Asymptomatic Urinary Tract
Infection
Edward L. Goodman, MD
October 13, 2003
A Common Problem: Prevalence
of AB in Ambulatory Persons
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Young women: 1-2%
Women >60 years: 6-10%
Men >65 years: >5%
Swedish city
– At 72 years, 6% men, 16% women
• VA outpatient men
– 65-74 years old: 9%
– 75-84 years old: 15.3%
Nicolle. Inf Dis Clin NA, 1997; 11: 647
Elderly Institutionalized
• Prevalence
– Men: 15 – 35%
– Women: 25 - 50%
• Incidence Studies
– NH with negative culture on admission
• 11% men positive at one year
• 23% women at one year
– Another study: 10% acquire every 3 months
Nicolle IDCNA 1997
So, it’s common- big deal!
• We’ve got The Sanford Guide
–
–
We can look it up conveniently
Who needs a lecture?
• For those of us who can’t read the small
print
– We’ve got Epocrates
– Current house staff were all born with a Palm
Pilot™ clutched in their palm!
• What’s the big deal – just treat it!
BUT
• All antibiotic use ultimately leads to microbial
resistance
• Resistance results in increased morbidity,
mortality, and cost of healthcare; and
• Appropriate antimicrobial stewardship should
prevent or slow the emergence of resistance
among organisms (Clin Inf Dis 1997; 25:584-99.)
• Antibiotics are used as “drugs of fear”
(Kunin et al. Ann Int Med 1973;79:555)
Antibiotic Misuse
• Surveys reveal that:
– 25 - 33% of hospitalized patients receive
antibiotics (Arch Intern Med 1997;157:1689-1694)
– 22 - 65% of antibiotic use in hospitalized
patients is inappropriate (Infection Control 1985;6:226-230)
Consequences of Misuse of
Antibiotics
• Contagious RESISTANCE
– Nothing comparable for overuse of
procedures, surgery, other drugs
• Morbidity - drug toxicity
• Mortality - MDR bacteria harder to treat
• Cost
Definitions: Asymptomatic
Bacteriuria
• “Gold standard” for bacteriuria =
>=100,000 CFU/ml voided urine
– Applied to Asymptomatic Bacteriuria
– Almost always present in acute pyelonephritis
– Kass, EH. Trans Assoc. Amer. Phys 69:56, 1956
Definitions: Symptomatic
Bacteriuria
• Acute cystitis in women: >= 100 CFU/ml
– 95% sensitivity; 85% specificity*
• Acute pyelonephritis: > 100,000/ml**
• (The standard 0.001 ml loop cannot detect
<1000 organisms/ml)
• *Stamm WE. NEJM 3229:1328, 1982
• **Kass 1956
Infectious Disease Society
Consensus Definition
• Cystitis: >=10³ cfu/ml
– Sensitivity 80%; Specificity 90%
• Pyelonephritis: >=10,000 cfu/ml
• Can be identified in routine micro labs
using 0.001 ml loop
• Rubin et al. Clinical Infectious Disease, 1992
Symptoms
• Acute: irritation, obstruction or
inflammation – correlate with significant
bacteriuria
• Chronic: incontinence, hesitancy, hematuria
– do not correlate with bacteriuria in elderly
• In demented: non-specific symptoms such
as altered mentation are fairly sensitive for
systemic infection
Colonization vs. Infection
• Bacteriuria is almost always associated with
a host response
– Pyuria
– Cytokinuria
• HENCE, THE TERM COLONIZATION
OF URINE IS OBSOLETE. It is infection,
asymptomatic or symptomatic
Why So Many Urine Cultures?
• Annually 10,400 urine cultures are submitted to
the PHD Microbiology Laboratory
– Exceeded only by 14,000 blood cultures
• At least one third from catheterized patients
– Often cath specimens are mislabeled as voided
– It is an effort to obtain a clean catch urine from a
hospitalized patient
– Catheter urine is so convenient to culture!
• Nursing preferences play a major role
HCW’s Attitudes and Perceptions
• HCW interpret bacteriuria as symptomatic
in presence of nonspecific symptoms
• Urine cultures are thus ordered for
nonspecific changes in patient’s status –
part of the “panculture” mentality
• Difficulty in eliciting information about
symptoms in frail elderly
Attitudes and Perceptions –2
• Physician’s uncertainty about significance
and management of positive urine culture
• Liability concerns
– A positive culture left untreated looks “bad” in
the chart
• Walker et al. CMAJ 2000; 163 (3): 273
Refrain: Prevalence of AB in
Ambulatory Persons
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•
•
•
Young women: 1-2%
Women >60 years: 6-10%
Men >65 years: >5%
Swedish city
– At 72 years, 6% men, 16% women
• VA outpatient men
– 65-74 years old: 9%
– 75-84 years old: 15.3%
Nicolle, Inf Dis Clin NA, 1997
Refrain II: Elderly
Institutionalized
• Prevalence
– Men: 15 – 35%
– Women: 25 - 50%
• Incidence Studies
– NH with negative culture on admission
• 11% men positive at one year
• 23% % women at one year
– Another study: 10% acquire every 3 months
Nicolle 1997
Does Rx for AB Help?
• All data is from elderly in long term care facilities
• Early studies (Platt, NEJM 1982;307:637) suggested AB
associated with three fold higher mortality
– Therapy had no protective effect
– AB seems to be a marker of debility
• More recent comparative studies confirm no
benefit from Rx and no higher mortality in non Rx
Nicolle et al. NEJM Male veterans,
1983;309:1420
Average age 82
2 yrs: no difference
in incidence of sx
UTI, prevalence or
mortality
Nicolle et al. Am J
Med 1987; 83:27
Women, NH,
average age 83
1 yr: monthly prev.
31% down; incid.
of sx UTI and
mortality no diff;
more ADR and
MDR
Abrutyn et al. Ann
Intern Med 1994;
120: 827
Women, geriatric
apartment, average
81
8 yr: mortality
similar
Ouslander et al.
Ann Intern Med
1996; 122: 749
Incontinent NH
both sexes
No decrease in freq
or volume of
incontinence
Case Presentation
• 91 year old woman admitted from NH with
fever, altered mental state and drainage
from recent hip incision, no urinary sx
• Urine culture from cath inserted in ER:
>100,000 Pseudomonas aeruginosa
• Diagnosis: “Urosepsis”
– BUT
Case continued
• Blood and hip aspirate cultures: MRSA
• No response to anti-pseudomonas Rx: still
confused
• Woke up with Vancomycin
• Diagnoses:
– Infected total hip with secondary bacteremia –
MRSA
– Asymptomatic bacteriuria - Pseudomonas
Fever and UTI in Elderly
Institutionalized
• Prospective study
– Jan 1, 1989 through Dec 31, 1990
– Two LTCF in Canada
• Demographics
– M:F 3:1
– Majority >65 years
– Catheters 5.7% to 9.3%
Nicolle, AJM 1996; 100:71.
Fever and UTI in Elderly
Institutionalized
• Entry Criteria – Fever
• Urine cultures, UA at enrollment and Q4
weeks
• Monitored serum antibody
– Major Outer Membrane Protein (MOMP) of E
coli for all enterobacteriaceae
– IgG to other organisms
Fever and UTI in Elderly
Institutionalized: Definitions
• Fever >38 (100.4)
• Sx UTI for non cath required at least 3:
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Fever or chills*
New or increased lower tract irritation
New flank or suprapubic pain or tender
Change in character of urine
Worsening mental status*
– *our case
Definitions continued
• Indwelling catheter: two symptoms
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Fever or chills
New flank or suprapubic pain/tender
Change in character of urine
Worsening mental status
• Bacteriuria
– Non cath >= 100,000/ml of one or two bugs
– Condom cath >=100,000 of <3 bugs
– Cath: any number
Febrile Morbidity in long term
care patients
• Prevalence of bacteriuria - 50%
– <10% were catheterized
• Positive Predictive Value of bacteriuria for
clinical UTI – 11%
• PPV of bacteriuria for serologic UTI – 12%
• <10% of episodes of unexplained fever were
attributable to UTI
• Nicolle, AJM 1996; 100:71.
To Summarize
• Bacteriuria very common in uncatheterized
long term care patients
• Poor correlation of bacteriuria with
symptoms attributable to urinary tract
• Bacteriuria rarely explains fever in absence
of localizing symptoms
• Most treatment for AB is inappropriate
Should AB ever be treated?
• Pregnant women
– AB Prevalence: 4-7%
– Optimal time to screen is 16th week
– Symptomatic infection develops in 20-40% of those
with AB (1-3% of all pregnancies)
– Premature labor in 20-50% with symptomatic UTI
– Successful Rx of AB reduces rate of symptomatic UTI
by 80-90%
– Patterson TF, Andriole VT. Inf Dis Clin NA 1997;11:593-608
When to Rx AB – cont’d
• Prior to renal transplant
• Prior to invasive urinary procedures
– TURP, biopsy prostate
– not insertion of catheter (except if valvular
heart disease and infected urine)
• Unclear before insertion of non urinary
prosthesis: heart valve, total hip or knee
Case Presentation 2
• 39 woman, 250 pounds, three previous
THR. No urinary sx.
• Pre op: “dirty” voided UC: 30k E coli and
Klebsiella
• Three days of Cefamandole and Tobra
starting at time of surgery
• 6 weeks later, E coli in hip
– Different biotypes and MIC’s
Case 2 - continued
• She sued the surgeon alleging negligence
for replacing hip in setting of positive urine
culture
• Defense expert testified
– the two organisms were unrelated
– the literature didn’t support any increased risk
of SSI from asymptomatic UTI*
*Review of literature on urine
cultures prior to hip surgery
• Lawrence, Kroenke. Arch Int Med 1988;
148:1370-1373
– Chart review 200 consecutive knee procedures
• Excluded insertion of prostheses
– Criteria for abnormal UA established
– 10% UA’s indicated, 90% not
– SSI: 1/166 with normal UA; 0/23 with WBC
• Overall infection rate 0.5% (95% CI: 0-2.3%)
Literature - continued
• Health Technology Assessment 1997; 1:4347
– No controlled trials on value of routine preop
urine testing
– Routine preop urine abnormal 1%-34.1%
• Leads to change in management in only 0.1%-2.8%!
– No good evidence that preop abnormal UA is
associated with any postop complication
Case - continued
• Plaintiff’s expert stated “An E coli is an E
coli is an E coli. Don’t bother me with
genetics.”
• SHE WON THE CASE!
Catheter Associated UTI
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Short term catheter <30 days
Long term catheter >30 days
Prevention of bacteriuria
Prevention of complications of bacteriuria
Avoidance of urethral catheters
Warren Inf Dis Clin NA 1997; 11: 609-622
How Significant is Pyuria in
Foley Urine?
• Definition
– Standard: 5 WBC/hpf
– Hemocytometer: 10 WBC/µl
• Does not correlate with catheter related
symptomatic infection.
• SHOULD NOT BE USED AS REASON TO
OBTAIN FOLEY URINE CULTURE
• Tambyah, Maki. Arch Int Med 2000; 160: 673
Short Term Catheter
• 15-25% of acute care patients have catheter
– Mean/median duration between 2 and 4 days
– At 3% to 10% incidence/day, 10% to 30% will
develop catheter associated bacteriuria (CAB)
during their hospital stay
–Warren Inf Dis Clin NA 1997; 11: 609-622
Risk Factors for CAB
Platt. Am J Epid 1986; 124: 977
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Duration of catheter
Absence of urinometer
Colonization of drainage back/back flow
Diabetes
No receipt of antibiotics
Female
For other than surgery or output measures
Abnormal serum creatinine
Errors in catheter care
Complications of Short Term
Catheter
• Most episodes of AB are asymptomatic
• Fever or UTI sx in up to 30%
– <5% associated with bacteremia
– Attributable mortality <15% of bacteremic
• Given large number of short term catheters
nationwide, up to 15% of nosocomial
bacteremias are from UTI
PHD 2001 Survey
Data courtesy of Sharon Williamson, MT(ASCP) and Bobby Moore, MT
(ASCP) PHD Microbiology Lab
• Review Micro Lab Computer for
– All patients with positive urinary catheter
culture and
– Positive blood cultures drawn same day
• Exclude urine positive for Staph aureus and
Candida since
– Literature states these are more likely causes of
the bacteriuria rather than the consequence
Cases with same isolate in
BC/UC
• Total 19 cases
– 14 E coli
– 2 Proteus mirabilis
• 1 had three other urinary isolates as well
– 2 Klebsiella pneumoniae
– 1 Morganella morganii
Cases with different isolates
• 55 total cases
– Skin flora in blood: 40
• Seven had 2 + BC for CNS – likely pathogens
• 33 had single + BC – unclear significance
– Definite pathogens in blood: 16
– Combined definite and likely: 23 cases
Likelihood of Positive Foley
Culture As Cause of “urosepsis”
• 19/42 (45%) bacteremic episodes in this
cohort of catheterized patients were
attributable to urine isolate
• 23/42 (55%) bacteremic episodes not
related to urine isolate – would have been
missed if therapy based on urine only!
Conclusion
• In an acute care hospital, cannot assume
that a positive urine culture from
catheterized patient is the cause of a febrile
episode
• Must always draw blood culture before
initiating therapy
• Keep an open mind about other sites for
fever
Long Term Catheters
• Prevalence: more than 100,000 NH patients
in USA
• Incidence of bacteriuria still 3% to 10%/day
• At 30 days, almost 100% prevalence!
– 95% polymicrobial
– Catheter bugs not the same as bladder bugs at
least 25% of the time (biofilm theory)
Complications of Long Term
Catheters
• Two thirds of febrile episodes in aged LTC
attributed to UTI
– Incidence: one febrile episode per 100 catheter
days
– MOST SELF LIMITED (<1 day)
– Therapy not usually indicated
Other Complications of LTC
• Catheter obstruction
– Related to biofilm production
• Infection stones
• Chronic renal inflammation
– Chronic pyelo usually only with
obstruction/stones
• Urethritis/fistulae, epididymitis, prostatitis
• Bladder cancer
Prevention of CA Bacteriuria
• Closed catheter system
• Remove catheter when possible
• Delay onset
– Coated catheters largely ineffective
– Systemic antibiotics work but ultimately
• Adverse effects
• Multidrug resistant isolates emerge
Prevent Complications of CA
Bacteriuria?
• Search out and treat AB?
– Prospective trial (Warren JAMA 1982;248:454)
• no effect on preventing fever
• Marked increase in resistance
• DO NOT TREAT CAB except in
– epidemics or clusters
– High risk patients
• Pregnancy, renal transplant, urologic surgery
What about symptomatic UTI in
catheterized patient?
• Always look for non-UTI explanations as well
– Blood cultures
• Treat with specific therapy for 10-14 days
assuming occult pyelonephritis
– Change catheter and obtain new culture before Rx
• Clinical and bacteriologic outcomes better
• More reliable culture from newly inserted catheter with no
biofilm
– Raz. J Urol 2000;164:1254
What about Candiduria?
• 10% of positive urine cultures in referral hospitals
yield candida sp.
• Symptomatic candiduria should be treated
• What about catheter associated candiduria?
– Short term eradication with 14 days fluconazole
– No effect on candiduria two weeks after therapy
– No effect on mortality
Sobel. Clin Inf Dis 2000; 30:19
Recommendations for screening
and treatment of AB
Nicolle L.E. Infect Dis Clin N Am (2003): 367
• Screening and treatment beneficial
– Pregnant women
– Before traumatic genitourinary procedure
• Screening and treatment may be beneficial
– Renal transplant, first 6 month post-tranplant
– Women with persistent cath-acquired
bacteriuria after cath removal
Screening and Treatment not
beneficial
Nicolle 2003
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Healthy infants, children, adults
Elderly in the community or long term care
Women with diabetes
HIV patients
Patients with short or long term urinary catheters
Patients with intermittent catheterization
Patients with neurologic impairment of voiding
Patients with chronic urologic devices
Conclusions
• Don’t seek out Asymptomatic Bacteriuria
– Except in pregnant women, prior to renal
transplant or invasive urologic procedures
• Don’t assume that foley associated AB is
cause of patient’s deterioration
– Look for other causes even while you treat the
UTI
Conclusions 2
• Don’t bother with post treatment cultures
• When Rx given for catheter associated UTI,
change the catheter, obtain second culture
and treat 10-14 days
• Avoid use of drugs needed for treating other
serious infections
– Reduce risk of selection of resistance
Thanks to the following persons
for their assistance:
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Sharon Williamson, MT (ASCP)
Bobby Moore, MT (ASCP)
Tammy Chung, Pharm.D
Carla Philmon, Pharm.D
Teri Smith, Pharm.D
Judith Marshall, R. Ph