Urinary Tract Infections
Dr. Lamya Alnaim, PharmD
Introduction
• UTIs represent a wide variety of
syndromes including urethritis,
cystitis, prostatitis, and
pyelonephritis.
• One of the most commonly occurring
infections.
Introduction
• Young women are particularly
susceptible, 40% of all women will
suffer at least one UTI at some
point.
• Infection in men occurs less
frequently until the age of 50,
when incidence in men and women is
similar.
Definition
• It is the presence of
microorganisms in the urinary tract
that cannot be accounted for by
contamination.
• The organisms have the potential to
invade the tissues of the UT and
adjacent structures.
Definition
• A UTI can manifest as several
syndromes associated with an
inflammatory response to microbial
invasion that range from
asymptomatic bacteriuria to
pyelonephritis.
Classification
According to anatomic site of
involvement:
• Lower tract infection: cystitis,
urethritis, prostatitis
• Upper tract infection:
pyelonephritis, involving the kidneys
Classification
According to Degree
1-Uncomplicated
• Occur in individuals who lack
structural or functional
abnormalities in the UT that
interfere with the normal flow of
urine.
• Mostly in healthy females of
childbearing age
Classification
According to Degree
2-Complicated
predisposing lesion of the UT such as
congenital abnormality or distortion
of the UT, a stone a catheter,
prostatic hypertrophy, obstruction,
or neurological deficit
• All can interfere with the normal
flow of urine and urinary tract
defenses.
Recurrent UTIs
• Multiple symptomatic infections with
asymptomatic periods
• Reinfection: caused by a different
organism than originally isolated and
account for the majority of
recurrent UTIs.
• Relapse: repeated infections with
the same initial organism and
usually indicate a persistent
infectious source.
Other Definitions
Asymptomatic bacteriuria
• Common among the elderly
• Bacteiruria > 105 bacteria/ml of
urine without symptoms
Symptomatic abacteriuria:
• Symptoms of frequency and dysuria
in the absence of significant
bacteriuria
Other Definitions
Significant bacteriuria
• More than 105 bacteria /ml (CFU)
of urine in clean catch specimen
• 1/3 of symptomatic women have
CFU counts below this level
• A bacterial count of 100 CFU/ml
has a high positive predictive value
of cystitis in symptomatic women
Other Definitions
Count less than 105 may represent
true infection in certain situations
• Concurrent antibacterial drug
administration
• Rapid urine flow
• Low urine PH
• Upper tract obstruction
Etiology
The microorganism that cause UTIs
usually originate from the bowel
flora of the host
Uncomplicated UTI:
• E.coli accounts for 85%
• S.saprophyticus 5-15%
• K.pneumoniae, protues sp,
Pseudomonas, and Enterococcus 510%
• S.epidermidis if isolated should be
considered a contamination
Etiology
Complicated UTIs
• More varied and generally more
resistant
• E.coli 50%
• K.pneumoniae, protues sp,
Pseudomonas, Enterococcus,
Enterobactor sp
Etiology
Complicated UTIs
• Enterococcus fecalis 2nd most
frequently isolated organism in
hospitalized patients
• S.aureus infection is more commonly
a result of bacteremia producing
metastatic abscesses in the kidney
• Candida sp is common cause of UTI
in critically ill and chronically
catheterized patients
Etiology
• The majority of UTIs are caused
by a single organism
• In patients with stones , indwelling
catheter, or chronic renal
abscesses multiple organisms may
be isolated
• Although this may be due to
contamination and a repeat
evaluation should be done.
Predisposing factors
Abnormalities in the UT that
interfere with natural defenses
1-Obstruction can inhibit urine flow,
disrupting the natural flushing and
voiding effect in removing bacteria
from the bladder and resulting in
incomplete emptying
Predisposing factors
Abnormalities in the UT that
interfere with natural defenses.
2-Condition that result in residual
urine volumes e.g. prostatic
hypertrophy, urethral stricture,
calculi, tumors, and drug such as
anticholinergic agents, neurological
malfunctions associated with stroke,
diabetes, and spinal cord injuries.
Predisposing factors
Abnormalities in the UT that
interfere with natural defenses.
3-Other risk factors include: urinary
catheter, mechanical
instrumentation, pregnancy, and the
use of spermicidies and diaphragms
Clinical presentations
Lower tract infection:
• Include dysuria, urgency,
frequency, nocturia, suprapubic
heaviness, and hematuria in women.
• No systemic symptoms
Upper tract infection:
• Flank pain, costovertebral
tenderness, abdominal pain, fever,
nausea, vomiting and malaise.
Clinical presentations
Elderly patients:
• Frequently do experience specific
urinary symptoms
• Altered mental status, change sin
eating habits, or GI symptoms
Patients with catheters
• Will have no lower tract symptoms
• Just flank pain and fever
Laboratory findings
• Symptoms alone are unreliable for
diagnosis
• Examination of the urine is the
cornerstone of diagnosis
Collection of urine:
• Mid stream clean catch method is
preferred method
Laboratory findings
Collection of urine:
• 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.
Diagnosis:
• Based on isolation of significant
numbers of bacteria from a urine
specimen
Microscopic examination
• is performed by preparing a gram
stain that indicates the morphology
of the organism and help direct
the selection of an appropriate AB.
Diagnosis:
Microscopic examination
• The presence of one organism per
oil-immersion field in an un
centrifuged sample correlates with
100,000 bacteria/ml
Diagnosis:
Pyuria: WBC > 10 WBC/mm3
• it only signifies the presence of
inflammation
Sterile pyuria is associated with
urinary tuberculosis, chlamydial,
and fungal infections
Diagnosis:
Hematuria, non-specific, may indicate
other disorders such as calculi or
tumor
Protenuria is found in the presence of
infection
Diagnosis
Biochemical tests
1-dipstick test for nitrite: bacteria
in the urine reduce nitrate→ nitrite
• false –negatives are common and
caused by
• gm+ve or pseudomonas that do not
reduce
• low urinary PH
• frequent voiding and dilute urine
Diagnosis
Biochemical tests
2- leukocyte esterase dipstick test
• rapid screening test for detecting
the presence of pyuria
• LE is found in neutrophills
• Specific for detecting more than 10
WBC/mm3
Diagnosis
Quantitative urine culture
• Based on properly collected urine
• Urine is normally sterile
• Determines the number of bacteria
present in a urine sample
• 1/3 of symptomatic women have
bacteria < 105
Diagnosis
Quantitative urine culture
• one organism per oil immersion field
correlates with 100,000 CFU/ml by
culture
Susceptibility
• determine bacterial susceptibility to
different antimicrobials
Common Urinalysis Dipstick Findings in Urinary Tract Infection
Finding
Significance
Color
Typically pale
Change in urine color is not synonymous with urinary tract
yellow to colorless infection (UTI) or disease.
Clarity
Typically clear
Pyuria causes urinary turbidity
Odor
Mild characteristic
odor
Rancid or ammonia odor in urea-splitting organism
Specific
Dilute urine = SG
gravity (SG) </= 1.008
Comment
Dilute or concentrated urine may influence the results of urine
chemstrip testing.
Concentrated urine
= SG > 1.020
Leukocyte
esterase
(LE)
Test for enzyme
present in white
blood cell (WBC)
Positive results indicated presence of neutrophils > 4
WBCs/hpf, an indicator of UTI, reported sensitivity of 75% to
90%. Results not valid in neutropenic patient. Decreased
sensitivity with increased urinary glucose concentration, high
urinary SG, and presence of antimicrobial in urine.
Nitrites
Surrogate marker for bacteriuria.
Presence indicates bacterial
reduction of dietary nitrates to
nitrites by select Gram-negative
uropathogens including Escherichia
coli, Proteus spp.
Normally absent in sterile urine and
infection caused by enterococci,
staphylococci.
Best done on well-concentrated urine such as
first AM void. For nitrites to be present, urine
should be held in bladder for >/= 1 hour for
nitrate-to-nitrite conversion to take place; dietary
nitrate intake must be adequate. False negative
possible with low colony-count infections.
Protein
Dipstick testing most sensitive for
albumin
Common in febrile response or represents
presence of protein-containing substance such
as white blood cells, bacteria, mucous. In UTI,
usually trace to 30 mg/dL (1+), seldom >/= 100
mg/dL.
pH
Average pH = 5-6
Acid pH = 4.5-5.5
Alkaline pH = 6.5-8
If alkaline urine is found in presence of UTI
symptoms and positive leukocyte esterase,
likely urea splitting such as Proteus, allowing
urea to be split into CO2 and ammonia, causing
a rise in the urine's normally acid pH.
Red
blood
cells
(RBCs)
Low number of RBCs noted.
Gross hematuria may occur in
uncomplicated UTI but may be
present in infection complicated by
nephrolithiasis
Microscopic hematuria common with urinary
tract infection but not in urethritis or vaginitis.
Treatment
Desired outcome
• Prevent or treat systemic
consequences of infection
• Eradicate the invading organism
• Prevent reoccurrence of infection
Treatment
Non-specific therapies
1-fluid hydration:
• rapid dilution of bacteria and
removal of infection through
increased voiding
2-cranberry juice
• increase the antibacterial activity
of urine
Treatment
Non-specific therapies
3-urinary analgesics
• phenazopyridine
• has little clinical role in infection
because symptoms respond rapidly
to anitmicrobial therapy
Acute uncomplicated cystitis
Most common form of UTI?
• Occur in women of childbearing age
• Can be explained by
–
–
–
–
sexual activity
anatomy (short urethra)
delay in micturation
use of diaphragm and spermicidal
Causes
• Mostly cause E.coli
• Other causes : S.saprophyticus.
K.pneumonia, Proteus mirabilis
Table 1. Clinical Findings in Women With Dysuria and Pyuria [3,9]
Clinical Findings in Addition to Dysuria
and Pyuria
Possible
Etiology
Comment
Suprapubic tenderness, pelvic discomfort
especially pre- and immediately postvoid,
urinary urgency and frequency, small
volume voiding, hematuria (micro or
macroscopic).
Cystitis, lower
urinary tract
infection
Gram-negative bacilli (Escherichia
coli, Proteus, Klebsiella, others),
select Gram-positive organism
(Staphylococcus saprophyticus).
Flank pain, fever, CVA tenderness,
nausea and vomiting, bacteremia;
suprapubic tenderness, urinary urgency
and frequency present or absent.
Pyelonephritis
Pathogenic organisms revealed by
urine culture include Gramnegative bacilli (E coli, Proteus,
Klebsiella, others). Kidney stones
and obstructive uropathy may be
contributors.
Urethral, vaginal discharge in the absence
of suprapubic pain or tenderness, urinary
frequency, urgency, fever; numerous
white blood cells found on microscopic
wet mount examination of vaginal
discharge
Urethritis
Most common as sexually
transmitted infection such as
Chlamydia trachomatis, Niesseria
gonorrhoeae, Trichomonas
vaginalis
Irritative voiding symptoms, purulent or
mucopurulent vaginal or cervical
discharge, report of postcoital bleeding,
edema and/or erythema of cervix or
cervical os, brisk bleeding induced by
endocervical swabbing, numerous white
blood cells found on microscopic wet
mount examination of vaginal discharge
Mucopurulent
cervicitis
N gonorrhoeae, C trachomatis,
others.
Irritative voiding symptoms, purulent or
mucopurulent vaginal or cervical
discharge, fever, abdominal pain, edema
and/or erythema of cervix or cervical os,
brisk bleeding induced by endocervical
swabbing, cervical motion tenderness,
possible evidence of tubal-ovarian mass,
numerous white blood cells found on
microscopic wet mount
Pelvic
inflammatory
disease
N gonorrhoeae, C trachomatis, E
coli, micro-organisms that normally
comprise vaginal flora (anaerobes,
Helicobacter influenzae, enteric
Gram-negative rods, Streptococcus
agalactiae), Mycoplasma and
Ureaplasma species, others.
Acute uncomplicated cystitis
Management:
• Urinanalysis including microscopic
examination, cell count, and LE
test
• C&S add little to the choice of
therapy empiric therapy
• Regarding the use of laboratory tests to diagnose
urinary tract infections, which of the following
statements is correct?
• A. In a patient with suspected cystitis, urine dipstick
results should be confirmed with a urinalysis
B. The urine should always be cultured in outpatients with
acute cystitis
C. Urine dipstick results usually provide the laboratory
information needed to manage young otherwise healthy
patients with acute cystitis
D. The use of urine dipsticks should be avoided; urinalysis
is the test of choice.
Acute uncomplicated cystitis
Management:
1- Single dose therapy
• 65-100% cure rate with SMXTMP, amoxicillin
advantages of single does:
• less expensive
• better compliance
• low side effects
• low potential for development of
resistance
Acute uncomplicated cystitis
1- Single Dose Therapy
• Not all agents are effective as single
dose
•
2 DS TMP/SMX is most effective
•
Flouroquniolones: 800 mg norfloxacin,
125 mg ciprofloxacin, 200 ofloxacin
•
B-lactam are less effective due to
increasing resistance and because they
are eliminated rapidly and do not
achieve high urine concentrations
Acute uncomplicated cystitis
2-Three day course
• single dose Tx was blamed for high rate
of recurrence within six weeks
• this may be due to failure to eradicate
gm-ve bacteria from the rectum
• TMP/SMX or fluoroquinilones is superior
to single dose
• Amoxicillian, nitrofurantion, and
sulfonamides are not appropriate due to
increasing resistance of E.coli
Acute uncomplicated cystitis
Management:
Short course therapy is not
appropriate for
• Patient with previous infection with
a resistant bacteria
• Male patients
• Complicated UTI
Acute uncomplicated cystitis
Management:
• If symptoms do not respond or they
reoccur, a urine culture should be
obtained and conventional therapy
started
Fluoroqunilones should not be used unless
•
•
patient cannot tolerate TMP/SMX
They’re a high frequency of resistance
due to recent antibiotic use
Acute uncomplicated cystitis
Management:
3-Seven-day course
• in pregnant women
• diabetic women
• women who have had symptoms for
more than one week and are at
higher risk for pyelonephritis
Oral treatment regimens for acute uncomplicated cystitis
Agent
Normal dosage
Side effects, cautions
Ciprofloxacin
250 mg bid for 3 d Drowsiness; increases theophylline levels; avoid in
pregnancy; avoid divalent and trivalent cations;
Fosfomycin
3-g single dose
Increased incidence of diarrhea and nausea and
increased relapse rate
Gatifloxacin
200 mg/d for 3 d
Avoid in pregnancy; avoid divalent and trivalent
cations
Levofloxacin
250 mg/d for 3 d
Avoid in pregnancy; avoid divalent and trivalent
cations
Nitrofurantoin
100 mg bid for 7 d Idiosyncratic pulmonary fibrosis; avoid in patients
with estimated monohydrate/ creatinine clearance <
100 mg qid for 7 d 60 mL/min
Nitrofurantoin
Norfloxacin
400 mg bid for 3 d Avoid in pregnancy; avoid divalent and trivalent
cations
Ofloxacin
200 mg bid for 3 d Avoid in pregnancy; avoid divalent and trivalent
cations
Trimethoprim
100 mg bid for 3 d Nausea
Trimethoprimsulfamethoxazole
1 double-strength Nausea; rash;
tablet bid for 3 d
Symptomatic abacteriuria
Acute urethral syndrome
• In females, present with dysuria
and pyuria
• Urine culture reveals < 105 bacteria
/ml
• Accounts for half the complaints
of dysuria in women
• Most likely infected with a small
number of bacteria
Symptomatic abacteriuria
Causes:
• E.coli, S. saprophyticus, or
chalmydia
• Other causes:
• Most patients will require short
course therapy as above
Symptomatic abacteriuria
Chlamydial treatment
1g of azithromycin or doxycycline
100 mg bid for 7 days
• Concomitant treatment of sexual
partner is required to cure this
infection and prevent recurrence
Asymptomatic bacteriuria
• Patients with no urinary symptoms
• Have two consecutive urine
cultures with > 105
• The majority are elderly and
female
Asymptomatic bacteriuria
• Aggressive treatment does not
affect infection, complications or
mortality
• Also present in pregnant women
• Relapse and reinfection are
common and chronicity occurs
which is difficult to eradicate
Asymptomatic bacteriuria
Management
Groups who benefit from treatment:
• pregnant women
• patient with renal transplant
• Patient who will undergo urinary
procedure
Asymptomatic bacteriuria
Management
• Depend on age and whether they
are pregnant
• In children: conventional treatment
because of greater risk for renal
damage
• In non-pregnant female:
controversial
Asymptomatic bacteriuria
Management
• In elderly: two groups
–
Persistent bacteriuria:
–
Intermittent bacteriuria
• Mostly seen as a benign disease
and does not warrant treatment
• Two cultures should be obtained to
confirm the presence of bacteria
Asymptomatic bacteriuria
Management
• Ambulatory treatment is effective
in removing bacteria for 6 months
• Only 50% remained free of
bacteria for 1 year
• Hospitalized patients: therapy in
non-efficacious
Case 1
• A 24-year-old woman comes to the clinic to
discuss recent laboratory results. She went to
a local walk-in clinic asking to be screened for
a urinary tract infection. She comes to the
clinic to review them with
you. She is asymptomatic and has no past
medical history. She is married and has a 3year-old boy. Her physical exam is
unremarkable. A urinalysis showed 1+
leukocyte esterase; a urine culture revealed
>100000 CFU of Escherichia coli.
Case 1
Which of the following management strategies is
the most appropriate for this patient?
• A. Explain that even though the urine culture was
positive she does not need treatment
B. Start oral ciprofloxacin for three days
C. Repeat a urine dipstick, and if the presence of
pyuria is confirmed start treatment
D. Start oral ampicillin for seven days
Case 1
• The IDSA guidelines recommend screening for
and treatment of asymptomatic bacteriuria in
only three circumstances: pregnancy, before
invasive urologic procedures that are
associated with mucosal bleeding, and in women
who are found to have catheter-acquired
bacteriuria that persists 48 hours after the
catheter is removed
Complicated UTI
• Accurate urine culture and
susceptibility is necessary to target
the pathogen
• Treatment duration at least 10-14
days
Conditions associated with complicated urinary tract infections
Structural abnormalities







Infected renal cyst
Kidney abscess
Kidney stones
Nephrostomy tube
Obstruction
Ureteral stent
Vesicoureteral reflux
Specific patient populations





Patients receiving immunosuppressive therapy
Renal transplant recipients
Diabetic persons
Pregnant women
Men
Acute pyelonephritis
• Perform uniranalysis, gram stain,
C&S
Severely ill patients
• Should be hospitalized and treated
with IV Abs
• Use broad spectrum directed at
bacteremia or sepsis
Acute pyelonephritis
Empiric therapy:
• 3rd generation cephalosporin with
antipseudomanl activity as
ceftazidime, cefoperazone
• Ampicillian + gentamicin
• TMP/SMX OR Quionoles
• B-lactamase inhibitor combination:
ampicillian/Sulbactam,
ticarcillin/clavunate,
• Aztreonam or imipenem
Acute pyelonephritis
If the patient has been hospitalized
for > 6 months:
• Consider P.aeruginosa and
enterococci, and multiple organisms
Empiric therapy:
• Ticarcillin/clavunate,
• Piperacillin/tazobactam
• Aztreonam or imipenem
In combination with AG
Acute pyelonephritis
Management
Fluoroquinolones
• major advantages is their oral
formulation.
• Use as empiric therapy in this
setting may be limited because of
resistance rates.
Acute pyelonephritis
Management
• ceftazidime, cefepime, piperacillin,
piperacillin/tazobactam, and
aztreonam.
• They have reliable activity against
many nosocomially acquired gramnegative rods, including P
aeruginosa.
Acute pyelonephritis
Management
Carbapenems, imipenem-cilastatin and
meropenem.
have extremely broad-spectrum coverage
and should be reserved for only the most
severe forms of nosocomial infections,
such as multiresistant pathogens, sepsis
syndrome, overwhelming intra-abdominal
infections, or septic shock
Acute pyelonephritis
• Effective therapy should stabilize
patient within 12-24 hrs
• Bacterial load should reduce in 48
hrs
If the patient fails to respond in 3-4
days further investigation is
necessary to
• Exclude bacterial resistance
• Exclude obstruction
• Or other disease process
Acute pyelonephritis
• Oral therapy can be started when
the patient is febrile for 24 hrs
• Oral therapy should be continued
for 2 wks
• Follow-up urine cultures should be
obtained 2 wks after end of
therapy
Acute pyelonephritis
Mild cases:
• can be treated orally as
outpatients for at least 2 w ks
• Gram –ve bacilli: TMP/SMX or
fluoroquiolones
• Gram +ve: cocci: consider
enterococcus fecalis, DOC
Ampicillin
Treatment of acute pyelonephritis
Agent
Ceftriaxone
Normal dosage
1 g/d, IV
or
Cefotaxime ± Aminoglycoside 1 g q8h, IV
Ciprofloxacin
400 mg q12h, IV
500 mg bid, PO
Gentamicin
±
Ampicillin
1.5 mg/kg q8h or 5 mg/kg q24h, IV
Levofloxacin
500 mg/d, PO or IV
1 g q6h, IV
If gram-positive organisms seen on Gram stain:
Ampicillin/sulbactam
±
Aminoglycoside
1.5 g q6h, IV
Trimethoprimsulfamethoxazole*
10 mg/kg/d in 2 - 4 divided doses, IV or 1 or 2 double-strength
tablets bid, PO
Case 2
22 year-old woman without any significant past
medical history presents to the emergency room
with 2 days of worsening fever, urinary
frequency, back pain, nausea and vomiting. She
is not able to keep food or liquids down. On
physical examination she is febrile and
tachycardic. The abdominal exam is normal
except for the presence of moderate
costovertebral angle tenderness. A blood
pregnancy test is negative. A urinalysis is
obtained and reveals >50 PMN per high power
field and 10-25 red blood cells. Blood cultures
are sent to the lab.
Case 2
Which of the following management strategies is
the most appropriate for this patient?
A. Order an ultrasound to confirm your clinical
impression, and start intravenous antibiotics if
needed
B. Admit the patient for administration of
intravenous antibiotics, and obtain imaging studies
only if the patient does not improve after a few
days
C. Start intravenous antibiotics, and order abdominal
CT scan to rule out complicated pyelonephritis
D. Discharge the patient home on an oral
fluoroquinolone
Infection in males
• Infection in males are considered
complicated
• Occur in presence of functional or
structural abnormalities that
disrupt the normal defense
mechanism of urinary tract.
Clinical Findings in Men with Dysuria and Pyuria
Clinical Findings in
Addition to Dysuria and
Pyuria
Possible
Etiology
Comment
Back pain, fever, CVA
tenderness, nausea and
vomiting, bacteremia
Pyelonephritis Consider urinary tract obstructive process such as
BPH, stones. Pathogenic organisms revealed by
urine culture include Gram-negative bacilli
(Escherichia coli, Proteus, Klebsiella, others)
Back pain, fever, arthralgia, Acute
myalgia, rectal pain
prostatitis
obstructive voiding
symptoms, tender, boggy
prostate
Urine culture reveals pathogenic organisms (E coli,
Proteus, Klebsiella, others)
Scrotal swelling and
redness, fever, epididymal
tenderness
Pyuria rate = approximately 25%. May be caused
by sexually transmitted organism (Chlamydia
trachomatis, Neisseria gonorrhoeae) or
uropathogen such as E coli in man with recent
urinary tract instrumentation
Acute
epididymitis
Urethral discharge in the
Urethritis
absence of suprapubic pain,
urinary frequency, urgency,
fever
Most common as sexually-transmitted infection (C
trachomatis, N gonorrhoeae)
Infection in males
The most common causes are
• Instrumentation
• Catheterization
• Renal and urinary stones
• In the elderly the most common
cause is bladder outlet obstruction
due prostatic hypertrophy.
Infection in males
Treatment
• Urine culture is needed because
causative organism is not easily
predictable
• A urine culture with>100 CFU/ml is
best sign of infection
• If Gm –ve is TMP/SMX or FQ
• Duration therapy should be 10-14
days
Infection in males
Treatment
Parental therapy may be required in
• Severely ill patients
• The presence of acute prostatitis
(may need 6-12 weeks)
• Patient who cannot tolerate oral
MEDs
Repeat a follow up culture 4-6 weeks
after treatment
Case 3
• A 53 year-old man with history of benign
prostatic hypertrophy comes to the emergency
room complaining of burning with urination and
increased urinary frequency. He is afebrile,
denies back pain, nausea or vomiting. His past
medical history is also significant for
hypertension and diabetes. He takes
hydrochlorothiazide, enalapril, aspirin,
metformin and terazosin. On physical
examination his prostate is enlarged, but is not
tender. Urine dipstick shows 3+ leukocyte
esterase.
Case 3
• A 53 year-old man with history of benign
prostatic hypertrophy comes to the emergency
room complaining of burning with urination and
increased urinary frequency. He is afebrile,
denies back pain, nausea or vomiting. His past
medical history is also significant for
hypertension and diabetes. He takes
hydrochlorothiazide, enalapril, aspirin,
metformin and terazosin. On physical
examination his prostate is enlarged, but is not
tender. Urine dipstick shows 3+ leukocyte
esterase.
Case 3
Which of the following interventions is the most
appropriate for this patient?
• A. Start ciprofloxacin, and order urine culture
B. Start Levofloxacin, and order urine culture only
of the patient fails to improve after five days of
symptoms.
C. Start nitrofurantoin empirically
D. Admit the patient for intravenous
piperacillin/tazobactam
Recurrent infection
Reinfections:
• 80% 0f recurrent infection
• Infection by an organism different
from the initial infection
• Mostly occurs in females where
reinfection rate is 20%
Factors contributing to infection:
1-sexual intercourse
2-diaphram and spermicidal use
3- postmenopausal women
Recurrent infection
Divided into two groups:
1-Those with less than 2 or 3
episodes per year
• Each episode should be treated as
a separate infection
• Short course therapy is
appropriate
• Can be self administered
Recurrent infection
Divided into two groups:
2-Those with more than 3 episodes
per year
• Long-term prophylaxis may be
needed
• Patient should be treated
conventionally before prophylaxis is
started
Recurrent infection
Regimen:
• TMP/SMX ½ SS tables OD
• TMP 100 mg OD
• Fluroqunilone
• Nitrofurantion 50-100 mg OD
• Continued for 6 months
• Urine cultures followed monthly
• If symptomatic episodes develop
they should be treated with a full
course
Recurrent infection
Infection related to sexual activity:
• Voiding after intercourse
• Single-dose prophylactic with
TMP/SMX taken after intercourse
In postmenopausal women
• Recurrent episodes related to
decreased estrogen and changes in
bacterial flora
• TX: topical estrogen cream
Relapses
• Persistence of the infection with
the same organism after therapy
• Usually indicate structural
abnormality, renal involvement, or
chronic bacterial prostatitis
Relapses
In women:
• If relapse after short course treat
with 2 week course
• In-patient who relapse after 2 wk
course continue for another 2-4
wks
• If relapse after 6 wks of therapy,
urologic evaluation and any
obstruction corrected
• May need therapy for 6 months
Relapses
In males
• Relapse usually indicate bacterial
prostaitis
• TMP/SMX and fluroquniolones
appear to be highly effective for
relapses
Case 4
• A 26-year-old woman comes to the clinic
complaining of recurrent cystitis. Over the
previous year she has had 5 episodes of cystitis
that were treated with antibiotics. The
symptoms improved rapidly after each course of
therapy. The episodes have happened once
every two to three months for the last year.
Her past medical history is otherwise
unremarkable. She uses oral contraceptives for
contraception. She has had two urine cultures
done during the previous year that showed
pansusceptible Escherichia coli. The patient
asks for ways to prevent these infections from
coming back.
Case 4
Based on the history and test results, which of
the following interventions is indicated on this
patient?
A. Ask the patient to report the onset of infection
as soon as possible, and start treatment if a urine
dipstick is positive
B. Offer antibiotic prophylaxis
C. Change her contraception to spermicides and
diaphragms
D. Obtain abdominal ultrasound to look for a
secondary cause of recurrent UTIs
E. Perform an immunologic evaluation to rule out
an underlying immune deficiency
Pregnancy
Predisposing factors:
• Dilation of the renal pelvis and
ureters
• Decrease urethral peristalsis
• Reduced bladder tone
• All lead to urine stasis and reduced
defenses against reflex of bacteria
to the kidney
• Hormonal changes predispose to
infection
Pregnancy
• Asymptomatic bacteriuria Occur in
4-7%
• 20-40% will develop acute
pyelonephritis
• Routine screening for bacteriuria
should be performed at the initial
prenatal visit and at 28 wks
Pregnancy
• Significant bacteriuria should be
treated regardless of symptoms
• Organism is the same for
uncomplicated UTI
• Therapy should be for 7 days
Pregnancy
Regimen
• Sulfonamide (not in 3rd trimester)
• amxoicillin
• augmentin
• cephalexin
• nitrofurantion
• Not TCN, fluoroquinoloes
• Follow up urine culture 1-2 wk
after completing therapy, then
monthly until gestation
FDA Pregnancy Risk and Hale's Lactation Risk Categories for Commonly
Prescribed Antimicrobials in Urinary Tract Infection
Cat B, L1, L2
Cat C, L3
Cat D, L3
Nitrofurantoin
Amoxicillin with clavulanate
Amoxicillin
Cephalosporins
Fluoroquinolones
TMP-SMX
Doxycycline
Lactation Risk Category[23]
L1 -- Safest, controlled study = Fails to demonstrate risk
L2 -- Safer, limited number of woman studied without risk
L3 -- Moderately safe, no controlled study or controlled study shows minimal,
nonlife-threatening risk
L4 -- Hazardous, positive evidence of risk, may be used if maternal life-threatening
situation
L5 -- Contraindicated, significant, and documented risk
FDA Pregnancy Risk Categories[23]
Category A
Category B
Category C
Category D
Category X
Wellcontrolled
human study
= no fetal risk
in first
trimester.
No evidence
of risk in
second, third
trimesters.
Risk to fetus
appears
remote.
Animal studies do
not demonstrate
fetal risk but no
controlled study
in humans.
OR
Animal studies
show adverse
effect but not
demonstrated in
human study.
No controlled
study in
humans
available.
Animals
reveal
adverse fetal
effects.
Positive
evidence of
human fetal
risk.
Use in
pregnant
woman
occasionally
acceptable
despite risk.
Animal or
human studies
demonstrate
fetal
abnormality.
Evidence of
fetal risk based
on human
study.
No indication
in pregnancy.
Catheterized patients
• Most common cause of hospital aquired
UTI
• diagnosis is difficult,
– patients often have some degree of pyuria
– Virtually all patients with catheters for 1 to
2 wks exhibit bacteriuria, making
differentiation of infection from colonization
difficult.
– often lack symptoms
• Occur in 5% of patients
Catheterized patients
Etiology
• often polymicrobial.
• Causative agents include P aeruginosa and
nosocomial gm –ve rods, with more
resistant susceptibility profiles;
enterococci; and Candida species.
• Diagnosed with > 100 CFU/ml of urine
from catheter
• Urinalysis and urine cultures should
always be obtained.
Catheterized patients
Management
1-Asymptomatic,
• Remove the catheter
Do not treat unless
• immunosuppresed patient
• Patient at risk of endocarditis
• Patient who will undergo urinary
tract instrumentation
Catheterized patients
Management
2-Symptomatic
• Remove the catheter and treat as
complicated UTI
Vancomycin-Resistant
Enterococci
• VRE are often isolated from urine
cultures of patients who have been
hospitalized for a prolonged period.
• Most commonly, a urinary catheter is
present.
• If the organism is E.faecalis, then
penicillin/ampicillin susceptibility is
frequently maintained, and ampicillin is
the treatment of choice.
VRE
• However, most VRE are E. faecium
that are also resistant to ampicillin
(VARE) and to multiple other
antimicrobials.
• Many VARE are susceptible to
nitrofurantoin, and it can be used
as long as the patient has a CrCL
>60 mL/min
VRE
• Chloramphenicol or novobiocin, with or
without other drugs, have been used.
• Two newer antibiotics,
quinupristin/dalfopristin and linezolid,
have been marketed for gram-positive
infections and have activity against
VARE.
VRE- Quinupristin/dalfopristin
• The 1st injectable streptogramin antibiotic.
• It inhibit protein synthesis and has bactericidal
effect with the exception of VARE.
• spectrum is mostly gm+ve and includes
Staphylococcus species (both methicillinsusceptible and methicillin-resistant
Staphylococcus aureus), E faecium, and VARE.
• It is not active against other enterococci
including E faecalis.
VRE- Quinupristin/dalfopristin
• toxicities
– chemical phlebitis (especially when
infused via a peripheral line)
– myalgias and arthralgias (particularly
in patients with hepatic insufficiency).
– It is a potent, noncompetitive inhibitor
of cytochrome P-450 3A4.
significantly increase plasma levels of
cyclosporine and long-acting
benzodiazepines
VRE- Linezolid
• The first oxazolidinone antibiotic.
• available as parenteral and oral formulations.
• It inhibits protein synthesis.
• It displays a bacteriostatic effect, except with
Streptococcus pneumoniae.
• Its spectrum is broad against gm+ve and
includes M-susceptible and MR S aureus,
coagulase-negative staphylococci, and many
enterococci (including E faecalis, E faecium,).
VRE- Linezolid
Toxicity
– Thrombocytopenia that most commonly
occurs after prolonged therapy (more
than 17 days).
• Given that linezolid has broader spectrum
against the enterococci and is available
as an oral formulation, it may be
preferred over quinupristin/dalfopristin in
the treatment of VARE UTIs.
Fungal Infection
• Many patients with a long-term
catheter will have colonization of
their bladder with Candida species
or, rarely, other fungi.
Fungal Infection
• Usually funguria in the absence of
pyuria should not be treated, and
the catheter should be removed.
• Funguria should be treated in
– renal transplant recipients
– those undergoing an elective urologic
procedure.
Fungal Infection
Diagnosis
• pyuria (> 20 WBC/hpf)
• > 105 fungal organisms / ml of
urine.
• Patients may or may not have
systemic findings, such as fever
and leukocytosis.
Fungal Infection
Treatment
• The catheter should be removed,
since this will result in cure in some
patients.
• If C.albicans infection, then oral
fluconazole, 100 mg/d, should be
prescribed for a 2- to 5-days
• IV fluconazole should be reserved for
patients without the ability to take
oral medications or in those with ileus
or bowel obstruction.
Fungal Infection
Treatment
• Non-albicans Candida species, including
C.parapsilosis, C.glabrata, and C.krusei,
are becoming more common.
• The Tx should be either low-dose IV
amphotericin B (0.1 mg/kg/d) or
continuous amphotericin B bladder
irrigation.
• Both regimens are effective when given
for 2 to 5 days.