Essential Urology for the Gynecologist: Urinary Tract Infections d Mi - and Microhematuria i Jennifer T. Anger, MD, MPH Associate Professor of Urology
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Essential Urology for the Gynecologist:
Urinary Tract Infections
andd Mi
Microhematuria
h t i
Jennifer T
T. Anger
Anger, MD
MD, MPH
Associate Professor of UrologyMany Urologists Don’t Like Female
Urology
Many Female Urologists Don’t Like
Female Urology
“I have bladder spasms and vaginal pain. I don’t believe in
Western medicine. However, I tried placing crystals over the area
and it wasn’t working, so I decided to come see you.”
“If you would only refer to the 3-ring binder I brought you, you
will see that I’m allergic to all ‘mycins’, epinephrine, and Haldol.”
“I was treated with four courses of antibiotics. The last culture
was negative, but I know the bacteria is hiding. Something really
i on.””
BAD iis goingCase presentation
p
• 34 year old woman present post-partum s/p VBAC for f/u of left-
sided renal cyst and microhematuria
• History of left-sided pyelonephritis 10 years ago
• Patient diagnosed with complex renal cyst at time of prenatal
ultrasound
• Repeat ultrasound unchanged, patient also found to have bladder
cystt
• Fishy?Case presentation
p
• Office cystoscopyCase presentation
pCase presentation
p
QuickTime™ and a
decompressor
are needed to see this picture.
QuickTime™ and a
decompressor
are needed to see this picture.Case presentation
pCase presentation
pCase presentation
pIntroduction • UTI: The chief complaint in 8 million clinic and ED visits (Foxman 2002) • Antimicrobials account for 15% of all outpatient prescriptions • Annual cost of UTI is estimated at $1.6 billion
Epidemiology
p gy
• 1/3 of women experience symptomatic UTI by age 24
• According to NHANES III, lifetime prevalence of UTI
in women is 53,067 per 100,000 (more than 1 in 2)
• Strong tendency toward recurrence: From 27-46%
within one year (Nicolle LE, 1987)Susceptibility
p y Factors
• Short female urethra
• Proximity of female urethra to two “hearty bacterial
reserviors”, the rectum and vagina (Dielubanza and
Schaeffer, 2011)
• Distance between urethral meatus and anus“But I’m so clean and I shower every
da Sho
day. Shouldld I break up
p with
ith m
my
boyfriend?”
• Sexual Intercourse
– Prospective
p studyy of 796 sexuallyy active women
– RR of UTI for intercourse:
• 1/7 days: 1.4
• 3/7 days: 2.8
28
• 5/7 days: 5.7
Hooton et al, 1996
• Use of Spermicides
– Nonoxonol-9: alters vaginal flora and facilitates periurethral
colonization with uropathogens
Dielubanza and Schaeffer, 2011Behavioral Factors
• NO DEMONSTRATED EFFECT OF:
– Postcoital voiding
– Direction of wiping
– Amount of fluid intake
(Scholes, 2000, Beisel 2002)Genetic Factors
• Genetic differences in mucosal properties
• Lewis blood group antigen nonsecretor and
recessive
i phenotypes
h t are associated
i t d with
ith
increased risk of UTI (OR 3.4, Shenfield, 1989)
• Human Leukocytey Antigeng A3 (HLA-A3)
( )
expression: Present in 34% of patients with
recurrent UTI vs. 8% of controls
(Schaeffer,1982)Age-specific Factors
• E
Estrogen
t status:
t t TheTh mostt important
i t t age-specific
ifi risk
ik
determinant for UTI
• Estrogen: promotes acidic pH in vagina and
lactobacillus proliferation
p
• Menopause: shift from predominance of Lactobacillus
to E. coli and other Enterobacteriaceae
• RCT of intravaginal estrogen replacement:
– E group had restoration of lactobacillus
– 0.5 UTI episodes
p in E ggroup
p vs 5.9 in pplacebo ggroup
p at one
year
Stamm et al, 1999Work-up: Cystitis
• Problems with the dipstick
• Urine culture is the gold standard diagnostic modality
for UTI- catheterized specimen ideal
• Clean catch least reliable: nearly 1/3 are contaminated
• Conventional teaching: + culture when 100,000
colonies of single
g organism
g
• 20-40% of women with cystitis
y have colonyy counts of
only 100-10,000 CFU/mL
Dielubanza and Schaeffer, 2011Work-up:
p Cystitis
y
• Further Evaluation not indicated unless concerning patterns of
infection (Dielubanza & Schaeffer,
Schaeffer 2011):
– Rapid reinfection with same bacterial species
– Persistence of UTI despite appropriate treatment
– Breakthrough while on antibiotic prophylaxis
– Cystitis symptoms with negative culture
• Renal
R l U/S combined
bi d with
ith cystoscopy
t andd PVR usually
ll adequate
d t
• CT Urogram
g with cystoscopy
y py
– Gross or microhematuria when cultures are negative
– Pyuria without bacteriuria (r/o TB vs. malignancy)
– Complicated history (pyelonephritis or prior urologic surgery)Treatment: Uncomplicated
C titi
Cystitis
• Nitrofurantion 100mg: 1 po bid x 5d
• TMP-SMX 160/800mg (Bactrim DS): 1 po bid x 3d (if
resistance in geographic area is low, less than 20%)
• Fosfomycin (Monurol): 1 3g oral dose
• Fluoroquinolones: should be reserved for resistant
organisms or in patients with allergies to first-line
agentsPersistent vs. Recurrent Cystitis
y
• Recurrence defined as 2 or more UTIs in one
year
• When patient has persistent symptoms after one
course of antibiotics, must check a urine culture
• Many women with persistent symptoms are
cured after first course of tx, but are overtreated
with antibioticsWork-up: Pyelonephritis
(F b il UTI)
(Febrile
• Upper tract imaging warranted
• May begin with ultrasound if no history of
nephrolithiasis
• CT Urogram with and without contrast
– R/o obstructed pyelonephritis in the setting of a
kidney stone (a urologic emergency)
• Contrast
C t t phase
h to
t diagnose
di pyelonephritis
l h iti
• Non-contrast phase to diagnose kidney stoneWork-up:
p Pyelonephritis
y p
Non-obstructing kidney stone
( i h obstruction
(with b i
from another stone)
PyelonephritisOutpatient Treatment:
Pyelonephritis
• Do not use: Nitrofurantoin or Fosfomycin
• TMX-SMX DS (160/800 mg) twice daily for 14 days
• Ciprofloxamin 500mg po bid x 7d +/-
+/ an initial 400mg
IV loading dose
• Criteria for outpatient (vs inpatient) treatment:
– Imaging shows no obstruction,
obstruction tolerating poAntimicrobial Prophylaxis: An antibiotic a day keeps the doctor away • Most commonly used: – Nitrofurantoin 50mg – TMX-SMX single strength (Bactrim SS) – For Sulfa allergy: Trimethoprim 100 mg – Pregnant or breastfeeding: Cephalexin 500mg • Usually once daily, but may use every other day • Upper tract imaging and cystoscopy if breakthrough occurs • Usually stop at 6 months, re-start as needed
Post-Coital Prophylaxis
• Very effective in preventing intercourse-related
UTIs
– Pill should be taken within one hour of intercourse
(before or after)
– Only pursue cystoscopy with upper tract imaging if
patient has breakthrough UTIRe: Antibiotic Prophylaxis
“
“But ’ like
I really don’t i taking
i
antibiotics. Isn’t
Isn t all that medicine
bad for you?”
1. Recurrent UTIs require much more antibiotics than
does antibiotic prophylaxis.
2 There is no magical cure for UTIs
2.
3. For this patient a trial of cranberry tablets may be
3
worthwhileThe Role of the Cranberry in
P
Preventing
ti UTIs
UTI
• American cranberry, Vaccinium macrocarpon, a
well-known folk remedy used to prevent UTIsThe Role of the Cranberry in
P
Preventing
ti UTIs
UTI
• Many observational studies and small RCTs suggest that
regular cranberry juice reduces recurrent UTIs
• In a randomized, blinded study of 137 women aged 45+
with
ith 2 or more UTI
UTIs in
i the
th pastt year:
– 500mg cranberry capsules vs. 100mg prophylactic
trimethoprim
p
– 25 UTIs in cranberry group vs. 14 in TMP group
(RR 1.6, 95% CI: 0.93-2.79)
McMurdo, 2009Cranberry Juice Fails to Prevent
R
Recurrent t UTI
UTIs
• Double
Double-blind,
blind placebo-controlled
placebo controlled trial randomized 319
college women to placebo vs. 8 oz. of 27% cranberry
jjuice twice dailyy
• Overall recurrence rate at 6 months was 16.9% (95%
CI 12.8%-21.0%)
– 20% in cranberry group
– 14% placebo group
Barbosa-Cesnik et al, 2011Cranberry Pills Less Effective
th Antibiotic
than A tibi ti Prophylaxis
P h l i
• Double-blind trial of 221 pre-menopausal women
randomized to daily TMP-SMX (480 mg) vs cranberry
capsules 500mg po bid
• Mean number of UTIs in one year was 4.0 (95% CI 2.3-
5 6) in cranberry group vs.
5.6) vs 1.8
1 8 (0.8
(0 8-22.7)
7) in TMP
TMP-SMX
SMX
group
• TMP-SMX associated with more antibiotic resistance
(but returned to baseline after 3 months of
di
discontinuation)
ti ti )
Beerepoot, et al, 2011Conclusions regarding
C
Cranberry
b P
Products
d t
• Prophylaxis with low-dose antibiotics has a modest
advantage over cranberry tablets in recurrent UTI.
• Cranberry products well-tolerated
• Dosage:
D ttablets
bl t att 500mg
500 po bid
• An alternative for patients who wish to
avoid prophylactic antibioticsWhen Antimicrobial Prophylaxis
F il The
Fails: Th Role
R l off Methenamine
M th i
• Methenamine salts:
-Methenamine mandelate (Mandelamine)
-Methenamine hippurate (Hiprex/Urex)
-Usually start with 1g po bid
• In the presence of acidic urine pH, compound breaks
down into formaldehyde
• Requires daily Vitamin C to acidify urine
• Risk of GI side effects, usually mildSpecial Cases: Catheterization • Incidence of bacteriuria with catheterization – 3-6% per day with indwelling catheters – 1-3% per day on CIC • Avoid prophylactic antibiotics: Treat based on symptoms – Symptoms not always clear in patients with neurologic deficits • Maintain a closed drainage system (indwelling) • Consider methenamine
Who Needs Catheterization?
• Many women carry a post-void residual (PVR) as they age
• Such a residual predisposes to recurrent UTIs
• For an elderly women with a large PVR, we often avoid
catheterization as long as possible (arthritis prevents
catheterization)
• Consider CIC not to prevent UTIs but to maintain ability to void
b t
between catheterization.
th t i ti
• For women on CIC, need to cath with enough frequency to keep
bladder volumesSpecial Cases: Pregnancy
• Incidence of asymptomatic bacteriuria same in pregnant
and non-pregnant women (2%-7%)
• Pregnancy a risk factor for pyelonephritis:
– Progesterone-induced
P t i d d relaxation
l ti off ureteric
t i smooth th muscle
l
– Increased blood volume GFR, more upper tract dilation
• 25-40% of pregnant women with untreated bacteriuria
develop pyelonephritis
• Daily antibiotic prophylaxis recommendedSpecial Cases: Sling Surgery
• Increased risk of UTI after sling surgery
• Multivariable logistic regression analyses were performed on
data from 1,252 women randomized in two surgical trials, Stress
Incontinence Surgical Treatment Efficacy trial (SISTEr) and
Trial Of Mid-Urethral Slings (TOMUS)
Nygaard, et al 2011
• Risk factors for UTI after sling
– Pre-operative recurrent UTI
– Bladder
l dd perforation
f i
– Self-cath
– Elevated PVRCase presentation
pCase presentation
p
• Elected not to perform renal scan:
– D
Decision
i i maded to
t remove tumor
t andd incise
i i ureterocele
t l
(assumption made that upper pole moiety non-functional)
• Cystoscopic incision of ureterocele:Two ureteral orifices
Incision of ureterocele
Proximal UOHematuria: Overview
»
• Sign of a pathological process of the urinary tract
• Hematuria
H i can arise
i from
f any condition
di i that
h results
l in
i
infection, inflammation, or injury to the urinary system
• Degree of hematuria does not correlate with the
seriousness of the underlying cause
• A single episode of unexplained gross hematuria
warrants investigationHematuria – Upper Tract • Kidneys • Ureters – Lower Tract • Bladder • Urethra
Hematuria
• Significance and
causes of hematuria
vary with age
• Any person with
h
hematuria
t i over the
th
age of 40 requires
evaluation for GU
malignancyMedically Treatable Causes of Hematuria
• Infection
– Cystitis
y
– Acute and chronic pyelonephritis
• Primary Glomerulonephritis
– IgA nephropathy
– Membranoproliferative glomerulonephritis
– Focal glomerular sclerosis
• Secondary Glomerulonephritis
– Lupus
– HUS syndrome
y
– Henoch
Henoch--Schonlein syndrome
• Vasculitis
– Polyarteritis nodosa
– Wegner’sMedically Treatable Causes of Hematuria
• Familial Conditions
– Alport
Alport’ss Syndrome
– Polycystic Kidney Disease
• Medications
– Antibiotics
– ASA, NSAIDS
– Chemotherapeutic Agents (Cyclophosphamide)
– *Anticoagulants*
• DM (papillary necrosis)
• HTN
• Sickle Cell AnemiaUrological Causes of Hematuria
• Malignancy
– Renal,
R l ureteral,
l bladder,
bl dd urethral
h l
• Benign Lesions
– Polyps,
P l urethral
th l diverticulum,
di ti l stricture,
ti t ulcers
l
• Stones
• Foreign
F i Bodies
B di
• Trauma“Other” Causes of Hematuria • Strenuous Exercise • AV Malformations • Renal Infarction • Renal Vein Thrombosis
Gross Hematuria
• Blood visible in the urine
• 1/5 of a teaspoon or 1/8 of an ounce of blood in a 1/2 a
quartt off urine
i isi enoughh blood
bl d to
t be
b visible
i ibl to
t the
th naked
k d
eye
• About 3% of the population will develop gross hematuria
in their lifetime
• Gross Hematuria necessitates a Urologic Evaluation!Microscopic Hematuria
• Symptomatic
y p Microscopic
p Hematuria
– Evaluation and treatment
• Asymptomatic
A t ti Microscopic
Mi i Hematuria
H t i
– Exclude benign causes (menses, sexual activity, infection,
trauma)
– Proteinuria, dysmorphic RBC’s, or elevated BUN/Cr…
Nephritic Evaluation
– No evidence of primary renal disease or high risk factors:
Urologic Evaluation according to AUA RecommendationsAsymptomatic Microscopic
Hematuria in Adults: Summaryy
of the AUA Best Practice Policy
R
Recommendations
d tiAsymptomatic Microscopic Hematuria in
Ad lt Summary
Adults: S off the
th AUA B
Bestt
Practice Policyy Recommendations
• The AUA convened a Best Practice Policy Panel to
formulate recommendations for the evaluation of patients
p
with asymptomatic microhematuria
• The panel did not offer recommendations regarding
routine screening for microscopic hematuria
• The recommendations were based on extensive review of
the literature and the panel members’ expert opinions
– Urologists
– Family
F il physician,
h i i nephrologist
h l i andd a radiologist.
di l i
Grossfeld, GD et al Am Fam Physician 2001;63:1145-54Asymptomatic Microscopic Hematuria in
Ad lt Summary
Adults: S off the
th AUA B
Bestt
Practice Policyy Recommendations
• The initial determination of microscopic hematuria should
be based on microscopic examination of urinary sediment
from a freshly voided, clean-
clean-catch, midstream urine
specimen.
p
• The recommended definition of microscopic hematuria is
three or more red blood cells per HPF on microscopic
evaluation of urinary sediment from two of three properly
collected urinalysis specimens
Grossfeld, GD et al Am Fam Physician 2001;63:1145-54Summary of the AUA Best Practice Policy
R
Recommendations
d ti
• High
High--risk patients should be considered for full urologic
evaluation after one properly performed urinalysis
documenting the presence of at least three red blood cells
per high-
high-power field
– Smoking history
– Exposure to chemicals or dyes (benzenes or aromatic amines)
– History of gross hematuria
– Age >40 years
– History of urologic disorder or disease
– History of irritative voiding symptoms
– History of urinary tract infection
– Analgesic abuse
– History of pelvic irradiation
Grossfeld, GD et al Am Fam Physician 2001;63:1145-54Summary of the AUA Best Practice
Policy
li Recommendations
d i
• If a careful
f l hi
history suggests a potential
i l “b
“benign”
i ” cause for
f
microscopic hematuria, the patient should undergo repeat
urinalysis 48 hours after cessation of the activity
– e,g. menstruation, vigorous exercise, sexual activity or trauma
• No additional evaluation is warranted if the hematuria has
resolved.
• Patients with persistent hematuria require evaluation
Grossfeld, GD et al Am Fam Physician 2001;63:1145-54Asymptomatic Microscopic Hematuria in
Ad lt Summary
Adults: S off the
th AUA B
Bestt
Practice Policyy Recommendations
• UTI’s should be treated appropriately, and urinalysis
repeated
t d six
i weeks
k after
ft treatment
t t t
– If hematuria resolves no additional evaluation is necessary
Grossfeld, GD et al Am Fam Physician 2001;63:1145-54Asymptomatic Microscopic Hematuria in
Ad lt Summary
Adults: S off the
th AUA B
Bestt
Practice Policyy Recommendations
• In women, urethral and vaginal examinations should be
performed
f d tto exclude
l d local
l l causes off microscopic
i i
hematuria
• A catheterized urinary specimen is indicated if a clean
catch specimen cannot be reliably obtained
– Vaginal contamination or obesity
Grossfeld, GD et al Am Fam Physician 2001;63:1145-54Asymptomatic Microscopic Hematuria in
Ad lt Summary
Adults: S off the
th AUA B
Bestt
Practice Policyy Recommendations
• Urine Cytology
– Voided
V id d urinary
i cytology
l is
i recommended
d d in
i all
ll patients
i who
h
have risk factors for bladder cancer
– In patients without risk factors for bladder cancer, cytology or
cystoscopy may be used
– If cytology is chosen and malignant or atypical/ suspicious cells
are identified,
identified cystoscopy is required
Grossfeld, GD et al Am Fam Physician 2001;63:1145-54Asymptomatic Microscopic Hematuria in
Ad lt Summary
Adults: S off the
th AUA B
Bestt
Practice Policyy Recommendations
• Imaging
– Intravenous urography,
g p y ultrasonography
g p y and computedp
tomography are used to evaluate the urinary tract in patients
with microscopic hematuria
– Because of lack of impact data,
evidence--based imaging guidelines
evidence
cannot be formulated
Grossfeld, GD et al Am Fam Physician 2001;63:1145-54Asymptomatic Microscopic Hematuria in
Ad lt Summary
Adults: S off the
th AUA B
Bestt
Practice Policyy Recommendations
• Cystoscopy
– Complete visualization of the bladder mucosa, urethra and
ureteral orifices is necessary to exclude the presence of bladder
cancer
– Cystoscopy is recommended in all adult patients more than 40
yyears of age
g and in patients
p less than 40 years
y of age
g with risk
factors for bladder cancer
Grossfeld, GD et al Am Fam Physician 2001;63:1145-54Asymptomatic Microscopic Hematuria in
Ad lt Summary
Adults: S off the
th AUA B
Bestt
Practice Policyy Recommendations
• Patients with microscopic hematuria, a negative initial
urologic evaluation and no evidence of glomerular
bleeding are considered to have isolated hematuria
• Although
lh h many suchh patients
i may have
h structurall
glomerular abnormalities, they appear to have low risk for
progressive renal disease
disease.
• Should be followed for the development of hypertension,
renal insufficiency or proteinuria
Grossfeld, GD et al Am Fam Physician 2001;63:1145-54Asymptomatic Microscopic Hematuria in
Ad lt Summary
Adults: S off the
th AUA B
Bestt
Practice Policyy Recommendations
• Hematuria can be measured quantitatively by:
– Determination of the number of red blood cells per milliliter of
urine excreted (chamber count),
– Direct examination of the centrifuged urinary sediment
(sediment count)
– Indirect examination of the urine by dipstick
• Prevalence
P l iin 5 population-
population
l ti -based
b d studies
t di was 0.19-
0.19
0 19-16.1%
16 1%
– Differences in age, sex, the amount of follow-
follow-up and the number
of screening studies per patient
Grossfeld, GD et al Am Fam Physician 2001;63:1145-54Asymptomatic Microscopic Hematuria in
Adults: Summary of the AUA Best Practice
Policy Recommendations for Follow Up
• Additional evaluation, including repeat imaging and
cystoscopy may be warranted in patients with persistent
cystoscopy,
hematuria in whom there is a high index of suspicion for
significant
g underlying
y g disease
• In this setting,
g, the clinical judgment
j g of the treatingg
physician should guide further evaluation
Grossfeld, GD et al Am Fam Physician 2001;63:1145-54Asymptomatic Microscopic Hematuria in
Adults: Summary of the AUA Best Practice
Policy Recommendations for Follow Up
• Immediate urologic re-
re-evaluation, with consideration of
cystoscopy cytology or repeat imaging,
cystoscopy, imaging should be
performed if any of the following occur:
– Gross hematuria,
– Abnormal urinary cytology
– Irritative voiding symptoms in the absence of infection
• If none of these occurs within three years, the patient does
not require further urologic monitoring
Grossfeld, GD et al Am Fam Physician 2001;63:1145-54You can also read
