UPDATES IN THE MANAGEMENT OF URINARY TRACT INFECTIONS

Matthew Miller, PharmD, BCPS (AQ-ID)Infectious Diseases Pharmacist / Clinical InstructorUniversity of Colorado Hospital / University of Colorado Skaggs School of Pharmacy

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Audience Response Instructions

•Go to Kahoot.it on your mobile device (or use the mobile App Kahoot)

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Disclosure and FundingStatement of Disclosure

• I have no relevant financial relationships with commercial interests pertaining to the content presented in this program.

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Objectives

At the conclusion of this presentation, audience members will be able to:

• Identify current epidemiology and antibiotic prescribing habits for urinary tract infections, and the collateral damage incurred from antibiotic misuse.

• Explore opportunities for antimicrobial stewardship in urinary tract infections through accurate diagnosis and treatment plan selection.

• Discuss preventative strategies.

• Provided clinical situations construct an appropriate treatment plan.

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“…. the microbes are educated to resist penicillin and a host of penicillin-fast organisms is bred out… In such cases the thoughtless person playing with penicillin is morally responsible for the death of the man who finally succumbs to infection with the penicillin-resistant organism. I hope this evil can be averted.”

- Sir Alexander Fleming, June 1945

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Contributions of Antibiotics

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Antibiotic Discovery was the “magic bullet” of its time Following sulfanilamide discovery in 1938,

mortality has significantly declined Antibiotics have enabled medical

advancements in other areas: Cancer treatment Surgery Transplantation Obstetrics Auto-immune/rheumatologic conditions

Trends in Antibiotic Use - Outpatient• In 2015, ~269 million prescriptions dispensed by outpatient pharmacies

• CDC estimates 30% of these were unnecessary

Available at: https://www.cdc.gov/antibiotic-use/stewardship-report/index.html

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Trends in Antibiotic Use - Inpatient• > 50% of inpatients receive at least one antibiotic during their hospital stay, 30% of which is unnecessary or inappropriate• Use is relatively unchanged between 2006-2012• Significant increases in vancomycin and carbapenem use

Available at: https://www.cdc.gov/antibiotic-use/stewardship-report/index.html

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How are Antibiotics Being Used

Outpatient• Acute respiratory tract infections – 38%

• 74% broad spectrum

• Genitourinary – 22%

• 68% broad spectrum

• Skin/Mucosal – 13%

• 38% broad spectrum

Hospitalized Patients• 2010 and 2011

• Lower respiratory tract infections – 34.6%

• Genitourinary – 22.3%

• Skin and Soft Tissue – 16.1%

Shapiro DL, et al. J Antimicrob Chemother. 2014; 69: 234-40. Magill SS, et al. JAMA. 2014; 312 (14): 1438-46.

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Uncomplicated UTI Antibiotic Prescriptions• Retrospective cohort of outpatient

and ED visits within a commercial insurance dataset

• Women 18-44 years with UTI diagnosis and concurrent antibiotic prescription between 2009-2013

• 654,432 women met criteria

>75% of prescriptions for non-recommended durations

Durkin MJ, et al. Open Forum Infect Dis. 2018; 5(9): ofy 198

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Why Should I Care• Resistance

• Fluoroquinolones• ESBLs• CRE

• Side effects• Antibiotic related adverse effects #2 reason (16.1%) for ED visits related to

medication side effects

• C. difficile infection (CDI)• Antibiotic use is #1 driver for CDI and recurrence ↑↑ morbidity/mortality

• Increased costs https://www.cdc.gov/antibiotic-use/healthcare/evidence.htmlShehab N, et al. JAMA. 2016; 316(20): 2115-25.

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Case Question22 year old otherwise healthy, non-pregnant female without significant medical history presents to her primary care provider for routine physical. A urinalysis was ordered which showed some mild pyuria and positive nitrite. The patient denies having any urinary symptoms and is feeling fine otherwise. The lab reflexed a culture based on the urinalysis results, which found >100,000 CFU/mL E. coli.

What do you do about the urine culture:

A. Treat with antibiotics

B. Antibiotics should not be prescribed

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DIAGNOSIS

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EpidemiologyIncidence• 8-10 million ambulatory visits each year

• 50% women have ≥ 1 UTI in their lifetime, annual incidence ~13%

• Annual incidence in men ≥ 18 years, 3%

• Higher frequency among young (15-29 years) and old (> 60 years)

• Estimated 1 million cases of nosocomial UTIs per year• 80% attributed to indwelling catheters

Microbiology• >60-85% of all UTIs caused by E. coliFoxman B. Nat Rev Urol. 2010; 7(12): 653-60.Schappert SM. National health statistics reports; no 8. Hyattsville, MD: National Center for Health Statistics; 2008.

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Pathophysiology

PeriurethralColonization

Asymptomatic Bacteriuria

Pyelonephritis Risk Factors Protective Factors

Host FactorsHost ResponseBacterial Factors

Host ResponseBacterial Adaptation

Host FactorsBladder FunctionManipulationInstrumentationSexual ActivityBacterial Factors

UrinationHost Response

Cystitis

Foxman B. Nat Rev Urol. 2010; 7(12): 653-60.

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DiagnosisApproach• Based on systemic and localized symptoms in conjunction with culture

• Host characteristics useful in classification – uncomplicated vs complicated

+Urinalysis +Urine Culture SymptomsAsymptomatic Bacteriuria (ASB)

Yes Yes None

Cystitis Yes Yes Dysuria, frequency, urgency, suprapubic tenderness

Pyelonephritis Yes Yes Fever, flank pain, nauseaCAUTI Yes Yes Fever, suprapubic and/or flank

painUrosepsis Yes Yes SIRS + above symptoms

Grigoryan L. JAMA. 2014; 312(16): 1677-84.Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 8th ed.

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UrinalysisPositive in both asymptomatic and symptomatic UTIs• Poor positive predictive values

• Positive results lead to over culturing and subsequently overtreatment of ASB

Test Sensitivity Specificity PPV NPVPyuria (> 5 WBCs/HPF) 90-96% 47-50% 56-59% 88-98%Hematuria (> 5 RBCs/HPF) 18-44% 88-89% 27% 82%Nitrite 19-48% 92-100% 50-83% 70-88%Leukocyte Esterase 72-97% 41-86% 43-56% 82-91%Bacteria (any amount) 46-58% 89-94% 54-88% 77-86%

Gordon LB. J Am Geriatr Soc. 2013; 61: 788-92.Simerville JA. Am Fam Physician. 2005; 71(6): 1153-62.

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ASB Prevalence by Patient PopulationPopulation Prevalence Population PrevalenceChildren

BoysGirls

< 1%1 – 2%

Persons w/ Indwelling Catheter UseShort-TermLong-Term

3 – 5%/day catheter100%

Health Women Premenopausal PregnantPostmenopausal

1 – 5%1.9 – 9.5%2.8 – 8.6%

Persons with Kidney TransplantFirst Month Posttransplant1-12 Months Posttransplant> 12 Months Posttransplant

23 – 24%10 – 17%2 – 9%

DiabetesWomenMen

11 – 16%1 – 11%

Patients with Spinal Cord InjuryIntermittent Catheter UseSphincterotomy/Condom Catheter

23 – 69%57%

Elderly (age ≥ 70 years)Women (community)Women (institutionalized)Men (community)Women (institutionalized

11 – 16%25 – 50% 4 – 19%15 – 50%

Nicolle LE, et al. Clin Infect Dis. 2019; 68(10): e83-75.

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Urine Cultures for ScreeningIDSA 2019 Guideline for ASB Recommendations

• Pregnant women• Individuals undergoing urologic procedures

• Obtain urine culture before procedure and target antibiotic therapy

• Duration 1-2 doses, initiate 30-60 minutes prior to procedure

• ASB in elderly with delirium/functional decline, but no localizing or systemic symptoms of infection – DO NOT start antibiotics

• Complications associated with unnecessary antibiotics for ASB• Antibiotic resistance

• Adverse Effects – medication side effects and C. difficile infection

• Symptomatic UTI – Antibiotic treatment for ASB independent risk factor (HR 3.09, 2.14-4.2)Nicolle LE, et al. Clin Infect Dis. 2019; 68(10): e83-75.

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Audience QuestionWhat is the best way to distinguish infection from colonization?

A. Urinalysis with > 10 WBCs/hpf

B. Urine culture positivity

C. Urinalysis positive nitrite

D. Symptomology

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To Reflex or Not to ReflexHow often misused tests generate misleading thoughts: an argument for the appropriate use of the urinalysis to rule out urinary tract infections.

—Adapted from Herbert Spencer

Humphries RM, et al. J Clin Microbiol. 2016; 54(2): 254-258 Garcia R, et al. Am J Infect Control. 2017; 45(10): 1143-53.Epstein L, et al. Infect Control Hosp Epidemiol. 2016: 37(5): 606-9. Dietz J, et al. Am J Infect Control. 2016; 44(12): 1750-51.

Urinalysis and urine cultures are frequently ordered inappropriately• Up to 68% of reasons for urine culturing are inappropriate or not reported and had no clear indication

available after review

Absence of pyuria on UA has high (>90%) negative predictive value for negative urine culture in most• Epstein L et al. - Reflex urine cultures in ICUs led to decreased urine cultures (p=0.0012) and decreased

CAUTIs (0.04) – no mention of antibiotic use

Up to 90% of asymptomatic elderly patients have a positive UA for pyuria or leukocyte esterase• Dietz J et al. – removed reflex cultures, leading to decreased urine cultures (p = 0.004) and non-

significant trend towards reduced antibiotic prescribing

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Example

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To Reflex or Not to ReflexTake Home Points:

• UA is a poor test to rule in UTI presence• Negative UA results for pyuria in most patients has a high NPV for bacteriuria • Reflex culture from UA results may reduce unnecessary cultures in those with

negative results, but on the flip side may increase culturing rates in those with asymptomatic bacteriuria leading to increased antibiotic use

• Clinical discretion is still needed to determine the presence of infection vs. asymptomatic colonization

• Improve appropriate ordering of UA and cultures • Symptomology is the best way to discriminate UTI vs. ASB

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When to Treat Without Routine Testing

Testing• Meta-analysis

• Women with ≥ 2 symptoms of UTI with absence of vaginal discharge

• 90% probability of acute cystitis

• Urinalysis unlikely to improve further likelihood of true infection

• Prospective study from VA cohort assessing urine cultures and antibiotic use

• High-count culture growth without symptoms associated with antibiotic (OR 22.1, p < 0.05)

• 13% (43/351) of patients with urine cultures performed had UTI symptoms

Grigoryan L. JAMA. 2014; 312(16): 1677-84.Drekonja DM. Infect Control Hosp Epidemiol. 2014; 35(5): 574-76.

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TREATMENT

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Resources Available

• Infectious Diseases Society of America (IDSA) • ASB Guidelines: http://cid.oxfordjournals.org/content/40/5/643.full.pdf+html• CAUTI Guidelines: http://cid.oxfordjournals.org/content/50/5/625.full.pdf+html• Uncomplicated UTI: http://cid.oxfordjournals.org/content/52/5/e103.full.pdf+html

• American Academy of Pediatrics (AAP)• UTI guidelines:

http://pediatrics.aappublications.org/content/early/2011/08/24/peds.2011-1330

• Local antibiogram data + evidence to create empiric treatment guides/pathways

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Antibiotic Selection - CystitisUncomplicated Cystitis• Organisms

• E. coli – 81%

• Staphylococcus saprophyticus – 5%

• Proteus mirabilis – 3%

• Enterobacter aerogenes – 2%

• Klebsiella pneumoniae – 2%

• Enterococcus spp. – 1%

• Lower rate of antibiotic resistance• Bactrim resistance may be high

IDSA Recommended Treatment

• Nitrofurantoin

• Fosfomycin

• Bactrim (Avoid if local resistance > 20%)

• Alternatives:

• Beta-lactams

• Fluoroquinolones (Increasing resistance and side effects)

Moffett SE. Am J Emerg Med. 2012; 30(6): 942-9. Mazzulli T. Can J Urol. 2012; 19(S1): 42-8.Gupta K. Clin Infect Dis. 2011; 52(5): 103-20.

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Case ScenarioWhich of the following choices is NOT an appropriate empiric antibiotic selection for uncomplicated cystitis in otherwise healthy, young, ambulatory female patient.

A. Bactrim 1DS PO BID x 3 days

B. Nitrofurantoin 100mg PO BID x 5 days

C. Fosfomycin 3g PO x 1 dose

D. Ciprofloxacin 250mg PO BID x 3 days

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Fluoroquinolone Use – FDA Cautions Use in Uncomplicated Infections

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Summary of Treatment Selection OutcomesDosing Duration Clinical Cure Bacterial Cure

Nitrofurantoin(monohydrate/macrocrystals) 100mg BID 5 days

7 days90%

93-95%92%86%

SMZ/TMP 1DS BID 3 days7 days

90-100%86-95%

91-100%85-93%

Fosfomycin 3gm x 1 1 day 83-95% 78-98%

Ciprofloxacin 250mg BID 3 days7 days(NF)

89-95%84%

88-92%87%

Levofloxacin 250mg QD 3 days - 83%Cephalexin

Cefpodoxime

250-500mg 4x/day

100mg BID

5 days7 days3 days

91%94%98%

83%82%98%

Grigoryan L. JAMA. 2014; 312(16): 1677-84. Menday AP. Int J Antimicrob Agents. 2000; 13(3): 183-7Gupta K. Clin Infect Dis. 2011; 52(5): 103-20. Vachhani AV. Infez Med. 2015; 23(2): 155-60.Elhanan G. Antimicrob Agents Chemother. 1994; 38(11): 2612-4.

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5 days Nitrofurantoin vs. Single-Dose FosfomycinHuttner et al. – JAMA. 2018• Multinational, open-label, randomized trial of nonpregnant women ≥ 18 years

old with uncomplicated cystitis• Randomized 1:1 to nitrofurantoin (NF) 100mg TID or fosfomycin (FM) 3g once• Primary endpoint = clinical response at day 28• Results:

• Median age = 43 & 46 years; Positive cultures in 75-80% (E. coli only 57-65%)

• Primary outcome of response at day 28: 70% NF vs. 58% FM (p=0.004)• Bacteriologic success at through day 28: 74% NF vs. 63% FM (p=0.04)• Duration of symptoms (4 vs 3 days) and progression to pyelo (0.4% vs. 1.6%) were NS

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What to Pick Considerations:

• Patient factors (allergies, kidney fxn, prior infections, etc.)

• Guidelines/Efficacy for treatment

• Local epidemiology/resistance

• Avoid Bactrim empirically

• Tolerability/Safety

• Avoid Fluoroquinolones

• Cost

• Fosfmoycin $$$

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Antibiotic Selection - PyelonephritisUncomplicated Pyelonephritis• Organisms

• E. coli – 85.4%

• Klebsiella spp. – 4.7%

• S. saprophyticus – 2.3%

• Enterococcus spp. – 1.9%

• Streptococcus agalactiae – 1.9%

• Proteus mirabilis – 1.4%

IDSA Recommended Treatment • Initial parenteral antibiotic

• IV/PO fluoroquinolone• Not requiring hospitalization

• Local resistance prevalence < 10%

• Ceftriaxone

• Consolidated dose aminoglycoside

• Oral antibiotic therapies• Fluoroquinolone

• Cephalosporin

• Bactrim – if susceptiblePeterson J. Clin Ther. 2007; 29(10): 2215-21. Gupta K. Clin Infect Dis. 2011; 52(5): 103-20.

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QuestionIn most patients without significant complications (stones, stents, etc.) what is the most appropriate duration of antibiotics for pyelonephritis?A. 5-7 daysB. 10 daysC. 14 days

Should patients with uncomplicated bacteremia 2/2 pyelonephritis receive longer antibiotic duration?A. YesB. No

For those with pyelonephritis (with or without bacteremia) initially managed with IV antibiotics, would you feel comfortable transitioning to non-fluoroquinolone PO treatment?A. YesB. No

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Summary of Treatment Selection Outcomes

Grigoryan L. JAMA. 2014; 312(16): 1677-84. Menday AP. Int J Antimicrob Agents. 2000; 13(3): 183-7Gupta K. Clin Infect Dis. 2011; 52(5): 103-20. Vachhani AV. Infez Med. 2015; 23(2): 155-60.Elhanan G. Antimicrob Agents Chemother. 1994; 38(11): 2612-4. Vouloumanou EK. Curr Med Res Opin. 2008; 24(12): 3423-34.Tamma PD, et al. JAMA Intern Med. 2019; epub

Antibiotic Dosing Duration Clinical Cure Bacterial Cure

Ciprofloxacin 500mg BID 7 days14 days

97%96% ___

LevofloxacinCiprofloxacin

750mg daily500/400mg daily

5 days10 days

83%79%

80%78%

CiprofloxacinTMP/SMX

500mg daily1 DS tab daily

7 days14 days

96%83%

99%89%

CeftriaxoneCeftriaxone/cefditoren

2g daily2g/400 mg daily

10 days10 days

95%100%

64%60%

Following initial IV antibiotics, transition to active PO antibiotic is not associated with differences in outcomes (Including beta-lactams)

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Presence of Bacteremia and Impact on Duration

Eliakim-Raz N, et al. J Antimicrob Chemother. 2013; 68: 2183-91.

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Yahav D, et al. Clin Infect Dis. 2018; epub ahead of print

Duration of Antibiotics in GN BacteremiaDesign/Methods

• Prospective, randomized, multicenter, open-label, non-inferiority trial• Hospitalized, monomicrobial bacteremia secondary to Gram-negative organism

• Exclusion: immunosuppression, uncontrolled focus of infection, Brucella spp. or Salmonella spp.

• Randomized at day 7 to short course (7 days) or long course (14 days) antibiotic therapy• Primary endpoint: composite of all-cause 90-day mortality, failure, re-admission, extended hospital stay

Baseline Characteristics• N=604 included for short (n=306) and long (n=298) antibiotic duration• No major differences; UTI source (68%), Enteric GNRs (90%), Resistant organism (18%)

Results (short vs. long duration)• Primary: 45.8% (140/306) vs. 48.3% (144/298); difference -2.6, 95% CI -10.5 – 5.3• Secondary: 90-day mortality = 11.8% vs. 10.7%; Relapse = 2.6% vs. 2.7%

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Oral Step Down in Bacteremic PatientsTamma PD, et al. JAMA Intern Med. 2019; epub ahead of print• Retrospective, multicenter, propensity matched cohort of hospitalized patients with monomicrobial

Enterobacteriaceae bacteremia comparing IV only vs. IV to Oral antibiotic switch

• N=739 matched patients per group, mostly UTI source (40%) followed by GI source (20%)

• Median duration of IV therapy in PO group = 3 days with total median duration of 14 days in both groups

• Highly bioavailable agents used in 83.5% (mostly fluoroquinolones)

• 30-day all cause mortality = 13.1% PO vs. 13.4% IV; HR 1.03; 95% CI, 0.82-1.3

Mercuro NJ, et al. Int J Antimicrob Agents. 2018; 51(5): 687-92.• Retrospective comparison of PO step down to beta-lactam (BL, n=84) vs. fluoroquinolone (FQ, n=140) in

patients with Enterobacteriaceae bacteremia

• Results: Clinical success: BL-86.9% vs. FQ-87.1% (p=0.96)

• 30-day all cause mortality: BL-1.2% vs. FQ-0.7%

• BL better tolerated vs. FQ (p=0.05)

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Take Home Points - Pyelonephritis• Empiric antibiotic selection guided by patient characteristics, local

epidemiology, previous infection history, and formulary

• Empiric fluoroquinolones should be avoided when local resistance is > 10%

• Empiric ceftriaxone or extended-interval aminoglycosides preferred initial therapy

• With clinical improvement and organism identification/susceptibilities, consider step-down to appropriate PO therapy (Beta-lactams are appropriate)

• Presence of bacteremia without other complicating features does not impact overall course in choosing PO step-down therapy or overall duration

• Duration of therapy should generally not exceed 7 days

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Antibiotic Selection - cUTIComplicated UTI• Definition:

• Anatomic/functional abnormality

• Presence of foreign body

• Impaired host immunity• Immunosuppression, transplant, diabetes, pregnancy

• Recent antibiotic use/recurrent UTI

• Male

• Recent urologic procedure

• Identified Organisms• E. coli – 56.5%

• Klebsiella pneumoniae – 12.9%

• Enterococcus faecalis – 7.5%

• Citrobacter spp. – 4.5%

• Proteus mirabilis – 3.9%

• Enterobacter spp. – 3.9%

• Pseudomonas aeruginosa – 1.9%

• Staphylococcus aureus – 1.3%

• Resistance more frequentPeterson J. Clin Therap. 2007; 29: 2215-21.Mazzulli T. Can J Urol. 2012; 19(S1): 42-8.

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Antibiotic Resistance cUTIElderly patients with UTIs• Retrospective case series

• 435 patients with UTI, 37% had MDR bug

• Risk factors for MDR pathogen• Urinary catheter: OR 2.6; 95% CI, 1.4-4.8

• Age ≥ 65 years: OR 3; 95% CI 1.7-5.4

• Antibiotic use: OR 4.6; 95% CI 2.8-7.5

• Urine E. coli isolates from nursing home• 60% Fluoroquinolone resistant

• 27% Bactrim resistant

05

101520253035

2000 2003 2006 2010

% R

esis

tanc

e

Year

Adult, 16-64yGeriatric, ≥65y

Wright SW. Am J Emerg Med. 2000; 18(2): 143-6. Das R. Infect Control Hosp Epidemiol. 2009; 30(11): 1116-19.Sanchez GV. J Antimicrob Chemother. 2013; 68: 1838-41.

Outpatient Ciprofloxacin Resistance

00.5

11.5

22.5

33.5

4

2000 2003 2006 2010

% R

esis

tanc

e

Year

Adult, 16-64yGeriatric, ≥65y

Outpatient Ceftriaxone Resistance

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Take Home Points - cUTI• Utilize local resistance patterns and risk factors when selecting empiric therapy

• Those at high risk of resistant pathogens (prior history of MDR pathogen, severe sepsis/shock, transplant, resident of nursing home/long-term care facility, recent antibiotic use/hospitalization)

• Provide empiric antibiotic therapy with anti-pseudomonal activity and broad gram-negative activity (based on hospital antibiogram)

• Complicated UTIs without above risk factors

• Consider initial parenteral therapy (i.e. ceftriaxone) with change to orally active agents once susceptibilities available

• Consider agents recommended for uncomplicated cystitis

• Short course (3 day) therapies should be avoided in most instances

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Managing CAUTI• Remove catheters prior to treatment

• Shorter time to afebrile status, improved clinical status at 72 hours, and lower relapse vs retained catheter, p < 0.015

• Treatment• Single dose Bactrim vs 10 days of Bactrim – no difference

• Outcomes for single-dose improved in women ≤ 65 years old

• Mild CAUTI – similar clinical cures at 3 vs 10 (TMP/SMZ) vs 14 (Cipro) days

• Complicated UTI or pyelonephritis study, n=68 catheterized patients• Microbiologic eradication:

• Levofloxacin 750mg daily x 5 days – 79%

• Ciprofloxacin 500mg BID x 10 days – 53% (95% CI, 3.6-47.7)

Raz R. J Urol. 2000; 164(4): 1254-8. Hooton TM. Clin Infect Dis. 2010; 50: 625-63.Peterson J. Urology. 2008; 71(1): 17-22.

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Treatment Duration for CAUTI – IDSA

Recommended Durations• 3 days

• Women ≤ 65 years old, catheter out, and no upper urinary tract findings

• 5 days• Non-severe presentation, fluoroquinolone used (levofloxacin studied)

• 7 days• Rapid improvement (within 2-3 days) and outside above criteria

• 10-14 days• Delayed improvement, bacteremic, severe presentation

Hooton TM. Clin Infect Dis. 2010; 50: 625-63.

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PREVENTATIVE STRATEGIES

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Prevalence of CAUTI• National Prevalence in 2013, 2.6 per 1,000 urinary catheter days

• Up 6% from 2009

• 65-70% of CAUTIs are preventable

• Prevention translates to • ~95,000-380,000 fewer infections

• ~2,000-9,000 fewer deaths

• $115 million - $1.82 billion savings

• Collateral damage reduction from fewer antibiotic doses

Risk Factors for CAUTIsModifiable Non-modifiableDuration of catheterization Female sex

Non-adherence to aseptic catheter care

Severe underlying illness

Lower training of inserter Nonsurgical disease

Insertion outside OR Aged >50y, diabetes, creatinine >2mg/dL

Dudeck MA. Am J Infect Control. 2015; 43: 206-21.Umscheid CA. Infect Control Hosp Epidemiol. 2011; 32(2): 101-14.

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Steps in Prevention

Placement

• Avoid unnecessary use (21-50% inappropriate) • Institutional protocols for placement• Alternatives (condom, intermittent catheterization)

Care

Aseptic/sterile insertion/hand hygieneClosed system and gravity drainageMultidisciplinary, evidence-based practices

Removal

• Early removal• Daily assessment and reminders• Nurse directed removal

Colonization of catheters occurs at a rate of 5% per day after 48 hours

Saint S. Am J Infect Control. 2000; 28(1): 68-75. Hooten TM. Clin Infect Dis. 2010; 50: 625-63.Chenoweth CE. Infect Dis Clin Am. 2014; 105-19. Trautner BW. Cur Opin Infect Dis. 2010; 23(1): 76-82.

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Avoidance StrategiesReducing indwelling urinary catheters• UCH Quality Improvement Initiative

• Pre/post implementation assessment

• Focus groups held to determine current practices and barriers

• Evidence-based, decision support tool developed and distributed to ED nurses and EMTs with education and steps taken to minimize identified barriers

Scott RA. J Emerg Nurs. 2014; 40(3): 237-44.

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Minimizing Duration

Nursing Directed Interventions• Nursing identified patients with inappropriate urinary catheters

• Discontinuation of catheter recommended to provider

• Reported outcomes:• CAUTI rates significantly declined, 28-100% reduction

• Significant decreased catheter use duration , average 20-79% fewer days

Informatics Led Interventions• Indications required for ordering and reminders in CPOE system

• CAUTI rates decreased, 6-76% reduction

• Significant decreased catheter duration , average 38-73% fewer days

Bernard MS. Urol Nurs. 2012; 32(1): 29-37.

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Case QuestionWhat is the one of the most effective strategies to reduce the frequency of recurrent UTIs?A. Increased water intakeB. Continuous low-dose antibiotic prophylaxisC. Cranberry D. Probiotics

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Continuous Antibiotic ProphylaxisFisher H, et al. Lancet Infect Dis. 2018; 18(9): 957-68.• Randomized, open-label, superiority trial to compare daily low-dose antibiotic

prophylaxis vs. no prophylaxis for 12 months with recurrent UTIs (≥ 2 episodes or ≥ 1 hospitalized episode in last year)• Nitrofurantoin 50mg, trimethoprim 100mg, or cephalexin 250mg

• 61-65% had ≥ 4 episodes per year, 99% self catheterized• Frequency of symptomatic antibiotic treated UTIs fell from 2.6->1.3 (p<0.0001)

• Febrile UTIs were not significantly different between groups (0.11 vs. 0.16, p=0.24)

• Side effects more common (9% vs. 2%) with prophylaxis, and recovery of resistance to prophylactic agent higher vs. control (p=0.038)

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Effect of Increased Water Intake on UTI

Hooton TM, et al. JAMA Int Med. 2018, Oct. 1 – epub ahead of print• Randomized, open-label, controlled, 12-month study comparing increased daily

water intake (added 6 glasses over usual intake) vs. usual daily intake• Included 163 health, pre-menopausal women with recurrent cystitis (≥ 3

episodes/year)• Primary outcome: frequency of recurrent cystitis over 12 months• Results:

• Mean 24-hour urine volumes increased by 1.3L in the water group (p< 0.001), with increased innumber of voids per day (8.2 vs. 5.9, p < 0.001) and decreased osmolality

• Mean number or recurrent episodes decreased significantly in the water group (1.7 vs. 3.2, p <0.001)

• Mean number of antibiotic courses for cystitis decreased in water group (1.9 vs. 3.6, p< 0.001)

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Summary of Prevention MeasuresPreventative Measure Evidence Comments/Recommendation

Behavioral Recent sexual intercourse and use of spermicides increases UTI risk

Avoid spermicides. No direct evidence, but consider counseling pre- and post-intercourse voiding.

Fluid Increasing water intake increases urine voiding, which decreases UTIs

Low risk for most with potential high reward in preventing recurrent UTI

Cranberry Evidence is mixed – some positive and others not different vs. placebo

Most beneficial studies in women with recurrent UTIs. Low risk profile compared to other options.

NSAIDs No evidence for prevention, mixed findings for cystitis treatment

Use in uncomplicated cystitis associated with longer duration of symptoms and higher incidence of pyelo

Antibiotics Continuous and post-coital prophylaxis shown to reduce UTI

Risks = resistance, side effects, C. difficile infection

Probiotics Mixed data related to heterogeneity of probiotic formulations/routes studied

L. rhamnosus GR-1 and L. reuteri RC-14 have more consistently shown reduction in UTI vs. other strains.

Methenamine Effective in preventing recurrent UTI Minimal side effects and no risk of antibiotic resistance. Caution in renal impairment.

Estrogen Vaginal estrogen preparations show significantly lower rUTI rates

Post-menopausal women. Cream may be slightly more effective than rings or pessaries.

D-Mannose Prevents bacterial colonization. One small RCT showed lower rUTI rates.

More data needed, but appears promising for prevention of rUTI with fewer side effects than daily nitrofurantoin.

Sihra N, et al. Nat Rev Urol. 2018; epub.

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Conclusion and Stewardship OpportunitiesOptimize Diagnosis and Prevent Treatment of ASB• Judicious ordering of urine testing

Prevention• Increase water intake and avoid/limit daily prophylaxis when possible

Tailor Antibiotic Selections• Utilize local resistance patterns to guide empiric selections• Avoid fluoroquinolones if possible given propensity towards collateral damage (resistance, side effects,

and C. difficile infection)• Narrow therapy with organism identification and susceptibilities, step-down to PO in most cases

Appropriate Treatment Durations • Consider site of infection, antibiotic used, and patient characteristics

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Questions

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MANAGEMENT OF URINARY TRACT INFECTIONS

Matthew Miller, PharmD, BCPSInfectious Diseases Pharmacist / Clinical InstructorUniversity of Colorado Hospital / University of Colorado Skaggs School of PharmacyMatthew.Miller@UCHealth.org

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Symptoms in Elderly Fevers• Definition adjusted in elderly• Non-specific, high suspicion for infectious

etiologies

Delirium• Rate of 30-35% in elderly with UTI vs 7.7-8%

without UTI• Non-specific, other etiologies

• Dehydration, medications, comorbidities

Functional Status Decline• Non-specific, present in up to 77%

UTI Symptoms• Fever

• Dysuria, frequency, urgency

• Gross hematuria

• New/worsening incontinence

• Flank and/or suprapubic pain

Urine appearance/findings• In absence of symptoms, likely to be positive given

high prevalence of asymptomatic bacteriuria

• 10-50%

High KP. J Am Geriatr Soc. 2009; 57: 375-94Balogun SA. Can Geriatr J. 2014; 17(1): 22-26.

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Options for MDROsRecently approved therapies• Ceftolozane/tazobactam (Zerbaxa®)

• Ceftazidime/avibactam (AvyCaz®) • Meropenem/vaborbactam (Vabomere®)

• Plazomicin (Zemdri®)

Older Therapies• Broad-spectrum β-lactams (carbapenems, cefepime, ceftazidime, piperacillin-tazobactam)

• Aminoglycosides and polymyxins

• Combinations

Other Consideration• Complicated cystitis – fosfomycin 3g PO q48h x 3 doses

• Microbiology efficacy, 84% (26/31) and Clinical efficacy, 63% (42/67)

• Activity against vancomycin-resistant enterococci and ESBLsQiao LD. BMJ Open. 2013; 3: e004157.

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Team Effort on Antibiotic Duration

0

2

4

6

8

10

12

Q3-2015 Q4-2015 Q1-2016 Q2-2016 Q3-2016 Q4-2016 Q3-2017 Q4-2017 Q1-2018 Q2-2018

Med

ian

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s Ad

min

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red/

Pres

crib

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Antibiotic Duration for Hospitalized Urinary Tract Infections at UCH, 2015-2018

InpatientOutpatientTotalLinear (Total)

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