David E. Soper
• Vaginitis is diagnosed by office-based testing.
• More prolonged antifungal therapy is indicated for women with complicated vulvovaginal candidiasis (VVC) than for those with uncomplicated disease.
• 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.
• Cervicitis is commonly associated with bacterial vaginosis (BV), which, if not treated concurrently, leads to significant persistence of the symptoms and signs of cervicitis.
• Women with mild-to-moderate pelvic inflammatory disease (PID) can be treated as outpatients.
• 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.
• Because false-negative results are common with herpes simplex virus (HSV) cultures, especially in patients with recurrent infections, type-specific glycoprotein G-based antibody assay tests are useful in confirming a clinical diagnosis of genital herpes.
• 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 patients 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. These cyclic variations do not occur when oral contraceptives are used and ovulation does not occur.
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.
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 epithelial cells, few white blood cells (less than 1 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 an 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 occurs 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 (6–9). Pregnant women with BV are at risk for premature rupture of the membranes, preterm labor and delivery, chorioamnionitis, and postcesarean endometritis (10,11). In women with BV who are undergoing surgical abortion or hysterectomy, perioperative treatment with metronidazole eliminates this increased risk (12,13).
Diagnosis
Office-based testing is required to diagnose BV. It is diagnosed on the basis of the following findings (14):
1. A fishy vaginal odor, which is particularly noticeable following coitus, and vaginal 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, aminelike 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 (15). 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 also be prescribed.
The overall cure rates range from 75% to 84% with the aforementioned regimens (16). 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 (16).
Trichomonas Vaginitis
Trichomonas vaginitis is caused by the sexually transmitted, flagellated parasite, Trichomonas vaginalis. 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 (17).
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 (17,18).
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 is usually 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 trichomonal vaginitis may be related to BV. Patients with trichomonas vaginitis are at increased risk for postoperative cuff cellulitis following hysterectomy (8). 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), particularly Neisseria gonorrhoeae and Chlamydia trachomatis. Serologic testing for syphilis and HIV infection should be considered.
Treatment
The treatment of trichomonal vaginitis can be summarized as follows:
1. 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. The sexual partner should be treated.
3. Metronidazole gel, although effective for the treatment of BV, should not be used for the treatment of vaginal trichomoniasis.
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.
Vulvovaginal Candidiasis
An estimated 75% of women experience at least one episode of vulvovaginal candidiasis (VVC) during their lifetimes (19). Nearly 45% of women will experience two or more episodes (20). 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 C. glabrata and C. 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) (21).
Factors that predispose women to the development of symptomatic VVC include antibiotic use, pregnancy, and diabetes (22–25). Pregnancy and diabetes are associated with a qualitative decrease in cell-mediated immunity, leading to a higher incidence of candidiasis.
It is helpful to categorize women with VVC as having either uncomplicated or complicated disease (Table 18.1)
Table 18.1 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 |
|
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 symptoms of VVC consist of vulvar pruritus associated with a vaginal discharge that typically resembles cottage cheese.
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 number 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 a 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 (16) (Table 18.2). 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. Although the shorter period of therapy implies a shortened duration of treatment, the short-course formulations have higher concentrations of the antifungal agent, causing an inhibitory concentration in the vagina that persists for several days.
Table 18.2 Vulvovaginal Candidiasis—Topical Treatment Regimens
|
Butoconazole |
|
2% cream, 5 g intravaginally for 3 daysa,b 2% cream, 5 g BI-BSR, single intravaginal applicationa |
|
Clotrimazole |
|
1% cream, 5 g intravaginally for 7–14 daysa,b 100-mg vaginal tablet for 7 daysa,b 100-mg vaginal tablet, two tablets for 3 daysa 500-mg vaginal tablet, single dosea |
|
Miconazole |
|
2% cream, 5 g intravaginally for 7 daysa,b 200-mg vaginal suppository for 3 daysa 100-mg vaginal suppository for 7 daysa,b |
|
Nystatin |
|
100,000-U vaginal tablet, one tablet for 14 days |
|
Tioconazole |
|
6.5% ointment, 5 g intravaginally, single dosea |
|
Terconazole |
|
0.4% cream, 5 g intravaginally for 7 daysa 0.8% cream, 5 g intravaginally for 3 daysa 80-mg suppository for 3 daysa |
|
aOil-based, may weaken latex condoms. bAvailable as over-the-counter preparation. |
|
Adapted from Centers for Disease Control and Prevention. The sexually transmitted diseases treatment guidelines. MMWR 2006;55:[RR-11]:1–94. |
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. Women with complicated VVC (Table 18.1) 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 be helpful in relieving some of the external irritative symptoms.
Recurrent Vulvovaginal Candidiasis
A small number of women develop recurrent VVC (RVVC), defined as four or more episodes in a year. These women experience persistent irritative symptoms of the vestibule and vulva. Burning replaces itching as the prominent symptom in patients with RVVC. The diagnosis should be confirmed by direct microscopy of the vaginal secretions and by fungal culture. 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. 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 (27).
Inflammatory Vaginitis
Desquamative inflammatory vaginitis is a clinical syndrome characterized by diffuse exudative vaginitis, epithelial cell exfoliation, and a profuse purulent vaginal discharge (28). 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.
Initial therapy is the use of 2% clindamycin cream, one applicator full (5 g) intravaginally once daily for 7 days. Relapse occurs in about 30% of patients, who should be retreated with intravaginal 2% clindamycin cream for 2 weeks. When relapse occurs in postmenopausal patients, supplementary hormonal therapy should be considered (28).
Atrophic 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 in areas. 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 estrogentherapy, 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. In fact, 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, N. gonorrhoeae and C. trachomatis infect only the glandular epithelium (29).
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” (30).
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. In addition, 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 field). 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, should be performed. The microbial etiology of endocervicitis is unknown in about 50% of cases in which neither gonococci nor chlamydia is detected.
Treatment
Treatment of cervicitis consists of an antibiotic regimen recommended for the treatment of uncomplicated lower genital tract infection with both chlamydia and gonorrhea (16) (Table 18.3). Fluoroquinolone resistance is common in Neisseria 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. Cervicitis is commonly associated with BV, which, if not treated concurrently, leads to significant persistence of the symptoms and signs of cervicitis.
Table 18.3 Treatment Regimens for Gonococcal and Chlamydial Infections
|
Neisseria gonorrhoeae endocervicitis |
|
Cefixime, 400 mg orally (single dose), or Ceftriaxone, 125 mg intramuscularly (single dose) |
|
Chlamydia trachomatis endocervicitis |
|
Azithromycin, 1 g orally (single dose), or Doxycycline, 100 mg orally twice daily for 7 days, or Ofloxacin, 300 mg orally twice daily for 7 days, or Levofloxacin, 500 mg orally for 7 days |
|
Adapted from Centers for Disease Control and Prevention. Update to CDC’s sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections. MMWR 2007;56:332–336; and Centers for Disease Control and Prevention. The sexually transmitted diseases treatment guidelines. MMWR 2006;55[RR-11]:1–94. |
Pelvic Inflammatory Disease
PID is caused by micro-organisms 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. 18.1).
Figure 18.1 Micro-organisms originating in the endocervix ascend into the endometrium, fallopian tubes, and peritoneum, causing pelvic inflammatory disease (endometritis, salpingitis, peritonitis). (From [MB11]Soper DE. Upper genital tract infections. In: Copeland LJ, ed. Textbook of gynecology. Philadelphia, PA: Saunders, 1993:521.)
PID is commonly caused by the sexually transmitted micro-organisms N. gonorrhoeae and C. trachomatis (31–33). Recent evidence suggests that Mycoplasma genitalium can cause PID and presents with mild clinical symptoms similar to chlamydial PID (34). Endogenous micro-organisms found in the vagina, particularly the BV micro-organisms, are often isolated from the upper genital tract of women with PID. The BV micro-organisms include anaerobic bacteria such as Prevotella and peptostreptococci as well as 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 (35). 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 (36).
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 (37). Some women may develop PID without having any 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 (38). 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 (39) (Table 18.4). These tests include endometrial biopsy to confirm the presence of endometritis, ultrasound or radiologic tests to characterize a tubo-ovarian abscess, and laparoscopy to confirm salpingitis visually.
Table 18.4 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[MB9][MB9] Leukocytosis Positive test for gonorrhea or chlamydia |
|
Elaborate criteria |
|
Ultrasound documenting tubo-ovarian abscess Laparoscopy visually confirming 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(16,40). Recommended regimens for the treatment of PID are listed in Table 18.5. An outpatient regimen of cefoxitin and doxycycline is as effective as an inpatient parenteral regimen of the same antimicrobials (41). 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 (<99.5°F 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 (42).
Table 18.5 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 |
|
Cefoxitin, 2 g intravenously every 6 hours, or Cefotetan, 2 g intravenously every 12 hours Plus: Doxycycline, 100 mg orally or intravenously every 12 hours |
|
Regimen B |
|
Clindamycin, 900 mg intravenously every 8 hours Plus: Ceftriaxone, 1–2 g intravenously every 12 hours, or Gentamicin, loading dose intravenously or intramuscularly (2 mg/kg of body weight) followed by a maintenance dose (1.5 mg/kg) every 8 hours |
|
aUse[MB10]of topical metronidazole recommended in those cases in which bacterial vaginosis is diagnosed concurrently with PID. |
|
Adapted from Soper DE. Pelvic inflammatory disease. Obstet Gynecol 2010;116:419–428. |
Sexual partners of women with PID should be evaluated and treated for urethral infection with chlamydia or gonorrhea (Table 18.3). One of these STDs usually is found in the male sexual partners of women with PID not associated with chlamydia or gonorrhea (43,44).
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 micro-organisms through an ovulatory site. Tubo-ovarian abscess is treated with an antibiotic regimen administered in a hospital (Table 18.5). 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 (45). 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 (46).
Other Major Infections
Genital Ulcer Disease
In the United States, most patients with genital ulcers have genital HSV or syphilis (47–50). Chancroid is the next most common cause of sexually transmitted genital ulcers, 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’s 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 (50). 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 or direct immunofluorescence testing for Treponema pallidum, culture or antigen 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 after 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. 18.2) and knowledge of the most likely cause in their patient population (48).
Figure 18.2 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 microhemagglutinin–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. 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. A culture test is the most sensitive and specific test; sensitivity approaches 100% in the vesicle stage and 89% in the pustular stage and drops to as low as 33% in patients with ulcers. Nonculture tests are about 80% as sensitive as culture tests. Because false-negative 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 erythromycinbase, 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, 1.0 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 suppressive therapy (acyclovir, 400 mg orally twice daily; or famciclovir, 250 mg twice daily; or valacyclovir, 1.0 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. Suppressive treatment partially, but not totally, decreases symptomatic and asymptomatic viral shedding and the potential for transmission (49).
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 serologic tests should be repeated at 6 months and again at 12 months. An initially high 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 (51). The nononcogenic HPV types 6 and 11 are usually responsible for external genital 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.
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, convenience, and potential adverse effects (Table 18.6). 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, and 18 can be prevented by vaccination.
Table 18.6 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 |
|
aMay be self-applied by patients at home. bExpensive; reserve for patients who have not responded to other regimens. |
||
Human Immunodeficiency Virus
It is estimated that almost 40% to 50% of individuals with HIV are women. Intravenous drug use and heterosexual transmission are responsible for most of the cases of AIDS in women in the United States (52). 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. 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. 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 (48). Routine HIV screening is recommended for women aged 19 to 64 years and targeted screening for women with risk factors outside of that age range, for example, sexually active adolescents (53).
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
Decisions regarding the initiation of antiretroviral therapy should be guided by monitoring the laboratory parameters of HIV RNA (viral load) and CD4+ T-cell count, and the clinical condition of the patient. The primary goals of antiretroviral therapy are maximal and durable suppression of viral load, restoration or preservation of immunologic function, improvement of quality of life, reduction of HIV-related morbidity and mortality, and prevention of HIV transmission. Antiretroviral therapy should be initiated in all women with a history of an AIDS-defining illness or with a CD4 count less than 350 cells per mm3. Antiretroviral treatment should be started regardless of CD4 count in women with the following conditions: pregnancy, HIV-associated nephropathy, and hepatitis B coinfection when treatment of hepatitis B is indicated. 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 better durable clinical benefit than monotherapy.
Patients with less than 200 CD4+ T cells per μL should receive prophylaxis against opportunistic infections, such as trimethoprim-sulfamethoxazole[MB1] or aerosol pentamidine for the prevention of PCP pneumonia. Those with less than 50 CD4+ T cells per uL should receive azithromycin prophylaxis for mycobacterial infections (54).
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 (55–57).
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 (58). Staphylococcus saprophyticus is present in an additional 5% to 15% of patients with 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. Despite a similar increase in E. coli resistance (9%–18%) to trimethoprim-sulfamethoxazole[MB2], 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 [MB3]orally twice daily for 3 days) are the optimal choices for empirical therapy for uncomplicated cystitis (59).
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 micro-organisms. Patients may be treated by one of three strategies: (i) continuous prophylaxis, (ii) postcoital prophylaxis, or (iii) 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. gonorrhoeae, or genital herpes may cause acute urethritis. Pyuria is present on urinalysis, but hematuria is rarely seen. Treatment regimens for chlamydia and gonococcal infections are presented in Table 18.3.
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 cystitislike illness with mild flank pain. E. coli accounts for more than 80% of these cases (58). 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, and are pregnant should be hospitalized[MB4]. Outpatient treatment regimens include trimethoprim-sulfamethoxazole (160/800 mg[MB5] 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 (1–2 g daily), ampicillin (1 g every 6 hours), and gentamicin (especially if Enterococcus species are suspected) or aztreonam (1 g every 8–12 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 (60).
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