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– 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• HENCE, THE TERM COLONIZATION OF URINE IS OBSOLETE.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: • 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– 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; 1:43-47– 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

• 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

• 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 SurveyData 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:

• 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

• 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!