1. Genitourinary Tract Infections: An Evidence-Based Approach
Ralph Gonzales, MD, MSPH
Associate Professor of Medicine; Epidemiology & Biostatistics

2. Self-Assessment Questions -35 yo woman calls with 2-3 days of painful urination, increased urinary frequency and urgency.
a) What are the key questions that will help determine if she can be treated by telephone?
b) If she fulfills criteria for telephone treatment, what is her probability of having a true UTI?
c) If she happened to stop by your office, is there any value to performing a urinalysis?
d) What would you treat her with?
e) Does she need follow-up appointment or urine culture?
f) Patient doesn’t get better, dysuria continues. Other causes?

3. Self-Assessment Questions -35 yo woman calls with 4-5 days of new, foul-smelling vaginal discharge.
a) What are the key questions that will help determine if she can be treated by telephone?
b) What is her probability of having a candidal vaginitis (ie, available OTC therapy)?
c) How helpful are findings on history and physical examination in establishing an etiology?
d) How helpful is microscopy?
e) What management options should be considered for recurrent yeast infections?

4. Background: Acute Uncomplicated UTI is Common
Uncomplicated UTI is an extremely common disorder in women
Over 7 million office visits annually
Affects half of women at least once during their lifetime
Direct costs attributed to these infections in the US: $1 billion yearly

5. Background: Microbiology and Pathogenesis of Cystitis
Organisms:
E. coli, S. saprophyticus, Proteus, Klebsiella
Pathogenesis:
Fecal flora Vaginal introitus Urethra Bladder

6. Important Risk Factors for Cystitis in Women
Past history of cystitis, especially if recurrent
Recent sexual intercourse
Recent diaphragm and/or spermicide use
Unmarried
Lack of urination after sexual intercourse
Presence of asymptomatic bacteruria

7. Clinical Manifestations of UTI
Clinical features of cystitis
Dysuria +/- frequency, urgency, suprapubic pain
Clinical features of pyelonephritis
Fever, flank pain, CVA tenderness, nausea, vomiting
Differential Diagnosis
For cystitis: urethritis or vaginitis
For pyelonephritis: an abdominal process

8. Clinical Features of Complicated UTIs
recent UTI
structural abnormalities
Genetic/surgical/nephrolithiasis
diabetes
immunosuppression
pregnancy
urethral instrumentation
Red Flags…

9. How Good is History for the Diagnosis of Cystitis (vs. vaginitis)?

10. Positive Predictive Values for Combinations of Symptoms
Prob UTI, % Summary LR
-Dysuria Present
-Frequency Present
-Vaginal Discharge Absent
-Vaginal Irritation Absent
Overall %
-Dysuria Absent
-Vag D/C or Irritation Present
Overall %
-Dysuria or Frequency Present
-Vag D/C or Irritation Absent
Overall %
Bent et al, JAMA 2002

11. How Good are Lab Tests for the Diagnosis of Cystitis (vs. vaginitis)?

12. How Effective is Treatment of Cystitis? Pooled Results from RCTs

13. Irritable Voiding Symptoms
35 yo woman c/o 2-3 d painful urination, increased frequency, urgency. Denies fever, back pain.
Question #1:
When should I perform urinalysis?

14. Urinary Tract Infections -Test Characteristics (Bent et al)
Likelihood Ratios
positive negative
Dysuria ( ) 0.5 ( )
Frequency ( ) 0.6 ( )
Hematuria ( ) 0.9 ( )
Fever ( ) 0.9 ( )
Flank Pain ( ) 0.9 ( )
Vaginal Discharge (Hx) ( ) 3.1 ( )
Vaginal Irritation ( ) 2.7 ( )
Back Pain ( ) 0.8 ( )
Vaginal Discharge (PEx) ( ) 1.1 ( )
CVAT ( ) 0.9 ( )
Urinalysis
MAIN FINDINGS from a meta-analysis… thus, aggregated CIs.
Multiple voiding symptoms increase probability
Notice impact of absence of vaginitis…
Let’s see how this plays-out in real life…
What do people think is the baseline probability of UTI in a woman who present with voiding symptoms?

15. Goal of Diagnostic Testing
Treatment Threshold
Diagnostic Threshold 0%
50%
100%
Probability of Disease

16. Goal of Diagnostic Testing
Treatment Threshold
Diagnostic Threshold 0%
50%
100%
Probability of Disease

17. Dysuria Case UTI Prob
1.5dys*1.8freq*3.1d/c-*2.7irr-=23
Step 1:
-12/88 = 0.141
Step 2:
x 23 = 3.22
Step 3:
-3.22 /4.22 = 76%

18. UTI Post-Test Probabilities
Well, it varies quite a bit. I’m using 12% from Komaroff...
PreTest Prob
Bent et al.

20. Voiding symptoms cont. Question #1: Why perform urinalysis?
Positive test: ppv = 93%
Negative test: npv = 49%
You diagnose uncomplicated UTI and refrain from performing UA
… what are your treatment options?

21. Uncomplicated UTI Rx
TMP-sulfa DS bid x 3 days
ciprofloxacin, bid x 3 days
keflex 250 tid x 7 days
macrobid 100 bid x 7 days
amoxicillin 500 tid x 7 days
Follow-up: No visit or Cx if asymptomatic after 3 days, else return for re-eval.
Prevention: avoid spermicides; sexual activity
?Cranberry

22. Suspected UTI Algorithm
Woman > 1 UTI Sx
yes
Risk Factors?
Consider UCx, Empirial Rx
yes
Fever, Back Pain, N/V?
Consider UCx, Empirial Rx
yes
Vaginitis Sx?
About 20% UTI
Perform Pelvic
Multiple UTI Sx Present
yes
High Prob UTI,
Rx w/o Testing
Perform Urinalysis
Adapted from Bent et al

23. When should we consider STD Testing?

24. STDs can present with dysuria: -gonorrhea, chlamydia, trichomonas
Shapiro et al. Bronx, NY, ED setting (Acad Emerg Med. 2005)
All women had straight cath urine cultures and pelvic exams
Used low bacteria count criteria for UTI in symptomatic women (100 cfu)
Excluded if new vaginal D/C or other reasons to suspect STD present
Mean duration of symptoms: 6.8 days
RESULTS
Urine culture (+) = 57%
Chlamydia (+) = 10%; GC (+) = 1% (n=1); Trich (+) = 8%
STD rates equivalent in UCx positive and negative groups
**Only predictor of STD was # sexual partners in past year
Conclusion: Consider STD testing all women with dysuria seeking ED care, particularly those with >1 sexual partner in the past year.

25. Is Non-Invasive STD Testing Ready for Prime Time?

26. Non-invasive (urine) testing for GC and chlamydia
Systematic review
Cook et al. Ann Intern Med 2005;142:
Pooled Pooled
Sensitivity Specificity
Polymerase chain reaction >97%
-chlamydia women/men %/84%
-GC women %
Transcription-mediated amplification >97%
-chlamydia women %/88%
-GC women %
Strand displacement amplication >97%
-chlamydia women %/93%
-GC women %
Conclusion: non-invasive testing equivalent to cervical swab testing
Except for GC PCR
?confirmatory test when screening low (<5%) prevalence population
If spec=98%, then about 1/3 positives are false-positives
If spec>99%, probably not necessary…

28. Vaginitis Symptoms
35 yo woman c/o 4-5 days of foul-smelling, cheesy vaginal discharge and severe itching. Calls by telephone.
Question #1:
What clinical features can be used to reliably diagnose vulvovaginal candidiasis?
When should I perform microscopy?

29. Etiology of Vaginitis in PC
40% Bacterial Vaginosis
30% Unknown
20% Candida
10% Trichomonas
Other Causes
GC/chlamydia?… investigate when fever/lower abd pain
HSV
allergic reaction (chemical, latex, semen)
atrophic vaginitis

30. Challenges in History Women buying OTC yeast preps
candida=33%; BV=19%; mixed=21%; normal exam=12%; trichomonas=2%
Patients and physicians disagree on key findings
patient physician
clear d/c 21% %
yellow d/c 15% %
white/gray d/c 42% %
Poor agreement between call center nurse diagnosis and physician
If a woman presents with suspected yeast… ppv goes from 20% to 33%
All of these problems have led toward recommendations for accurate diagnosis to be based on physical examination

31. Vaginitis -Likelihood Ratios for Hx/PEx (Anderson et al)
positive negative
YEAST
Cheesy Discharge ( ) 0.5 ( )
Watery Discharge ( ) 1.5 ( )
Itching ( ) 0.3 ( )
Chief Complaint ( ) 0.8 ( )
Malodor ( ) ( )
Curdy D/C or Vulvar Inflamm (8.8-32) ( )
Curdy D/C + Itching (20-100) ( )
Fishy Odor (PEx) (0-0.5) ( )
BACTERIAL VAGINOSIS
Malodor (Hx) ( ) 0.07* ( )
“High Cheese” Odor (PEx) ( ) ( )
MAIN FINDINGS
** tricky, since unlike PNA and UTI… we are trying to diagnose specific etiologies… So each cause get’s its own set of LRs
WARNING… many of these studies are single or multiple small trials… hence the wide confidence intervals.
Watery does not equate with Yeast
Malodor does no equate with Yeast
vulvar/vaginal inflammation (erythema, edema, excoriations) are all strong predictors of Yeast

32. Candida Vaginitis Post-Test Probabilities.
So, you might perform microscopy to confirm that vulvar inflammation is due to yeast… when positive it yields a 70% prob… but when negative, it’s still almost 50%!!
PreTest Prob
Anderson et al.

33. Vaginitis Case: Yeast Prob
2.4chs*1.5wtry-*3.3itch *0.5odor =5.9
Step 1:
-20/80 = 0.251
Step 2:
x 5.9 = 1.492
Step 3:
/2.492 = 60%

34. Vaginitis symptoms cont.
Question #2: Why perform microscopy?
Agreement between clinician-read microscopy & culture is poor.
Rapid commercial tests are here/around the corner
You diagnose candidal vaginitis… you treat with fluconazole 150 mg x 1, but patient returns 1 week later with recurrence. What now?

35. Complicated Candidiasis CDC MMWR 2002;51:RR-6
Recurrent vulvovaginal candidiasis
obtain vaginal culture to assess for non-albicans species
treatment: topical therapy x 7-14 d; or fluconazole 150 mg, po, repeated in 3 d
maintenance (x 6 mo): clotrimazole 500 mg vag supp q week; fluconazole mg q week; itraconazole 400 mg q month or 100 mg q d.
Severe vulvovaginitis
Non-albicans vulvovaginitis
treatment: d non-fluconazole azole drug; if recurs, 600 mg boric acid in gelatin capsule qd x 2 wks

36. Bacterial Vaginosis CDC MMWR 2002;51:RR-6
Criteria
3 of 4 present:
vaginal discharge
clue cells
vaginal pH > 4.5
whiff test (fishy odor after 10% KOH
Management of Sex Partners
response to Rx and relapse are not affected by Rx of sex partner
Clinical Criteria
Treatment
Recommended Regimen*
metronidazole 500 mg bid x 7 d, OR
metronidazole gel 0.75%, one full applicator (5 g) iv, qd x 5 d, OR
clindamycin cream 2%, one full applicator (5 g) iv qhs x 7d
Alternative Regimens
metronidazole 2 g po x 1, OR
clindamycin 300 mg po bid x 7 d, OR
clindamycin ovules 100 g iv qhs x 3 d

37. Trichomoniasis CDC MMWR 2002;51:RR-6
Counseling
Management of Sex Partners
treat sex partners
Microscopy or Cx
Treatment
Recommended Regimen*
metronidazole 2 g po x 1
Alternative Regimens
metronidazole 500 mg bid x 7 d

38. SUMMARY UTI Typical Voiding Sx and no vaginitis... Empiric Rx
Know local E.coli antibiotic-resistance rates
Threshold 20-30% sulfa-resistance to switch to FQ first-line…
Consider STD testing, particularly in young, sexually active women (prevalence >=10%)… particularly for Chlamydia
Non-invasive testing is a reliable option
Vaginitis
Curdy discharge + vulvar inflamm/itching = Yeast
Malodor = non-yeast
Absence of malodor history may rule-out BV.