Download Breakout B-Ask the Infectious Disease Specialist - Thomas

Objectives
• Distinguish asymptomatic bacteriuria (ASB) from
symptomatic urinary tract infection (UTI)
• Discuss common clinical scenarios and associated myths
surrounding bacteriuria and UTIs
Asymptomatic Bacteriuria & UTIs:
Dispelling the Myths
Thomas L. Walsh, MD
Medical Director
Antimicrobial Stewardship Program
Allegheny Health Network
Page 2
Asymptomatic Bacteriuria (ASB)
• Infectious Disease Society of America (IDSA) Definition:
Isolation of a specified quantitative count of bacteria in an
appropriately collected urine specimen obtained from a person
WITHOUT symptoms or signs referable to urinary infection
• Simply stated:
– Bacteria in the urine
– 102 vs 103 vs 105 → does not matter
– NO urinary symptoms or signs of systemic infection
Page 3
ASB is Highly Prevalent in
Community Dwelling Adults
Population
Prevalence
Reference
Healthy, pre-menopausal women
1 - 5%
Nicolle LE. Infect Dis Clin North Am 2003
Pregnant women
2 - 9.5%
Nicolle LE. Infect Dis Clin North Am 2003
Post-menopausal women
(50-70 years)
2.8 – 8.6%
Nicolle LE. Infect Dis Clin North Am 2003
Diabetic women
9 – 27%
Zhanel G et al. Rev Infet Dis 1991
1 – 11%
Zhanel G et al. Rev Infet Dis 1991
Page 5
Definition of UTI
• Acute uncomplicated UTI
− SYMPTOMATIC bladder infection characterized by
frequency, urgency, dysuria, or suprapubic pain in a
non-pregnant woman with normal GU tract
• Complicated UTI
− SYMPTOMATIC urinary infection involving either the
bladder or the kidneys in individuals with functional
or structural GU tract abnormalities
Hooton TM et al. Infect Dis Clin North Am 1997
Nicolle LE. Drugs Aging 2001
Nicolle LE et al. Clin Infect Dis 2005
Rubin RH et al. Clin Infect Dis 1992
Nicolle LE et al. Clin Infect Dis 2005
Diabetic men
(Reference)
• Know when to test and treat (and when NOT to)
ASB Prevalence Increase with Age
• Elderly persons in the community:
− Women: 10.8 – 16%
− Men: 3.6 - 19%
• Elderly persons in long term care:
− Women: 25 – 50%
− Men: 15 - 40%
The bladder is normally colonized in many elderly patients
Nicolle LE et al. Infect Dis Clin North Am 2003
Nicolle LE. Infect Dis Clin North Am 1997
Nicolle LE et al. Clin Infect Dis 2005
ASB Prevalence
ASB Prevalence with Indwelling Catheters
Population
Prevalence
Reference
Intermittent catheter use
89%
Bakke A et al. Scand J Infect Dis 1991
Condom catheter in place
57%
Waites KB et al. Arch Phys Med Rehabil 1993
Short-term indwelling catheter
9 - 23%
Stamm WS. Am J Med 1991
Long-term indwelling catheter
100%
Warren JW et al. J Infect Dis 1982
Patients with spinal cord injuries
UTI is a Clinical Diagnosis
• If you check it, they will
come………
Why Do We Confuse ASB with UTI?
• The bladder is normally colonized in many elderly
patients
• It’s ingrained in all of us (physicians, nurses, aides)
to look for infection
• A positive urinalysis or culture is the absence of
symptoms often reveals colonization, not infection
• We confuse presence of bacteria with infection
• Cannot diagnose a UTI by looking at a UA/culture
– Need history and objective data to differentiate colonization
from infection
• Very easy to order a urinalysis and urine culture
• Patients and families are anxious about it and
request testing/treatment
Too often, we all want an easy fix
Page 9
Obtaining the Urine Sample
What Does a Urine Test Do?
• Urine tests lead to antibiotic treatment
– The simple act of obtaining a urine test results in treatment
regardless of presence or absence of UTI (multiple studies)
• Urine tests have a pretest probability of a false positive
result in 1 out of 2 individuals
• Urine tests DO NOT diagnose or define a UTI
– Only role is to identify what bacteria and sensitivities once a
UTI is diagnosed
Page 11
Nace DA, et al. Am Med Dir Assoc, 2014.
• Clean Catch
• Catheterization
Not so easy in an elderly
hospitalized patient
Page 12
The Clean Catch
Straight Catheterization
Straight Cath Technical Difficulties
Interpretation Pitfalls
• The obese patient
• The arthritic patient
• The delirious patient
Page 15
Page 16
Simerville J, et al. American Fam Phys, 2005.
a
Myth #1
Common
Clinical
Scenarios:
Dispelling the
Myths
Positive urine culture and abnormal urinalysis (+ nitrates or
leukocytes) always indicates a UTI and requires antibiotics
Fact
Positive urine culture and urinalysis in a patient without
symptoms is consistent with ASB
Treatment with antibiotics is contraindicated
Page 18
Nicolle LE et al. Clin Infect Dis 2005
ASB is NOT Associated with Adverse Events
• Multiple cohort studies:
– no adverse outcomes of untreated ASB
• No short-term or long-term benefits to treating ASB
• RCT of 1 week of nitrofurantoin vs. placebo
• Antibiotic group:
– Significantly lower prevalence of bacteriuria at 6 mos, not at 1 yr
– No change in mortality
– No change in subsequent GU symptoms
– No change in frequency of falls
Treatment of ASB neither decreases frequency of
symptomatic UTI nor prevents further episodes of ASB
• No difference in frequency of symptomatic UTIs 1 year
after therapy
Page 19
Asscher AW et al. BMJ 1969
Page 20
Hooten TM et al. N Engl J Med 2000
Alwall N. Acta Med Scand 1978
Evans DA et al. Lancet 1982
Mims AD et al. J Am Geriatr Soc 1990
Bengtsson C et al. Scand J Urol Nephrol 1998
Tencer J. Scand Jour Urol Nephrol 1988
Asscher AW et al. BMJ 1969
ASB Significance in
Patients with Spinal Cord Injuries
• When ASB treated in a cohort of spinal cord–injured subjects
• RCT of antibiotic therapy vs. no tx for diabetic women with ASB
• Continued ASB screening q3mos
• Antibiotics did NOT delay or decrease:
• Frequency of symptomatic UTI
• # of hospitalizations for UTI
• Progression of diabetic complications
• Antibiotic therapy arm:
• 5x as many days of exposure
• Significantly more adverse antibiotic events
Page 21
Harding GKM et al. N Engl J Med 2002
– Early recurrence of bacteriuria after therapy was the usual outcome
– After 7 days of antibiotic therapy:
• 93% of subjects were again bacteriuric within 30 days
– After 28- day course of antibiotic therapy:
• 85% were bacteriuric by 30 days
• Re-infecting strains showed increased antimicrobial resistance
Numerous consensus guidelines uniformly recommend treatment
only of symptomatic UTI in patients with spinal cord injuries
Page 22
ASB Significance in Patients with
Indwelling Long-Term Catheters
Myth #2
Positive urine culture in a patient with chronic indwelling
urinary catheter indicates a UTI and requires antibiotics
Fact
A chronic indwelling urinary catheter is associated with
bacteriuria 100% of the time
National Institute on Disability and Rehabilitation Research Consensus Statement. J Am Paraplegia Soc 1992
Waites KB et al. Paraplegia 1993
Nicolle LE et al. Clin Infect Dis 2005
Ditunno JF et al. N Engl J Med 1994
Cardenas DD et al. Arch Phys Med Rehabil 1995
• RCT of cephalexin vs. no therapy for ASB in patients with
long-term indwelling GU catheters and susceptible
organisms
- No difference in rates of fever for 12-44 weeks
- No difference in rates of re-colonization
• 75% of organisms in control group remained susceptible
• 36% remained susceptible in cephalexin arm
Treatment with antibiotics is contraindicated unless patient
has symptoms consistent with a UTI
Page 23
Warren JW et al. J Infect Dis 1982
Nicolle LE et al. Clin Infect Dis 2005
Page 24
Warren JW et al. JAMA 1982
Nicolle LE et al. Clin Infect Dis 2005
Myth #3
• Pyuria indicates a true UTI and requires antibiotic therapy
Fact
Pyuria accompanying ASB: NOT an indication for treatment
Nicolle LE et al. Clin Infect Dis 2005
Pyuria
• Evidence of inflammation of the GU tract
• Common in subjects with ASB
Patient Population
Prevalence of Asymptomatic
Pyuria with ASB
Reference
Young women
32%
Hooton TM et al. N Engl J Med 2000
Pregnant women
70%
Kincaid-Smith P et al. Lancet 1965
Diabetic women
70%
Zhanel GG et al. Clin Infect Dis 1995
Elderly institutionalized
90%
Nicolle LE. Infect Dis Clin North Am 1997
Hemodialysis patients
90%
Chaudhry A et al. Am J Kid Dis 1993
Short-term catheters
75%
Tambyah PA et al. Arch Intern Med 2000
Long-term catheters
100%
Steward DK et al. Am J Infect Control 1985
Nicolle LE et al. Clin Infect Dis 2005
Pyuria
Myth #4
• Also accompanies other inflammatory conditions or GU tract in
pts with negative urine culture results
• Thus, presence of pyuria is NOT sufficient to diagnose UTI
• Cannot differentiate ASB from UTI
IDSA Guidelines
• Cloudy or malodorous urine is always diagnostic of a UTI
Fact
These changes are most often due to dehydration,
certain medications, and diet
Nicolle LE et al. Clin Infect Dis 2005
Simerville J, et al. American Fam Phys, 2005.
Myth #5
• Patients going for elective surgery always need to be
screened for ASB as part of the pre-operative process
Fact
Most people do not
Some people may, but there are very specific indications
Rule of Thumb:
If it smells bad: Stop smelling it
Who to Screen/Treat for ASB
Myth #6
• Pregnant woman (A-I)
Elderly patients often have UTI with no symptoms except
for a change in mental status or delirium
– 20 - 30x increased risk of developing pyelonephritis during pregnancy
– Antibiotic therapy for ASB during pregnancy decreases risk of subsequent
pyelonephritis from 20 – 30% to 1 – 4%
Fact
– Higher rates of premature delivery and low birth weight infants
• Before transurethral resection of the prostate (TURP) (A-I)
• Other urologic procedures for which mucosal bleeding is
anticipated (A-III)
Change in mental status or delirium is a non-specific
syndrome and requires an exploration of alternative causes
–
–
–
–
– High rates of post-procedure bacteremia and sepsis
– Bacteremia occurs in up to 60% of ASB patients who undergo TURP
Page 31
Nicolle LE at al. Clin Infect Dis 2005
Smaill F. Cochrane Database Syst Rev 2001
Elder HA et al. Am J Obstet Gynecol 1971 LeBlanc AL et al. Biol Med 1964
Grabe M. J Urol 1987
Cafferkey MT et al. J Antimicrob Chemother 1982
Grabe M et al. Eur J Clin Microbiol 1987
Allan WR et al. Brit J Urol 1985
Dehydration
Constipation
Polypharmacy
Urinary retention
- Metabolic derangements
- Head trauma
- Sensory deprivation
- Environmental changes
Page 32
Myth #6
Complete List of High-Quality Studies
Establishing UTI as a Common Cause of
Delirium:
AKA
The Plague of Willingness to Call ANYTHING a UTI
Page 33
Many conditions cause delirium
•
Physiological insults:
* Relative Risk ≥ 4
o Increased serum BUN
in a General
Medicine
o Increased BUN/crt ratio
Population
o Abnormal serum albumin
o Abnormal glucose/electrolytes
Iatrogenic insults:
o Medications, restraints
Metabolic acidosis
Unless specific signs/symptoms
specific for UTI, no role for
Infection
antibiotics
Pain
*
• Medline search 1966 through 2012
• Only 5 studies that address association of UTI and
delirium in elderly patients
• 4 retrospective, 1 cross sectional
• No RCT to evaluate this association
• No clear criteria used for diagnosis of delirium or UTI
• Many just relied on chart review/diagnosis codes
•
•
•
•
*
Inouye SK et al, Lancet, 2014.
Myth #7
Better safe than sorry, and we should treat for UTI
when we aren’t sure
A few days of an antibiotic won’t hurt
Fact
Overuse of antibiotics causes an enormous amount of
collateral damage
Page 37
Widespread Inappropriate Abuse of Antibiotics for ASB
Study Design
Study Population
Findings
References
Prospective,
observational over 1 mo
29 inpts with urinary
catheters and ASB
52% were prescribed
unnecessary Abx
Dalen et al. 2005
Prospective, observation
over 1 yr
137 inpt with + UCx
64% of pts with ASB
were treated
Silver et al. 2009
Retrospective review
over 3 mo
197 inpts with urinary
catheters and + UCx
31% of Abx courses
were for ASB
Cope et al. 2009
Retrospective review
over 3 mo
414 inpts
26% of Abx courses
were for ASB
Gandhi et al. 2009
Retrospective review
over 3 mo
339 pts with Enterococcal
bacteriuria
33% of episodes of ASB
inappropriately treated
with Abx
Lin et al. 2012
Retrospective review
over 6 mo
80 inpts with indwelling
urinary catheters
58% received
unnecessary Abx
Chiu et al. 2013
Retrospective review
over 6 mo
16 nursing home pts with
indwelling catheters
83% of treated episodes
were for ASB
Phillips et al. 2012
Page 38
ASB Treatment Harm
• Collateral damage
– Clostridium difficile infection (CDI)
– Drug-drug interactions
Trautner BW et al. Infect Dis Clin N Am 2014
World Economic Forum: 2013
“arguably the greatest risk…to human health comes in the
form of antibiotic-resistant bacteria.
We live in a bacterial world where we will never be able to
stay ahead of the mutation curve.
– Adverse drug events
– Increased healthcare costs
A test of our resilience is how far behind the curve we allow
ourselves to fall.”
– Worsening antimicrobial resistance
Howell L. World Economic Forum 2013
Page 39
Page 40
Sobering Facts
Sobering Facts
• 15 of 18 largest pharm companies totally left the antibiotic field
• No new class of antibiotics for Gram (-) bacilli in 4 decades
• Only 2 drugs with new targets (linezolid & daptomycin) have
been introduced in the past 15 years
Page 41
Infectious Diseases Society of America. Clin Infect Dis 2010
Page 42
Infectious Diseases Society of America. Clin Infect Dis 2010
Since 2000…..
Enormous expansion of infections resistant to Abx
E
S
K
A
P
E
nterococcus
Most important causes of Abx resistance crisis
taphylococcus
lebsiella (KPC)
cinetobacter
seudomonas
SBL
MRSA kills more Americans every year (~19,000)
than COPD, HIV, Parkinson’s, homicide combined
Cost to healthcare system of resistant infections:
$21 – $34 billion/yr
> 8 million additional hospital days/yr
Boucher HW et al. Clin Infect Dis 2009 Mauldin PD et al. Antimicrob Agents Chemother 2010
Klevens RM et al. JAMA 2007
Roberts RR et al. Clin Infect Dis 2009
Page 43
Page 44
Take Home:
Antibiotic Apocalypse
Who NOT to Screen/Treat for ASB
New Antimicrobials
♦ Premenopausal, non-pregnant women (A-I)
♦ Diabetic women (A-I)
Resistance
We are here
♦ Older persons living in the community (A-II)
♦ Elderly, institutionalized patients (A-I)
♦ Persons with spinal cord injury (A-II)
♦ Catheterized patients while the catheter remains in situ (A-I)
Then
Now
Bartlett JG. Medscape
♦ Pyuria accompanying ASB is not an indication for treatment (A-II)
Page 46
Nicolle LE et al. Clin Infect Dis 2005
Take Home: How to Avoid Harm
• Appropriate ordering of urine culture
Summary:
Treating ASB: All Harm, No Benefit
– If no signs of UTI or sepsis, no urine culture
– Remember older adults frequently have ASB
– Do not send for non-specific symptoms
(weakness, fatigue, confusion)
Habitual
Testing
• Treat dehydration, polypharmacy, constipation
• Consult with geriatrician
Page 47
Page 48
Prevalent
Colonization
Unnecessary antibiotics while
missing the real diagnosis