antimicrobial therapy of UTI

1. URINARY TRACT INFECTIONS
(UTIS)

2. ILOS
 Provide medical students with evidence-based
information for the prevention and treatment of
urinary tract infections (UTIs).
 Optimize antibiotic use whilst minimizing
unintended effects of antimicrobials such as
Clostridium difficile infections, toxicity, and
emergence of resistant bacterial strains

3. DEFINITIONS:
 Uncomplicated UTIs
Acute, sporadic or recurrent lower (uncomplicated
cystitis) and/or upper (uncomplicated
pyelonephritis) UTI, limited to:
• Non-pregnant premenopausal women
• With no known relevant anatomical and functional
abnormalities within the urinary tract
• With no co-morbidities.
Recurrent UTIs: Recurrences of uncomplicated and/or
complicated UTIs, with a frequency of at least three
UTIs/year or two UTIs in the last six months.

4. DEFINITIONS:
 Complicated UTIs
All UTIs, (complicated cystitis) and/or (complicated
pyelonephritis) which are not defined as
uncomplicated.
UTIs in a patient with an increased chance of a
complicated course: i.e.
• All men,
• Pregnant women,
• Patients with relevant anatomical or functional
abnormalities of the urinary tract,
• Patients with urinary catheters,
• Patients with renal diseases,
• Patients with other concomitant immunocompromising
diseases for example, diabetes.

5. CLASSIFICATION:

8. URINARY ANTISEPTICS
1. Nitrofurantoin
Mech. Of action: Nitrofurantoin
causes bacterial DNA damage.
Uses: It is used only as a urinary
antiseptic in uncomplicated
cystitis.
Adverse effects:
 Hemolytic anemia in patients with
G-6-PD deficiency.
 Peripheral neuritis
 Dark brown urine.
 Contraindicated in renal failure.

9. URINARY ANTISEPTICS
2. Fosfomycin:
2. Mech. Of action: a bactericidal
antibiotic that interferes with
cell wall synthesis in both
Gram-positive and gram negative
bacteria.
3. Uses: It is used only as a
urinary antiseptic in
uncomplicated cystitis.

10. UNCOMPLICATED CYSTITIS

11. UNCOMPLICATED CYSTITIS
 Definition:
 Epidemiology:
 Up to 50% of women have at least one symptomatic
uncomplicated cystitis during their lifetime.
 Young, sexually active women 18–24 years of age have
the highest incidence.
 Causative organism: The most common causative
agent of uncomplicated cystitis is E. coli (75-95%),
followed by Staphylococcus saprophyticus (5-15%).

12. UNCOMPLICATED CYSTITIS
 Diagnosis:
• Clinical diagnosis
A history of lower urinary tract symptoms (dysuria,
frequency and urgency) and the absence of vaginal
discharge or irritation.
• Laboratory diagnosis
leads only to a minimal increase in diagnostic accuracy
 Urine analysis: assessment of white and red blood cells and
nitrite
 Urine culture: is recommended in patients with atypical
symptoms, as well as those who fail to respond to appropriate
antimicrobial therapy.

13. UNCOMPLICATED CYSTITIS
 Treatment:
• Goals of therapy:
Symptomatic relief is a high priority in patients with cystitis.
With appropriate antibiotic therapy, clinical response
occurs within 24 hours

14. Antimicrobial therapy in uncomplicated cystitis
Duration of therapyAntimicrobial
First-line
3g onceFosfomycin
5 daysNitrofurantoin
3-5 daysPivmecillinam
If the local resistance pattern for E. coli is < 20%
5 daysTrimethoprim
3 daysTrimethoprim-sulphamethoxazole
Alternatives
5-7 daysAmoxicillin/clavulanic acid
5-7 daysCephalosporins (e.g. cefpodoxime or
cephalexin)

15. UNCOMPLICATED CYSTITIS
 Treatment:
 Amoxicillin/clavulanic acid and oral cephalosporins are
not effective as short-term therapy and are not
recommended for empirical therapy due to ecological
collateral damage
 Fluoroquinolones (e.g. ciprofloxacin or levofloxacin)
should be avoided because of adverse effects including
negative ecological effects.
Ecological collateral damage: the selection of drug-resistant
strains and the development of infection or colonization of
multidrug-resistant bacteria.

16. CYSTITIS IN PREGNANCY
Not all antimicrobials are suitable during pregnancy. In
general, the following antibiotics can be considered:
 Penicillins,
 Cephalosporins,
 Fosfomycin,
 Nitrofurantoin (not in case of glucose-6-phosphate
dehydrogenase deficiency and during the end of
pregnancy),  increased incidence of neonatal jaundice.
 Trimethoprim (not in the first trimenon)
 and sulphonamides (not in the last trimenon).?
?

17. CYSTITIS IN MEN
Treatment with antimicrobials penetrating into the prostate
tissue is needed in males with symptoms of cystitis.
A treatment duration of at least 7 days is recommended,
preferably with:
 Trimethoprim-sulphamethoxazole or a
 Fluoroquinolone if in accordance with susceptibility testing.

18. UNCOMPLICATED
PYELONEPHRITIS

19. UNCOMPLICATED PYELONEPHRITIS
Definition:
Diagnosis:
 Clinical diagnosis:
Fever (> 38°C), chills, flank pain, nausea, vomiting, or costo-vertebral
angle tenderness, with or without the typical symptoms of cystitis
 Laboratory diagnosis
 Urinalysis: is recommended for routine diagnosis
 Urine culture and antimicrobial susceptibility testing: in all cases of
pyelonephritis.
 Imaging diagnosis to differentiate between uncomplicated and
complicated mostly urinary obstruction or renal stone disease
 US
 CT
 Excretory urography

20. UNCOMPLICATED PYELONEPHRITIS
 Agents such as nitrofurantoin,
fosfomycin, and pivmecillinam
should be avoided because they do
not achieve adequate renal tissue
levels.
 Fluoroquinolones are the first-line
agents that can be recommended for
oral empirical treatment.
 In case of fluoroquinolone
hypersensitivity or resistance, other
acceptable choices include an oral
cephalosporin or trimethoprim-
sulfamethoxazole, And an initial
intravenous dose of a long-acting
parenteral cephalosporin (e.g.
ceftriaxone) should be administered,
 Treated initially with an i.v
antimicrobial regimen (a
fluoroquinolone, an
aminoglycoside (with or
without ampicillin), or an
extended-spectrum
cephalosporin or an
extended-spectrum
penicillin.
 Carbapenems only in
patients with early culture
results indicating the
presence of multi-drug
resistance organisms.
 Patients initially treated with
parenteral therapy who
improve clinically may
transition to oral antimicrobial
therapy
Outpatient (empirical oral)
Inpatient (empirical
parentral)

21. UNCOMPLICATED PYELONEPHRITIS
First-line treatment
Flouroquinolones
(Ciprofloxacin or
Levofloxacin)
5-7 days
Second-line treatment
Ceohalosporins
(Cefpodoxime)
10 days
Trimethoprim-
sulfamethoxazole
14 days
First-line treatment
7 daysFlouroquinolones
(Ciprofloxacin or
Levofloxacin)
Second-line treatment
14 daysCeohalosporins
(Ceftriaxone, Cefepime,
…)
Piperacillin/tazobactam
Aminoglycosides (gentamicin,
amikacin)
Carpapenems (imipenem,
meropenem)
Outpatient (empirical oral)
Inpatient (empirical
parentral)

22. COMPLICATED UTIS

23. COMPLICATED UTIS
 Definition:
 Diagnosis:
 Clinical diagnosis: symptoms (e.g. dysuria, urgency,
frequency, flank pain, costo-vertebral angle tenderness,
suprapubic pain and fever .
 Laboratory diagnosis:
 Urine culture and antimicrobial susceptibility testing: The
spectrum is much larger and the bacteria are more likely to be
resistant than those isolated in uncomplicated UTIs.
Enterobacteriaceae predominate (60-75%), with E. coli as the
most common pathogen

24. COMPLICATED UTIS
 Treatment
 Management of the urological abnormality or the
underlying complicating factor is mandatory.
 Antimicrobial susceptibility testing should be performed,
and initial empirical therapy should be followed by
administration of an appropriate antimicrobial agent on
the basis of the isolated microorganism.
 Based on the current local resistance percentages of
amoxicillin, amoxicillin-clavunic acid, trimethoprim and
trimethoprim-sulphamethoxazole, these agents are not
suitable for the empirical treatment of cUTI. The
same applies to fluoroquinolones.

25. COMPLICATED UTIS
 Treatment
 Patients with a complicated UTI requiring hospitalization
should be initially treated with an i.v antimicrobial
regimen, such as an aminoglycoside +/- amoxicillin
or a second or third generation cephalosporin or an
extended-spectrum penicillin +/- an aminoglycoside.
 Fluoroquinolones can only be recommended as
empirical treatment when the patient has had an
anaphylactic reaction to beta-lactam antimicrobials
 Antimicrobial treatment for 7-14 days is generally
recommended

26. RECURRENT UTIS

27. RECURRENT UTIS
 Definition:
Recurrences of uncomplicated and/or complicated UTIs, with a
frequency of at least three UTIs/year or two UTIs in the
last six months.
 Risk factors:
 Diagnosis:
 Urine analysis & culture  uncomplicated recurrences
 + urological imaging  complicated recurrences.
Post-menopausal and
elderly women
Young and pre-
menopausal women
•Functional abnormalities
(urinary incontinence,
Atrophic vaginitis, etc).
•Urine catheterisation
•Sexual intercourse
•Use of spermicide
•A new sexual partner

28. RECURRENT UTIS
 Definition:
Recurrences of uncomplicated and/or complicated UTIs, with a
frequency of at least three UTIs/year or two UTIs in the
last six months.
 Risk factors:
 Diagnosis:
 Urine analysis & culture  uncomplicated recurrences
 + urological imaging  complicated recurrences.
Post-menopausal and elderly
women
Young and pre-menopausal
women
•Functional abnormalities (urinary
incontinence, Atrophic vaginitis, etc).
•Urine catheterisation
•Sexual intercourse
•Use of spermicide
•A new sexual partner

29. RECURRENT UTIS
 Prevention:
 Treatment of risk factors
 Non-antimicrobial measures
 Behavioural modifications
Avoid reduced fluid intake, habitual and post-coital delayed urination,
wiping from front to back after defecation, douching and wearing
occlusive underwear).
 Hormonal replacement
In post-menopausal women vaginal oestrogen replacement showed a
trend towards preventing rUTI.
 Prophylaxis with probiotics & cranberry
 Antimicrobial prophylaxis

30. RECURRENT UTIS
 Prevention:
Antimicrobial prophylaxis, either:
 Continuous low-dose antimicrobial prophylaxis for 3-6
months)
 Post-coital antimicrobial prophylaxis.
Regimens include:
 Nitrofurantoin once daily,
 Fosfomycin every ten days
 During pregnancy, cephalosporin (cephalexin) once daily.

31. CASE STUDIES

32. CASE 1:
A 20-year-old woman experiences increasing
urinary frequency, urgency and dysuria for 2
days. Over the next 12 hours or so, these
symptoms persist and her urine is pink or bloody.
Vital signs are: T = 37.5ºC, R = 18, and BP =
105/70 mm Hg. The only abnormal finding on
physical examination is a mild tenderness to deep
palpation in the suprapubic area. No genital ulcers
are noted. There is no vaginal discharge. The
patient has no previous history of similar
complaints. However, she has recently become
sexually active and has been using a diaphragm
with spermicide.

33. CASE 1:
 Question 1: What is your preliminary diagnosis and what
tests you can carry out to confirm it?
Answer: most likely acute uncomplicated cystitis.
The patient's history might indicate a sexually transmitted
disease. However, she does not have any signs or symptoms
(e.g., genital lesions or purulent discharge) that might
specifically point to sexually transmitted diseases. The primary
symptoms of dysuria, frequency, and urgency would appear to
indicate a UTI. In the absence of significant fever and flank
pain (which might indicate pyelonephritis), it is most likely
cystitis.
The appropriate lab tests to confirm this diagnosis would include
a urinalysis for bacteria and pyuria. A urine culture is not
indicated for a case with no fever and no evidence for
pyelonephritis, diabetes, or other complications. These tests
will not change the outcome and are not cost effective.

34. CASE 1:
Urine analysis shows innumerable white cells,
moderate numbers of red cells, and noticeable
bacteria. A Gram stain of the urine reveals Gram-
negative rods.
 Question 1.2: What is your final diagnosis and
what is the most likely causative agent?
The lab tests confirm a diagnosis of acute
uncomplicated cystitis.
The most common causative agent of uncomplicated
cystitis is E. coli (75-95%), followed by
Staphylococcus saprophyticus (5-15%).

35. CASE 1:
 Question 3: What predisposing factors did this
patient have for this type of infection?
1. Women are generally far more susceptible than men
to lower UTIs. The comparatively short length of the
female urethra facilitates transport of bacteria from the
periurethral area to the bladder.
2. The onset of sexual activity. Apparently, sexual
intercourse mechanically introduces bacteria upward
into the bladder. As a result, voiding shortly after
intercourse helps to reduce the risk of cystitis.
3. The use of a contraceptive diaphragm interferes with
complete emptying of the bladder. Urine retained in
the bladder encourages the growth of bacteria therein
and greatly promotes infection.

36. CASE 1:
 Question 4: How should this infection be
treated?
A single dose or short course of appropriate antibiotic
is usually sufficient to treat uncomplicated cystitis.
The current drugs of choice include: Fosfomycin
once, Nitrofurantoin for 5 days, or Pivmecillinam
for 3-5 days. Trimethoprim for 5 days or
trimethoprim-sulfamethoxazole for 3 days can be
used if the local resistance pattern for E. coli is <
20%

37. CASE 1:
 Question 4: if this patient was pregnant, how
should her infection be treated?
The following antibiotics can be considered:
 Penicillins (e.g. Amoxicillin/clavulanic acid) for 5-7
days.
 Cephalosporins (e.g. cefpodoxime or cephalexin) for
5-7 days.
 Fosfomycin.

38. CASE 2
A 27-year-old woman suddenly develops an obvious
fever and shaking chills, along with nausea and
vomiting. She also has some dysuria with
urgency and frequency. Shortly after the fever
and chills appear, she develops excruciating flank
pain, becomes concerned, and comes to see you
for advice. Her vital signs are: T = 39.5ºC, R = 18,
and BP = 110/70 mm Hg. Physical examination
reveals marked tenderness on deep pressure in
both costovertebral angles, but there are no other
remarkable findings.

39. CASE 2
 Question 1: What is your preliminary diagnosis and
how can you confirm it?
Most likely acute uncomplicated pyelonephritis
The dysuria, frequency, and urgency point to a UTI. The
systemic symptoms (fever, nausea, vomiting, etc.) are
not overly definitive by themselves. In combination with
the flank pain and costovertebral angle tenderness, they
are all consistent with a kidney infection.
UTIs are most easily confirmed with a urinalysis
(including microscopic examination) and urine culture.
Additional tests that might be useful include renal
imaging.

40. CASE 2:
Microscopic examination of the urine sample reveals the
presence of Gram-negative rod-shaped bacterial cells and
leukocytes.
 Question 2: What is the most likely causative agent and
what is your recommendation on empiric antibiotic
therapy for the patient?
More than 80% of uncomplicated UTIs are caused by E coli, and
the Gram stain is consistent with E. coli in this case.
i.v Ciprofloxacin or levofloxacin can be prescribed empirically
until her nausea subsides, then she can be transitioned to
oral flouroquinolone therapy based on results of
antimicrobial susceptibility tests.
 Question 3: what is the mech. Of action of the selected
drug?
They inhibi ttype II DNA topoisomerase (DNA gyrase) that is
necessary for bacterial replication..

41. CASE 2:
 Question 4: If the results of antimicrobial susceptibility
tests show resistance to the selected drug, then what
is your recommendation on antibiotic therapy for this
patient?
i.v cephalosporin (e.g. Ceftriaxone) can be prescribed
empirically, then she can be transitioned to oral
cephalosporin for 10 days or
trimethoprim/sulfamethoxazole for 14 days.
 Question 5: If this patient was pregnant, then what
is your recommendation on empiric antibiotic
therapy for her?
A third-generation cephalosporin such as ceftriaxone
i.v can be given.

42. ASYMPTOMATIC BACTERIURIA IN
ADULTS

43. ASYMPTOMATIC BACTERIURIA IN ADULTS
 Definition:
Urinary growth of bacteria in an asymptomatic
individual; corresponds to a commensal colonization.
The spectrum of bacteria in Asymptomatic bacteriuria is
similar to species found in uncomplicated or
complicated UTIs
Asymptomatic bacteriuria may protect against
superinfecting symptomatic UTI, thus treatment of ABU
should be performed only in cases of proven benefit for
the patient.

44. ASYMPTOMATIC BACTERIURIA IN ADULTS
 Screening and treatment:
 Based on available evidence, only: pregnant women and
patients undergoing urological procedures should be
screened and treated for ABU
 The same choice of antibiotics and treatment duration as in
symptomatic UTI could be given.
 Treatment is not empirical and should be tailored to the
results of urine culture and antimicrobial susceptibility and.