Urethritis, Vulvovaginitis, and Cervicitis 51
51 Urethritis, Vulvovaginitis, and Cervicitis
Paula K. Braverman
URETHRITIS
Urethritis is inflammation of the urethra. The clinical presentation
includes dysuria, urinary frequency, and urethral discharge or itching.
Neutrophils usually are found in urethral secretions.1 According to the
Centers for Disease Control and Prevention (CDC), urethritis is docu-
mented by one of the following: visibly abnormal urethral discharge, a
positive leukocyte esterase (LE) test result for a man younger than 60
years of age without other urinary tract disease that could cause pyuria,
Gram stain of a urethral smear showing at least 2 white blood cells per
high-power field (WBCs/HPF), and a positive LE test result for the first-
void urine or 10 or more WBCs/HPF in the first-void urine sediment.2,3
However, studies have demonstrated that symptoms of urethritis can
occur without microscopic evidence of pyuria on the Gram stain of
urethral swab specimens or in the first-void urine samples.4,5
It may be difficult to establish the diagnosis of urethritis in women
because they may not have localized symptoms and some pathogens
simultaneously infect multiple genital areas.6 In the absence of a docu-
mented urinary tract infection, female dysuria can represent vulvar
inflammation from vaginitis or vulvar dermatoses, interstitial cystitis, or
urethral infection with a sexually transmitted infection (STI).6,7
Etiologic Agents
Infectious Causes
Organisms associated with STIs are the most significant etiologic agents
in urethritis. Newer, more sensitive molecular diagnostic testing modali-
ties for STIs have advanced the understanding of specific pathogens that
cause urethritis.
Male Patients.  Chlamydia trachomatis and Neisseria gonorrhoeae are
common causes of urethritis in men.1 N. gonorrhoeae is estimated to
cause one third of acute urethritis cases and is differentiated from other
agents, which cause nongonococcal urethritis (NGU).8 NGU is the most
common clinical STI syndrome in men. Rates of specific etiologic agents
vary by geography, socioeconomic factors, age, race, and sexual orienta-
tion or practices.1,5,8–14 Coinfection with multiple pathogens can occur,
and in 25% to 40% of cases, no pathogen is identified.15 Approximately
15% to 40% of NGU in men is caused by C. trachomatis, 15% to 25% by
Mycoplasma genitalium, 10% to 20% by Trichomonas vaginalis, and 10%
to 20% by Ureaplasma urealyticum.15,16
There has been confusion in the literature regarding the role of U.
urealyticum as a cause of nongonococcal, nonchlamydial infection in
men.2,5,11,15,17–23 The genus Ureaplasma has two types: biovar 1 (U. parvum)
and biovar 2 (U. urealyticum). Biovar 2 is the biotype most likely
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associated with urethritis.15,17–24 Further analysis has revealed that within
biovar 2, only specific subtypes may be independently associated with
NGU.18
T. vaginalis traditionally was considered a less common cause of ure-
thritis in men. However, a nucleic acid amplification testing (NAAT) such
as polymerase chain reaction (PCR) and transcription-mediated ampli-
fication (TMA) demonstrate that T. vaginalis is associated with 10% to
20% of cases of urethritis.10,15,25–27 T. vaginalis can be demonstrated in
males without clinical signs of urethritis and commonly is associated
with other STIs.15,28–30
Herpes simplex virus (HSV) is a less common cause of urethritis in
men.5,11,31 Urethritis develops in 30% of men with primary HSV infection
and is found in 2% to 3% of cases of NGU.15 Studies reported in 2006
found that HSV-1 was responsible for more cases of NGU than HSV-2
and that HSV-1 was more likely to be associated with men engaging in
oral-genital sex and men with male partners.5,11 Infrequent causes of
urethritis in men include adenoviruses, Haemophilus species, and Neis-
seria meningitidis; coliforms can be an etiologic agent in men who have
sex with men (MSM).1,5,11,15 Identification of some pathogens associated
with urethritis suggests that infection with oropharyngeal flora, which
are normal nonpathogenic organisms in monogamous partners, is
possible.11
Nonsexually transmitted NGU is associated with urinary tract infec-
tion (UTI), bacterial prostatitis, urethral stricture, phimosis, and urethral
catheterization.1 In 25% to 40% of cases, the cause of NGU in male
patients remains unknown.15
Female Patients.  Urethritis in female patients can be caused by N.
gonorrhoeae, C. trachomatis, HSV, and M. genitalium. T. vaginalis typically
causes vaginitis in women but is known to infect the urethra and is
associated with pyuria.6,7,10,29,32–36
Noninfectious Causes
In men and women, urethritis can accompany noninfectious systemic
diseases such as Stevens-Johnson syndrome, or it can result from chemi-
cal irritation.1,6
Epidemiology
One half of new STIs occur in adolescents and young adults between the
ages of 15 and 24 years.37 Population-based data for this age group
derived from the National Health and Nutrition Examination Survey
(NHANES) showed the prevalence of C. trachomatis was 1.7% among
males and 3.2% among females (2005–2008 data); prevalence of N.
gonorrhoeae was 0.3% among males and 0.6% among females (1999–2008
357
 PART II  Clinical Syndromes and Cardinal Features of Infectious Diseases: Approach to Diagnosis and Initial Management
SECTION G  Genitourinary Tract Infections

data); and prevalence of T. vaginalis was 0.9% among males and 1.5%
among females (2001–2004 data).37
Other studies have demonstrated that prevalence rates of T. vaginalis
infection increase with age; they are highest among black women, lower
among black men, and lowest among whites.38,39 Similar ethnic or racial
differences have been found for C. trachomatis and N. gonorrhoeae.40 Data
from several studies, including the CDC’s 2013 sexually transmitted
disease (STD) surveillance report, illustrate that the STI rates vary by
specific populations.25,38,40,41 Youth in correctional facilities and the
National Job Training Program have among the highest STI rates.2,40,41
Sexual practices and behavior can influence the epidemiology of
urethritis. Urethritis due to C. trachomatis, N. gonorrhoeae, or HSV
among adolescent women correlates with having new sex partners.6
Adenovirus and HSV-1 have been associated with oral-genital contact
and having a male partner, whereas M. genitalium and C. trachomatis
have been associated with vaginal sex.5 In one study, N. gonorrhoeae and
U. urealyticum urethritis were found in heterosexual men, C. trachomatis
urethritis was associated with MSM, and T. vaginalis was more common
in men older than 30 years of age.42
Urethritis due to STI pathogens also can occur in prepubertal boys
and, less frequently, in prepubertal girls. In this age group, transmission
commonly results from sexual abuse with genital-to-genital contact (see
Chapter 54).
Clinical Manifestations and Differential Diagnosis
Symptomatic urethritis in adolescent males is characterized by dysuria,
urethral discharge, or urethral pruritus. Discharge can be mucoid,
mucopurulent, or purulent. Gonococcal urethritis compared with NGU
usually has a shorter incubation period, more acute onset, and more
profuse discharge (Table 51.1).1 Discharge in patients with NGU can be
so scant that it is only noticed in the morning or is apparent as crusting
on the meatus or as stains in underwear.1 Urethral infection with N.
gonorrhoeae and the various organisms causing NGU also can be
asymptomatic.43
Urethritis must be differentiated from UTI, particularly in adolescent
boys with dysuria but no discharge. In contrast to UTI, frequency,
TABLE 51.1  Clinical Manifestations of Nongonococcal and
Gonococcal Urethritis
Nongonococcal Gonococcal
Characteristic Urethritis Urethritis
Incubation period 2–3 weeks 2–6 days
Onset Insidious Abrupt
Dysuria +, may wax and wane ++, continuous
Discharge Scant to moderate, Profuse, absent
may be absent in <10%
+, modest discomfort; ++, more severe discomfort.
hematuria, and urgency are uncommon in urethritis. However, if the
male adolescent is sexually active, pyuria is more likely to be caused by
urethritis than UTI because UTI is uncommon in this age group. A
focused STI history (see Chapter 49) and thorough medical history can
help establish relative risks of urethritis and UTI.
In adolescent girls, dysuria is the cardinal feature of urethritis, which
must be differentiated from acute bacterial cystitis and vulvovaginitis
(Table 51.2). The literature differentiates internal and external dysuria.
Internal dysuria is pain that is felt internally during voiding. External
dysuria is discomfort that is felt as urine passes over the labia.7 Internal
dysuria, urinary frequency, and isolation of more than 102 uropathogens
per milliliter of voided urine suggest acute bacterial cystitis; isolation of
102 or fewer uropathogens per milliliter suggests acute urethritis due to
STI pathogens.6 Pain that is felt internally only at the end of urination is
consistent with bacterial cystitis.7 External dysuria can occur with vulvo-
vaginitis. Female adolescents can have vaginitis alone or a concurrent
UTI and may not be able to adequately distinguish between internal and
external dysuria.7,44 Any female patient suspected of having urethritis
requires an STI-directed history and physical examination to identify
other STIs or STI syndromes (e.g., pelvic inflammatory disease [PID]).
In prepubertal boys and girls, urethritis due to STI pathogens can
manifest with dysuria and urethral or vaginal discharge. There may be
vague lower abdominal pain, unwillingness to void, and in boys, irritation
in the distal urethra or meatus. Dysuria in a prepubertal child is much
more likely to be caused by UTI than urethritis associated with STI.
Urethritis is more probable in the setting of a discharge or a history of
sexual abuse, especially if genital-to-genital contact has occurred.
Laboratory Findings and Diagnosis
Male Patients.  For male patients, specimens are obtained to document
urethritis and to detect common causes such as N. gonorrhoeae and C.
trachomatis. The definitive diagnosis is enhanced if the patient has not
voided recently; examination in the morning before voiding is ideal.1 A
meatal swab specimen of a discharge can be taken for Gram stain; the
finding of gram-negative intracellular diplococci of the typical kidney
bean morphology pattern (Fig. 51.1) or at least 2 neutrophils per oil
immersion field (×1000) is diagnostic of urethritis.1,2 A Gram stain smear
is sensitive and specific in diagnosing gonococcal urethritis if intracel-
lular diplococci are detected. If the Gram stain is equivocal, negative, or
unavailable and the criteria for urethritis are met, NAAT for N. gonor-
rhoeae and C. trachomatis is indicated.2
In all patients, regardless of whether N. gonorrhoeae is suspected by
Gram stain, a first-voided urine or urethral specimen should be obtained
for detection of C. trachomatis by NAAT. The optimal specimen from
male patients is a first-voided urine.2,45 NAAT for N. gonorrhoeae and C.
trachomatis may detect infection in male patients with symptoms of
urethritis but no objective evidence of urethral inflammation.2
The diagnosis of T. vaginalis in men is more challenging than in
women. Wet mount preparation of a urethral smear detects only 30% of
T. vaginalis infections in men.28 Culture can be performed on urine,
semen, or urethral specimens and appears to yield better results if

TABLE 51.2  Distinguishing Features of Urethritis, Acute Bacterial Cystitis, and Vulvovaginitis in Adolescent Females
Feature Urethritis Acute Bacterial Cystitis Vulvovaginitis
Symptoms Internal dysuria Internal dysuria, frequency, urgency, External dysuria, vaginal discharge,
hematuria vulvar burning, itching
Duration of symptoms Often ≥7 days Usually ≤4 days Varies with cause
Signs Mucopurulent cervicitis Suprapubic tenderness Vulvar lesions and inflammation,
Vulvar lesions vaginal discharge
Epidemiologic associations New sex partner Previous cystitis History of genital herpes
Previous STI Onset of symptoms within 24 hours Sex partner with genital herpes
Sexual partner with STI of intercourse Antibiotic use
Use of diaphragm Previous vulvovaginitis
Use of a spermicide Candidiasis
STI, sexually transmitted infection.
Modified from Holmes KK, Stamm WE, Sobel JD. Lower genital tract infection syndromes in women. In: Holmes KK, Sparling PF, Mardh P-A, et al. (eds). Sexually Transmitted Diseases, 4th ed. New
York, McGraw-Hill, 2008, pp. 987–1016.

358
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A mens can be collected by the healthcare personnel or the patient.2,45
B
C is indicated. Treatment without signs for urethral inflammation has not
FIGURE 51.1  (A) Gram stain of urethral discharge from an male adolescent with
urethritis shows multiple neutrophils and intracellular diplococci with the kidney-
bean morphology typical of Neisseria gonorrhoeae (magnification ×1000). (B) Gram
stain of vaginal fluid from an adolescent with bacterial vaginosis shows clue cells
and squamous vaginal epithelial cells covered with coccobacilli, which gives them
a stippled or granular appearance. Notice the absence of rods with blunt ends
(i.e., lactobacilli) (magnification ×2000). (C) Wet mount of vaginal secretions from
a female adolescent with bacterial vaginosis shows clue cells. Notice the stippled
epithelial cells with ragged (i.e., bacteria-covered), ill-defined borders (magnification
×200).
multiple sites are tested.2,29,46 The InPouch culture system (BioMed
Diagnostics, San Jose, CA) is equivalent to the gold standard Diamond
media, and urethral or urine sediment specimens can be inoculated.25
However, studies have shown that NAAT is superior to a wet mount
preparation or culture to detect T. vaginalis in male patients.10,26,28,29,47–49
Although the TMA test is approved only in the United States for female
specimens, it may be used in laboratories that have conducted validation
procedures on male specimens.2,46,50 T. vaginalis PCR is not commercially
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Urethritis, Vulvovaginitis, and Cervicitis 51
available. Specific testing of men for T. vaginalis should be considered for
cases of nongonococcal urethritis in high-prevalence areas or
populations.2
Cultures for U. urealyticum are not available readily, and M. genitalium
is difficult to isolate.1,32,51 In research studies, both are diagnosed and
evaluated using NAAT. However, these tests are not cleared for use by the
US Food and Drug Administration (FDA), and management relies on the
clinical presentation and exclusion of other causes.2
Female Patients.  Endocervical or vaginal and urethral specimens
should be obtained for NAAT for N. gonorrhoeae and C. trachomatis in
adolescent girls with urethritis because concurrent infection is common.2,6
Urinalysis and urine culture also are indicated because simultaneous UTI
and STI can occur in sexually active females.7 Urine testing using NAAT
for C. trachomatis and N. gonorrhoeae is not as sensitive as endocervical
specimen testing.2,45 Studies using NAAT for vaginal specimens have
shown good correlation with cervical specimens, and the vaginal speci-
T. vaginalis can be diagnosed by a variety of methods, including wet
mount preparation, culture, nucleic acid probe, immunochromato-
graphic capillary flow dipstick technology, and NAAT.2,25,48,49,52,53 As for
male patients, wet mount microscopy has poor sensitivity compared with
other methods.2 NAAT for T. vaginalis (e.g., strand displacement ampli-
fication [SDA]), and TMA are FDA cleared for use in women for endo-
cervical, vaginal, or urine specimens.2,48,52
Treatment
Initial treatment for male patients can be based on Gram stain results
(Table 51.3).2 Patients with evidence of N. gonorrhoeae by Gram stain
should be treated with dual single-dose therapy, including intramuscular
ceftriaxone and oral azithromycin to reduce the development of
antimicrobial-resistant N. gonorrhoeae. Although oral cefixime can be
substituted for ceftriaxone, it is not the first-line drug due to resistance
patterns and poor efficacy if there is a concomitant pharyngeal
infection.2
All patients with negative Gram stain results should be tested for C.
trachomatis and treated if positive. For NGU, a single dose of azithromy-
cin may be preferred over a 1-week course of doxycycline in adolescents
because of adherence.2 Single-dose azithromycin is also preferred because
it is most effective in treating M. genitalium, which is the most common
cause of persistent and recurrent NGU.2 Confirmed cases of N. gonor-
rhoeae or C. trachomatis must be reported to the local health authorities,
and sexual partners should be contacted for assessment and treatment.
Immediate follow-up and repeat testing for N. gonorrhoeae or C. tra-
chomatis urethritis in adolescents are not recommended routinely if
appropriate treatment is completed, signs and symptoms disappear, and
no re-exposure to an untreated partner occurs. However, because of the
high rate of reinfection after initial treatment, repeat testing for N. gonor-
rhoeae and C. trachomatis is recommended in 3 months.2 If symptoms
persist despite good adherence and no re-exposure and the person meets
diagnostic criteria for persistent or recurrent NGU, further management
been demonstrated to be effective.2,54,55
M. genitalium is the most common cause of persistent or recurrent
NGU.2 If doxycycline was used initially, single-dose azithromycin should
be tried because it is more effective than multidose doxycycline for this
organism.2 However, resistance has developed to azithromycin, and
studies have demonstrated treatment failure in men treated with both
single-dose and extended-dosing regimens of azithromycin, possibly
related to the selection of resistant organisms with the common use of
single-dose azithromycin for treatment of N. gonorrhoeae and C. tracho-
matis. Seven days of moxifloxacin (400 mg daily) is effective for treatment
failures for M. genitalium.2,16,51,54–57 Fluoroquinolone resistance has also
been demonstrated.57,58
For male patients with persistent urethritis, culture of a urethral speci-
men or first-void urine for T. vaginalis should be performed because of
the high prevalence of T. vaginalis infection among men with nongono-
coccal, nonchlamydial urethritis and coinfection with these organisms. If
there has been laboratory validation, testing of urethral or urine speci-
mens with NAAT is preferred.2 If T. vaginalis is diagnosed, metronidazole
or tinidazole is prescribed (see Chapter 274). Current CDC guidelines
recommend presumptive treatment with metronidazole or tinidazole in
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 PART II  Clinical Syndromes and Cardinal Features of Infectious Diseases: Approach to Diagnosis and Initial Management
SECTION G  Genitourinary Tract Infections

TABLE 51.3  Recommended Treatment of Urethritis in Postpubertal Children and Adolescents

Gram Stain Suggested Treatment
RESULTS AVAILABLE
Increased Neutrophils Gram-Negative
Intracellular Diplococci
Present Presenta Treat for gonococcal and chlamydial urethritis.
For Neisseria gonorrhoeae: for postpubertal children >45 kg and adolescents, ceftriaxone
(250 mg IM once) or cefixime (400 mg PO once) and azithromycin (1 g PO once)
For Chlamydia trachomatis: for postpubertal children ≥8 years and adolescents, azithromycin (1 g
PO once) or doxycycline (100 mg bid PO for 7 days)
Present Absent Treat for nongonococcal urethritis. Azithromycin (1 g PO once) or doxycycline (for 7 days) or
ofloxacin (300 mg PO bid for 7 days) or levofloxacin (500 mg PO once daily for 7 days) or
erythromycin base (500 mg PO qid for 7 days) or erythromycin ethylsuccinate (800 mg PO qid
for 7 days)
Absent Absent Defer treatment until microbiologic results are available, or if patient is high risk by history and
follow-up cannot be ensured, treat for gonococcal and chlamydial urethritis
RESULTS NOT AVAILABLE
Urethral discharge — Treat for gonococcal and chlamydial urethritis
No urethral discharge — Defer treatment until microbiologic results are available, or if patient is high risk and follow-up
cannot be ensured, treat for gonococcal and chlamydial urethritis
RECURRENT OR PERSISTENT URETHRITIS
— — Azithromycin (1 g PO once) if not used for initial episode; for failure, moxifloxacin (400 mg PO qd
for 7 days) to cover Mycoplasma genitalium; metronidazole (2 g PO once) or tinidazole (2 g PO
once) to cover Trichomonas vaginalis
a
Gram stains are considered inadequate to evaluate prepubertal children for N. gonorrhoeae.
IM, intramuscularly; IV, intravenously; PO, orally.
Data from Workowski KA, Bolan GA. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep 2015;64(RR- 3):1–137.

cases of persistent urethritis in areas of high prevalence for men who have
sex with women.2 U. urealyticum can be difficult to eradicate, and resis-
tance to tetracyclines has been demonstrated.1,51 Patients who do not
respond to therapy should be referred to a urologist.
Female patients with findings suggesting bacterial cystitis can be
treated presumptively for UTI. However, if urethritis is suspected, a single
dose of azithromycin (1 g) or a 7-day course of doxycycline (100 mg
twice per day) is indicated pending results of urine culture and STI
testing.2 If symptoms of dysuria due to vulvovaginitis are found, treat-
ment should be directed at the cause. Although the CDC’s 2015 STD
treatment guidelines do not specifically discuss persistent urethritis in
females, treatment of M. genitalium should be considered when other
causes have been ruled out, and ideally, testing for this organism should
be done.35
Complications
Complications of urethritis include disseminated gonococcal infection
(0.5% to 3%) and reactive arthritis syndrome (i.e., Reiter syndrome). In
male patients, epididymitis (1% to 2%) and, rarely, prostatitis and bala-
noposthitis also occur.1,16 Female patients with N. gonorrhoeae, C. tracho-
matis, and M. genitalium infection also are at risk for PID and
infertility.7,16,36,59 M. genitalium has been associated with preterm birth
and spontaneous abortion.2,59 In male and female patients, STIs associ-
ated with urethritis increase susceptibility to infection with, viral shed-
ding, and transmission of HIV.2,60,61
Prevention
Correct and consistent use of condoms is the most effective means of
preventing and reducing transmission of the STIs associated with
urethritis.
VULVOVAGINITIS
Vulvovaginitis (i.e., inflammation of the vagina or vulva) is a common
gynecologic problem in prepubertal and adolescent girls. The cause,
pathogenesis, and management are substantially different for the two age
groups.7 Vaginitis and vulvitis are a continuum in young children,
whereas they are distinct clinical entities in adolescents.
Vulvovaginitis in Prepubertal Girls
Etiologic Agents and Epidemiology
Prepubertal girls can have specific or nonspecific vaginal infections.7
Several factors predispose young girls to vulvovaginal irritation, includ-
ing proximity of the vagina to the rectum, poor hygienic practices, lack
of protective labial fat pads and pubic hair, and lack of an estrogen effect
on vaginal mucosa.7,62 Prepubertal girls are more likely than postpubertal
girls to experience vulvar irritation and trauma from soaps, bubble baths,
and clothing.7 The lack of estrogen effect in prepubertal girls promotes
an environment with a neutral pH, predisposing to overgrowth with a
variety of potential pathogens.6,62 Vaginal microbial infections that are
not STIs usually are caused by respiratory tract and enteric pathogens.
T. vaginalis is rare in prepubertal children because lack of estrogen
makes the vagina resistant to this infection.7 Isolation of Gardnerella
vaginalis in prepubertal vaginitis is not diagnostic of bacterial vaginosis
(BV) but has been reported in prepubertal girls after sexual assault.7
Candida vulvovaginitis is not common in prepubertal girls unless there
are other risk factors, such as antibiotic use, diabetes mellitus, immuno-
suppression, or use of diapers; 3% to 4% of prepubertal girls have
Candida spp. as part of normal vaginal flora.7,62
Although prepubertal vulvovaginitis is not often sexually transmitted,
sexual abuse must be considered if pathogens such as C. trachomatis, N.
gonorrhoeae, T. vaginalis, human papillomavirus (HPV), or HSV are
identified.7,62 Attributing HPV to sexual abuse rather than vertical trans-
mission or inoculation from caregivers and autoinoculation is challeng-
ing because of the lack of studies in this age group regarding incubation,
latency to clinical presentation, and cutoff ages for vertical transmis-
sion.62 Similar to the cervical epithelium of postpubertal girls, the
cuboidal vaginal epithelium of prepubertal girls is susceptible to N.
gonorrhoeae and C. trachomatis.6 Other causes of vulvovaginitis include
foreign body, vulvar skin disorders, and allergic reactions (Box 51.1).

360
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 Urethritis, Vulvovaginitis, and Cervicitis 51
BOX 51.1  Etiologic Factors in Prepubertal Vulvovaginitis BOX 51.2  Testing Vaginal Discharge or Aspirate Specimens From
Prepubertal Girls With Vulvovaginitis
NONSPECIFIC CAUSES
Contact or Allergic Reactions (Common) Gram stain for bacteria and white blood cellsa
Culture for aerobic and anaerobic bacteria
• Bubble-bath preparations
Culture for Neisseria gonorrhoeae and Chlamydia trachomatisb
• Shampoos, soaps
Wet mount to detect clue cellsc or trichomonadsd
• Laundry detergents
Potassium hydroxide preparation to detect fungal elementsd and
• Clothing (e.g., nylon undergarments)
note odor
Physical Factors (Common) Scotch tape specimen from perianal area in early morning if
pinworms are suspected
• Foreign body
• Sand (e.g., sandbox) a
Gram stain should not be used to diagnose or exclude N. gonorrhoeae in prepubertal
• Poor hygiene (e.g., wet diapers) children.
b
Nonculture tests usually are not recommended in cases of abuse due to the risk of false-
SPECIFIC MICROBIOLOGIC CAUSES positive results, but nucleic acid amplification testing (NAAT) of vaginal or urine specimens
may be an acceptable alternative particularly in other circumstances.
Not STI Related c
Clue cells are stippled epithelial cells whose borders are obscured by adherent bacteria.
• Shigella spp. d
Culture also can be performed for Trichomonas vaginalis and yeast. NAAT for Trichomonas
• Yersinia enterocolitica vaginalis has not been adequately studied in prepubertal children.
• Enteric bacilli
• Staphylococcus aureus
• Group A Streptococcus
• Haemophilus influenzae otoscope head is used. Examination with the patient under anesthesia
• Enterobius vermicularis may be necessary in some cases.
• Moraxella catarrhalis
• Streptococcus pneumoniae
• Neisseria meningitidis
Laboratory Findings and Diagnosis
• Candida spp. Samples of a vaginal discharge are obtained (Box 51.2) using a sterile,
saline-moistened swab for potassium hydroxide (KOH) preparation,
Possibly STI Related (Less Common) Gram stain, and culture.62 A vaginal wash using nonbacteriostatic saline
• Neisseria gonorrhoeae or vaginal aspiration using an eyedropper are alternative methods of
• Chlamydia trachomatis specimen collection.7,62 However, the latter specimens may not be as
• Trichomonas vaginalis sensitive for identification of C. trachomatis if few epithelial cells are
• Herpes simplex virus collected, which are necessary because the organism is an obligate intra-
cellular pathogen. Culture confirmation of N. gonorrhoeae and C. tracho-
Vulvar Skin Disorders matis is the most admissible legal evidence for cases of suspected sexual
• Eczema abuse.
• Psoriasis
NAAT for vaginal or urine specimens may be an alternative to culture
for testing of vaginal secretions in girls.2 T. vaginalis can be detected
STI, sexually transmitted infection. in vaginal wash specimens or by culture.7,53 If Enterobius infestation
is suspected, the parent is instructed to examine the perianal region
at night for the small, white pinworms, and a Scotch tape swab or
paddle specimen is collected from the perianal area immediately on
the child’s awakening. Samples for culture for yeast should be consid-
Clinical Manifestations, Differential Diagnosis, and ered if itching persists or the history suggests risk factors for candidal
Clinical Approach infection.7,62

The clinical features of vulvovaginitis in children include vaginal dis-

charge, vulvar irritation, pruritus, dysuria, bleeding, genital inflamma-
tion, and foul smell.7,62 When associated with a foreign body, the discharge
can be profuse, foul smelling, and blood tinged.7 Parents often are
unaware that the child has inserted something into the vagina. In Entero-
bius vermicularis–associated vulvovaginitis, recurrent symptoms and
vulvar or anal pruritus are common. Discharge can be bloody in cases of
vulvovaginitis caused by Shigella spp. or Streptococcus pyogenes infec-
tion.6,7,62 Bleeding also should raise concern about trauma. Diffusely
hyperemic vulvar mucosa suggests streptococcal vulvovaginitis. Discharge
associated with gonococcal infection is commonly green and purulent,
whereas discharge is less common with chlamydial infection.
All prepubertal children with vulvovaginitis require a careful history
and physical examination. Vaginitis due to S. pyogenes can occur after a
pharyngeal or skin infection in the patient or family members. Finding
a sibling with an STI raises concern about sexual abuse by someone
associated with the family.7,62 Gynecologic examination includes abdomi-
nal inspection and palpation. In a gentle and supportive manner, inspec-
tion of the perineal skin, vulva, and perirectal and genital areas is
performed to detect excoriation, erythema, ulcers, or structural abnor-
malities. Visualization of the vagina and cervix without instrumentation
usually is possible with the patient in the knee-chest position.7 This
facilitates detection of a foreign body, especially if a magnifying lens or
Treatment
The mainstay of treatment for nonspecific vulvovaginitis is education,
attention to personal hygiene, and avoidance of agents such as bubble
baths and tight nylon undergarments that provoke the problem.62 Sitz
baths in warm water without soap may be helpful. Vitamin A and D
ointment or petroleum jelly can protect the vulva, and a short course of
1% hydrocortisone cream can alleviate acute exacerbations of irritant
vulvitis.7,62 In severe cases, an estrogen cream may be applied for several
weeks to ameliorate symptoms.7,62 If a foreign body is detected, removal
usually resolves the problem.
Treatment of vulvovaginitis due to specific pathogens is initiated on
the basis of the Gram stain, wet mount preparation, culture, or NAAT
results. Recommended treatments for N. gonorrhoeae are ceftriaxone
alone for patients who weigh 45 kg or less and ceftriaxone along with
azithromycin for those who weigh more than 45 kg. For C. trachomatis,
erythromycin is given to patients who weigh less than 45 kg, azithromycin
for those younger than 8 years of age and who weigh 45 kg or more, and
azithromycin or doxycycline for older girls. For Candida, an antifungal
agent, such as clotrimazole, is used, or oral fluconazole is used if topical
therapy is not effective. Treatment for S. pyogenes is penicillin or amoxi-
cillin. Other antimicrobial agents are chosen on the basis of vaginal bacte-
rial culture results.2,7,62

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 PART II  Clinical Syndromes and Cardinal Features of Infectious Diseases: Approach to Diagnosis and Initial Management
SECTION G  Genitourinary Tract Infections
Complications
The follow-up of children with vulvovaginitis depends on the cause.
Fortunately, gonococcal and chlamydial vulvovaginitis rarely are associ-
ated with upper tract disease, and impairment of fertility is unlikely if
the infection is treated adequately.7 For recurrences due to S. pyogenes,
pharyngeal colonization in the patient and carriage in family members
are considered.62
Vaginitis in Pubertal Girls
Etiologic Agents and Epidemiology
Under the influence of estrogen at puberty, the vaginal epithelium shifts
from cuboidal to a glycogen-containing stratified squamous epithelium,
and there is an associated increased growth of lactobacilli that produce
lactic acid and hydrogen peroxide.6,7,63 This results in a decrease in vaginal
fluid pH from a prepubertal level of about 7.0 to about 4.0. Changes in
the epithelium, colonizing flora, and pH render the vaginal environment
relatively resistant to infection caused by C. trachomatis and N. gonor-
rhoeae. In adolescents, these two organisms cause cervicitis rather than
vulvovaginitis.
Leukorrhea, the normal white mucous vaginal discharge that repre-
sents the effect of estrogen on the vaginal mucosa in adolescents, must
be distinguished from pathologic discharge. Saline wet mount examina-
tion of vaginal secretions reveals sheets of epithelial cells without inflam-
matory cells, yeast, clue cells, or trichomonads. Leukorrhea sometimes is
considered excessive by patients, and they need reassurance.7,63
The major causes of vaginitis in adolescents are BV, candidiasis, and
T. vaginalis infection. BV has replaced the term nonspecific vaginitis
because the condition usually is not inflammatory but arises from a
change in the vaginal flora.7,64 Less common causes of vaginitis in ado-
lescents include ulceration and infection associated with tampons, cervi-
cal caps, vaginal contraceptive ring, and other foreign bodies; chemical
agents such as those found in douches and spermicides; and toxin-
producing Staphylococcus aureus.6,7,65
Bacterial Vaginosis.  BV is the most common cause of vaginitis in
postpubertal women, affecting approximately one third of women.63,66–68
BV represents a disruption in the normal vaginal flora, with a decrease
in lactobacilli and overgrowth of a variety of primarily anaerobic organ-
isms. BV-associated organisms include G. vaginalis, genital mycoplasmas
(M. hominis), U. urealyticum, Bacteroides, Prevotella, Porphyromonas,
Peptostreptococcus, Fusobacterium, and Mobiluncus species.63,64,69–71
Although many patients with BV have moderate to heavy concentrations
of vaginal Gardnerella species, detection of this organism is not diagnostic
because vaginal colonization is common in patients without BV and not
specific for the diagnosis.63,64,71
New technologies employing amplification of ribosomal RNA are
being used to characterize bacterial species that are not identified by
culture 64,70–72 They include three clostridial bacteria, Leptotrichia and
Megasphaera species, and Eggerthella-like bacteria.70–72 In one study,
detection of these noncultivatable bacteria had excellent sensitivity and
specificity for diagnosing BV compared with standard diagnostic
criteria.71
In a multivariate analysis of NHANES data from 2001 through 2004,
risk factors for BV included a higher number of lifetime sex partners,
douching, low educational achievement, and being non-Hispanic black.68
BV has also been associated with poverty, smoking, having a female
sex partner, high body mass index, and previous pregnancy.68,73,74 The
prevalence of BV among women attending STI clinics is higher (30%
to 37%) than among college students (4% to 15%)7 and the prevalence
of BV in a nationally representative sample of 14-19 year old women
was 18.5%.68
BV is more common among adolescents and young adults who are
sexually active and have multiple sexual partners. However, designating
BV as an STI has been controversial because some studies have found BV
in sexually inexperienced females.64,66,68,75,76 One study of women entering
the military found that 19% of subjects denying a history of vaginal
intercourse met criteria for BV compared with 28% who had been active
sexually.75 Another study questioned the accuracy of sexual histories
having failed to find BV in truly sexually inexperienced college students.77
Studies have shown a concordance between the presence of G. vaginalis
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in the urethra of male sex partners of women diagnosed with BV but did
not find this organism in male controls.64 Sexual activity, multiple sexual
partners, receptive oral sex, and vaginal insertion of sex toys that were
not cleaned are associated with BV, whereas the use of condoms appears
to be protective.64,73,74,77–80 Treatment of sex partners does not appear to
prevent recurrence.64 However, a systematic review of randomized, con-
trolled trials of male partner treatment for BV criticized these studies for
having methodologic flaws.81
Up to one third of women experience recurrent episodes of BV within
3 months of treatment.66 In one study, factors associated with recurrence
over a 12-month period included a history of BV and having a female
sex partner or a regular sex partner.82 Recurrence may be related to
reinfection from an infected partner or to failure to re-establish lactoba-
cilli dominance with persistence of pathogenic bacteria.63,67,72 Some
investigators have postulated that the recurrence of BV is related to
persistence of a biofilm containing G. vaginalis and other organisms that
adheres to the epithelial cells and provides protection from systemic and
topical antibiotics.72,83–85
Candidiasis.  Vulvovaginal candidiasis has an estimated lifetime inci-
dence of up to 75%.86 Candidal colonization of the vagina usually origi-
nates from the gastrointestinal tract, and sexual transmission is not an
important mode of acquisition.2,63,86 As many as 30% of healthy asymp-
tomatic women are colonized with yeast, and Candida albicans is the
organism found in most uncomplicated cases.63,66 Risk factors include
pregnancy, poorly controlled diabetes, immunosuppression, receptive
oral sex, use of estrogen, and use of various contraceptives, including
intrauterine devices, diaphragms, vaginal rings, and possibly spermi-
cides.63,65,66,86 Antibiotic use is mentioned frequently, but it is not a major
cause of infection in most women. Rather, colonization by species of
Candida may place a subpopulation of women at higher risk for symp-
tomatic infection.66,86–88 For approximately one half of girls and women,
no risk factors are identified.63,66
Most women experience uncomplicated vulvovaginal candidiasis, with
infrequent mild to moderate episodes caused by C. albicans.86 However,
10% to 20% of women have complicated vulvovaginal candidiasis that is
more severe, recurrent, or caused by other Candida species. These women
are more likely to have underlying medical risk factors such as diabetes
or immunocompromise.2,86 Approximately 5% of women have recurrent
disease (i.e., ≥4 episodes in a 12-month period), which is more likely to
be associated with C. glabrata and other non-albicans Candida
species.2,66,86,89 Most women with recurrent vulvovaginal candidiasis do
not have diabetes mellitus or immunosuppression, but these conditions
increase the risk. It is postulated that some patients may have a genetic
predisposition to recurrent vulvovaginal candidiasis, suppression of local
immunity due to virulence factors produced by the Candida species, or
an alteration in local innate response leading to an aggressive inflamma-
tory leukocytic response to yeast colonization.63,66,86,90,91
Trichomonas vaginalis.  T. vaginalis is the third most common cause of
infectious vaginitis and has a worldwide distribution, with prevalence in
community-based studies ranging from 2% to 46% of women.10,63 It is
the most prevalent curable STI worldwide, with most cases found in
women.27 In the United States, an estimated 3.7 million people are
infected.37
Studies using PCR testing of urine or vaginal swabs from girls and
women between the ages of 14 and 26 years have shown T. vaginalis
prevalence rates of approximately 2% to 3%, which was higher than the
rate for gonorrhea among the same people.52 Certain populations may
have a higher prevalence, including 26% of symptomatic and 7% of
asymptomatic women at STI clinics, up to 18% of patients at adolescent
clinics, 10% of women in college health programs, and up to 47% of
incarcerated women.2,10,52 Other risk factors include being African Ameri-
can, smoking, using alcohol and drugs, having multiple partners, and
adolescents having an older sexual partner.2,10 T. vaginalis facilitates
transmission and acquisition of HIV and commonly is associated with
other STIs.
Clinical Manifestations and Differential Diagnosis
Clinical presentations that help differentiate BV from candidal vulvovagi-
nitis and trichomonal vaginitis are shown in Table 51.4. In the sexually
active adolescent, cervicitis also must be excluded because it can occur as
a coinfection or as the sole cause of the vaginal discharge.92
 Urethritis, Vulvovaginitis, and Cervicitis 51
TABLE 51.4  Characteristics and Recommendations for Treatment of Vaginitis in Adolescents
Bacterial Vaginosis Candidal Vaginitis Trichomonal Vaginitis
SYMPTOMS
Odor of vaginal discharge Malodorous Usually not malodorous May be malodorous
Vulvar itch Sometimes Yes or discomfort Yes
Dysuria Sometimes Yes Yes
Dyspareunia Sometimes Yes Yes
Other symptoms No Symptoms often exacerbated No
before menses
SIGNS
Appearance of vaginal Thin, homogeneous, white, clings to vaginal wall, Thick, curd-like Heavy, grey or yellow-green, frothy
discharge ± frothy
Other signs No Vulvar and vaginal erythema, vulvar Vulvar and vaginal erythema
edema
LABORATORY FINDINGS
pH >4.5 <4.5 >4.5
KOH preparation Fishy, amine odor when mixed with 10% KOH Hyphae or pseudohyphae Occasionally positive whiff test
(positive whiff test)
Saline preparation Clue cells, few neutrophils Neutrophils and epithelial cells in Motile trichomonads, neutrophils
equal numbers
Gram stain Few gram-positive bacilli; abundant mixed flora Hyphae or pseudohyphae or Trichomonads visualized rarely
blastospores
Culture Not useful Can be useful if KOH negative Culture more sensitive than wet mount
TREATMENT
Oral Topical intravaginala Oral
Metronidazole (500 mg bid for 7 days) or Butoconazole cream Metronidazole (2 g for 1 dose or
clindamycin (300 mg bid for 7 days) or Clotrimazole cream 500 mg bid for 7 days) or tinidazole
tinidazole (2 g qd for 2 days) or tinidazole (1 g Miconazole cream or vaginal (2 g in a single dose)
qd for 5 days) suppository
Topical intravaginal Terconazole cream or vagina
Clindamycin cream 2% (one full applicator suppository
amount per vagina at bedtime for 7 days) or Tioconazole ointment
clindamycin ovules (100 mg per vagina at Oral
bedtime for 3 days) Fluconazole (150 mg once)
Metronidazole 0.75% gel (one full applicator
amount per vagina qd for 5 days)
a
Intravaginal therapies are available in 1- to 14-day regimens.
KOH, potassium hydroxide.

Symptomatic BV manifests with a thin, white-grey, homogeneous
vaginal discharge that adheres to the vaginal walls and has a fishy odor.64,66
Women with symptomatic candidal infection commonly complain of
vaginal pruritus and burning, dysuria, and dyspareunia. Discharge
can be thick and white with a cottage cheese appearance or can be
watery and homogeneous. Discharge usually is not malodorous, and
in many cases, women do not notice a change in vaginal discharge.66,86
Patients with symptomatic trichomoniasis often have pruritus and a
malodorous, frothy, yellow or greenish discharge and can have dysuria,
abdominal pain, vulvar erythema and edema, and bloody vaginal
discharge. Cervicitis can occur, with punctuate hemorrhages (i.e., straw-
berry cervix) and friability. Asymptomatic T. vaginalis infection occurs
commonly.10
Laboratory Findings and Diagnosis
Laboratory features that help distinguish BV from candidal vulvovaginitis
and trichomonal vaginitis are shown in Table 51.4.
Bacterial Vaginosis.  The diagnosis of BV is commonly established in
the clinical setting by the finding of three or more of the following Amsel
criteria: (1) thin, homogeneous vaginal discharge; (2) vaginal pH >4.5;
(3) characteristic fishy or amine odor released when 10% KOH is added
to the vaginal fluid specimen (i.e., positive whiff test); and (4) 20% or
more of epithelial cells having the appearance of clue cells, which are
stippled epithelial cells whose borders are obscured by adherent bacteria
(see Fig. 51.1).64 Diagnostic accuracy increases with use of the Amsel
criteria.25 Alternative tests include the use of Gram stain to group bacteria
into morphologic types (i.e., Nugent scoring). Amsel criteria and Nugent
scores show good correlation.2,93
Alternative testing includes nonmicroscopic point-of-care testing.
Some tests detect the metabolic products of BV-related organisms such
as sialidase and prolineaminopeptidase.2,64 A DNA probe for G. vaginalis
ribosomal RNA is available but is not useful if rapid results are needed.
This test is most helpful as a supplemental marker to detect high con-
centrations of G. vaginalis.22,93
Routine aerobic and anaerobic vaginal cultures are not helpful, and
molecular diagnostic techniques are primarily a research tool.2,67 BV
usually does not produce an inflammatory response, and the finding of
WBCs on a vaginal smear indicates concurrent vaginitis or cervicitis due
to another cause.92,93
Candida species.  Candida vaginitis is diagnosed by demonstrating
budding, hyphae, pseudohyphae, or blastospores on microscopic exami-
nation of a saline or 10% KOH preparation.2,63 This technique has a
sensitivity of about 50% because organisms such as C. glabrata, which
does not form hyphae or pseudohyphae, are easily missed on microscopy.2
If the KOH preparation is negative, culture can confirm the diagnosis in
symptomatic people.67,86 Culture may be particularly helpful for patients
with ongoing nonspecific symptoms in whom BV and trichomoniasis

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 PART II  Clinical Syndromes and Cardinal Features of Infectious Diseases: Approach to Diagnosis and Initial Management
SECTION G  Genitourinary Tract Infections
have been excluded.86 In cases of complicated vulvovaginal candidiasis,
culture is important in identifying the species of the organism because
therapy may be different or longer.63,94 Culture can also demonstrate
eradication of the organism, and for patients with persistent symptoms,
an alternative cause should be investigated.63,94 It is useful to measure
vaginal pH because the vaginal pH remains low (<4.5) in vaginal candi-
diasis, unlike BV or trichomoniasis.86
Trichomonas vaginalis.  Diagnosis of trichomoniasis can be made by
visualizing the motile protozoa on a wet mount preparation; however,
the test result is negative in 30% to 50% of cases.2,67 Culture using
Diamond media or the InPouch T. vaginalis culture system is more sensi-
tive.2,25,67 Culture can be performed on vaginal specimens, including
patient self-collected specimens.
Conventional and liquid Papanicolaou (Pap) tests are not considered
diagnostic because of high false-positive and false-negative rates.2,95 A
DNA probe test has a sensitivity of 63% and specificity of 99% compared
with culture and TMA. It usually is best performed in the laboratory
rather than the office setting because the test is moderately complex and
requires about 45 minutes to complete.2
One point-of-care test that uses an immunochromatographic capillary
flow assay with monoclonal antibodies takes 10 minutes to complete and
has 82% to 95% sensitivity and 97% to 100% specificity.2 PCR has excel-
lent sensitivity and specificity (85% to 100%) but is not available com-
mercially.10 TMA has 95% to 100% sensitivity and 95% to 100% specificity
and is approved for endocervical, urine, and vaginal swab specimens in
women.2,47,48 NAAT using SDA is approved for use with female endocervi-
cal, vaginal, and urine specimens.2
Because urine or vaginal specimens collected without use of a specu-
lum can be used to detect trichomoniasis, vulvovaginal candidiasis, N.
gonorrhoeae, and C. trachomatis, it is possible to avoid the more invasive
speculum examination to determine the cause of vaginitis in
adolescents.
Management
Bacterial Vaginosis.  Metronidazole administered orally for 7 days is
the recommended therapy for women with symptomatic BV,2 and it is
preferred over single-dose therapy because of superior efficacy.2,25,64,69
Alternative regimens with intravaginal metronidazole or clindamycin,
which are outlined in Table 51.4, have fewer gastrointestinal side effects
and cure rates similar to those for oral metronidazole at 1 month
after treatment.2,25,67,69 Clindamycin cream should not be used when
condoms are used because the oil base weakens the latex.2 Alternate
therapeutic regimens have included the use of tinidazole, which has
fewer side effects than metronidazole but is more expensive, and oral
clindamycin.2,66,96
A Cochrane review found insufficient evidence to recommend for or
against probiotics. The 2015 STD treatment guidelines do not recom-
mend this therapy or currently available lactobacillus formulations as
adjunctive or replacement therapy to restore normal vaginal flora.2,97
There are no current standard recommendations for treatment of
recurrent BV infection, which occurs within 3 months in approximately
one third of women.69 Treatment may only suppress biofilm-embedded
infection and allow organisms to evade host defense responses. Recur-
rences may be due to relapse rather than reinfection.67,69,85 A large, mul-
ticenter study demonstrated the 70% efficacy of twice-weekly maintenance
therapy using metronidazole vaginal gel, but it only suppressed BV in
many subjects and led to vaginal candidiasis as a complication.98,99 One
uncontrolled study showed promising results with nitroimidazole and
boric acid used to disrupt the biofilm and allow penetration of the
antibiotic.100 Other regimens that have been evaluated include oral
nitroimidazole and intravaginal boric acid followed by suppressive
metronidazole gel and a combination of monthly oral metronidazole and
fluconazole.100,101 The latter regimen was associated with decreased BV
episodes and increased colonization with normal flora.
Long-term treatment with vaginal metronidazole is well tolerated,
unlike oral treatment, which can be associated with neutropenia or
peripheral neuropathy. Prolonged treatment with clindamycin increases
the risk of C. difficile colitis.69 Resistance to metronidazole and clindamy-
cin has been seen in cases of recurrent BV.68 The 2015 STDs treatment
guidelines do not recommend treating asymptomatic nonpregnant
women.2
364
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Candidiasis.  Topical therapy with azoles, such as clotrimazole, tercon-
azole, miconazole, butoconazole, and tioconazole, is effective for vulvo-
vaginal candidiasis in 1- to 7-day regimens. Many of these topical
formulations are available over the counter. Single-dose fluconazole
(150 mg) therapy has efficacy that is comparable to topical therapy.2,63,66,102
Symptomatic relief and negative fungal cultures are achieved in up to
90% of patients with uncomplicated vulvovaginal candidiasis. Sexual
partners usually do not require therapy unless they have candidal
balanitis.2
Recurrent or chronic candidal vulvovaginitis merits investigation for
predisposing conditions, which includes obtaining cultures to confirm
the diagnosis and identify the pathogen.63 These infections may require
a longer duration of topical (7 to 14 days) or oral therapy including
nonfluconazole imidazole drugs.2,66,67,86 Topical boric acid in the form of
suppositories (600 mg in a gelatin capsule) and topical flucytosine have
been useful in patients with non-albicans Candida species and imidazole-
resistant species. Alternative therapies are useful, especially in cases of
non-albicans Candida species.66,86,94 When using fluconazole, patients
with recurrent vulvovaginal candidiasis can be treated initially with a
single dose every 3 days for a total of three doses, followed by 100 mg,
150 mg, or 200 mg once each week for 6 months.2 For women who
cannot take fluconazole, repeated topical imidazole therapy has been
effective.2,66,67
Suppressive therapy usually is continued for 6 months, but recurrence
is common after therapy is discontinued because organisms are sup-
pressed rather than eradicated. Prophylaxis can be reinstituted.2,63,86
Fluconazole resistance and clinical failure is uncommon but increasing,
and although not usually warranted, in patients with breakthrough
Candida infection, susceptibility testing may be helpful.2,103 Only topical
azole medications are recommended in pregnancy.2
Trichomonas vaginalis.  Systemic therapy with oral metronidazole or
tinidazole is indicated for treatment of trichomoniasis.2 Metronidazole
has an 84% to 98% cure rate with a 7-day course (500 mg twice daily)
or a large single dose (2 g taken orally). Most recurrent infections are
from reinfection, and although uncommon, metronidazole resistance has
been reported in approximately 4% to 10% of cases.2,49,67,69 Topical
therapy with metronidazole gel is not effective because the gel does not
penetrate the urethral and perivaginal glands adequately.2,10,49
Single-dose tinidazole (2 g taken orally) has a 92% to 100% cure rate
and reports of 1% resistance.2 Studies show tinidazole to be equivalent
or superior to single-dose metronidazole for cure and symptom resolu-
tion.2 One study found a 92% cure rate using a combination of oral and
vaginal tinidazole in patients unresponsive to metronidazole.104 Tinida-
zole appears to be better tolerated than metronidazole and has fewer
gastrointestinal tract and central nervous system side effects.
Sexual partners should be evaluated for STIs and treated for tricho-
moniasis. For treatment failures, susceptibility testing is recommended
for metronidazole and tinidazole.2,49 Women with HIV infections should
be treated with metronidazole for 7 days rather than single-dose therapy
because the latter is less effective in these patients due to concurrent BV,
impaired immunity, and concurrent antiretroviral therapy, which may
impact clearance and reduce the efficacy of metronidazole.2,105 There are
no contraindications to using metronidazole during pregnancy, but
tinidazole should not be used because of concerns about moderate
adverse risks.2
Complications
Bacterial Vaginosis.  BV has been associated with chorioamnionitis,
postpartum endometritis, posthysterectomy vaginal cuff cellulitis, post­
abortion PID, premature rupture of membranes, preterm labor and
delivery, low birth weight, spontaneous abortion, and intra-amniotic
infection.25,64,76,106 The risk of preterm delivery is restricted to a small
subset of women; risk may be related to the genetic host response to
inflammation and cytokine production.25,64,76 Vaginal microorganisms
can ascend to the upper tract, causing infection and inflammation in the
decidua, chorioamnion, or amniotic fluid.64
Data are conflicting about whether the treatment of pregnant women
for BV prevents complications.2,25,64,76,107–110 Two systematic reviews found
little evidence that screening and treating all pregnant women prevents
preterm birth.108,109 The evidence for screening asymptomatic women at
low risk for preterm delivery were poor, and evidence for women at high

risk for preterm delivery were conflicting. The 2015 STD treatment
guidelines state that the evidence is insufficient to recommend screening
of asymptomatic pregnant women at low or high risk for preterm deliv-
ery, but they do recommend treatment for all symptomatic pregnant
women using any oral or vaginal regimen.2
BV has been associated with an elevated risk of acquiring T. vaginalis,
N. gonorrhoeae, C. trachomatis, and HSV-2.2,109,111 Studies also have
shown an association between BV and cervicitis and PID, but a causal
relationship remains unproved.64,66 Organisms associated with BV have
been found in the upper genital tracts of women with PID. Studies using
endometrial biopsies have found an association between BV and endo-
metritis, which may be silent clinically or manifest as intermenstrual or
increased bleeding.64
Women with BV are more likely to have PID, and women with PID
are more likely to have BV.25,64,76 Treatment of BV has been associated
with decreased PID in women undergoing abortion and decreased
postoperative cuff cellulitis.64,76 Intravaginal treatment of BV has been
associated with improved rates of resolution of cervicitis.64 However, the
relationship between BV and PID for women not undergoing abortion
or uterine instrumentation is not clear.25,76,112 There is no current recom-
mendation for treatment of nonpregnant, asymptomatic women as a
standard clinical practice.2,64
Trichomonas vaginalis.  Trichomoniasis has been associated with pre-
mature rupture of membranes, preterm delivery, and low-birth-weight
infants,.2,25,113 T. vaginalis has also been associated with an increased risk
of PID in women who are HIV positive.2,113 Although treatment of T.
vaginalis during pregnancy does not appear to reduce complications, the
2015 CDC STD treatment guidelines recommend that all symptomatic
pregnant women should be tested and considered for treatment at any
stage of pregnancy.2,107,114 Although a single dose of metronidazole has
been demonstrated to be safe at all stages of pregnancy, more studies are
needed regarding use of tinidazole, and current recommendations rec-
ommend avoiding use in pregnancy.2
Human Immunodeficiency Virus.  BV and T. vaginalis enhance acquisi-
tion of HIV and transmission to a partner.2,25,29,64,76,105,115 Vulvovaginal
candidiasis has been associated with increased HIV seroconversion in
HIV-negative women and higher levels of cervicovaginal HIV shedding
in HIV-positive women. Treatment of T. vaginalis reduces HIV viral
shedding in vaginal secretions.105 However, no studies have demonstrated
similar effects on viral shedding in subjects with BV or vulvovaginal
candidiasis.2,25
Vulvitis in Adolescents
Inflammation of the vulva in adolescents most commonly is caused by
HSV and yeasts (see Table 51.4). HSV often causes painful genital ulcers,
along with vulvar inflammation and inguinal lymphadenopathy (see
Chapter 50).7 Occasionally, inflammation can be associated with T. vagi-
nalis infection.
Prevention
Correct and consistent use of condoms is the most effective means of
preventing and reducing transmission of the STIs associated with
vulvovaginitis.
CERVICITIS
Cervicitis is inflammation of the endocervix or ectocervix. Both are
common problems among adolescents, but neither is common in prepu-
bertal girls. Under the influence of estrogens after puberty, the vaginal
epithelium and ectocervix become cornified and relatively resistant to
infection with a number of pathogens, including N. gonorrhoeae and C.
trachomatis.7 In contrast, the endocervix continues to be lined with
columnar epithelium and remains susceptible to infection with these
organisms. In adolescents and adult women, these organisms usually
cause endocervicitis in the absence of vaginitis.
A normal developmental finding in adolescents is the ectropion, an
erythematous area surrounding the os at the junction between columnar
and stratified squamous epithelium. During adolescence, the ectropion
recedes as the result of squamous metaplasia. Although some adolescents
with a large ectropion may have significant vaginal discharge, this is not
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Urethritis, Vulvovaginitis, and Cervicitis 51
a pathologic or infectious process. The ectropion usually is not friable,
and edema or friability suggests infection.6
Ectocervicitis
Ectocervicitis represents infection of the stratified squamous epithelium
of the ectocervix. Ectocervicitis can occur in conjunction with trichomo-
nal vaginitis and HSV infection. HSV causes ectocervicitis and
endocervicitis.6
Endocervicitis
Etiologic Agents and Epidemiology
Endocervicitis represents infection of the endocervical columnar epithe-
lium and can produce mucopurulent cervicitis. Common pathogens that
cause endocervicitis are N. gonorrhoeae, C. trachomatis, M. genitalium,
and HSV.6,116–119 Multiple studies have demonstrated an association
between M. genitalium and mucopurulent cervicitis.16,33,36,59,116–118,120–123
There also is a possible association with BV because cervicitis is more
likely to resolve when patients also are treated for BV.25,116–118,120 Theories
about this relationship include proinflammatory vaginal cytokines in
patients with BV and the glycosidases and proteinases produced by
BV-associated organisms that may degrade cervicovaginal mucus.116,117
The prevalence of cervicitis varies from 22% to 41% depending on the
definition used, which is inconsistent among the various studies in the
literature.116 A randomized, multicenter study that ruled out C. tracho-
matis, N. gonorrhoeae, T. vaginalis, and M. genitalium by NAAT found
that 61% of subjects had mucopurulent cervicitis of unknown origin.124
Clinically apparent cervicitis is not caused solely by sexually transmit-
ted agents. Other entities include tuberculosis, noninfectious causes such
as sarcoidosis and Behçet disease, and local insults due to chemical
douches, spermicides, and foreign bodies.116–119
Clinical Manifestations and Differential Diagnosis
Endocervicitis often is overlooked and underdiagnosed because signs and
symptoms can be mild or absent. PID is one consequence of untreated
mucopurulent cervicitis.6 Sexually active adolescents with vaginal dis-
charge, lower abdominal pain, abnormal vaginal bleeding, or deep dys-
pareunia should be evaluated for endocervicitis.6 Evaluation also is
indicated if a sexual partner has an STI.
Cervical abnormalities associated with endocervicitis range from
subtle changes to a yellow endocervical discharge and an edematous,
erythematous, and easily friable appearance to the cervix.6 There is no
consensus definition for mucopurulent cervicitis, which makes evalua-
tion of the research literature difficult.116,117 Definitions include inflam-
mation of the endocervix with possible edema, yellow-green endocervical
discharge, increased numbers of neutrophils on microscopic examina-
tion of cervical secretions, and inducible endocervical bleeding.
The 2015 CDC STD treatment guidelines outline the two major
diagnostic criteria as purulent or mucopurulent endocervical discharge
and sustained endocervical bleeding.2 Mucopurulence is characterized by
a yellow or green color on a cotton-tipped applicator obtained from the
endocervix. The number of neutrophils considered significant varies in
different studies from at least 30 cells per 400× magnified microscopic
field to more than 10 cells per 1000× magnified microscopic field.
Although the use of a 30-cell cut point provides greater specificity, detec-
tion of yellow endocervical mucopus is more accurate than the number
of WBCs.2,6,117–119
Laboratory Findings and Diagnosis
Specific microbiologic diagnosis informs appropriate treatment. Patients
should be tested for N. gonorrhoeae, C. trachomatis, T. vaginalis, and BV.
Gram-negative intracellular diplococci are seen on Gram stain in about
one half of cases of gonococcal endocervicitis.6 Given the poor sensitivity
of the Gram stain and the possibility of infection in the absence of any
abnormality, evaluation for gonococcal endocervicitis must include
NAAT.2 Inflammatory changes can be even less remarkable with endo-
cervicitis caused by C. trachomatis. NAAT is recommended in all cases of
suspected C. trachomatis infection.2 A saline wet mount preparation can
365
 PART II  Clinical Syndromes and Cardinal Features of Infectious Diseases: Approach to Diagnosis and Initial Management
SECTION G  Genitourinary Tract Infections

TABLE 51.5  Treatment of Cervicitis in Adolescents
Results
Mucopurulent or purulent
endocervical discharge and/
or sustained easily induced
endocervical bleeding
Trichomonas seen on wet
mount or identified on rapid
test, culture, NAAT
Bacterial vaginosis diagnosed
Clinical presentation suggesting
herpes simplex virus
infection
Persistent or recurrent cervicitis
BV, bacterial vaginosis; CDC, Centers for Disease Control and Prevention; NAAT, nucleic acid
amplification test, STIs, sexually transmitted infections.
a
Data from Workowski KA, Bolan GA. Sexually transmitted diseases treatment guidelines,
2015. MMWR Recomm Rep 2015;64(RR-3):1–137.
Suggested Treatment
Treat for Chlamydia trachomatis or
Neisseria gonorrhoeae with positive
test results or consider presumptive
treatment for C. trachomatis and N.
gonorrhoeae if prevalence is high in
patient population or community
(e.g., known contact, new and/or
multiple sex partners, age ≤25,
unprotected sex) and testing not
possible and/or follow-up cannot be
ensured; if at low risk for STIs,
treatment can be deferred pending
microbial results
Treat with oral metronidazole or
tinidazole
Treat with oral metronidazole or
tinidazole or intravaginal
metronidazole or clindamycin
Consider oral acyclovir or famciclovir or
valacyclovir
Rule out re-exposure or treatment failure
for N. gonorrhoeae and C.
trachomatis or other identified STIs
and exclude BV. Testing for
Mycoplasma genitalium in settings
with validated assays can be
conducted. Moxifloxacin can be used
if NAAT results are positive and initial
treatment with azithromycin (1 g PO
once) failed. CDC recommends
deferring therapy until further
microbial results are availablea
at lower risk for STIs, treatment can await the results of diagnostic
testing.2
More data are needed about the treatment of M. genitalium cervicitis.
The antibiotics directed at treating N. gonorrhoeae and C. trachomatis are
not adequate to treat cervicitis caused by other organisms, and the
standard treatment regimen for PID with cefoxitin and doxycycline is
ineffective for women with M. genitalium associated with PID.120,125,126
Testing for M. genitalium is recommended for women with persistent
cervicitis or persistent PID for whom re-exposure to an infected partner
or nonadherence has been ruled out.2,35,116 If the initial treatment did not
include azithromycin, the antibiotic should be given. According to CDC
guidelines, moxifloxacin can be given based on having positive M. geni-
talium test results.2 Other investigators have suggested considering this
treatment for recurrent or persistent cervicitis when testing is not avail-
able,35 but some have questioned the treatment of cervicitis of unknown
origin because the clinical cure described is not related to antibiotic
therapy.127
The need to consider M. genitalium in the adolescent population was
demonstrated in several studies. One showed a cumulative rate over a
27-month period among 14- to 17-year-old girls to be 14%, which was
concordant with their male partners.128 Another study of girls and women
14 to 21 years old found a rate of 22%.129
Follow-up after completion of therapy is recommended for adoles-
cents with persistent symptoms.2 The management of mucopurulent
cervicitis also requires evaluation and treatment of all sexual partners for
STIs, and it provides an opportunity to reinforce STI prevention
measures.2
Complications
Complications of untreated mucopurulent cervicitis include PID and the
possible long-term sequelae of ectopic pregnancy and infertility. The
relationship between N. gonorrhoeae or C. trachomatis and PID is well
established, and there is increasing evidence that M. genitalium also is
associated with PID.6,59,118,130–132 Cervicitis also increases the risk of trans-
mission and acquisition of HIV infection. Viral shedding of HIV decreases
with effective treatment for cervicitis.2,6,118
Prevention
Consistent use of condoms can reduce transmission of STI pathogens
associated with cervicitis.

All references are available online at www.expertconsult.com.

be used to diagnose T. vaginalis and to help establish the diagnosis of

BV.2,6,7,117 Because of the poor sensitivity of wet mounts, further testing
for T. vaginalis by culture, antigen-based tests, or NAAT should be con-
ducted if the wet mount result is negative.
If HSV is suspected, a culture or PCR test should be obtained, although
the utility of HSV testing remains unknown.2 NAAT for M. genitalium is
not available commercially but may be available in laboratories where
validation testing has been completed.2
Treatment
The initial management of endocervicitis depends on the clinical findings
and risk of the adolescent for certain STIs (Table 51.5). A positive labora-
tory test result for N. gonorrhoeae, C. trachomatis, T. vaginalis, or HSV
defines treatment. However, empiric treatment can be considered if there
is a strong suspicion of N. gonorrhoeae or C. trachomatis based on a high
prevalence of either microbe in the community or a concern that the
patient may be at risk for loss to follow-up.2,120
BV should be treated because some studies have shown higher rates
of resolution of endocervicitis with treatment of BV.117 For women
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