In most patients, the pathogenesis of recurrent VVC cannot be
Treatment of recurrent C. albicans vulvovaginitis should include a prolonged (7–
14-day) course of topical therapy or a three-dose regimen of oral fluconazole (100,
150, or 200 mg) administered every 3 days. A 6-month maintenance regimen should
be initiated after remission has been achieved (Table 72-7). Despite the efficacy of
these regimens, discontinuation of therapy after 6 months can result in relapse in 30%
2 Azole-resistant strains of C. albicans are rare; therefore, culture
and sensitivity testing is not usually performed to help guide treatment before
Maintenance Regimens for Recurrent Vulvovaginal Candidiasis
Clotrimazole 200 mg Intermittently
Clotrimazole vaginalsuppositories 500 mg Intermittently
Fluconazole tablets 100, 150, or 200 mg Weekly for 6 months
aGiven as examples only, CDC does not indicate a preferred regimen.
Adapted from Workowski KA, Bolan GA; Centers for Disease Control and Prevention (CDC). Sexually
transmitted diseases treatment guidelines, 2015. 2015;64(RR-03):1–137.
Vulvovaginal Candidiasis During Pregnancy
CASE 72-11, QUESTION 12: What teratogenic risks are associated with the use of azole preparations?
Vaginal colonization with Candida and symptomatic VVC are common during
125 Asymptomatic colonization is not associated with increased maternal
or fetal risks and need not be treated.
126 However, symptomatic VVC should be
treated. Although doses of oral fluconazole used to treat VVC have not been
associated with increased fetal defects, higher doses may be teratogenic. Therefore,
topical antifungal agents are preferred for treatment of VVC in pregnant women. The
CDC currently recommends a 7-day course of topical antifungal therapy for VVC
during pregnancy; however, a 3-day regimen with appropriate follow-up to assess
efficacy has been shown to be effective in mild-to-moderate cases. Clotrimazole is
also classified as a category B drug for fetal risk, and the remaining vaginally
administered azoles are designated as category C.
Trichomoniasis is the most prevalent nonviral STD caused by the protozoan T.
2 The overall prevalence is estimated at 3.1% with the highest prevalence
among African Americans at 13.3%. Trichomoniasis in women is asymptomatic or
with minimal symptoms about 70% to 85% of the time. In men, T. vaginalis
presumably infects the urethra, although the site of infection (urethra vs. prostate) is
uncertain. Classic symptoms of trichomoniasis in women include a diffuse, yellow–
green discharge with pruritus, dysuria, and a “strawberry” cervix (cervical
microhemorrhages). The latter are typically seen only in 2% to 25% of cases.
almost all cases of trichomoniasis, a vaginal pH greater than 5 is observed.
Papanicolaou smear is associated with a 48.4% error in diagnosis when used
127 Direct microscopic observation of trichomoniasis using a wet mount is
inexpensive and yields a high specificity, but it has a low sensitivity.
options include culturing, rapid antigen tests, and NAATs.
CASE 72-12, QUESTION 2: How should N.B.’s trichomoniasis be treated?
The only class of drugs that is effective for the treatment of trichomoniasis is the
nitroimidazoles. In the United States, metronidazole and tinidazole are the only
available nitroimidazoles and both are CDC-recommended first-line agents given as
a single 2 g oral dose. In addition, sexual partners should be simultaneously treated
to prevent reinfection. Metronidazole cure rates are reported to be 84% to 98%,
whereas tinidazole cure rates are reported to be 92% to 100%; concurrently treating
might increase these rates. Tinidazole offers other advantages, such as higher
serum and genitourinary levels, a longer half-life, and fewer gastrointestinal adverse
Approximately 4% to 10% of T. vaginalis isolates exhibit a low-level resistance
to metronidazole therapy and 1% to tinidazole therapy; however, higher-level
resistance appears to be rare.
If metronidazole 2 g PO for one dose fails and
reinfection is excluded, metronidazole 500 mg PO twice daily for 7 days can be
used. However, if this regimen fails either metronidazole or tinidazole 2 g PO as a
single dose for 7 days should be used. In the case of allergy to nitroimidazole
compounds, patients should be desensitized to metronidazole and subsequently
CASE 72-12, QUESTION 3: N.B. was treated with metronidazole 2 g as a single dose; however, while
N.B.’s symptoms be caused by metronidazole?
Minor side effects associated with metronidazole therapy include nausea, vomiting
(especially with single-dose therapy), headache, skin rashes, and alcohol intolerance.
The alcohol intolerance may be attributable to a metronidazole-induced inhibition of
aldehyde dehydrogenase, which results in the buildup of high serum acetaldehyde
levels, although the true risk of this interaction has been debated.
manufacturer, patients should be warned about the possibility of nausea, vomiting,
flushing, and respiratory distress after alcohol consumption, although reliable
123 As a general rule, patients should avoid alcohol ingestion
during treatment and for 72 hours after metronidazole or tinidazole therapy. In those
patients who cannot otherwise tolerate oral metronidazole or tinidazole, a
combination of intravaginal miconazole and metronidazole may be an effective
trichomoniasis is confirmed by a wet-mount examination of vaginal secretions revealing numerous
well as that of her fetus. Can metronidazole be used for S.G.?
During pregnancy, trichomoniasis is associated with premature rupture of the
membranes, preterm delivery, and low birth weight. In one study, rates of preterm
delivery appeared to increase in women who received metronidazole, but a
definitive causation could not be determined.
134 However, caution should still be
exercised if metronidazole must be administered within the first trimester.
Metronidazole is mutagenic in facultative bacteria and contains a nitro-reductase
enzyme. Long-term, high-dose metronidazole in laboratory mice is associated with
the development of pulmonary and hepatic tumors. Midline facial defects have been
documented in humans, but two literature reviews indicate that metronidazole is not a
In contrast, the use of metronidazole in asymptomatic women has not
been shown to decrease rates of preterm labor despite eliminating the organism from
CASE 72-13, QUESTION 2: How should S.G. be treated?
All symptomatic women should be treated with metronidazole 2 g PO as a single
dose. Metronidazole is classified as pregnancy category B. Tinidazole 2 g PO as a
single dose could be suggested as an alternative regimen; however, it is classified as
The word herpes is of Greek origin and means “to creep.” HSV is a DNA-containing
virus that consists of two antigenically distinct serotypes: HSV-1 and HSV-2. The
primary cause of herpes labialis (cold sores), herpes keratitis, and herpetic
encephalitis is HSV-1. Genital herpes and neonatal herpes primarily are the result of
HSV-2 infections. However, up to 50% of all reported cases of primary genital
herpes are caused by HSV-1 infections acquired through oral sex.
Most people are exposed to HSV-1 early in life with more than half being positive
for HSV-1 antibodies before 18 years and more than 90% of the population positive
140 The infection is often asymptomatic and generally acquired
through primary infection of mucocutaneous surfaces. The initial, primary disease is
a gingivostomatitis characterized by vesicles in the oral cavity and occasionally an
elevated temperature; life-threatening encephalitis or keratitis may appear during this
interval. Usually after primary exposure, HSV-1 enters cells of the trigeminal
ganglion, where it may remain latent for the lifetime of the host.
Initial HSV-2 infections usually occur after puberty and coincide with the onset of
sexual activity, although transfer to a neonate from an infected mother can occur.
After primary infection, the virus enters a state of latency in the sacral dorsal root
ganglia in many infected individuals; a high percentage of infected persons may never
manifest the disease clinically.
In both HSV-1 and HSV-2 infections, the latent virus can reactivate. Recurrent
disease may occur even when circulating antibody and sensitized lymphocytes are
present. Clinically, the lesions periodically erupt usually at the same location, and
the interval between episodes varies widely between individuals.
Although herpes was recognized several thousand years ago, genital herpes was not
described until the 18th century. The seroprevalence of genital herpes (HSV-2) has
remained the same in the United States since 1999—at approximately 16.2% overall
in 19- to 49-year olds, but 20.9% in women and 39.2% in non-Hispanic blacks—
making it still one of the most common STDs in the United States.
physicians saw more than 300,000 new patients presenting with genital herpes
simplex and nearly 20% of non-Hispanic white females and more than double that in
non-Hispanic black females are already seropositive in the United States.
Demographic characteristics obtained at the University of Washington indicate that
the mean number of lifetime sexual partners before acquisition of the disease was 8.8
in women compared with 32.8 in men, with the overall chance of acquiring HSV-2 of
144 The range of time from the last sexual exposure to the
onset of disease is 5 to 14 days.
142 Whether causal or not, HSV-2 infection increases
145 Of recent concern, the seroprevalence of HSV-1 in 14-
to 19-year olds declined by 23% from 1999 while the rate of HSV-2 remained
unchanged, indicating that many young adolescents will not have protective HSV-1
antibodies at sexual debut and HSV-2 prevalence may rise.
Most initial episodes of genital herpes, especially in the male, are symptomatic.
As illustrated by B.J., the symptoms usually start about 1 week after the initial
exposure with prodromal signs of tingling, itching, paresthesia, or genital burning.
The prodromal stage, which can last from a few hours to several days, is followed by
the appearance of numerous vesicles. The vesicles eventually erupt, resulting in
painful genital ulcers. The pain and edema associated with genital herpetic lesions,
especially if they are infected secondarily, can be severe enough to result in dysuria
and urinary retention. Bilaterally distributed lesions of the external genitalia are
characteristic. The lesions usually are limited to the glands, corona prepuce, and
shaft of the penis in males and to the vulva and vagina in females. However, lesions
can occur on the buttocks, thighs, and urethra.
142 Asymptomatic or mucopurulent
cervicitis occurs in about 15% to 20% of women with primary HSV-2 infections.
Rectal and perianal HSV-2 infections are more common in MSM and
immunocompromised individuals.
148 Symptoms include anorectal pain and discharge,
Prior infection with HSV-1 may ameliorate the severity of the first episode of
genital herpes, but it does not impact the rate of recurrence.
the local symptoms of pain, itching, and urethral or vaginal discharge last from 11 to
14 days, with a complete disappearance of lesions in 3 to 6 weeks.
course of primary herpes is presented in Figure 72-7. Most patients have minor
symptoms or are asymptomatic and unaware of their disease; they are most infectious
within the first year of acquisition of the virus.
CASE 72-14, QUESTION 2: Is B.J.’s infection likely to recur?
Most first episode HSV-2 symptomatic patients experience a recurrence of their
2 The rate of recurrent infections varies among individual patients.
Approximately 38% experience at least six episodes, and 20% have more than 10
150 Natural infection with HSV-2 induces type-specific immunity against
exogenous reinfection, but it does not affect recurrences.
primary episode and recurrence appear to be influenced by the host’s immune status,
especially a depressed T-cell response.
142 Recurrent infections usually appear at or
near the site of the initial infection, and prodromal symptoms are reported by about
50% of persons with recurrent infection. Men recur more frequently than women. In
contrast with primary infections, there are fewer lesions and they are often
142 Constitutional symptoms such as lymphadenopathy, fever, and malaise
generally are also milder. Recurrent infections are shorter in duration (average, 1
week); local symptoms such as pain and itching last 4 to 5 days and the lesions
142 Although there is wide variability, patients may have
four to five recurrences during the first year, but reactivation frequency can decline
by three reactivations per year during the first 2 years.
154 By about 5 years after the
initial infection, recurrence rates decrease greatly.
155 Genital infections with HSV-1,
however, recur infrequently and decrease by 50% between 1 and 2 years after
Transmission of HSV occurs by direct contact with active lesions or from a
symptomatic or asymptomatic person shedding virus at a peripheral site, mucosal
157 Genital HSV-2 infections usually are acquired through sexual
(vaginal or anorectal) intercourse, whereas genital HSV-1 infections are acquired
through orogenital sexual practices. Because HSV is inactivated readily by drying
and exposure to room temperature, aerosol and fomite spread are unusual means of
158 Condoms may act as an effective barrier to viral transmission in
women, but this method does not offer complete protection for men as women often
159 Evidence suggests that the frequency of correct condom
use is directly proportional to protection against acquisition of HSV-2 and that
condoms are more likely to be worn when lesions are present.
A patient with genital herpes is contagious only when shedding the virus. The
patient begins to shed virus during the prodromal phase, which may be several hours
to days before the actual lesions first appear. Patients can, however, be
asymptomatically diagnosed by serology and subsequently develop clinical lesions
or be symptomatic on diagnosis and have recurrent episodes of clinical lesions.
Symptomatic viral shedding occurs twice as often than in asymptomatic HSV-2
seropositive individuals, but subclinical viral shedding (i.e., no lesions present) still
occurs approximately 10% of days, regardless of gender.
standpoint, unrecognized subclinical shedding may indicate a greater need for
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