Urinary Tract Infection and Prevention of Recurrent UTI

Urinary Tract Infection and Prevention
of Recurrent UTI
Dobie Giles, MD, MS
Chief, Female Pelvic Medicine and Reconstructive Surgery
Division of Gynecology
Assistant Professor
3/12/2014
Disclosures
 None
Objectives
 Discuss the incidence of Urinary Tract Infections
 Discuss the diagnosis and treatment of Urinary
Tract Infections
 Discuss treatment and prevention strategies for
Recurrent Urinary Tract Infections
Case:
 A 30 y/o woman calls you to report a 2-day history
of worsening dysuria, urinary urgency, and
frequency. She denies fever, chills, back pain,
vaginal irritation or discharge.
 One month ago, you treated her with a 3-day
course of trimethoprim-sulfamethoxazole for
presumptive cystitis, and her symptoms resolved.
 She is otherwise healthy, but this is her 2nd
episode in the past year. How would you manage
this patient?
Case
 Diagnosis?
Uncomplicated
UTI
Incidence - UTI
 Most common bacterial infection encountered in
the ambulatory care setting in the U.S.
 8.6 million office visits in 2007 (84% were women)
 $3,500,000,000.00/year
 By age 32, 50% of women will have had a UTI
 Infection recurs in 25% of women within 6 months
of the first UTI
 3-5% have multiple recurrences
 Acute uncomplicated pyelonephritis is less
common (1 case pyelo per 28 cases of cystitis)
Definitions
 Asymptomatic bacteriuria: Bacteriuria with no
symptoms
 Cystitis: infection limited to lower UT with symptoms
of dysuria, frequency, urgency, and suprapubic
tenderness
 Acute pyelonephritis: infection of the renal
parenchyma and pelvicaliceal system accompanied
by significant bacteriuria, usually with fever and back
pain
 Relapse: Recurrent UTI with same organism after
adequate therapy within two weeks of treatment
 Reinfection: Recurrent UTI caused by bacteria
previously isolated after adequate treatment or new
isolate, with negative intervening UCx
“Uncomplicated” Classification
 Healthy, premenopausal, non-pregnant women
with no history suggestive of an abnormal urinary
tract.
 All others are complicated
 Distinction guides choice and duration of
antimicrobial treatment
Features of Uncomplicated vs.
Complicated Cystitis and Pyelo
Variable
Uncomplicated
Complicated
Typical patient
Healthy female with no
history suggestive of
anatomical or functional
urinary tract abnormality
Men, women, children
with function, metabolic,
or anatomical condition
that increase risk of
treatment failure or
serious outcome
Clinical spectrum
Mild cystitis to severe
pyelo
Mild cystitis to lifethreatening pyelo
Diagnosis
On the basis of typical
symptoms; UA/C&S not
routinely needed for
cystitis but recc’d for
pyelo
Typical symptoms or
atypical symptoms,
UA/C&S indicated
Pathogenesis
 Urinary pathogens from bowel or vagina
colonize the periurethral mucosa and ascend
through the urethra to the bladder and in some
cases through the ureter and kidney
 E. coli – predominant pathogen – 75-95%
 Potential for enhanced virulence (fimbriae,
flagella, adhesins, toxins, etc)
 Staphylococcus saphrophyticus, Proteus,
Klebsiella, Pseudomonas, Enterococcus,
Morganella
Risk Factors
Sporadic or Recurrent
•
•
•
•
•
Sexual intercourse
Use of spermicides
New sex partner
Previous UTI
FH of UTI in first
degree female relative
• Urethra to anus
distance
• Postmenopausal
NOT associated
• Coital voiding patterns
• Daily beverage
consumption
• Frequency of urination
• Wiping patterns
• Tampon use
• Douching
• Use of hot tubs
• Type of underwear
Diagnosis
Symptoms
Cystitis
Pyelonephritis
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•
•
•
•
•
•
•
•
•
•
Dysuria
Frequency
Urgency
Suprapubic pain
Hematuria
Fever > 38
Chills
Flank pain
CVA-tenderness
Nausea/vomiting
+/- cystitis
symptoms
Cystitis vs. Vaginitis
 Women with symptoms of dysuria and frequency
AND NO vaginal discharge or irritation, had > 90%
probability of acute cystitis
 Do we need to do a urinalysis?
 Do we need a urine culture?
• Bent S, et al. JAMA. 2002;287(20):2701-2710.
Differential Diagnosis
Symptoms
DDx
Suprapubic tenderness
Cystitis, symphysitis
Dysuria
Urethritis, cystitis, cervicitis, bacterial
vaginitis, atrophic vaginitis, urethral
diverticulum
Frequency
Cystitis, urethritis, IC, foreign body (stone,
mesh)
Flank pain
Pyelonephritis, nephrolithiasis
Hematuria
Hemorrhagic cystitis, pyelonephritis, IC,
nephrolithiasis, neoplasm
Urine Dip
 Leukocyte esterase – enzyme released from
leukocytes
 PPV: 19-88%
 NPV: 97-99%
 Nitrites – some bacteria (Enterococcus) reduce
nitrates to nitrites
 PPV: 94%
 NPV: Low
 Together –
 Both +: Specificity: 98-99.5%; PPV:90+%
 Both -: NPV: 80-90%
Diagnosis – Putting it together
 Woman with symptoms of UTI (acute onset dysuria,
frequency, or urgency)
 No complicating conditions (pregnant, known voiding
abnormalities, co-morbid conditions -> complicated UTI)
 No back pain (if present -> consider pyelonephritis)
 No vaginal discharge (if present -> consider STD, vaginitis)
→ then > 90% probability of acute cystitis
 If hx not clear
 Use dipstick
• positive = 90% cystitis (consider tx for UTI)
• negative = 20% cystitis (dipstick not very specific so 1/5th of these
cases might still have real UTI – consider urine cx, close f/u, other
diagnoses)
• Bent S, et al. JAMA. 2002;287(20):2701-2710
Urine Specimen
 Midstream, Catheterized, Suprapubic aspiration
 Midsteam
 Least invasive
 Give clear instructions to minimize contamination
 Cath/SP aspiration
 Physically disabled, obese, unable to comply with
instructions
 Aseptic technique to minimize introducing infection
Urinalysis / Microscopy
 Micro:
 PPV 100% when pyuria (>8 WBC/mm) and
bacteriuria +
 NPV 100% when absent
 Casts and crystals provide information about renal
involvement
Urine Culture
 Gold standard in diagnosing UTI
 Number, type, and sensitivity/resistance of
bacteria
 Paramount in complicated UTI’s
 Limitation: 1-2 days for results
 Bacteriuria: >10x5, although if positive symptoms,
10x3 can be considered positive
Culture vs. No-Culture
 Complicated UTI: Anatomic, functional or metabolic
abnormality of the urinary tract
 Pregnant
 Diabetes, immunocompromised, post-menopausal,
elderly
 Catheter, calculi, neurogenic bladder
 h/o Multi-drug resistance
 Pyelonephritis (even if uncomplicated)
 Get a urine culture; start empiric antibiotics; tailor
therapy based on culture
Imaging
 Useful if:
 Recurrent or severe symptoms, conventional
treatment has failed, unusual organism (Proteus),
compromised condition, history of calculi, childhood
UTI, or non-pregnant pyelo
 Renal ultrasound:
 Hydronephrosis, nephrolithiasis, perinephric
abscess
 CT:
 Study of choice, best identification of extent of
disease, image renal parenchyma
Cystoscopy
 Used for recurrent UTI evaluation
 Risk factors for abnormalities:
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Proteus
Calculi
Hematuria
Obstructive symptoms
Pyelo
Age > 50yo
Previous surgery (TVT)
Mesh in the Bladder
Management
Management
 Benign condition
 25-42% spontaneously resolve
 Rare progression to pyelo
 Antimicrobial resistance
 E. coli resistance to amoxicillin, bactrim > 20%
 Fluoroquinolones, cephalosporins, amoxicillinclavulanate <10% resistance
 Nitrofurantoin, fosfomycin, pivmecillinam – lowest
rates of resistance
 Infectious Diseases Society of America (IDSA)
Guidelines - “Collateral Damage” , ecologic adverse
effects
Collateral Damage
 “Collateral damage” is a term used to refer to
ecological adverse effects of antibiotic therapy:
 Selection of drug-resistant organisms - VRE, MRSA
 Unwanted development of colonization or infection
with multidrug-resistant organisms
 Clostridium difficile (do you know how they are
treating this?)
• Paterson DL. 2004; 38 Suppl 4:S341-S345.
Resistance Rates
Empirical Treatment of Cystitis
Antimicrobials
Efficacy
Comments
Nitrofurantoin
93% for 5-7d
Avoid if pyelo suspected
TMP-SMX
93% for 3d
Avoid if sulfa allergy, OR if
resistance >20% or used in
prior 3-6m
Fosfomycin
91% single dose
Avoid if pyelo suspected.
Most labs do not check
resistances
Pivmecillinam
55-82% for 3-7d
Not available in US
Fluoroquinolones
90% for 3d
Ecologic adverse events
Beta-lactams
89% for 3-5d
Avoid empiric amoxicillin or
ampicillin
First Line Therapy
Second Line Therapy
Empirical Treatment of Cystitis
 Choice of agent should be individualized based on
patient’s allergy and compliance history, local
practice patterns/resistance prevalence,
availability, cost, patient/provider threshold for
failure
 IF a 1st line agent is not a good choice based on
these factors, use fuoroquinolone or beta lactam
 Preferable to minimize due to ecologic adverse
effects and resistances
 Unfortunately, 2nd line therapies are most
commonly used for UTI in ambulatory settings
Nitrofurantoin
 Macrobid
 100mg twice daily for 5-7d
 Inhibits several bacterial enzyme systems
including acetyl CoA interfering with metabolism
and possibly cell wall synthesis
 Minimal ecologic adverse effects
 Common side effects: nausea, headache,
flatulence
 Monitor use in elderly due to potential for
pulmonary toxicity, increased risk of hepatic
toxicity and peripheral neuropathy
TMP-SMX
 Bactrim
 Interferes with bacterial folic acid synthesisDS
160/800mg bid x 3d
 Fewer ecologic effects than fluoroquinolones
 Bacterial resistance and sulfa allergy are limiting
factors
 Common side effects: N/v, rash, urticaria,
hematologic complications, photosensitivity
Fosfomycin
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Monurol
Phosphonic acid derivative
Inhibits cell wall synthesis
Oral sachet – 3g single oral dose
Active against wide spectrum of GP and GN
organisms, including ESBL, VRE
 Resistance is chromosomally encoded rather than
plasmid – little cross-reactivity with R to other agents
 Minimal ecologic adverse effects
 Common side effects: nausea, diarrhea, headache,
vaginitis
Fluoroquinolones
 Cipro 250mg bid x 3d; Levo 250mg daily x 3d
 Inhibits DNA-gyrase in susceptible organisms
 Propensity for ecologic adverse effects,
recommended for uses other than cystitis when
possible
 Common side effects: n/v/d, headache,
drowsiness
 Adverse effects (tendon rupture, QT changes)
may be increased in the elderly
Beta-lactams
 Amoxicillin-clavulanate, cefdinir, cefaclor, etc
 Amoxicillin, cephalosporins inhibits bacterial cell
wall synthesis, Clavulanic acid inhibits betalactamases
 Probably fewer ecologic adverse effects than
parenteral broad spectrum cephalosporins
 Common side effects: n/v/d, rash, urticaria
UW Resistance Rates
Inpatient
Outpatient
TMP/SMX
26%
32%
Cipro
22%
15%
Nitro
4%
3%
Amoxicillin
23%
15%
Empirical Treatment of
Pyelonephritis
 Most pyelo now treated in outpatient setting
 Urine culture and susceptibilities should be
performed
 Inpatient therapy if severe, hemodynamic
instability, complicating factor (stones, pregnancy,
DM), if oral meds unable to be tolerated, or
concern for non-adherence to treatment
Empirical Treatment of
Pyelonephritis
Antimicrobials
Efficacy
Comments
Fluoroquinolones
96% for cipro 500mg bid Drug of choice
x 7d
86% for levo 750mg qday
x 5d
TMP-SMX
83% for 14d
Inferior choice due to high
rates of resistance unless
culture confirmed
susceptibility
Oral beta lactams
10-14d, Inferior to above
Use only when other
recommended agents cannot
be used
Follow-up
 Repeat culture unnecessary after uncomplicated
cystitis/pyelo if symptoms resolve, except in
pregnant women
 Consider further eval if early recurrences with
same bacteria, persistent hematuria or cystitis
symptoms
Special Topics
Recurrent UTI
asymptomatic bacturia
Recurrent UTI
 If symptoms persist or recur in 1-2 wks of
treatment, resistance likely, therefore use broad
spectrum, fluoroquinolone
 If symptoms recur >1m, repeat short-course firstline treatment, using another 1st line drug,
especially if Bacrim was used
 Goal for long-term recurrent UTI: improve QOL
while minimizing antimicrobial exposure
 Antimicrobial prophylaxis reduces risk by 95%
 Use only if >3 culture proven UTI/1yr and if nonantimicrobial strategies have not been effective
 Self-diagnosis and treatment also useful
Non-antimicrobial Prevention of Recurrent UTI
Strategy
Comments
Behavioral
Abstinence
Often not feasible
No spermicides
Strong risk factor, especially if used
with a diaphragm
Urinate after intercourse, drink fluids
liberally, wipe front to back, avoid
douching, tight fitting underwear
Not effective in case control studies,
but low risk and maybe effective so
reasonable to suggest
Biologic
Cranberry
Inhibition of uropathogen adherence
to uroepithelial cells, RCT showed no
benefit
Topical estrogen
Normalizes vaginal flora, effective in
postmenopausal.
RCT showed benefit
Adhesin blockers
D-mannose, blocks E.coli adhesion
to uroepitelium. No studies
Antimicrobial Management of Recurrent UTI
Strategy
Comments
Self-diagnosis and treatment
First line anti-microbials rx’ed for future
use at onset of UTI symptoms
Women w h/o cystitis can accurately
self diagnose 85-95% of time, leads
to higher patient satisfaction and less
antimicrobial exposure
Antimicrobial prophylaxis
Postcoital – single dose
-Nitrofurantoin 50-100mg
-TMP-SMX 40/200
-Cephalexin 250mg
Continuous – qhs
-Nitrofurantoin 50-100mg
-TMP-SMX 3x/wk or qday
-Cephalexin 250mg
-Fosfomycin 3g q 10d
Useful if UTI’s are temporally related
to coitus.
Beneficial in 92%
Reduce cystitis by 95%, 6-month
trial recommended
Asymptomatic Bacteriuria
 Definition: culture with >10x5 cfu/ml in 2
consecutive voided specimens or > 100 cfu/ml in a
cath specimen from a patient without associated
symptoms
 Treatment debatable
 Abx may make an avirulent strain  virulent strain
 Allergic or adverse reaction to abx
 ISDA currently does not recommend treating:
Catheter-associated Urinary Tract
Infections (CaUTI)
 Among UTI’s acquired in the hospital
 75% are associated with a catheter
 15-25% of hospitalized patients receive a catheter
Catheter-associated Urinary Tract
Infections (CaUTI)
 Only use if necessary
 Take out as soon as possible
 UWHC
 2011 - 169
 2013 - 99
Case:
 A 30 y/o woman calls you to report a 2-day history
of worsening dysuria, urinary urgency, and
frequency. She denies fever, chills, back pain,
vaginal irritation or discharge.
 One month ago, you treated her with a 3-day
course of trimethoprim-sulfamethoxazole for
presumptive cystitis, and her symptoms resolved.
She is otherwise healthy, but this is her 2nd
episode in the past year.
 How would you manage this patient?
Case:
 Given recent exposure to TMP-SMX, offer another
first line antimicrobial agent (nitrofurantoin)
 Counsel regarding non-antimicrobial preventive
approaches
 If recurrences continue, consider selfdiagnosis/self-treatment, postcoital or continuous
antimicrobial prophylaxis
Conclusions
 UTI is a common problem for women
 Knowledge of community bacterial resistance
rates and prescribing recommendations is key
According to the 2010 American Urologic Associate Guidelines, all
of the following are acceptable treatment regimens for acute
pyelonephritis, EXCEPT:
 A) Amoxicillin 500mg three times daily for 14
days with initial dose of 3gm fosfomycin
 B) Oral ciprofloxacin 500mg twice daily, for 7
days with initial 400mg dose of intravenous
ciprofloxacin
 C) Oral ciprofloxacin 500mg twice daily, for 7
days without initial 400mg dose of intravenous
ciprofloxacin
 D) Oral levofloxacin 750mg daily for 5 days
According to the 2010 American Urologic Associate Guidelines, all
of the following are acceptable treatment regimens for acute
pyelonephritis, EXCEPT:
 A) Amoxicillin 500mg three times daily for 14
days with initial dose of 3gm fosfomycin
 B) Oral ciprofloxacin 500mg twice daily, for 7
days with initial 400mg dose of intravenous
ciprofloxacin
 C) Oral ciprofloxacin 500mg twice daily, for 7
days without initial 400mg dose of intravenous
ciprofloxacin
 D) Oral levofloxacin 750mg daily for 5 days
Select the most accurate statement regarding prevention of
recurrent urinary tract infection in non-pregnant women.
 A) Continuous antibiotic prophylaxis for 6-12
months DOES NOT reduce the rate of UTI during
prophylaxis compared to placebo
 B) Continuous antibiotic prophylaxis for 6-12
months reduces the rate of UTI during prophylaxis
compared to placebo
 C) Continuous daily cranberry juice intake for 612 months reduces the rate of UTI
 D) Continuous daily cranberry powder intake for
6-12 months reduces the rate of UTI
Select the most accurate statement regarding prevention of
recurrent urinary tract infection in non-pregnant women.
 A) Continuous antibiotic prophylaxis for 6-12
months DOES NOT reduce the rate of UTI during
prophylaxis compared to placebo
 B) Continuous antibiotic prophylaxis for 6-12
months reduces the rate of UTI during prophylaxis
compared to placebo
 C) Continuous daily cranberry juice intake for 612 months reduces the rate of UTI
 D) Continuous daily cranberry powder intake for
6-12 months reduces the rate of UTI
Which of the following has NOT been shown to increase the risk
of urinary tract infection?
A) Sexual activity
B) Urethra-to-anus distance
C) Hormonal status
D) Use of spermicide combined with diaphragm
for contraception
 E) Voiding habits before or after intercourse




Which of the following has NOT been shown to increase the risk
of urinary tract infection?
A) Sexual activity
B) Urethra-to-anus distance
C) Hormonal status
D) Use of spermicide combined with diaphragm
for contraception
 E) Voiding habits before or after intercourse




What is the recommended first-line antibiotic therapy for
uncomplicated cystitis?
 A) ciprofloxacin 250mg PO BID for 5 days
 B) cephalexin 500mg QID PO for 3 days
 C) nitrofurantoin monohydrate/macrocrystals
100mg PO for 5 days
 D) amoxicillin 500mg PO TID for 7 days
What is the recommended first-line antibiotic therapy for
uncomplicated cystitis?
 A) ciprofloxacin 250mg PO BID for 5 days
 B) cephalexin 500mg QID PO for 3 days
 C) nitrofurantoin monohydrate/macrocrystals
100mg PO for 5 days
 D) amoxicillin 500mg PO TID for 7 days
Which of the following antibiotics is currently associated with the
highest rate of bacterial resistance in the United States?
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

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A) Nitrofuratoin monohydrate/macrocystals
B) Rocephin
C) Trimethoprim-sulfamethoxazole
D) Ciprofloxacin
E) Amoxicillin
Which of the following antibiotics is currently associated with the
highest rate of bacterial resistance in the United States?





A) Nitrofuratoin monohydrate/macrocystals
B) Rocephin
C) Trimethoprim-sulfamethoxazole
D) Ciprofloxacin
E) Amoxicillin
Questions?