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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