Genitourinary Infections and Sexually Transmitted Diseases
BS. Nguyễn Hồng Anh
KEY POINTS
1 Vulvovaginitis is diagnosed by office-based testing.
2 More prolonged antifungal therapy is indicated for women with complicated
vulvovaginal candidiasis (VVC) than for those with uncomplicated disease.
3 Women with normal physical examination findings and no evidence of fungal
infection disclosed by microscopy are unlikely to have VVC and should not be
treated empirically unless results of a vaginal yeast culture are positive.
4 Cervicitis is commonly associated with bacterial vaginosis (BV), which, if not treated
concurrently, leads to significant persistence of the symptoms and signs of cervicitis.
5 Women with mild-to-moderate pelvic inflammatory disease (PID) can be treated as
outpatients.
6 Trocar drainage, with or without placement of a drain, is successful in as many as
90% of patients with PID complicated by tubo-ovarian abscess that fails to respond
to antimicrobial therapy within 72 hours.
7 Because false-negative results are common with herpes simplex virus (HSV) cultures,
especially in patients with recurrent infections, type-specific glycoprotein G-based
(IgG) antibody assay tests are useful in confirming a clinical diagnosis of genital
herpes.
8 Suppressive treatment partially decreases symptomatic and asymptomatic viral
shedding and the potential for transmission.
Genitourinary tract infections are among the most frequent disorders for which
881patients seek care from gynecologists. By understanding the pathophysiology of
these diseases, and having an effective approach to their diagnosis, physicians can
institute appropriate antimicrobial therapy to treat these conditions and reduce
long-term sequelae.
THE NORMAL VAGINA
Normal vaginal secretions are composed of vulvar secretions from sebaceous,
sweat, Bartholin, and Skene glands; transudate from the vaginal wall; exfoliated
vaginal and cervical cells; cervical mucus; endometrial and oviductal fluids; and
micro-organisms and their metabolic products. The type and amount of exfoliated
cells, cervical mucus, and upper genital tract fluids are determined by biochemical
processes that are influenced by hormone levels (1). Vaginal secretions may
increase in the middle of the menstrual cycle because of an increase in the amount
of cervical mucus.
The vaginal desquamative tissue is made up of vaginal epithelial cells that are
responsive to varying amounts of estrogen and progesterone. Superficial cells, the
main cell type in women of reproductive age, predominate when estrogen
stimulation is present. Intermediate cells predominate during the luteal phase
because of stimulation by progesterone. Parabasal cells predominate in the
absence of either hormone, a condition that may be found in postmenopausal
women who are not receiving hormonal therapy.
The normal vaginal flora is mostly aerobic, with an average of six different
species of bacteria, the most common of which is hydrogen peroxide–
producing lactobacilli. The microbiology of the vagina is determined by factors
that affect the ability of bacteria to survive (2). These factors include vaginal pH
and the availability of glucose for bacterial metabolism. The pH level of the
normal vagina is lower than 4.5, which is maintained by the production of
lactic acid. Estrogen-stimulated vaginal epithelial cells are rich in glycogen.
Vaginal epithelial cells break down glycogen to monosaccharides, which can be
converted by the cells themselves, and lactobacilli to lactic acid.
[1] Normal vaginal secretions are floccular in consistency, white in color, and
usually located in the dependent portion of the vagina (posterior fornix).
Vaginal secretions can be analyzed by a wet-mount preparation. A sample of
vaginal secretions is suspended in 0.5 mL of normal saline in a tube, transferred
to a slide, covered with a slip, and assessed by microscopy. Some clinicians prefer
to prepare slides by suspending secretions in saline placed directly on the slide.
Secretions should not be placed on the slide without saline because this method
causes drying of the vaginal secretions and does not result in a well-suspended
preparation. Microscopy of normal vaginal secretions reveals many superficial
882epithelial cells, few white blood cells (less than one per epithelial cell), and few, if
any, clue cells. Clue cells are superficial vaginal epithelial cells with adherent
bacteria, usually Gardnerella vaginalis, which obliterates the crisp cell border
when visualized microscopically. Potassium hydroxide 10% (KOH) may be
added to the slide, or a separate preparation can be made, to examine the
secretions for evidence of fungal elements. The results are negative in women
with normal vaginal microbiology. Gram stain reveals normal superficial
epithelial cells and a predominance of gram-positive rods (lactobacilli).
VAGINAL INFECTIONS
Bacterial Vaginosis
Bacterial vaginosis (BV) is a polymicrobial clinical syndrome resulting in
alteration of normal vaginal bacterial flora that results in the loss of
hydrogen peroxide– producing lactobacilli and an overgrowth of
predominantly anaerobic bacteria (3,4). The most common form of vaginitis
in the United States is BV (5). Anaerobic bacteria can be found in less than 1%
of the flora of normal women. In women with BV, however, the concentration of
anaerobes, and G. vaginalis and Mycoplasma hominis, is 100 to 1,000 times
higher than in normal women. Lactobacilli are usually absent.
It is not known what triggers the disturbance of normal vaginal flora. It is
postulated that repeated alkalinization of the vagina, which can occur with
frequent sexual intercourse or use of douches, plays a role. After normal hydrogen
peroxide– producing lactobacilli disappear, it is difficult to reestablish normal
vaginal flora, and recurrence of BV is common.
Numerous studies show an association of BV with significant adverse
sequelae. Women with BV are at increased risk for pelvic inflammatory
disease (PID), postabortal PID, postoperative cuff infections after
hysterectomy, and abnormal cervical cytology (6–10). Pregnant women with
BV are at risk for premature rupture of the membranes, preterm labor and
delivery, chorioamnionitis, and postcesarean endometritis (8–9). In women
with BV who are undergoing surgical abortion or hysterectomy, perioperative
treatment with metronidazole eliminates this increased risk (10).
Diagnosis
Office-based testing is required to diagnose BV. It is diagnosed on the basis of the
following findings (11): clinical criteria require three of the following signs or
symptoms (Amsel Diagnostic Criteria):
1. A fishy vaginal odor, which is particularly noticeable following coitus, and
883vaginal discharge are present.
2. Vaginal secretions are gray and thinly coat the vaginal walls.
3. The pH of these secretions is higher than 4.5 (usually 4.7 to 5.7).
4. Microscopy of the vaginal secretions reveals an increased number of clue
cells, and leukocytes are conspicuously absent. In advanced cases of BV,
more than 20% of the epithelial cells are clue cells.
5. The addition of KOH to the vaginal secretions (the “whiff” test) releases a
fishy, amine-like odor.
Clinicians who are unable to perform microscopy should use alternative
diagnostic tests such as a pH and amines test card, detection of G. vaginalis
ribosomal RNA, or Gram stain (12). Culture of G. vaginalis is not recommended
as a diagnostic tool because of its lack of specificity.
Treatment
Ideally, treatment of BV should inhibit anaerobes but not vaginal lactobacilli. The
following treatments are effective:
1. Metronidazole, an antibiotic with excellent activity against anaerobes but
poor activity against lactobacilli, is the drug of choice for the treatment of
BV. A dose of 500 mg administered orally twice a day for 7 days should be
used. Patients should be advised to avoid using alcohol during treatment with
oral metronidazole and for 24 hours thereafter.
2. Metronidazole gel, 0.75%, one applicator (5 g) intravaginally once daily
for 5 days, may alternatively be prescribed.
The overall cure rates range from 75% to 84% with the aforementioned
regimens (5). Clindamycin in the following regimens is effective in treating
BV:
1. Clindamycin ovules, 100 mg, intravaginally once at bedtime for 3 days
2. Clindamycin bioadhesive cream, 2%, 100 mg intravaginally in a single
dose
3. Clindamycin cream, 2%, one applicator full (5 g) intravaginally at
bedtime for 7 days
4. Clindamycin, 300 mg, orally twice daily for 7 days
Many clinicians prefer intravaginal treatment to avoid systemic side
effects such as mild to moderate gastrointestinal upset and unpleasant taste.
Treatment of the male sexual partner does not improve therapeutic response
and therefore is not recommended (5).
884Trichomonas Vaginitis
Trichomonas vaginitis, the most prevalent nonviral sexually transmitted
infection in the United States is caused by the sexually transmitted,
flagellated parasite, Trichomonas vaginalis (5,13). The transmission rate is
high; 70% of men contract the disease after a single exposure to an infected
woman, which suggests that the rate of male-to-female transmission is even
higher. The parasite, which exists only in trophozoite form, is an anaerobe that
has the ability to generate hydrogen to combine with oxygen to create an
anaerobic environment. It often accompanies BV, which can be diagnosed in as
many as 60% of patients with trichomonas vaginitis (13–15). T. vaginalis
infection is associated with a two to threefold increased risk for HIV acquisition
(15).
Diagnosis
Local immune factors and inoculum size influence the appearance of symptoms.
Symptoms and signs may be much milder in patients with small inocula of
trichomonads, and trichomonas vaginitis often is asymptomatic (13–15).
1. Trichomonas vaginitis is associated with a profuse, purulent, malodorous
vaginal discharge that may be accompanied by vulvar pruritus.
2. A purulent vaginal discharge may exude from the vagina.
3. In patients with high concentrations of organisms, a patchy vaginal
erythema and colpitis macularis (“strawberry” cervix) may be observed.
4. The pH of the vaginal secretions could be variable or higher than 5.0.
5. Microscopy of the secretions reveals motile trichomonads and increased
numbers of leukocytes.
6. Clue cells may be present because of the common association with BV.
7. The whiff test may be positive.
Morbidity associated with trichomonas vaginitis may be related to BV. Patients
with trichomonas vaginitis are at increased risk for postoperative cuff cellulitis
following hysterectomy (7). Pregnant women with trichomonas vaginitis are
at increased risk for premature rupture of the membranes and preterm
delivery. Because of the sexually transmitted nature of trichomonas vaginitis,
women with this infection should be tested for other sexually transmitted diseases
(STDs).
Treatment
The treatment of trichomonas vaginitis can be summarized as follows:
8851. Metronidazole is the drug of choice for treatment of vaginal
trichomoniasis. Both a single-dose (2 g orally) and a multidose (500 mg twice
daily for 7 days) regimen are highly effective and have cure rates of about
95%.
2. Tinidazole 2 g orally in a single dose is another recommended regimen.
3. The sexual partner should be treated.
4. Women who do not respond to initial therapy should be treated again
with metronidazole, 500 mg, twice daily for 7 days. If repeated treatment is
not effective, the patient should be treated with a single 2-g dose of
metronidazole once daily for 5 days or tinidazole, 2 g, in a single dose for 5
days.
5. Patients who do not respond to repeated treatment with metronidazole or
tinidazole and for whom the possibility of reinfection is excluded should be
referred for expert consultation. In these uncommon refractory cases, an
important part of management is to obtain cultures of the parasite to determine
its susceptibility to metronidazole and tinidazole.
6. Retesting for T. vaginalis is recommended within 3 months following
initial treatment due to high rate of reinfection.
7. Metronidazole gel should not be used for the treatment of vaginal
trichomoniasis.
Vulvovaginal Candidiasis
An estimated 75% of women experience at least one episode of vulvovaginal
candidiasis (VVC) during their lifetimes (5,16). Nearly 45% of women will
experience two or more episodes (16). Few are plagued with a chronic, recurrent
infection. Candida albicans is responsible for 85% to 90% of vaginal yeast
infections. Other species of Candida, such as Candida glabrata and Candida
tropicalis, can cause vulvovaginal symptoms and tend to be resistant to therapy.
Candida are dimorphic fungi existing as blastospores, which are responsible for
transmission and asymptomatic colonization, and as mycelia, which result from
blastospore germination and enhance colonization and facilitate tissue invasion.
The extensive areas of pruritus and inflammation often associated with minimal
invasion of the lower genital tract epithelial cells suggest that an extracellular
toxin or enzyme may play a role in the pathogenesis of this disease. A
hypersensitivity phenomenon may be responsible for the irritative symptoms
associated with VVC, especially for patients with chronic, recurrent disease.
Patients with symptomatic disease usually have an increased concentration of
these micro-organisms (>104 per mL) compared with asymptomatic patients
(<103 per mL) (17).
886Factors that predispose women to the development of symptomatic VVC
include antibiotic use, pregnancy, immunosuppressive states, and diabetes (18–
20). Pregnancy and diabetes are associated with a qualitative decrease in cellmediated immunity, leading to a higher incidence of candidiasis.
It is helpful to categorize women with VVC as having either uncomplicated or
complicated disease (Table 15-1).
Table 15-1 Classification of Vulvovaginal Candidiasis
Uncomplicated Complicated
Sporadic or infrequent in
occurrence
Recurrent symptoms
Mild to moderate
symptoms
Severe symptoms
Likely to be Candida
albicans
Non-albicans Candida
Immunocompetent women Immunocompromised, e.g., diabetic women, HIV,
immunosuppressive therapy
From Sobel JD, Faro S, Force RW, et al. Vulvovaginal candidiasis: Epidemiologic,
diagnostic, and therapeutic considerations. Am J Obstet Gynecol 1998;178:203–211.
Diagnosis
The main symptom of VVC is vulvar pruritus associated with a vaginal
discharge that typically resembles cottage cheese. A few patients may have
minimal vaginal discharge.
1. The discharge can vary from watery to homogeneously thick. Vaginal
soreness, dyspareunia, vulvar burning, and irritation may be present. External
dysuria (“splash” dysuria) may occur when micturition leads to exposure of
the inflamed vulvar and vestibular epithelium to urine. Examination reveals
erythema and edema of the labia and vulvar skin. Discrete pustulopapular
peripheral lesions may be present. The vagina may be erythematous with an
adherent, whitish discharge. The cervix appears normal.
2. The pH of the vagina in patients with VVC is usually normal (<4.5).
3. Fungal elements, either budding yeast forms or mycelia, appear in as
many as 80% of cases. The results of saline preparation of the vaginal
secretions usually are normal, although there may be a slight increase in the
887number of inflammatory cells in severe cases.
4. The whiff test is negative.
5. A presumptive diagnosis can be made in the absence of fungal elements
confirmed by microscopy if the pH and the results of the saline
preparation evaluations are normal and the patient has increased
erythema based on examination of the vagina or vulva. A fungal culture is
recommended to confirm the diagnosis. Conversely, women with normal
physical examination findings and no evidence of fungal elements
disclosed by microscopy are unlikely to have VVC and should not be
empirically treated unless a vaginal yeast culture is positive.
Treatment
The treatment of VVC is summarized as follows:
1. Topically applied azole drugs are the most commonly available treatment
for VVC and are more effective than nystatin (Table 15-2) (5). Treatment
with azoles results in relief of symptoms and negative cultures in 80% to 90%
of patients who have completed therapy. Symptoms usually resolve in 2 to 3
days. Short-course regimens up to 3 days are recommended. The short-course
formulations have higher concentrations of the antifungal agent, causing an
inhibitory concentration in the vagina that persists for several days.
2. The oral antifungal agent, fluconazole, used in a single 150-mg dose, is
recommended for the treatment of VVC. It appears to have equal efficacy
when compared with topical azoles in the treatment of mild to moderate VVC
(26). Patients should be advised that their symptoms will persist for 2 to 3 days
so they will not expect additional treatment.
3. [2] Women with complicated VVC (Table 15-1) benefit from an additional
150-mg dose of fluconazole given 72 hours after the first dose. Patients
with complications can be treated with a more prolonged topical regimen
lasting 10 to 14 days. Adjunctive treatment with a weak topical steroid,
such as 1% hydrocortisone cream, may help relieve some of the external
irritative symptoms.
Table 15-2 Vulvovaginal Candidiasis—Topical Treatment Regimens
Butoconazole
2% cream (single dose bioadhesive product), 5 g intravaginally in a single
applicationa,b
Clotrimazole
8881% cream, 5 g intravaginally for 7–14 daysa,b
2% cream 5 g intravaginally for 3 days
Miconazole
2% cream, 5 g intravaginally for 7 daysa,b
200-mg vaginal suppository, one suppository for 3 daysa
100-mg vaginal suppository, one suppository daily for 7 daysa,b
4% cream 5 g intravaginally daily for 3 days
1,200-mg vaginal suppository, one suppository for 1 day
Nystatin
100,000-U vaginal tablet, one tablet for 14 days
Tioconazole
6.5% ointment, 5 g intravaginally, single dosea,b
Terconazole
0.4% cream, 5 g intravaginally daily for 7 daysa,b
0.8% cream, 5 g intravaginally daily for 3 daysa,b
80-mg suppository, one suppository daily for 3 days
aOil-based, may weaken latex condoms.
b
Available as over-the-counter preparation.
Adapted from Workowski KA, Bolan GA; Centers for Disease Control and
Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm
Rep 2015;64(RR-03):1–137.
Recurrent Vulvovaginal Candidiasis
A small number of women develop recurrent VVC (RVVC), defined as four
or more episodes in a year. Non-albicans candida species are observed in 10%
to 20% of RVVC. These women experience persistent irritative symptoms of the
vestibule and vulva. Burning replaces itching as the prominent symptom in
889patients with RVVC. The diagnosis should be confirmed by direct microscopy
of the vaginal secretions and by fungal culture. [3] Many women with RVVC
presume incorrectly they have a chronic yeast infection. Many of these
patients have chronic atopic dermatitis or atrophic vulvovaginitis.
The treatment of patients with RVVC consists of inducing a remission of
chronic symptoms with fluconazole (150 mg every 3 days for three doses).
Patients should be maintained on a suppressive dose of this agent
(fluconazole, 150 mg weekly) for 6 months (21). On this regimen, 90% of
women with RVVC will remain in remission. After suppressive therapy,
approximately half will remain asymptomatic. Recurrence will occur in the other
half and should prompt reinstitution of suppressive therapy (21). Patients with
RVVC should have a fungal culture performed to look for non-albicans candida,
and potential resistance to fluconazole. If recurrence persists or in patients with
non-albicans candida, Boric acid 600-mg vaginal suppository is recommended for
2 weeks (22,23).
Inflammatory Vaginitis
Desquamative inflammatory vaginitis is a clinical syndrome characterized by
diffuse exudative vaginitis, epithelial cell exfoliation, and a profuse purulent
vaginal discharge (24). The cause of inflammatory vaginitis is unknown, but
Gram stain findings reveal a relative absence of normal long gram-positive bacilli
(lactobacilli) and their replacement with gram-positive cocci, usually streptococci.
Women with this disorder have a purulent vaginal discharge, vulvovaginal
burning or irritation, and dyspareunia. A less frequent symptom is vulvar pruritus.
Vaginal erythema is present, and there may be an associated vulvar erythema,
vulvovaginal ecchymotic spots, and colpitis macularis. The pH of the vaginal
secretions is uniformly higher than 4.5 in these patients. Microscopy of the
vaginal secretions, shows an increase in inflammatory cells and parabasal
epithelial cells (immature squamous cells). Vaginal flora is abnormal and pH is
always elevated above 4.5.
Topical vaginal clindamycin and local vaginal corticosteroids are used as
treatment. Initial therapy is the use of 2% clindamycin cream, one applicator
full (5 g) intravaginally once daily for 4 weeks. Relapse occurs in about 30% of
patients, who should be retreated with intravaginal 2% clindamycin cream or
vaginal hydrocortisone 10% cream 3 to 5 g daily for 6 weeks. When relapse
occurs in postmenopausal patients, supplementary hormonal therapy should be
considered (28). Some women with relapse may benefit from maintenance
therapy.
890Atrophic Vaginitis
Estrogen plays an important role in the maintenance of normal vaginal ecology.
Women undergoing menopause, either naturally or secondary to surgical
removal of the ovaries, may develop inflammatory vaginitis, which may be
accompanied by an increased, purulent vaginal discharge. In addition, they
may have dyspareunia and postcoital bleeding resulting from atrophy of the
vaginal and vulvar epithelium. Examination reveals atrophy of the external
genitalia, along with a loss of the vaginal rugae. The vaginal mucosa may be
somewhat friable. Microscopy of the vaginal secretions shows a predominance of
parabasal epithelial cells and an increased number of leukocytes.
Atrophic vaginitis is treated with topical estrogen vaginal cream. Use of 1 g
of conjugated estrogen cream intravaginally each day for 1 to 2 weeks
generally provides relief. Maintenance estrogen therapy, either topical or
systemic, should be considered to prevent recurrence of this disorder.
Cervicitis
The cervix is made up of two different types of epithelial cells: squamous
epithelium and glandular epithelium. The cause of cervical inflammation depends
on the epithelium affected. The ectocervical epithelium can become inflamed by
the same micro-organisms that are responsible for vaginitis. The ectocervical
squamous epithelium is an extension of and is continuous with the vaginal
epithelium. Trichomonas, candida, and herpes simplex virus (HSV) can cause
inflammation of the ectocervix. Conversely, Neisseria gonorrhoeae and
Chlamydia trachomatis infect only the glandular epithelium (25,26).
Diagnosis
The diagnosis of cervicitis is based on the finding of a purulent endocervical
discharge, generally yellow or green in color and referred to as “mucopus”
(26).
1. After removal of ectocervical secretions with a large swab, a small cotton
swab is placed into the endocervical canal and the cervical mucus is
extracted. The cotton swab is inspected against a white or black
background to detect the green or yellow color of the mucopus. The zone
of ectopy (glandular epithelium) is friable or easily induced to bleed. This
characteristic can be assessed by touching the ectropion with a cotton swab or
spatula.
2. Placement of the mucopus on a slide that can be Gram stained will reveal
the presence of an increased number of neutrophils (>30 per high-power
891field). The presence of intracellular gram-negative diplococci, leading to the
presumptive diagnosis of gonococcal endocervicitis, may be detected. If the
Gram stain results are negative for gonococci, the presumptive diagnosis is
chlamydial cervicitis.
3. Tests for gonorrhea and chlamydia, preferably using nucleic acid
amplification tests (NAAT), should be performed. The microbial etiology
of endocervicitis is unknown in about 50% of cases in which neither
gonococci nor chlamydia is detected. Mycoplasma genitalium, an emerging
sexually transmitted disease, can be detected in 10% to 30% of women with
clinical cervicitis (5).
Treatment
Treatment of cervicitis consists of an antibiotic regimen recommended for the
treatment of uncomplicated lower genital tract infection with both chlamydia and
gonorrhea (5). Dual therapy is recommended for the treatment of gonorrhea, and
cefixime is no longer a first-line regimen (Table 15-3) (5). Fluoroquinolone
resistance is common in N. gonorrhoeae isolates, and, therefore, these agents are
no longer recommended for the treatment of women with gonococcal cervicitis. It
is imperative that all sexual partners be treated with a similar antibiotic regimen.
[4] Cervicitis is commonly associated with BV, which, if not treated concurrently,
leads to significant persistence of the symptoms and signs of cervicitis.
Table 15-3 Treatment Regimens for Gonococcal and Chlamydial Infections
Neisseria gonorrhoeae endocervicitis
Ceftriaxone, 250 mg IM in a single dose, PLUS
Azithromycin 1g orally in single dose
If ceftriaxone is not available:
Cefexime, 400 mg in a single dose, PLUS
Azithromycin 1 g orally in single dose
Chlamydia trachomatis endocervicitis
Azithromycin, 1 g orally (single dose), or
Doxycycline, 100 mg orally twice daily for 7 days
Adapted from Workowski KA, Bolan GA; Centers for Disease Control and
892Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm
Rep 2015;64(RR-03):1–137; Workowski KA, Berman S; Centers for Disease Control
and Prevention (CDC). Sexually transmitted diseases treatment guidelines, 2010. MMWR
Recomm Rep 2010;59(RR-12):1–110. Erratum in: MMWR Recomm Rep 2011 Jan
14;60(1):18. Dosage error in article text.
FIGURE 15-1 Micro-organisms originating in the endocervix ascend into the
endometrium, fallopian tubes, and peritoneum, causing pelvic inflammatory disease
(endometritis, salpingitis, peritonitis). (From Soper DE. Upper genital tract infections. In:
Copeland LJ, ed. Textbook of Gynecology. Philadelphia, PA: Saunders, 1993:521, with
permission.)
Pelvic Inflammatory Disease
PID is caused by microorganisms colonizing the endocervix and ascending to
the endometrium and fallopian tubes. It is a clinical diagnosis implying that
the patient has upper genital tract infection and inflammation. The
inflammation may be present at any point along a continuum that includes
endometritis, salpingitis, and peritonitis (Fig. 15-1).
PID is commonly caused by the sexually transmitted microorganisms N.
gonorrhoeae and C. trachomatis (27–29). Recent evidence suggests that M.
893genitalium can cause PID and presents with mild clinical symptoms similar to
chlamydial PID (30). Endogenous microorganisms found in the vagina,
particularly the BV microorganisms, are often isolated from the upper genital
tract of women with PID. The BV microorganisms include anaerobic bacteria
such as Prevotella, Peptostreptococci, and G. vaginalis. BV often occurs in
women with PID, and the resultant complex alteration of vaginal flora may
facilitate the ascending spread of pathogenic bacteria by enzymatically altering
the cervical mucus barrier (31). Less frequently, respiratory pathogens such as
Haemophilus influenzae, group A streptococci, and pneumococci can colonize the
lower genital tract and cause PID.
Diagnosis
Traditionally, the diagnosis of PID is based on a triad of symptoms and signs,
including pelvic pain, cervical motion and adnexal tenderness, and the
presence of fever. It is recognized that there is wide variation in many
symptoms and signs among women with this condition, which makes the
diagnosis of acute PID difficult. Many women with PID exhibit subtle or mild
symptoms that are not readily recognized as PID. Consequently, delay in
diagnosis and therapy probably contributes to the inflammatory sequelae in the
upper reproductive tract (32).
In the diagnosis of PID, the goal is to establish guidelines that are sufficiently
sensitive to avoid missing mild cases but sufficiently specific to avoid giving
antibiotic therapy to women who are not infected. Genitourinary tract symptoms
may indicate PID; therefore, the diagnosis of PID should be considered in women
with any genitourinary symptoms, including, but not limited to, lower abdominal
pain, excessive vaginal discharge, menorrhagia, metrorrhagia, fever, chills, and
urinary symptoms (33). Some women may develop PID without having overt
symptoms.
Pelvic organ tenderness, either uterine tenderness alone or uterine tenderness
with adnexal tenderness, is present in patients with PID. Cervical motion
tenderness suggests the presence of peritoneal inflammation, which causes pain
when the peritoneum is stretched by moving the cervix and causing traction of the
adnexa on the pelvic peritoneum. Direct or rebound abdominal tenderness may be
present.
Evaluation of both vaginal and endocervical secretions is a crucial part of
the workup of a patient with PID (34). In women with PID, an increased
number of polymorphonuclear leukocytes may be detected in a wet mount of
the vaginal secretions or in the mucopurulent discharge.
More elaborate tests may be used in women with severe symptoms because an
incorrect diagnosis may cause unnecessary morbidity (Table 15-4) (34). These
894tests include endometrial biopsy to confirm the presence of endometritis,
ultrasound or radiologic tests to characterize a tubo-ovarian abscess, and
laparoscopy to visually confirm salpingitis.
Treatment
Therapy regimens for PID must provide empirical, broad-spectrum coverage
of likely pathogens, including N. gonorrhoeae, C. trachomatis, M. genitalium,
gram-negative facultative bacteria, anaerobes, and streptococci (5,35).
Recommended regimens for the treatment of PID are listed in Table 15-5. [5] An
outpatient regimen of cefoxitin and doxycycline is as effective as an inpatient
parenteral regimen of the same antimicrobials (36). Therefore,
hospitalization is recommended only when the diagnosis is uncertain, pelvic
abscess is suspected, clinical disease is severe, or compliance with an
outpatient regimen is in question. Hospitalized patients can be considered for
discharge when their fever has lysed (<99.5çF for more than 24 hours), the
white blood cell count has become normal, rebound tenderness is absent, and
repeat examination shows marked amelioration of pelvic organ tenderness
(37).
Table 15-4 Clinical Criteria for the Diagnosis of Pelvic Inflammatory Disease
Symptoms
None necessary
Signs
Pelvic organ tenderness
Leukorrhea and/or mucopurulent endocervicitis
Additional Criteria to Increase the Specificity of the Diagnosis
Endometrial biopsy showing endometritis
Elevated C-reactive protein or erythrocyte sedimentation rate
Temperature higher than 38°C (100.4°F)
Leukocytosis
Positive test for gonorrhea or chlamydia
Elaborate Criteria
895Ultrasound documenting tubo-ovarian abscess
Laparoscopy visually confirming salpingitis
Sexual partners of women with PID should be evaluated and treated for
urethral infection with chlamydia or gonorrhea (Table 15-3). One of these STDs
usually is found in the male sexual partners of women with PID not associated
with chlamydia or gonorrhea (38).
Tubo-Ovarian Abscess
An end-stage process of acute PID, tubo-ovarian abscess is diagnosed when a
patient with PID has a pelvic mass that is palpable during bimanual examination.
The condition usually reflects an agglutination of pelvic organs (tube, ovary,
bowel) forming a palpable complex. Occasionally, an ovarian abscess can result
from the entrance of microorganisms through an ovulatory site. [6] Tubo-ovarian
abscess is treated with an antibiotic regimen administered in a hospital
(Table 15-5). About 75% of women with tubo-ovarian abscess respond to
antimicrobial therapy alone. Failure of medical therapy suggests the need for
drainage of the abscess (39). Although drainage may require surgical
exploration, percutaneous drainage guided by imaging studies (ultrasound or
computed tomography) should be used as an initial option if possible. Trocar
drainage, with or without placement of a drain, is successful in up to 90% of cases
in which the patient failed to respond to antimicrobial therapy after 72 hours (40).
Table 15-5 Guidelines for Treatment of Pelvic Inflammatory Disease
Outpatient Treatment
Cefoxitin, 2 g intramuscularly, plus probenecid, 1 g orally concurrently, or
Ceftriaxone, 250 mg intramuscularly, or
Equivalent cephalosporin
Plus:
Doxycycline, 100 mg orally 2 times daily for 14 days, or
Azithromycin, 500 mg initially and then 250 mg daily for a total of 7 days
Inpatient Treatment
Regimen A
896Cefoxitin, 2 g intravenously every 6 hrs, or
Cefotetan, 2 g intravenously every 12 hrs
Plus:
Doxycycline, 100 mg orally or intravenously every 12 hrs
Regimen B
Clindamycin, 900 mg intravenously every 8 hrs
Plus:
Ceftriaxone, 1–2 g intravenously every 12 hrs, or
Gentamicin, intravenously (5 mg/kg of body weight) daily
aOutpatient treatment only, that is, women treated for PID as an outpatient should also
receive metronidazole gel for BV if they have BV.
Adapted from Soper DE. Pelvic inflammatory disease. Obstet Gynecol 2010;116:419–428.
OTHER MAJOR INFECTIONS
Genital Ulcer Disease
In the United States, most patients with genital ulcers have genital HSV or
syphilis (5,41–44). Others causes of sexually transmitted ulcers include
chancroid, followed by the rare occurrence of lymphogranuloma venereum
(LGV) and granuloma inguinale (donovanosis). These diseases are associated
with an increased risk for HIV infection. Other infrequent and noninfectious
causes of genital ulcers include abrasions, fixed drug eruptions, carcinoma, and
Behçet disease.
Diagnosis
A diagnosis based on history and physical examination alone is often inaccurate.
Therefore, all women with genital ulcers should undergo a serologic test for
syphilis (42). Because of the consequences of inappropriate therapy, such as
tertiary disease and congenital syphilis in pregnant women, diagnostic efforts are
directed at excluding syphilis. Optimally, the evaluation of a patient with a genital
ulcer should include: dark-field examination; direct immunofluorescence testing
for Treponema pallidum, or PCR; culture or PCR testing for HSV; and culture for
Haemophilus ducreyi. Dark-field or fluorescent microscopes and selective media
to culture for H. ducreyi often are not available in most offices and clinics. Even
897after complete testing, the diagnosis remains unconfirmed in one-fourth of
patients with genital ulcers. For this reason, most clinicians base their initial
diagnosis and treatment recommendations on their clinical impression of the
appearance of the genital ulcer (Fig. 15-2) and knowledge of the most likely
cause in their patient population (41).
FIGURE 15-2 Showing the appearance of the ulcers of chancroid (A), herpes (B), and
syphilis (C). The ulcer of chancroid has irregular margins and is deep with undermined
edges. The syphilis ulcer has a smooth, indurated border and a smooth base. The genital
herpes ulcer is superficial and inflamed. (Modified from Schmid GP, Shcalla WO,
DeWitt WE. Chancroid. In: Morse SA, Moreland AA, Thompson SE, eds. Atlas of
Sexually Transmitted Diseases. Philadelphia, PA: Lippincott; 1990.)
Several clinical presentations are highly suggestive of specific diagnoses:
1. A painless and minimally tender ulcer, not accompanied by inguinal
lymphadenopathy, is likely to be syphilis, especially if the ulcer is
indurated. A nontreponemal rapid plasma reagin (RPR) test, or venereal
disease research laboratory (VDRL) test, and a confirmatory treponemal test—
fluorescent treponemal antibody absorption (FTA ABS) or
898microhemagglutinin–T. pallidum (MHA TP)—should be used to diagnose
syphilis presumptively. Some laboratories screen samples with treponemal
enzyme immunoassay (EIA) tests, the results of which should be confirmed
with nontreponemal tests. The results of nontreponemal tests usually correlate
with disease activity and should be reported quantitatively.
2. [7] Grouped vesicles mixed with small ulcers, particularly with a history
of such lesions, are almost always pathognomonic of genital herpes.
Nevertheless, laboratory confirmation of the findings is recommended because
the diagnosis of genital herpes is traumatic for many women, alters their
self-image, and affects their perceived ability to enter new sexual
relationships and bear children. Cell culture and PCR are preferred testing.
HSV culture’s sensitivity approaches 100% in the vesicle stage and 89% in the
pustular stage and drops to as low as 33% in patients with ulcers. NAAT,
including PCR assays for HSV DNA are more sensitive (5,43). Because falsenegative results are common with HSV cultures, especially in patients with
recurrent infections, type-specific glycoprotein G-based antibody assays are
useful in confirming a clinical diagnosis of genital herpes.
3. One to three extremely painful ulcers, accompanied by tender inguinal
lymphadenopathy, are unlikely to be anything except chancroid. This is
especially true if the adenopathy is fluctuant.
4. An inguinal bubo accompanied by one or several ulcers is most likely
chancroid. If no ulcer is present, the most likely diagnosis is LGV.
Treatment
Chancroid
Recommended regimens for the treatment of chancroid include azithromycin, 1 g
orally in a single dose; ceftriaxone, 250 mg intramuscularly in a single dose;
ciprofloxacin, 500 mg orally twice a day for 3 days; or erythromycin base, 500
mg orally four times daily for 7 days. Patients should be reexamined 3 to 7 days
after initiation of therapy to ensure the gradual resolution of the genital ulcer,
which can be expected to heal within 2 weeks unless it is unusually large.
Herpes
A first episode of genital herpes should be treated with acyclovir, 400 mg
orally three times a day; or famciclovir, 250 mg orally three times a day; or
valacyclovir, 1 g orally twice a day for 7 to 10 days or until clinical resolution
is attained. Although these agents provide partial control of the symptoms and
signs of clinical herpes, it neither eradicates latent virus nor affects subsequent
risk, frequency, or severity of recurrences after the drug is discontinued. Daily
899suppressive therapy (acyclovir, 400 mg orally twice daily; or famciclovir, 250 mg
twice daily; or valacyclovir, 1 g orally once a day) reduces the frequency of HSV
recurrences by at least 75% among patients with six or more recurrences of HSV
per year. [8] Suppressive treatment partially, but not totally, decreases
symptomatic and asymptomatic viral shedding and the potential for transmission
(5).
Syphilis
Parenteral administration of penicillin G is the preferred treatment of all
stages of syphilis. Benzathine penicillin G, 2.4 million units intramuscularly in a
single dose, is the recommended treatment for adults with primary, secondary, or
early latent syphilis. The Jarisch–Herxheimer reaction—an acute febrile response
accompanied by headache, myalgia, and other symptoms—may occur within the
first 24 hours after any therapy for syphilis; patients should be advised of this
possible adverse reaction.
Latent syphilis is defined as those periods after infection with T. pallidum
when patients are seroreactive but show no other evidence of disease. Patients
with latent syphilis of longer than 1 year’s duration or of unknown duration
should be treated with benzathine penicillin G, 7.2 million units total,
administered as three doses of 2.4 million units intramuscularly each, at 1-week
intervals. All patients with latent syphilis should be evaluated clinically for
evidence of tertiary disease (e.g., aortitis, neurosyphilis, gumma, and iritis).
Quantitative nontreponemal VDRL or RPR serologic tests should be repeated at 6
months and again at 12 months. An initially high antibody titer (1:32) should
decline at least fourfold (two dilutions) within 12 to 24 months.
Genital Warts
External genital warts are a manifestation of human papillomavirus (HPV)
infection (5,45). The nononcogenic HPV types 6 and 11 are usually responsible
for external genital warts. HPV types 16, 18, 31, 33, and 35 are occasionally
found in anogenital warts. The warts tend to occur in areas most directly affected
by coitus, namely the posterior fourchette and lateral areas on the vulva. Less
frequently, warts can be found throughout the vulva, in the vagina, and on the
cervix. Minor trauma associated with coitus can cause breaks in the vulvar skin,
allowing direct contact between the viral particles from an infected man and the
basal layer of the epidermis of his susceptible sexual partner. Infection may be
latent or may cause viral particles to replicate and produce a wart. External genital
warts are highly contagious; more than 75% of sexual partners develop this
manifestation of HPV infection when exposed.
900Table 15-6 Treatment Options for External Genital and Perianal Warts
Modality
Efficacy (%) Recurrence Risk
Cryotherapy
63–88 21–39
Imiquimod 5% creama
33–72 13–19
Podophyllin 10–25%
32–79 27–65
Podofilox 0.5%a
45–88 33–60
Trichloroacetic acid 80–90%
81
36
Electrodesiccation or cautery
94
22
Laserb
43–93 29–95
Interferon
44–61 0–67
Sinecatechin 15% ointment
60
ND
aMay be self-applied by patients at home.
b
Expensive; reserve for patients who have not responded to other regimens.
ND, no data.
The goal of treatment is removal of the warts; it is not possible to eradicate
the viral infection. Treatment is most successful in patients with small warts that
were present for less than 1 year. It is not determined whether treatment of genital
warts reduces transmission of HPV. Selection of a specific treatment regimen
depends on the anatomic site, size, and number of warts, and expense, efficacy,
901convenience, and potential adverse effects (Table 15-6). Recurrences more
often result from reactivation of subclinical infection than reinfection by a
sex partner; therefore, examination of sex partners is not absolutely
necessary. However, many of these sex partners may have external genital warts
and may benefit from therapy and counseling concerning transmission of warts.
HPV infection with types 6, 11, 16, 18, 31, 33, 45, 52, and 58 can be prevented
by vaccination (5).
Human Immunodeficiency Virus
It is estimated that almost 40% to 50% of individuals with human
immunodeficiency virus (HIV) are women. Intravenous drug use and
heterosexual transmission are responsible for most of the cases of AIDS in
women in the United States (46,47). Infection with HIV produces a spectrum of
disease that progresses from an asymptomatic state to full-blown AIDS. The pace
of disease progression in untreated adults is variable. The median time between
infection with HIV and the development of AIDS is 10 years, with a range from a
few months to more than 12 years. In a study of adults infected with HIV,
symptoms developed in 70% to 85% of infected adults, and AIDS developed in
55% to 60% within 12 years after infection. The natural history of the disease can
be significantly altered by antiretroviral therapy (ART). Early diagnosis and
linkage to care are essential for a patient’s health, and to reduce the risk of
transmitting HIV to others. U.S. guidelines recommend all persons with HIV
infection diagnoses be offered effective ART (47). Women with HIV-induced
altered immune function are at increased risk for infections such as tuberculosis
(TB), bacterial pneumonia, and Pneumocystis jiroveci pneumonia (PCP). Because
of its impact on the immune system, HIV affects the diagnosis, evaluation,
treatment, and follow-up of many other diseases and may decrease the efficacy of
antimicrobial therapy for some STDs.
Diagnosis
Infection is most often diagnosed by HIV antibody tests. However, tests for
HIV antibodies are often negative during the acute HIV phase (5). Antibody
testing begins with a sensitive screening test such as enzyme-linked
immunosorbent assay (ELISA) or a rapid assay. If confirmed by Western blot, a
positive antibody test result confirms that a person is infected with HIV and is
capable of transmitting the virus to others. HIV antibody is detectable in more
than 95% of patients within 6 months of infection. Women diagnosed with any
STI, particularly genital ulcer disease, should be offered HIV testing (5,15).
Routine HIV screening is recommended for women aged 19 to 64 years and
902targeted screening for women with risk factors outside of that age range (46).
The initial evaluation of an HIV-positive woman includes screening for
diseases associated with HIV, such as TB and STIs, administration of
recommended vaccinations (hepatitis B, pneumococcal, meningococcal and
influenza), and behavioral and psychosocial counseling. Intraepithelial
neoplasia is strongly associated with HPV infection and occurs in high
frequency in women with both HPV and HIV.
Treatment
ART is recommended for all HIV-infected individuals, regardless of CD4 Tlymphocyte cell count, to reduce the morbidity and mortality associated with
HIV infection. ART is recommended for HIV-infected individuals to prevent
HIV transmission (47). When initiating ART, it is important to educate
patients regarding the benefits and considerations regarding ART, and to
address strategies to optimize adherence. Patients must be willing to accept
therapy to avoid the emergence of resistance caused by poor compliance.
Dual nucleoside regimens used in addition to a protease inhibitor or
nonnucleoside reverse transcriptase inhibitor provide a more durable clinical
benefit, monotherapy is not recommended.
Patients with less than 200 CD4+ T cells per lL should receive prophylaxis
against opportunistic infections, such as trimethoprim/sulfamethoxazole or
aerosol pentamidine for the prevention of PCP pneumonia. Those with less than
50 CD4+ T cells per μL should receive azithromycin prophylaxis for
mycobacterial infections (47).
URINARY TRACT INFECTION
Acute Cystitis
Women with acute cystitis generally have an abrupt onset of multiple, severe
urinary tract symptoms including dysuria, frequency, and urgency associated with
suprapubic or low-back pain. Suprapubic tenderness may be noted on physical
examination. Urinalysis reveals pyuria and sometimes hematuria. Several factors
increase the risk for cystitis, including sexual intercourse, the use of a diaphragm
and a spermicide, delayed postcoital micturition, and a history of a recent urinary
tract infection (48–50).
Diagnosis
Escherichia coli is the most common pathogen isolated from the urine of
young women with acute cystitis, and it is present in 80% of cases (51).
Staphylococcus saprophyticus is present in an additional 5% to 15% of patients
903with cystitis. The pathophysiology of cystitis in women involves the colonization
of the vagina and urethra with coliform bacteria from the rectum. For this reason,
the effects of an antimicrobial agent on the vaginal flora play a role in the
eradication of bacteriuria.
Treatment
High concentrations of trimethoprim and fluoroquinolone in vaginal secretions
can eradicate E. coli while minimally altering normal anaerobic and
microaerophilic vaginal flora. An increasing linear trend in the prevalence of
resistance of E. coli (>10%) to the fluoroquinolones (e.g., ciprofloxacin) was
noted (52). Despite a similar increase in E. coli resistance (9% to 18%) to
trimethoprim/ sulfamethoxazole, therapeutic efficacy remains stable. In contrast,
no such increase in resistance was noted with nitrofurantoin. Nitrofurantoin
(macrocrystals, 100 mg orally twice daily for 5 days) or
trimethoprim/sulfamethoxazole (160/800 mg orally twice daily for 3 days) are the
optimal choices for empirical therapy for uncomplicated cystitis (52).
In patients with typical symptoms, an abbreviated laboratory workup followed
by empirical therapy is suggested. The diagnosis can be presumed if pyuria is
detected by microscopy or leukocyte esterase testing. Urine culture is not
necessary, and a short course of antimicrobial therapy should be given. No
follow-up visit or culture is necessary unless symptoms persist or recur.
Recurrent Cystitis
About 20% of premenopausal women with an initial episode of cystitis have
recurrent infections. More than 90% of these recurrences are caused by
exogenous reinfection. Recurrent cystitis should be documented by culture to
rule out resistant microorganisms. Patients may be treated by one of three
strategies: (1) continuous prophylaxis; (2) postcoital prophylaxis; or (3)
therapy initiated by the patient when symptoms are first noted.
Postmenopausal women may have frequent reinfections. Hormonal therapy
or topically applied estrogen cream, along with antimicrobial prophylaxis, is
helpful in treating these patients.
Urethritis
Women with dysuria caused by urethritis have a more gradual onset of mild
symptoms, which may be associated with abnormal vaginal discharge or bleeding
related to concurrent cervicitis. Patients may have a new sex partner or experience
lower abdominal pain. Physical examination may reveal the presence of
mucopurulent cervicitis or vulvovaginal herpetic lesions. C. trachomatis, N.
904gonorrhoeae, or genital herpes may cause acute urethritis. Nongonococcal,
nonchlamydial urethritis could be caused by M. genitalium (5). Pyuria is present
on urinalysis, but hematuria is rarely seen. Treatment regimens for chlamydia and
gonococcal infections are presented in Table 15-3.
Occasionally, vaginitis caused by C. albicans or trichomonas is associated with
dysuria. On careful questioning, patients generally describe external dysuria,
sometimes associated with vaginal discharge, and pruritus and dyspareunia. They
usually do not experience urgency or frequency. Pyuria and hematuria are absent.
Acute Pyelonephritis
The clinical spectrum of acute, uncomplicated pyelonephritis in young
women ranges from gram-negative septicemia to a cystitis-like illness with
mild flank pain. E. coli accounts for more than 80% of these cases (51).
Microscopy of unspun urine reveals pyuria and gram-negative bacteria. A urine
culture should be obtained in all women with suspected pyelonephritis; blood
cultures should be performed in those who are hospitalized because results are
positive in 15% to 20% of cases. In the absence of nausea and vomiting and
severe illness, outpatient oral therapy can be given safely. Patients who have
nausea and vomiting, are moderately to severely ill, or are pregnant should be
hospitalized. Outpatient treatment regimens include
trimethoprim/sulfamethoxazole (160/800 mg every 12 hours for 14 days) or a
quinolone (e.g., levofloxacin, 750 mg daily for 7 days). Inpatient treatment
regimens include the use of parenteral levofloxacin (750 mg daily), ceftriaxone (1
to 2 g daily), ampicillin (1 g every 6 hours), and gentamicin (especially if
Enterococcus species are suspected) or aztreonam (1 g every 8 to 12 hours).
Symptoms should resolve after 48 to 72 hours. If fever and flank pain persist after
72 hours of therapy, ultrasound or computed tomography should be considered to
rule out a perinephric or intrarenal abscess or ureteral obstruction. A follow-up
culture should be obtained 2 weeks after the completion of therapy (53)
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