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Urinary Tract Infection and

Asymptomatic Bacteriuria
Asymptomatic Bacteriuria
Urine cultures for Diagnosis Of UTIs in young woman

 9 million doctor visits/year!

 Customary urine test is the dip stick and the mid-stream culture of voided
urine. Up to 77% of cystitis cases are cultured

 Traditionally- >100,000 (10⁵)CFUs was called diagnostic of either UTI


(bladder infection present) or asymptomatic bacteruria.

 More recently as little as 100 CFUs in a voided sample has been positively
correlated with coliform (such as E. coli) bladder infection

 The problem with this cut off: Many labs will call 0 to 10,000 CFUs (<10⁴) as
a negative culture
……….
The way the urine test is done, diluting out
the urine 1000 times, there may be no
growth on the agar plates despite a bladder
infection being present
Voided Midstream Urine Culture and Acute Cystitis in Premenopausal Women
thomas M. Hooton, M.D., Pacita L. Roberts, M.S., Marsha E. Cox, B.S., and Ann E. Stapleton, M.D.

N Engl J Med 2013; 369:1883-1891November 14, 2013DOI: 10.1056/NEJMoa1302186

What does the results of the urine culture tell you ?


202 paired samples of mid stream collected urine cultures and catheterized bladder cultures in young
woman who had symptoms of uncomplicated cystitis, no features of pyelonephritis
70% of bladder cultures positive
78% of voided mid-stream cultures positive
As few as 10 CFUs of mid-stream cultures of E. coli or Klebsiella pneumoniae– highly correlated with a
true bladder infection ( 93% PPV).

In contrast – 22% of mid- stream cultures grew enterococcus or Group B strep- at even 100,000 (10⁵
CFUs) – there was no correlation with bladder cultures- These bugs were not found in the corresponding
bladder culture, but E.coli was still cultured in the bladder (but not in the mid-stream culture) in 62% of these
cases !

Take Home Message:


I. a young woman with classic cystitis symptoms can have a documented bladder infection, but her
midstream urine culture can still be a false negative test ( too few CFUs to be detected on standard urine
cultures)
II. Positive mid-stream cultures for enterococcus and Group B strep are most likely contaminants

III. In uncomplicated cases- obtaining cultures as a guide to therapy can be counter productive: either not
treating patients with actual infection, or treating patients for the wrong bacteria.
Question: Which of these options is the quickest, most
sensitive and cheapest way to diagnose a UTI?

 Ask the patient “do you feel like you have a bladder infection- do
you have both a sense of urgency and burning when you
urinate?”
 Do a dip stick and treat only if leukocytes or nitrite positive?

 Send the urine for culture, wait 2 days, and treat the patient only if
>100,000/ml colonies
Diagnosis of Uncomplicated Cystitis

 Symptoms only: +dysuria, +frequency, no discharge or


irritation:***90% chance of cystitis***

 Dipstick: leukocyte esterase + and/or nitrite + only 75% sensitive,


so symptoms more important even if dip is negative

 Culture:10⁵ (100,000) bacterial CFU- traditional criterion of UTI-


50% sensitive -will miss up to half of cases of UTI –counts of 100 to
10,000 colonies – all at levels that may be called as “no growth” by
micro lab. Least sensitive diagnostic test
Why treat Acute Cystitis?

 **Rarely progresses to severe disease even if untreated:


goal is to ameliorate symptoms

 In selecting therapy, efficacy as well as “ecologic collateral


damage” (selecting for antibiotic resistant bacteria, C. difficile
colitis) should be considered equally- fluoroquinolones should
be avoided, except in pyelonephritis

 Nitrofurantoin, Bactrim, fosfomycin are therefore first line agents

 New Study- still >50% of Rxs are for Cipro, most of the time for >
than 3 days. Bactrim #2, nitro #3 , fosfomycin-no Rx
Evolving concepts in the beneficial role of asymptomatic bacteruria:

The importance of treating cystitis to relieve symptoms, but NOT treating


asymptomatic bacteruria
New approach to Asymptomatic Bacteriuria (ABU)

Definition: presence of bacteria >100,000 cfu/ml in


urine of an individual without signs or symptoms of
UTI.
 This definition is independent of the presence or
absence of pyuria, odor, cloudy urine
Asymptomatic bacteriuria in the
non-catheterized patient

 Very Common:
i. Young healthy women : 3 to 5%
i. Pregnant women: 2 to 9.5%
ii. Women aged 65-80 years: 18 to 43%
iii. Women > 80 years: up to 43%
iv. Men 65-80 years: 2 to 15%
 Causes:
Obstructive uropathy, neuromuscular
disease, perineal soiling in dementia.
A new paradigm of asymptomatic bacteriuria (ABU)

 Traditional teaching:
the presence of bacteriuria defines a population at risk,
therefore:
Eliminating the “asymptomatic UTI” (oxymoron) minimizes
the risk for a clinically symptomatic disease
Modern Teaching:
 NO benefit to treatment (except in pregnancy and before
urologic procedure). Term changed to “asymptomatic
bacteriuria”
ABU in young women with history of recurrent UTI –is
this a precursor to symptomatic infection?

 3 to 5% of young women have ABU

 What role does this have in recurrent UTI’s? Many women get
follow-up urine studies and re-treatment after initial therapy for
UTI.

 Study in Clinical Inf. Disease -9/15/2012:


673 healthy non-pregnant woman followed after first UTI for one year.- all were
treated again at any time if had symptomatic UTIs. urine cultures were also
obtained at 3, 6 and 12 months-if positive but if patient asymptomatic only
half were treated, other half were not
Study Results of Asymptomatic Bacteruria
(ABU) in young healthy women
 Results after one year of observation:
Those treated for ABU- 46.8% had a symptomatic UTI later during
the year
Those not treated for ABU- only 13.1% had another UTI!
Conclusion: The paradoxical result was increased incidence of
symptomatic UTIs in patients given antimicrobials for
asymptomatic bacteruria!
Why this surprising result?

 Bacterial interference- the inability of pathogenic


bacteria to set up a bladder infection due to blockage
by commensal bacteria colonizing the bladder- was
disrupted by the treatment of ABU.

Conclusion :The human microbiome is a potent defense


mechanism against superinfecting pathogenic bacteria.
Applies to the bladder, as well as the GI tract and other
sites.
Take Home Message:
if it ain’t broke, don’t fix it – treatment of ASB just leads to
drug resistant bacteria and side effects from the antibiotic

 Antibiotic treatment of ASB does not reduce frequency of


symptomatic UTI
 Treatment of ASB in diabetes does not reduce adverse outcomes,
improve glucose control, or reduce symptomatic UTIs
 It does lead to untreatable drug resistant bacteria, e.g. c.diff

 Only exceptions are pregnancy where asymptomatic bacteriuria


is associated with pyelonephritis, growth retardation, neonatal
death… and patients undergoing urologic procedures (such as
prostate bx)
Choosing Wisely® – Advice for Seniors- an
initiative of the ABIM and American Geriatrics Society

 Many older patients get screening u/a’s and reflex cultures even
when they don’t have urgency and burning symptoms. They are then
treated for a “UTI”. This is a too common mistake…
 “older patients should not be tested or treated for UTI unless they
have symptoms”
 If you are treated for a true UTI: no follow-up test of cure should be
performed
 Antibiotics:
have side-effects
can cause future problems like yeast infection and colitis
lead to drug resistant bacteria
are a waste of money
Urinary Tract Infection

 Upper urinary tract Infections:


 Pyelonephritis
 Lower urinary tract infections
 Cystitis (“traditional” UTI)
 Urethritis (often sexually-transmitted)

 Prostatitis
Symptoms of Urinary Tract Infection

 Dysuria
 Increased frequency
 Hematuria
 Fever
 Nausea/Vomiting (pyelonephritis)
 Flank pain (pyelonephritis)
Findings on Exam in UTI
 Physical Exam:
 CVA tenderness (pyelonephritis)
 Urethral discharge (urethritis)
 Tender prostate on DRE (prostatitis)
 Labs: Urinalysis
 + leukocyte esterase
 + nitrites
 More likely gram-negative rods
 + WBCs
 + RBCs
Culture in UTI
 Positive Urine Culture = >105 CFU/mL
traditionally
 Most common pathogen for cystitis,
prostatitis, pyelonephritis:
 Escherichia coli
 Staphylococcus saprophyticus
 Proteus mirabilis
 Klebsiella
 Enterococcus
 Most common pathogen for urethritis
 Chlamydia trachomatis
 Neisseria Gonorrhea
Lower Urinary Tract Infection -
Cystitis
 Uncomplicated (Simple) cystitis
 In healthy woman, with no signs of systemic
disease
 Complicated cystitis
 In men, or woman with comorbid medical
problems.
 Recurrent cystitis
Uncomplicated (simple) Cystitis
 Definition
 Healthy adult woman (over age 12)
 Non-pregnant
 No fever, nausea, vomiting, flank pain
 Diagnosis
 Dipstick urinalysis (no culture or lab tests needed)
 Treatment
 Trimethroprim/Sulfamethoxazole for 3 days
 May use fluoroquinolone (ciprofoxacin or levofloxacin) in
patient with sulfa allergy, areas with high rates of bactrim-
resistance
 Risk factors:
 Sexual intercourse
 May recommend post-coital voiding or prophylactic antibiotic
use.
Complicated Cystitis
 Definition
 Females with comorbid medical conditions
 All male patients
 Indwelling foley catheters
 Urosepsis/hospitalization
 Diagnosis
 Urinalysis, Urine culture
 Further labs, if appropriate.
 Treatment
 Fluoroquinolone (or other broad spectrum antibiotic)
 7-14 days of treatment (depending on severity)
 May treat even longer (2-4 weeks) in males with UTI
Special cases of Complicated
cystitis
 Indwelling foley catheter
 Try to get rid of foley if possible!
 Only treat patient when symptomatic (fever, dysuria)
 Leukocytes on urinalysis
 Patient’s with indwelling catheters are frequently colonized with
great deal of bacteria.
 Should change foley before obtaining culture, if possible
 Candiduria
 Frequently occurs in patients with indwelling foley.
 If grows in urine, try to get rid of foley!
 Treat only if symptomatic.
 If need to treat, give fluconazole (amphotericin if resistance)
Recurrent Cystitis

 Want to make sure urine culture and


sensitivity obtained.
 May consider urologic work-up to
evaluate for anatomical abnormality.
 Treat for 7-14 days.
Pyelonephritis
 Infection of the kidney
 Associated with constitutional symptoms – fever, nausea,
vomiting, headache
 Diagnosis:
 Urinalysis, urine culture, CBC, Chemistry
 Treatment:
 2-weeks of Trimethroprim/sulfamethoxazole or fluoroquinolone
 Hospitalization and IV antibiotics if patient unable to take po.
 Complications:
 Perinephric/Renal abscess:
 Suspect in patient who is not improving on antibiotic therapy.
 Diagnosis: CT with contrast, renal ultrasound
 May need surgical drainage.
 Nephrolithiasis with UTI
 Suspect in patient with severe flank pain
 Need urology consult for treatment of kidney stone
Prostatitis
 Symptoms:
 Pain in the perineum, lower abdomen, testicles, penis, and with ejaculation,
bladder irritation, bladder outlet obstruction, and sometimes blood in the
semen
 Diagnosis:
 Typical clinical history (fevers, chills, dysuria, malaise, myalgias,
pelvic/perineal pain, cloudy urine)
 The finding of an edematous and tender prostate on physical examination
 Will have an increased PSA
 Urinalysis, urine culture
 Treatment:
 Trimethoprim/sulfamethoxazole, fluroquinolone or other broad spectrum
antibiotic
 4-6 weeks of treatment
 Risk Factors:
 Trauma
 Sexual abstinence
 Dehydration
Urethritis
 Chlamydia trachomatis
 Frequently asymptomatic in females, but can present with dysuria, discharge or
pelvic inflammatory disease.
 Send UA, Urine culture (if pyuria seen, but no bacteria, suspect Chlamydia)
 Pelvic exam – send discharge from cervical or urethral os for chlamydia PCR
 Chlamydia screening is now recommended for all females ≤ 25 years
 Treatment:
 Azithromycin – 1 g po x 1
 Doxycycline – 100 mg po BID x 7 days
 Neisseria gonorrhoeae
 May present with dysuria, discharge, PID
 Send UA, urine culture
 Pelvic exam – send discharge samples for gram stain, culture, PCR
 Treatment:
 Ceftriaxone – 125 mg IM x 1
 Cipro – 500 mg po x 1
 Levofloxacin – 250 mg po x 1
 Ofloxacin – 400 mg po x 1
 Spectinomycin – 2 g IM x 1
 You should always also treat for chlamydia when treating for gonnorhea!
Question #1

 An 18-year old woman presents with


urinary frequency, dysuria, and low-
grade fever. Urinalysis shows pyuria and
bacilli. She has never had similar
symptoms or treatment for urinary tract
infection.
Question # 1

 What category of UTI does this patient


have?
 Does this patient require further testing?
 Would you treat this patient, and if so,
with what and how long?
Question # 2

 An 18-year old woman present with her


third episode of urinary frequency,
dysuria, and pyuria in the past 4 months.
Question # 2

 What further questions do you have for


this patient?
 What type of UTI does this patient have?
 What testing might you perform in this
patient?
 How would you treat her, and for how
long?
Question #3

 A 24-year old woman presents with


fever, chills, nausea, vomiting, flank pain
and tenderness. Her temperature is
40°C, pulse rate is 120/min., and blood
pressure is 100/60 mm Hg.
Question # 3

 What further studies do you want in this


patient?
 How would you treat this patient?
 What might you do if she does not
improve after 3-4 days?
Question # 4

 A 78-year old female presents with an


indwelling foley catheter and pyuria.
Question # 4

 What would you do for this patient at this


time?
 How might your work-up/management
change if she was having fevers and
confusion?
Question # 5

 58-year old man presents with his first


episode of urinary frequency and
dysuria. Urinalysis shows pyuria and
bacilli.
Question # 5

 What type of UTI does this patient likely


have?
 How would you treat this man, and for
how long?
 What activities would put this patient at
risk for UTI?
Question # 6

 A 28-year old male had a sexual


encounter with a prostitute while on a
business trip in Seattle 1 week ago.
After returning home, he noted a burning
sensation on urination and a yellow
discharge in his underwear. Microscopic
examination of the discharge reveals 4+
leukocyte esterase, and the following
gram stain.
Question # 6
Question # 6
 Which of the following is the best course of action for
this patient?

a) Give the patient a prescription for doxycycline, 100 mg po BID


for 7 days
b) Give the patient two prescriptions for ofloxacin 300 mg po
QDay for 7 days, one for him, and one for his wife.
c) Administer ceftriaxone – 125 mg IV x 1 and Azithromycin – 1 g
po x 1, draw blood for a VDRL and HIV – antibody arrange for
his wife to be examined and treated.
d) Administer a single dose of Ceftriaxone – 125 mg IV x 1, and
ciprofloxacin – 500 mg po x 1 draw blood for a VDRL and HIV-
antibody, and arrange for his wife to be examined and treated.
e) Administer a single dose of cefixime – 400 mg, draw blood for
a VDRL and arrange for his wife to be examined and treated.
Final thoughts!
 Antibiotic choice and duration are determined
by classification of UTI.
 Biggest bugs for UTI are E. Coli, Staph.
Saprophyticus, Proteus mirabilis, Enterococci
and gram-negatives
 Don’t use moxifloxacin for UTI!
 Chlamydia screening is now recommended for
all women 25 years and under since infection
is frequently asymptomatic, and risk for
PID/infertility is high!
Final thoughts
 Think twice before ordering a urine culture- go by symptoms
and signs. Only culture in possible pyelonephritis, unclear
diagnosis, complicated cases or treatment failure

 Consider Nitrofurantoin or Bactrim as first line therapy,


quinolones if they are ill

 Mid-stream culture results with enterococcus and GBS can


be deceiving – rarely cause of UTI. Most likely still E. coli

 If the patient is asymptomatic –if it ain’t broke, don’t fix it!