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is almost always associated with a host response – Pyuria – Cytokinuria • HENCE, THE TERM COLONIZATION OF URINE IS OBSOLETE.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 16 th 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 2 nd 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 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:

• 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!