. Note-
AVOID in patients with impaired renal functions
•Nitrofurantoin, Nalidixic acid
•Aminoglycosides
•Potassium salt, and Acidifying agents

30. Urinary analgesics (Local)
•Phenazopyridine
Urinary antiseptics
•Nitrofurantoin
•Methenamine
To Summarize

31. Antimicrobials------(Q-BACTS)
•Quinolones -(Nalidixic acid, Norfloxacin……)
•Betalactams- Ampicillin/ Amoxicillin,
•Aminogycosides- Gentamicin, Amikacin, …
•Cephalosporins- Third generation
•Tetracyclines -
•Sulfonamides and Cotrimoxazole
•Other Antimicrobials-
•Chloramphenicol, Methicillin, Carbenicillin
etc……..

32. How many days you will treat a case
of uncomplicated cystitis?
• No other complication
– 3-Day regimens: oral TMP-SMX, TMP, quinolone
– 7-day regimen: nitrofurantoin
• Diabetes, symptoms >7 d, recent UTI, age >65 yrs
– 7-day regimen: oral TMP-SMX, TMP, quinolone
Pregnancy
– 7-day regimen: oral amoxicillin,
nitrofurantoin, cefpodoxime
– Continuous low-dose prophylaxis with
nitrofurantoin for recurrent infection

33. What would be the drug useful for
treatment of dysuria?
• Phenazopyridine – orange dye
 Urinary analgesic.
 No antiseptic property
 Tab. Pyridium 200 mg t.d.s

34. When will you treat
asymptomatic bacteriuria?
For a catheterized patient –
 Remove catheter;
 short course of antibiotic therapy
For a patient without catheter – Antibiotic needed for
pregnancy, neutropenia, renal transplants, obstruction
– Usually 7 day oral therapy
– Longer-term therapy (4–6 weeks) - in high-risk patients
with persistent asymptomatic bacteriuria

35. Thank you…