Genitourinary Tract Infections:
An Evidence-Based Approach
Ralph Gonzales, MD, MSPH
Associate Professor of Medicine;
Epidemiology & Biostatistics
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?
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?
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
Background:
Microbiology and Pathogenesis of Cystitis
Organisms:
E. coli, S. saprophyticus, Proteus, Klebsiella
Pathogenesis:
Fecal flora
Vaginal introitus
Urethra
Bladder
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
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
Clinical Features of Complicated
UTIs
• recent UTI
• structural abnormalities
– Genetic/surgical/nephrolithiasis
•
•
•
•
diabetes
immunosuppression
pregnancy
urethral instrumentation
How Good is History for the Diagnosis
of Cystitis (vs. vaginitis)?
Feature
Sensitivity
Specificity
LR +
LR -
Dysuria
89%
72%
3.2
0.16
Frequency
92%
91%
10.2
0.08
Absence of
Vaginal Discharge
89%
92%
12
0.11
(Komaroff et al Arch Intern Med 1978)
Positive Predictive Values for
Combinations of Symptoms
Overall
Prob UTI, %
-Dysuria Present
-Frequency Present
-Vaginal Discharge Absent
-Vaginal Irritation Absent
77%
Summary LR
24.6
Overall
-Dysuria Absent
-Vag D/C or Irritation Present
4%
0.3
Overall
-Dysuria or Frequency Present
-Vag D/C or Irritation Absent
9%
0.7
Bent et al, JAMA 2002
How Good are Lab Tests for the
Diagnosis of Cystitis (vs. vaginitis)?
Test
Sensitivity
Specificity
LR +
LR -
>2 Bacteria/HPF
58%
93%
8.6
0.45
>10 WBC/HPF
81%
79%
3.9
0.24
LE or Nitrite
positive
75%
82%
4.2
0.30
(Komaroff et al Arch Intern Med 1978)
(Hurlbut. J Clin Pathol 1991)
How Effective is Treatment of
Cystitis? Pooled Results from RCTs
REGIMEN
% CURED
Single dose TMP-SMX
87%
3 days of TMP-SMX
93%
> 7 days of TMP-SMX
94%
Single dose quinolone
88%
3 days of a quinolone
97%
(Warren et al Clin Infect Dis 1999)
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?
Urinary Tract Infections
-Test Characteristics (Bent et al)
Dysuria
Frequency
Hematuria
Fever
Flank Pain
Vaginal Discharge (Hx)
Vaginal Irritation
Back Pain
Vaginal Discharge (PEx)
CVAT
Urinalysis
Likelihood Ratios
positive
negative
1.5 (1.2-2.0)
0.5 (0.3-0.7)
1.8 (1.1-3.0)
0.6 (0.4-1.0)
2.0 (1.3-2.9)
0.9 (0.9-1.0)
1.6 (1.0-2.6)
0.9 (0.9-1.0)
1.1 (0.9-1.4)
0.9 (0.8-1.1)
0.3 (0.1-0.9)
3.1 (1.0-9.3)
0.2 (0.1-0.9)
2.7 (0.9-8.5)
1.6 (1.2-2.1)
0.8 (0.7-0.9)
0.7 (0.5-0.9)
1.1 (1.0-1.2)
1.7 (1.1-2.5)
0.9 (0.8-1.0)
4.2
0.3
Dysuria Case UTI Prob
1.5dys*1.8freq*3.1d/c-*2.7irr-=23
Step 1:
-12/88 = 0.141
Step 2:
-0.141 x 23 = 3.22
Step 3:
-3.22 /4.22 = 76%
UTI Post-Test Probabilities
urinalysis positive*
30
urinalysis negative*
30
Dysuria + Vag d/c,
irritation present
1
Dysuria/Freq + Vag d/c,
irritation absent
30
Dysuria + Vaginal
Discharge Absent
13
Dysuria
13
0
10
20
PreTest Prob
Bent et al.
30
40
50
60
Probability of UTI
70
80
90
100
Voiding symptoms cont.
• Question #1: Why perform urinalysis?
– Positive test:
– Negative test:
ppv = 93%
npv = 49%
• You diagnose uncomplicated UTI and
refrain from performing UA
– … what are your treatment options?
Uncomplicated UTI Rx
•
•
•
•
•
TMP-sulfa DS bid x 3 days
ciprofloxacin, 100-250 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
Suspected UTI Algorithm
Woman > 1 UTI Sx
Risk Factors?
Fever, Back Pain, N/V?
Vaginitis Sx?
Multiple UTI Sx
Present
Perform Urinalysis
yes
yes
yes
yes
Consider UCx,
Empirial Rx
Consider UCx,
Empirial Rx
About 20% UTI
Perform Pelvic
High Prob UTI,
Rx w/o Testing
Adapted from Bent et al
When should we consider
STD Testing?
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.
Is Non-Invasive STD Testing
Ready for Prime Time?
Non-invasive (urine) testing for GC
and chlamydia
•
•
Systematic review
Cook et al. Ann Intern Med 2005;142:914-25.
Pooled
Sensitivity
Polymerase chain reaction
-chlamydia women/men
83%/84%
-GC women
56%
Transcription-mediated amplification
-chlamydia women
93%/88%
-GC women
91%
Strand displacement amplication
-chlamydia women
90%/93%
-GC women
85%
Pooled
Specificity
>97%
>97%
>97%
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…
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?
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
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
– clear d/c
21%
– yellow d/c
15%
– white/gray d/c 42%
physician
13%
6%
71%
• Poor agreement between call center nurse
diagnosis and physician
Vaginitis
-Likelihood Ratios for Hx/PEx (Anderson et al)
Likelihood Ratios
positive
negative
YEAST
Cheesy Discharge
Watery Discharge
Itching
Chief Complaint
Malodor
Curdy D/C or Vulvar Inflamm.
Curdy D/C + Itching
Fishy Odor (PEx)
BACTERIAL VAGINOSIS
Malodor (Hx)
“High Cheese” Odor (PEx)
2.4 (1.4-4.2)
0.5 (0.3-0.9)
0.1 (0.02-0.8) 1.5 (1.2-1.9)
1.7 (1.3-2.4)
0.3 (0.1-0.8)
3.3 (2.4-4.8)
0.8 (0.7-0.9)
0.5 (0.3-0.9)
1.6 (1.1-2.4)
17 (8.8-32)
0.2 (0.1-0.4)
150 (20-100) 0.2 (0.1-0.4)
0.03 (0-0.5)
2.9 (2.4-5.0)
1.6 (1.3-2.0)
3.2 (2.1-4.7)
0.07* (0.01-0.5)
0.30 (0.2-0.5)
Candida Vaginitis Post-Test
Probabilities
31
Cheesy+Vulvar Inf + Neg Micro
46
Vulvar Inflamm + Pos Micro
15
Vulvar Inflamm (Trich)
32
Vulvar Inflammation
12
Cheesy and Foul-Smelling
Watery d/c
1
25
Cheesy d/c
0
10
20
30
40
50
60
Probability of Candidiasis
PreTest Prob
Anderson et al.
70
80
90
100
Vaginitis Case: Yeast Prob
2.4chs*1.5wtry-*3.3itch *0.5odor =5.9
Step 1:
-20/80 = 0.251
Step 2:
-0.251 x 5.9 = 1.492
Step 3:
-1.492 /2.492 = 60%
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?
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 100-150 mg q week; itraconazole 400 mg q month
or 100 mg q d.
Severe vulvovaginitis
• treatment: topical therapy x 7-14 d; or fluconazole 150 mg, po,
repeated in 3 d
Non-albicans vulvovaginitis
• treatment: 7-14 d non-fluconazole azole drug; if recurs, 600
mg boric acid in gelatin capsule qd x 2 wks
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
Clinical
Criteria
• response to Rx and
relapse are not affected
by Rx of sex partner
Treatment
Recommended Regimen*
Alternative Regimens
metronidazole 500 mg bid x 7 d, OR
metronidazole 2 g po x 1, OR
metronidazole gel 0.75%, one full
applicator (5 g) iv, qd x 5 d, OR
clindamycin 300 mg po bid x 7 d, OR
clindamycin cream 2%, one full
applicator (5 g) iv qhs x 7d
clindamycin ovules 100 g iv qhs x 3 d
Trichomoniasis
CDC
MMWR 2002;51:RR-6
Counseling
Microscopy
or Cx
Management of
Sex Partners
• treat sex partners
Treatment
Recommended Regimen*
metronidazole 2 g po x 1
Alternative Regimens
metronidazole 500 mg bid x 7 d
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.