BEST PRACTICES FOR None WOMEN WITH UTI S Michelle Y. Morrill MD - - PowerPoint PPT Presentation

BEST PRACTICES FOR WOMEN WITH UTIS

Michelle Y. Morrill MD Director of Urogynecology, Kaiser San Francisco Assistant Professor, Volunteer Faculty, Department of ObGyn, UCSF

Disclosures

• None

Objectives

1) review guidelines for diagnosis and management of uncomplicated UTIs 2) discussion of evidence based recommendations for prevention of UTIs 3) diagnosis, work up and management of complicated UTIs (pyelonephritis, recurrent UTI, chronic UTI) 4) initial diagnosis, work up and management of non- infectious bladder pain

Sources

Gupta et al. International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women: A 2010 Update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clinical Infectious Diseases 2011;52(5):e103–e120 Endorsed by: American College of Obstetrics and Gynecology American Urology Association Society for Academic Emergency Medicine

Sources

Hooton TM. Uncomplicated Urinary Tract Infection. N Engl J Med 2012;366:1028-37. Foxman B. Urinary Tract Infection Syndromes Occurrence, Recurrence, Bacteriology, Risk Factors, and Disease

• Burden. Infect Dis Clin N Am 2014;28:1–13

Definitions

Urinary Tract Infection (UTI or cystitis)

• Positive urine culture and symptoms
• Urgency/frequency
• Dysuria
• Hematuria
• Urinary incontinence
• Suprapubic pain

Not a UTI

• Asymptomatic bacteriuria

Definitions

• Uncomplicated UTI
• A short course of antibiotics will usually (90% efficacy)

resolve clinical symptoms

• Recurrent UTI
• ≥ 3 UTI’s in 12 month period or ≥2 UTIs in 6 months
• Often reinfection with colonized bacteria
• *Same bacteria repeatedly (by sensitivities) may

indicate nidus in urinary tract / chronic UTI

Hooton TM. Uncomplicated Urinary Tract Infection. N Engl J Med 2012;366:1028-37.

Epidemiology

• ~50% of 32yo women report having had at least 1 UTI
• 25% of young healthy women will have a recurrence

within 6 month of their initial UTI episode

• 20% of women >65yo have asymptomatic bacteriuria

Hooton TM. Uncomplicated Urinary Tract Infection. N Engl J Med 2012;366:1028-37. Treatment of urinary tract infections in nonpregnant women. ACOG Practice Bulletin No. 91. American College of Obstetricians and Gynecologists. Obstet Gynecol 2008;111:785–94.

Microbiology

• 75-95% of Uncomplicated UTIs are cause by E.

coli

• Uropathogenic E. coli are a specific subset of

extraintestinal pathogenic E. coli that have the potential for enhanced virulence.

• But there are plenty of others: Enterobacter,

Klebsiella, Pseudomonas, Proteus, Streptococcus faecalis, Morganella, Staphylococcus, Chlamydia

Hooton TM. Uncomplicated Urinary Tract Infection. N Engl J Med 2012;366:1028-37.

Risk Factors for UTI

Catheters

• Cause 30-40% of nosocomial infections
• One catheterization  2% risk of bacteriuria
• Every day of an indwelling catheter  3-10% risk of

bacteriuria

• Only treat for symptoms
• Place indwelling cath only for clear indications

(not for incontinence)

• Antibiotic prophylaxis should not be done

routinely

Hooton TM, et al. Diagnosis, Prevention, and Treatment of Catheter-Associated Urinary Tract Infection in Adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clinical Infectious Diseases 2010; 50:625–663 Foxman B. Urinary Tract Infection Syndromes Occurrence, Recurrence, Bacteriology, Risk Factors, and Disease

• Burden. Infect Dis Clin N Am 28 (2014) 1–13

Risk Factors for UTI

• Gender (female)
• Menopausal status
• Intercourse
• New sex partner
• Previous urinary tract infection
• Hx of UTIs in a 1st degree relative

Hooton TM. Uncomplicated Urinary Tract Infection. N Engl J Med 2012;366:1028-37.

Not Risk Factors for UTI

• Post coital (or pre-coital) voiding
• Fluid intake
• Delaying voids
• Wiping patterns
• Type of underwear

Hooton TM. Uncomplicated Urinary Tract Infection. N Engl J Med 2012;366:1028-37.

Diagnosis of Cystitis

• Urgency/frequency
• Dysuria
• Hematuria
• Urinary incontinence
• Suprapubic pain
• Caution
• Recent UTI?
• Recurrent UTI?
• Not UTI?

Hooton TM. Uncomplicated Urinary Tract Infection. N Engl J Med 2012;366:1028-37.

Then check UA/Cx

Urinary Microbiome

• Urine is NOT sterile
• 16S rRNA
• Expanded Quantitative Urine Culture
• Positive urine culture =
• Dysbiosis

Brubaker L, Wolfe AJ. The new world of the urinary microbiota in women. Am J Obstet Gynecol. 2015 Nov;213(5):644-9.

Diagnosis of Cystitis - UA Diagnosis of Cystitis - UA

• Nitrite

Turner LC, et al. Utility of dipstick urinalysis in peri- and postmenopausal women with irritative bladder

• symptoms. Int Urogynecol J (2014) 25:493–497
• 87/148 (59%) women with pos LE or nitrite had pos UCx
• 63/66 with neg UCx were given Abx.

Gordon LB., et al. Overtreatment of Presumed Urinary Tract Infection in Older Women Presenting to the Emergency Department. J Am Geriatr Soc 61:788–792, 2013.

Sensitivity Specificity 0.61 1

Diagnosis of Cystitis - UA

• In patients with urgency/frequency
• Pyuria (>10 WBC /hpf) had negative LE in 60%
• Pyuria for predicting positive Urine Culture

Sensitivity Specificity 0.42 0.73

Kupelian AS, et al. Discrediting microscopic pyuria and leucocyte esterase as diagnostic surrogates for infection in patients with lower urinary tract symptoms: results from a clinical and laboratory evaluation. BJU Int. 2013 Jul;112(2):231-8

Diagnosis of Cystitis - UCx

• If patient is symptomatic any growth of 1 or 2

bacteria should be considered a positive result

• On ‘Contamination’
• Squamous cells in 99/105 cath samples but no samples

had bacterial ‘contamination’ (mixed growth or <10K)

• Squamous cells in 101/105 clean catch samples; 21%

had bacterial ‘contamination’.

Walter FG, et al. Squamous cells as predictors of bacterial contamination in urine

• samples. Ann Emerg Med 1998;31(4):455-8

Asymptomatic Bacteriuria

• No benefit in treating
• Institutionalized Elderly
• Ambulatory Elderly
• Premenopausal Women
• Diabetic Women
• Renal transplant patients
• Only group in which treatment is

recommended is pregnant women

Zalmanovici Trestioreanu A, LadorA, et al. Antibiotics for asymptomatic bacteriuria. Cochrane Database of Systematic Reviews 2015, Issue 4. Art. No.: CD009534. Origüen J, López-Medrano F , et al. Should Asymptomatic Bacteriuria Be Systematically Treated in Kidney Transplant Recipients? Results From a Randomized Controlled Trial. Am J Transplant. 2016 Oct;16(10):2943-2953

Asymptomatic Bacteriuria

• Common in older people
• Not associated with decline in renal

function

Meiland R, et al. Association Between Escherichia coli Bacteriuria and Renal Function in Women Long-term Follow-up. Arch Intern Med. 2007;167:253-257 Foxman B. Urinary Tract Infection Syndromes Occurrence, Recurrence, Bacteriology, Risk Factors, and Disease

• Burden. Infect Dis Clin N Am 28 (2014) 1–13

Asymptomatic Bacteriuria

Treatment may cause UTI?

• Cai T, Mazzoli S, et al. The Role of Asymptomatic Bacteriuria in Young Women With

Recurrent Urinary Tract Infections: To Treat or Not to Treat? Clinical Infectious Diseases 2012;55(6):771–7

• 673 women 18-40yo randomized to Abx vs.

no Tx

• At 12 months 47% in the Abx vs. 13% in no

Tx had symptomatic UTI (P<.0001)

Treatment of Uncomplicated UTI Treatment of Uncomplicated UTI

Collateral Damage: ecological adverse effects of abx

• Selection of drug resistant bacteria
• Colonization or infection with multi-drug resistant

bacteria

Possibly due to effect on fecal flora

• Fluoroquinolones
• Broad spectrum cephalosporins
• Trimethoprim
• Ampicillin

International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women

Treatment of Uncomplicated UTI

2 reasons to consider collateral damage in choosing antibiotic treatment

1) minimal risk of progression (<1% progress to pyelo) spontaneous resolution in 25%–42% of women 2) UTI is common use for Abx many small increments amplify collateral damage

International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women Foxman B. Urinary Tract Infection Syndromes Occurrence, Recurrence, Bacteriology, Risk Factors, and Disease Burden. Infect Dis Clin N Am 28 (2014) 1–13

Treatment of Uncomplicated UTI

Nitrofurantoin monohydrate/macrocrystals 100 mg bid X 5 days Minimal risk of ‘collateral damage’ Avoid if pyelonephritis suspected Considerations: ≥64yo, renal insufficiency Trimethoprim-sulfamethoxazole (one DS tablet) bid X 3 days Note increasing resistance Fosfomycin 3 gm single dose (mix powder in ½ cup water) Minimal risk of ‘collateral damage’ Avoid if pyelonephritis suspected

International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women

Second Line Tx of Uncomplicated UTI

Fluoroquinolones x 3 days Propensity for collateral damage Should be reserved for uses other than acute cystitis Longer course has large increase in AE with same efficacy

International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women

FDA Fluoroquinolone Warning

• Associated with disabling and potentially permanent side

effects of the tendons, muscles, joints, nerves, and central nervous system

• For some serious bacterial infections the benefits of

fluoroquinolones outweigh the risks, and it is appropriate for them to remain available as a therapeutic option.

• Health care professionals should not prescribe systemic

fluoroquinolones to patients who have other treatment

• ptions for acute bacterial sinusitis, acute bacterial

exacerbation of chronic bronchitis, and uncomplicated urinary tract infections because the risks outweigh the benefits in these patients.

Second Line Tx of Uncomplicated UTI

Fluoroquinolones x 3 days Propensity for collateral damage Should be reserved for uses other than acute cystitis Longer course has large increase in AE with same efficacy β-lactams Generally have inferior efficacy and more adverse effects, compared with other UTI antimicrobials

• Does this include cephalexin?

International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women

Other Treatment Considerations

• Phenazopyridine
• Urinary pain reliever
• Nitrite positive (or UA indeterminate)
• Bladder pain may persist after infection is treated
• Clinical efficacy of any antibiotic regiment ~90%

So check UA/Cx for persistent or recurrent Sx

Foxman B. Urinary Tract Infection Syndromes Occurrence, Recurrence, Bacteriology, Risk Factors, and Disease

• Burden. Infect Dis Clin N Am 28 (2014) 1–13

Diagnosis of Pyelonephritis

• fever
• chills
• flank pain
• CVA tenderness
• nausea or vomiting

For any suspicion of pyelo always collect UA/Cx before starting antibiotics

• urgency/frequency
• dysuria
• hematuria
• urinary incontinence
• suprapubic pain

Outpatient Treatment of Pyelonephritis

• ciprofloxacin 500 mg PO bid x7d
• May add initial one dose IV agent
• Ciprofloxacin 400mg
• Ceftriaxone 1 g of ceftriaxone
• Consolidated 24-h dose of an aminoglycoside
• trimethoprim-sulfamethoxazole (DS) PO bid x14d
• Recommended to add initial one dose IV agent if sensitivities are

unknown

• β-lactam agents are less effective than other agents
• Recommended to add initial one dose IV agent

International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women

Outpatient Treatment Of Pyelonephritis

• What does standard of care treatment achieve?
• In women receiving 7 days of ciprofloxacin for

pyelonephritis, 6% had another symptomatic UTI within 30 days

• (as did 7% of women treated with TMP-SMX for 7d)
• 2 patients in ciprofloxacin group developed C difficile
• 1 patient in TMP-SMX group developed a rash

Fox MT, Melia MT, Same RG, Conley AT, Tamma PD. A Seven-Day Course of TMP-SMX May Be as Effective as a Seven-Day Course of Ciprofloxacin for the Treatment of Pyelonephritis. Am J Med. 2017 Jul;130(7):842-845

Inpatient Treatment of Pyelonephritis

• When unable to tolerate PO
• IV antibiotics
• Fluoroquinolones
• aminoglycoside, with or without ampicillin
• extended-spectrum cephalosporin or extended-

spectrum penicillin, with or without an aminoglycoside

• Carbapenem (ertapenem)

International Clinical Practice Guidelines for the Treatment of Acute Uncomplicated Cystitis and Pyelonephritis in Women

Yeast on urine micro or culture?

If asymptomatic then no further workup or treatment is indicated If pt has UTI symptoms check a new urine specimen

• Clean catch OK, cath if not possible.
• If indwelling cath present, change and collect new

specimen

• If immunocompromised she may not be able to mount a

response that would cause UTI symptoms

• If critically ill, yeast in urine may be a marker of

fungemia  collect blood cultures

Kaufman CA, et al. Candida Urinary Tract Infections—Diagnosis. Clinical Infectious Diseases 2011;52(S6):S452–S456

Recurrent UTIs

• Recurrent cystitis should be managed with

prophylactic antimicrobial therapy only when nonantimicrobial preventive strategies are not effective.

Hooton TM. Uncomplicated Urinary Tract Infection. N Engl J Med 2012;366:1028-37.

Prevention

1) Vaginal Estrogen

• Post-menopausal women are at significantly increased

risk of urinary tract infection

• Oral estrogen does not protect
• Brown JS, et al. Urinary tract infection in postmenopausal women: effect of hormone

replacement therapy and risk factors. Obstet Gynecol 2001;98(6):1045-52

• Vaginal estrogen does protect
• Estring: Eriksen B. A randomized, open, parallel-group study on the

preventative effect of an estradiol-releasing vaginal ring (Estring) on recurrent urinary tract infection in postmenopausal women. AJOG 1999;180(5):1072-9.

• Cream: Raz R, Stamm WE. A controlled trial of intravaginal estriol in postmenopausal

women with recurrent urinary tract infection. NEJM 1993;329(11):802-3.

Prevention

2) Cranberry

• 28 studies in 4,947 patients: significant reduction

in the risk of repeat UTIs with cranberry

• WRR = 0.68, 95% CI 0.55-0.80, p <0.0001
• Inhibits binding of E coli to urothelium
• Juice or capsules but pts tend to stop drinking

juice

Luís Â, Domingues F, Pereira L. Can Cranberries Contribute to Reduce the Incidence of Urinary Tract Infections? A Systematic Review with Meta-Analysis and Trial Sequential Analysis of Clinical Trials. J Urol. 2017 Sep;198(3):614-621.

Prevention

2) Cranberry

Foxman B, et al. Cranberry juice capsules and urinary tract infection post surgery: Results of a randomized trial. Am J Obstet Gynecol. 2015;213(2):194.e1-194.e8.

• Randomized patients post-op to cranberry

capsules vs. placebo bid x6w

• UTI definition: clinically diagnosed and treated
• UTIs
• 19% in Cranberry group
• 38% in Placebo group p=0.008

Prevention

3) Probiotics Cochrane review: “benefit cannot be ruled out … limited

information on harm and mortality … no evidence on the impact of probiotics on serious adverse events… cannot rule out a reduction or increase in recurrent UTI in women with recurrent UTI … insufficient evidence from one RCT to comment on the effect of probiotics versus antibiotics.”

Schwenger EM, Tejani AM, Loewen PS. Probiotics for preventing urinary tract infections in adults and children. Cochrane Database Syst Rev. 2015 Dec 23;(12):CD008772.

Prevention

3) Probiotics

• Vaginally place L. crispatus significantly

decreased recurrent UTI (27%  15%) in young women after 1 UTI

Stapleton AE, et al. Randomized, placebo-controlled phase 2 trial of a Lactobacillus crispatus probiotic given intravaginally for prevention of recurrent urinary tract infection. Clin Infect Dis. 2011 May;52(10):1212-7.

• Vaginally placed L. rhamnosus and L. reuteri

decreased recurrent UTIs (although not oral dosing)

Reid G, Bruce AW. Probiotics to prevent urinary tract infections: the rationale and evidence. World J

• Urol. 2006 Feb;24(1):28-32.

Oh…And….Umm… Prevention - Antibiotics

• Methenamine (add vitamin C)
• Lee BSB, Bhuta T, Simpson JM, Craig JC.Methenamine hippurate for preventing urinary tract
• infections. CochraneDatabase of Systematic Reviews 2012, Issue 10. Art. No.: CD003265.
• Post-coital or Fixed Dosing

Daily Nitrofurantoin 100mg Trimethoprim 100mg Cephalexin 250mg Less than Daily TPM-SMX 40/200 tiw Fosfomycin 3g q 10d

Lichtenberger P , Hooton TM. Antimicrobial prophylaxis in women with recurrent urinary tract infections. International Journal of Antimicrobial Agents 38S (2011) 36–41

Recurrent UTI Management

• Standing UA/Cx
• Prevention strategies
• Cranberry bid
• Vaginal estrogen on peri or post-menopausal
• Vaginal probiotics
• Antibiotic prophylaxis

Recurrent UTI Management

• Referral to FPMRS specialist

*Same bacteria repeatedly (by sensitivities) may indicate nidus in urinary tract / chronic UTI

A special note about…

Hematuria, frequency, urgency, pyuria, pelvic pain, suprapubic pain Also sound like Bladder Pain Syndrome

Bladder Pain Syndrome

Symptomatic diagnosis based on the presence of three key symptoms: pain, urgency, and frequency, as well as exclusion of a short list of other conditions that cause the same symptoms.

• Epidemiology of Interstitial Cystitis Interstitial Cystitis Epidemiology

Task Force Meeting NIDDK Executive Committee Summary and Task Force Meeting Report 2003

Bladder Pain Syndrome Diagnosis

An unpleasant sensation (pain, pressure, discomfort) perceived to be related to the urinary bladder, associated with lower urinary tract symptoms of more than six weeks duration, in the absence of infection or other identifiable causes.

Hanno P and Dmochowski R: Status of international consensus on interstitial cystitis/bladder pain syndrome/painful bladder syndrome: 2008 snapshot. Neurourology and Urodynamics 2009; 28: 274.

Treatment: First steps

1) Identify and avoid

Bladder Irritants

2) Ibuprofen +/-

acetaminophen

3) Phenazopyridine

(Azo Standard or Uristat)

So…

• Prevent
• Minimize indwelling catheter
• Diagnose
• Symptoms
• Watch for frequent episodes
• Limitations of urinalysis and culture
• Treat
• Appropriate selection of antibiotics
• Prophylaxis
• Cranberry, Estrogen, Probiotics, Antibiotics (as last resort)

Consider

• Is this a Recurrent UTI?
• Are we optimizing non-antibiotic prophylaxis?
• Is this the same bacteria over and over?
• Is this not a UTI?

Thank you!

• Questions?