Asymptomatic Urinary Tract
Infection
Edward L. Goodman, MD
FACP, FIDSA, FSHEA
October 12, 2009
Nicolle et al IDSA Guidelines for Asymptomatic Bacteriuria.
Clin Inf Dis 2005;40:643-54
So, it’s common- big deal!
• We’ve got The Sanford Guide
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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, Hopkins-abxguide.com
– Current house staff were all born with an IPhone™
clutched in their hands!
• What’s the big deal – just treat it!
– A whole lecture on this?
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OF URINE IS OBSOLETE.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
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
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
Nicolle et al IDSA Guidelines for Asymptomatic Bacteriuria.
Clin Inf Dis 2005;40:643-54
When to Rx AB – cont’d
• Prior to renal transplant
• Prior to invasive urinary procedures
– TURP, biopsy prostate
– not for insertion of catheter (even if valvular
heart disease even with infected urine)
• Unclear before insertion of prostheses: 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 (the first of the 2nd
generation cephalosporins) and tobramycin
starting at time of surgery
• 6 weeks later, E coli found in infected 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 RECEIVED A SETTLEMENT!
– Given more time, I would be happy to expound
on medical legal issues
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 (0.75% of
symptomatic patients with short term foley)
• Given large number of short term catheters
nationwide, up to 15% of nosocomial bacteremias
(symptomatic or not) 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!
– Recall Case #1
• Pseudomonas AB from foley; MRSA in blood
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/delay of CA Bacteriuria
• Closed catheter system
• Remove catheter when possible*
• Delay onset
– Coated catheters largely ineffective
– Systemic antibiotics work but at the cost of
ultimately causing
• 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
Incidentally
• 10/1/08 CMS announced that treatment for
hospital acquired UTI would not be compensated
– Should we screen new admissions for bacteriuria?
– If we do
• They will be treated!
• There will be increased MDR organisms including MRSA
• C diff will emerge
• THR Chief Quality Officers Council has agreed
that we WILL NOT ROUTINELY SCREEN FOR
AB ON ADMISSION
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
Historic overview on treatment of infections
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2000 BC: Eat this root
1000 AD: Say this prayer
1800’s: Take this potion
1940’s: Take penicillin, it is a miracle drug
1980’s – 2000’s: Take this new antibiotic, it
is even a bigger miracle!
• ?2010 and beyond: Eat this root!