Urinary Tract Infections: From Pyelonephritis to Asymptomatic Bacteriuria. Leslee L. Subak, MD

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1 Urinary Tract Infections: From Pyelonephritis to Asymptomatic Bacteriuria Leslee L. Subak, MD Professor Obstetrics, Gynecology & RS Epidemiology & Urology University of California, San Francisco UTI Prevalence Most common outpatient infection 8.6 million physician visits/year 50% of women 0.7 UTI / sexually active woman / year 0.07 UTI / postmenopausal woman / year 25% recur after first UTI 1 case Pyelo for every 28 UTI s $2 billion / year

UTI Classification Uncomplicated acute cystitis and pyelonephritis Healthy Premenopausal Non- pregnant women no history of an abnormal urinary tract Complicated UTI

2 UTI Classification Uncomplicated acute cystitis and pyelonephritis Healthy Premenopausal Non- pregnant women no history of an abnormal urinary tract Complicated UTI Microbiology Ascending infection E. coli (75-95%) Enterobacteriaceae (Klebsiella pneumoniae) Gram +: Staph. Saprophyticus Enterococcus, Group B Strep Older women: non - E. coli

3 UTI Risk Factors Younger women: Sexual intercourse New sex partner Spermicide use Previous UTI Pregnancy UTI 1 st degree female relative Older women: Diabetes, insulin Rx Lifetime h/o UTI Nursing home functional/mental status Bladder catheter Neurogenic bladder Risk Factors No evidence for UTI Risk Factor Pre- or post-coital voiding Urinary frequency, delayed voiding Fluid consumption Wiping Tampon use Douching Type of underwear BMI

4 Symptoms UTI Dysuria Frequency Urgency Suprapubic pain Hematuria Pyelonephritis Fever (T>38 C) Chills Flank pain Costovertebralangle tenderness Nausea, vomiting +/- UTI symptoms Think UTI > 90% probability UTI Dysuria, frequency, urgency Acute onset symptoms No vaginal discharge Unlikely UTI Vaginal discharge / irritation Bent JAMA 2002, Stamm NEJM 1993

5 Dipstick Urine Analysis Leukocytes - most valuable Blood - common LE + or Nitrite + Sensitivity: 75% Specificity: 82% LE - and Nitrite - Neg predictive value: 95% Bent Jama 2002; Hurlbut Am J Clin Path 1991; Deville 2004; Wilson 2004 Urine Culture Confirm presence of bacteriuria and antimicrobial susceptibility Positive if symptoms Traditional Criteria in voided urine: - UTI: > 10 5 CFU/ ml % of UTI s have 10 2 to 10 4 CFU/ml Most labs do not quantify below 10 4 CFU/ml - Interpret no growth in a woman with urinary symptoms with caution Bent JAMA 2002; Hooton Inf Dis Clin N Am 2003; Stamm NEJM 1993

6 Urine Culture Usually not needed Suspect Pyelo: Fever, chills, flank pain Atypical symptoms Persistent symptoms/new Rx Pregnancy Post treatment TOC not needed UTI Diagnosis Cost-effectiveness analysis Empiric Abx, dipstick UA, Cx Empiric Abx most cost-effective Dipstick UA if: Cost of Abx > $74 Prior probability of UTI < 30% Barry 1997; Fenwick 2000

7 Urine Culture Technique 242 women with UTI Sx randomized - Simple urination, clean container - Clean-catch, midstream urination - Above plus tampon in vagina Contamination rates for 3 groups the same (30%) Lifshitz 2000 UTI Treatment Rare progression to pyelo Morbidity of sx Antibiotics rapid resolution of sx antimicrobial resistance Infectious Diseases Society of America (IDSA) guidelines, consider ecologic adverse effects of antimicrobial agents collateral damage Gupta Clin Infect Dis 2011

8 Choosing optimal antimicrobial agent for empirical treatment of acute uncomplicated cystitis Gupta K et al. Clin Infect Dis. 2011;52:e103-e120 UTI Treatment Nitrofurantoin monohydrate macrocrystals 100 mg BID x 5 days TMP-SMX 160 mg-800 mg BID x 3 days Fosfomycin trometamol (Monurol) 3-g sachet x 1 Ciprofloxacin 250 mg BID or levofloxacin 250 mg or 500 mg QD x 3 days Beta-lactams (amoxicillin clavulanate, cefdinir, cefaclor) x 3 to 7 days Gupta 2011, Hooton 2012

9 Telephone Management RCT 72 women with suspected UTI - Telephone group: empiric Rx (N=36) - Office group: seen by MD (N=36) All had UA and culture TMP/SMZ (nitrofuratoin) x 7 days Barry et al. J Fam Pract 2001 Exclusion Criteria Sx or Hx of pyelonephritis New vaginal discharge Diabetes STI UTI or ABX within 1 month Sx > 14 days Hx kidney disease, renal surgery or chemotherapy Barry et al. J Fam Pract 2001

10 Outcomes Office Telephone Urine Culture + 68% 61% UTI Score - baseline day day Barry et al. J Fam Pract 2001 UTI Treatment Avoid specific antibiotic IF prevalence of resistance in community is: >20% for TMP/SMX >10% for fluoroquinilones Gupta 2011; Hooton 2012

11 TMP-SMX Resistance Western US: 22% Eastern US: 10% Consider TMP-SMX: No prior failure Call if no change Consider Fluoroquinolone-sparing: Nitrofurantoin Gupta 2001; Hooton 2004 UCSF Antibiotic Resistance Outpatient urine samples E. Coli RESISTANCE: TMP-SMZ 25% 30% 31% Ciprofloxaxin 10% 20% 21% Cefazolin 5% 11% 20% Nitrofurantoin 5% 2% 3%

12 UTI Treatment Literature review of effectiveness 3 d more effective than 1 dose 3 d and > 7 d are similar Nitrofurantoin - 5 d course Warren 1999; Cochrane 2005; Katchman 2005 Literature Review of Effectiveness Treatment Eradication Recurrence TMP/SMZ DS Nitrofurantoin Adverse Effects 28 Ciprofloxacin Norfloxacin Ofloxacin Cefadroxil * 30 Amoxicilin 86* * p < 0.05 compared to TMP/SMZ, fluoroquinolones Hooton 2012, Warren 1999

13 UTI Treatment Older women: 7-day course Complicated: 7-day fluoroquinolone sx or h/o pyelo, DM, pregnancy, immunosupression sx > 14 days, urinary tract anomaly Pyridium 200 mg TID x 3 d for dysuria Recurrent UTI 3 infections per year 4% of women Re-infection rather than relapse > 2 weeks Does not lead to health problems Reassure patient

14 Recurrent UTI Pathology: same as acute cystitis Diagnosis: urine culture Rarely serious, easy treatment Urologic Work Up Rarely indicated Proteus: Think stones R/O nephrolithiasis Spiral CT or renal U/S

15 Recurrent UTI Treatment Behavioral Change Abstinence, frequency coitus Stop spermacide use No evidence but low risk: Void after intercourse Hydration do not delay urination antimicrobial soap wipe front to back after defecation avoid tight-fitting underwear avoid douching Recurrent UTI Prevention Cranberry juice or capsules Topical vaginal estrogen Adhesion blockers (D-mannose) Patient-initiated therapy for Sx Abx prophylaxis with coitus Low dose, continuous abx prophylaxis

16 Cranberry for Prophylaxis? Inhibition of uropathogen adherence to uroepithelial cells Ten RCT studies (n = 1049) Cranberry/cranberry-lingonberry juice or cranberry tablets versus placebo, juice or water Cranberry products incidence of UTIs at 12 months vs. control - RR 0.65 (95% CI 0.46, 0.90) dropouts/withdrawals? dosage or method of administration Jepson RG. Cochrane Database of Systematic Reviews 2008 Recurrent UTI - Older women Postmenopausal intravaginal estrogen Cream or ring Effective prophylaxis Improved cytologic maturation Acidifies vagina Changes vaginal flora Stamm 2007; Eriksoen 1999; Griebling 1997; Raz 1993

17 Postmenopausal Vaginal Estrogen RCT, Recurrent UTI, N=93 E3 Vaginal Placebo Cream Cream UTIs/woman / year Days Abx use/woman Vaginal lactobacililli 61% 0% Mean vaginal ph Vaginal E. coli 31% 63% Raz NEJM 1993 Vaginal Estrogen RCT of Estring, 108 women, recurrent UTI Significantly fewer UTI s More women UTI-free Lower vaginal ph Eriksen 1999

18 Post Coital Rx Prophylaxis after intercourse Nitrofurantoin mg TMP-SMX SS or SS TMP 100 mg Cephalexin 250 mg RCT of post-coital vs. daily Cipro Equal efficacy Post-coital Rx used 2/3 less drug Melekos 1997 Self-Diagnosis & Treatment Pt initiates Rx at onset of symptoms % accuracy with self-diagnosis - Call if not resolved in 48 hrs patient satisfaction antimicrobial exposure vs. continuous antimicrobial prophylaxis Periodic urine culture to confirm UTI and drug susceptibilities Never leave home without Abx! Goopta 2001; Shaaffer 1999; Stapelton 1997

19 Daily Prophylaxis Long-term prophylaxis x 6 months Decreased UTI by 95% vs. placebo Nitrofurantoin mg TMP/SMZ SS or DS, TMP 100 mg Cephalexin mg Can consider 1-2 yrs Nicolle 2008; Stapelton 1997 Recurrent UTI Prevention Key: Prevent recurrent infections Behavior change Cranberry juice or capsules Topical vaginal estrogen Patient-initiated therapy for Sx Abx prophylaxis with coitus Low dose, continuous abx prophylaxis What would you like to do?

20 Acute Pyelonephritis Most uncomplicated Rare: complicated or chronic, renal scarring or renal failure Flank pain, nausea, vomiting, fever, pyuria, hematuria Get urine culture (E. Coli 82%) Think PID.vaginal symptoms Pyelonephritis Acute, uncomplicated OUT-patient treatment Do urine culture and susceptibility Admit if: pyelonephritis is severe hemodynamic instability any complicating factor (DM, renal stone, pregnancy) oral medications are not tolerated concern about adherence Hooton 2012

21 Pyelonephritis Treatment CIPROFLOXACIN 500 mg PO BID or 1 g (extended release) PO QD x 7 days Consider Cipro 400 mg IV x 1 Ceftriaxone 1 gm IV x 1 LEVOFLOXACIN 750 mg PO QD x 5 days TMP-SMX 160 mg-800 mg PO BID x 14 days Oral beta-lactams x 10 to 14 days Hooton 2012; Gupta 2011 Asymptomatic Bacteriuria 3-6% sexually active women risk with age, diabetes, catheter 2 consecutive clean catch specimens >10 5 cfu/ml Same strain of bacteria Nicolle 2005

22 Asymptomatic Bacteriuria Screening is NOT recommended - Including older age, DM, institutionalized, spinal cord injury, indwelling catheter DO Screen: Pregnant women Nicolle 2005 Asymptomatic Bacteriuria No treatment needed Rx doesn t: Prevent symptomatic UTI Improve urinary function Improve survival Treat in pregnancy, diabetes ISDA 2005

23 Additional Work-Up Persistent hematuria, multiple recurrences with same stain Severe pyelo, fever >48-72 hours > recurrences of pyelo Sx of stone, abscess, obstruction CT or Ultrasound Summary UTI: Think STI. Diagnosis by history Consider nitrofurantoin Recurrent UTI: Reassure Patient preference for prophylaxis Asymptomatic bacteriuria No screening or Rx

24 Hematuria Young patient: Common, transient > 50 yrs of age: consider malignancy Risk malignancy: Macro (gross) > Micro (1-2 RBC s/hpf) Smoking hx Analgesic abuse Increasing age Khadra 2000

25 W/U Hematuria Menstrating woman: tampon R/O UTI U/A dipstick: Rare FP, FN if positive: microscopic exam >50 yo: consider bladder/renal CA W/u not evidence-based Minimize radiation exposure among pts unlikely to have serious disease Concepts of Hematuria Refer to urologist: Gross Hematuria or > 50 RBC/HPF >3 RBC/HPF on 2 or 3 U/A s Urine C & S, Creatinine After neg w/u: Cancer within 2-5 yrs: 0-3% Persistent micro & smoking hx: refer No routine U/A Screening Kaiser 2007

26 Other Concepts Flank pain: Consider non-contrast CT CT or IVP + Renal U/S Refer to Urologist for Cystoscopy If + UTI: f/u in 6 weeks after treatment Kaiser 2007

TMP/SMZ DS Ciprofloxacin Norfloxacin Ofloxacin Cefadroxil * 30 Amoxicilin 86* 19 25

TMP/SMZ DS Ciprofloxacin Norfloxacin Ofloxacin Cefadroxil * 30 Amoxicilin 86* 19 25 Evidence-Based Evaluation and Treatment of UTI UTI Prevalence Leslee L. Subak, MD Associate Professor Obstetrics, Gynecology & RS Epidemiology & Biostatistics University of California, San Francisco 50%