James A. McGregor, Joel B. Lench
Infectious diseases are interesting and challenging disorders in gynecology. Some are difficult to treat and have frequent recurrences. Antibiotic resistance has recently changed the recommended treatment for one of the original “venereal diseases,” and vaccination has been introduced as a preventive tool for one of the more prevalent pelvic infections. The diagnosis and management of common reproductive tract infections in nonpregnant women are covered in this chapter.
Reproductive Tract Infections
Infections of the vulva, vagina, and cervix (lower reproductive tract) and the uterine corpus, fallopian tubes, and ovaries (upper reproductive tract) are common gynecologic problems. Many of these infections are sexually transmitted and require partner treatment for effective care. The term sexually transmitted infection (STI) is replacing sexually transmitted disease (STD) as a more accurate and appropriate term for these frequently asymptomatic disorders, emphasizing their infectious nature and the need for screening, early recognition, and treatment. A person with an STI may be infected and infect others without actually “having a disease.” The most common STIs are chlamydia, genital herpes, human papillomavirus (HPV), and gonorrhea.
Vulvovaginitis is a common pelvic infection caused by yeast, bacteria, or trichomonads, and pelvic inflammatory disease (PID) is the most serious form of upper reproductive tract infection. PID is frequently a consequence of an unrecognized or inadequately treated lower tract STI. PID is a common cause of infertility and is the reproductive tract infection that is most likely to require hospitalization and even surgery for adequate treatment.
Maintaining and restoring normal vaginal physiology and microbiology is an important measure for preventing pelvic infections.
Normal Physiology and Microecology of the Vagina
The vagina is lined by nonkeratinized stratified squamous epithelium, which is powerfully influenced by estrogen and progesterone. The vagina of the newborn is colonized by aerobic and anaerobic bacteria acquired while passing through the birth canal. The newborn’s vaginal epithelium is strongly estrogenized and rich in glycogen, which supports growth of lactic acid–producing lactobacilli. This results in a low pH (<4.7), which promotes further growth of acidophilic-protective microflora. Within days of birth, estrogen decreases, and the vaginal epithelium becomes thin, atrophic, and largely devoid of glycogen. In this environment, the pH rises, and acidophilic organisms no longer have a selective advantage. As a consequence, the predominant vaginal microflora becomes diverse gram-positive cocci and bacilli.
With the onset of puberty and ovarian steroidogenesis, the vagina again becomes estrogenized, and the glycogen content increases. Lactic acid– and hydrogen peroxide (H2O2)–producing lactobacilli again predominate, resulting in a self-sustaining vaginal pH of between 3.5 and 4.5. Even so, a wide variety of aerobic and anaerobic bacteria can be cultured from the normal vagina. Most women harbor at least three to eight types of bacteria at any given time. Lactic acid, H2O2, and other substances produced by “healthy” lactobacilli provide some protection in the lower reproductive tract from STIs, including human immunodeficiency virus (HIV).
Multiple factors may alter this protective microflora. Antibiotics suppress growth of commensal organisms, which can allow pathogenic strains (e.g., yeasts) to predominate. Douching with water or nonbuffered solutions may transiently alter the pH or selectively suppress endogenous bacteria. Sexual intercourse with introduction of semen raises the pH to as high as 7.2 for 6 to 8 hours, making the vaginal milieu receptive to STI pathogens. During coitus, vaginal transudate increases vaginal fluid and serves as lubrication. Vaginal transudate has the same pH as blood (7.4), which also favors attachment of abnormal microflora. The presence of a foreign body (e.g., forgotten diaphragm or tampon in adults or various small objects in children) dramatically disrupts normal vaginal cleansing mechanisms and may lead to secondary infection.
PHYSIOLOGIC VAGINAL FLUIDS
Vaginal fluid is a mixture consisting of cervical mucus (the major component), endometrial and oviductal fluid, exudates from the Bartholin’s and Skene’s glands, transudate from the vaginal squamous epithelium together with exfoliated squamous cells, and metabolic products of the microflora. Vaginal fluid is composed of proteins, polysaccharides, amino acids, enzymes, and immunoglobulins. Physiologic increases in vaginal and endocervical fluid occur during pregnancy, at mid menstrual cycle, and during intercourse. In postmenopausal women (not using estrogens), vaginal fluid may become markedly decreased, which predisposes to infection with various exogenous microflora (e.g., Escherichia coli and staphylococcal, and streptococcal species).
INVESTIGATION OF VAGINAL DISCHARGE
Patients with a vaginal infection frequently complain of a nonbloody vaginal discharge. The characteristics of the discharge (e.g., color, texture, viscosity, and odor) are helpful in making the correct diagnosis. Normal vaginal fluid has a pH of less than 4.7 in ovulatory women. Vaginal pH can be easily determined by using pH paper with an appropriate pH range (3.5 to 7.0). Self-care over-the-counter (OTC) tests, such as “pH on a stick” and “pH glove,” are available to test vaginal pH.
Testing for the presence of an amine odor (referred to as a positive whiff test) is performed by putting a few drops of 10% potassium hydroxide (KOH) in the spoon of a vaginal speculum after it is removed from the vagina. With healthy vaginal fluid, no odor is noted. An “amine” or “fishy” odor suggests trichomoniasis or bacterial vaginosis (BV).
A wet-mount preparation of the discharge should be evaluated. Using a cotton-tipped applicator, a sample of vaginal discharge from the posterior fornix is suspended in 2 mL of normal saline. A drop of this solution is placed on a glass slide, covered with a coverslip, and examined under the microscope. Motile trichomonads may be seen on this type of wet mount (Figure 22-1). Also, epithelial cells with irregular, granular edges (clue cells) are indicative of clumped bacteria on the cell wall and are highly suggestive of BV if present in more than 20% of epithelial cells (Figure 22-2). If the cells are not sufficiently separated, an aliquot of fluid is placed in a drop of saline or 10% to 20% KOH (to eliminate cellular and other debris while leaving mycelia) and examined microscopically, to visualize the pseudohyphae or spores of Candida infection. In complicated or atypical cases, bacterial and yeast cultures are required.
FIGURE 22-1 Microscopic view (high power) of a trichomonad in a saline wet-mount preparation. The organisms are usually motile in this type of preparation.
FIGURE 22-2 Microscopic view of clue cells in a saline wet-mount preparation. Note the irregular or serrated cell walls.
Vaginal Discharge Etiology
Vaginitis and complaints referable to the vagina (e.g., discharge, pruritus, burning, and “late” dysuria) are common. A correct diagnosis can be difficult because symptoms and signs may be nonspecific, patients frequently self-medicate with OTC products, multiple causes may be present, and accurate diagnostic tools are either not available or not properly employed.
Up to 90% of cases of vaginitis appear to be caused by three conditions. Bacterial vaginosis accounts for 40% to 50%, vulvovaginal candidiasis (VVC) for 20% to 25%, and trichomoniasis for 15% or less of cases. Mucopurulent cervicitis (“mucopus”) caused by chlamydia, Neisseria gonorrhoeae, mycoplasma, or BV-associated bacteria (seeFigure 22-6) may also cause vaginal irritation and discharge. Less common types include atrophic vaginitis (overgrowth with aerobic or anaerobic microflora in the absence of lactobacilli and with hypoestrogenized tissues), foreign-body vaginitis, genital ulcer diseases such as herpes and syphilis, desquamative vaginitis (most commonly group B streptococcal overgrowth), and lichen planus. Irritation from sexual activity and allergen-containing substances can also mimic infectious vaginitis.
FIGURE 22-3 Cottage cheese or curd-like appearance of vaginal discharge is typical of vulvovaginitis due to yeast.
Standard clinic or office diagnosis of vaginitis requires a working microscope, pH paper, KOH, saline solution, slides, coverslips, and the ability to recognize an amine odor (whiff test). In many settings, these rudimentary tools are not available. Newer, inexpensive “point of care” products can detect vaginal sialidase, amines, and proline aminopeptidase and other biomarker substances or nucleic acid–based tests. In difficult or refractory cases, additional tests for vaginal agents may be used such as culture for Trichomonas vaginalis, Candida, mycoplasmas, or predominant vaginal aerobic bacterial. Table 22-1lists the common causes, characteristics, and treatments for vulvar and vaginal infections.
TABLE 22-1 COMMON CAUSES OF VULVOVAGINITIS
BV is the most common cause of vaginal discharge but is often without other symptoms. BV occurs subsequent to a significant disruption of “healthy” vaginal microflora, (typically Lactobacillus jensenii and Lactobacillus crispatus) by a characteristic set of BV-complex microorganisms: Gardnerella vaginalis, genital mycoplasmas (Mycoplasma hominis, Ureaplasma urealyticum) and vaginal anaerobic bacteria, including Prevotella, Bacteroides, and Mobiluncus species. Risk factors for acquisition of BV include a new sexual partner, smoking, intrauterine device (IUD) use, and frequent douching.
Classic features of BV discharge include a profuse, milky, nonadherent discharge that demonstrates an amine or fishy odor after alkalization with a drop of KOH (positive whiff test).
The presence of BV heightens a nonpregnant woman’s risk for PID, postoperative infections (e.g., after hysterectomy or pregnancy termination), and HIV transmission. Partner treatment is generally not recommended.
VVC is the second most common cause of vulvovaginal-related symptoms. Wide use of OTC antifungal products for self-diagnosed candidiasis has resulted in a decreased frequency of doctor visits, but women who do present are less likely to present with textbook findings. Candida albicans formerly caused more than 90% of cases of VVC, but now less azole-susceptible species, such as Candida glabrata, are recognized as causative agents in 15% of cases. These less susceptible yeasts necessitate prolonged or alternative treatments. Because of Candida’s requirement for estrogenated tissues, VVC becomes more common after menarche and less common after menopause. An estimated 75% of women acquire VVC at some time in their life, and 5% suffer frequent symptomatic recurrences. VVC is considered recurrent when at least four episodes occur within 1 year. Risk factors for recurrent VVC include high-dose oral contraceptives, diaphragm use with a spermicide, diabetes mellitus, antibiotic use, pregnancy, immunosuppression from any cause (HIV/AIDS, transplantation, steroid use), and possibly tight occlusive clothing.
The classic presentation of VVC includes vaginal itching, burning, irritation, and possibly postvoiding dysuria. The discharge is usually odorless, has a pH of less than 4.7, and is thick or curdy with the appearance of cottage cheese (Figure 22-3). Examination often shows vulvovaginal erythema, with evidence of acute or chronic excoriation.
Microscopic examination of a wet-mount preparation is positive for budding yeast cells, pseudohyphae, or mycelial tangles (Figure 22-4) in 50% to 70% of cases. Women with suggestive clinical findings but absent wet preparation evidence may benefit from fungal culture.
FIGURE 22-4 Mycelial tangles of yeast pseudohyphae in KOH wet-mount preparation.
First-line treatments include topical or oral antifungal (imidazole) agents. Documented cases of recurrences can be effectively treated by confirming the diagnosis and treating with weekly suppressive doses of topical imidazoles. Boric acid (600 mg vaginal gelatin capsules) 3 times daily for 1 week is an effective treatment for imidazole-resistant species. Although VVC is not thought to be sexually transmitted in most cases, male partners sometimes reinfect their partners and are routinely treated by some practitioners.
Trichomoniasis (cervicitis, vaginitis, and urethritis) is caused by the protozoan T. vaginalis. About 50% of cases in women and men are asymptomatic. Symptomatic infection is classically manifested by a green-yellow, frothy vaginal discharge (Figure 22-5), with a “musty” odor. Dyspareunia, vulvovaginal irritation, and occasionally dysuria may be present. Male partners are often asymptomatic even though they demonstrate nongonococcal urethritis on direct examination.
FIGURE 22-5 Purulent “bubbly” cervical-vaginal fluid characteristic of trichomoniasis.
The diagnosis of trichomoniasis in patients and their sexual partners should be followed by screening for other prevalent STIs and empiric treatment of partners. Diagnosis is usually made on clinical grounds and can be confirmed by seeing the characteristic motility of trichomonads on a saline wet mount. Much more sensitive techniques, including culture, polymerase chain reaction (PCR), and antigen testing, are becoming available.
In addition to vulvovaginitis and urethritis, trichomoniasis is associated with upper reproductive tract symptoms, an increased risk for adverse pregnancy outcomes (prematurity, low birth weight), and increased transmission of HIV infection.
Metronidazole (2 g single oral dose) is the recommended treatment (see Table 22-1). Patients should not consume alcohol for 2 days after treatment. Although metronidazole is not known to be teratogenic in recommended dosages, it has been traditionally avoided during the first 12 weeks of pregnancy. Prompt early treatment during pregnancy relieves symptoms, reduces the risk for HIV transmission, and may improve pregnancy outcomes. Trichomoniasis should be treated before vaginal surgical procedures.
Metronidazole resistance is increasing and may be overcome by using tinidazole (now available in the United States; see Table 22-1) or using higher doses of metronidazole (2 g daily for 7 days). Reversible side effects of metronidazole include an “Antabuse-like reaction” with alcohol exposure, neutropenia, and peripheral neuropathy. Higher-dose treatment for resistant trichomoniasis in pregnancy should be prescribed with caution in consultation with experts.
Atrophic vaginitis is the most common cause of vaginal irritation among climacteric patients. As the term indicates, the atrophy of the vaginal epithelium results in secondary infection. The vulva and introitus quickly become involved because of the associated discharge, and the situation may be exacerbated by a foreign body (such as a pessary). Patients complain of vulvar irritation and discharge, which may be clear or purulent and yellow but occasionally will be blood tinged. Associated symptoms of frequency, urgency, and stress incontinence may occur.
Examination of the external genitalia may reveal a watery discharge with generalized vulvar erythema, often with excoriation. Speculum examination reveals a pale epithelium with patches of erythema. Superficial blood vessels are visible and may bleed easily on contact. If bleeding is present, the examiner must consider the possibility of a coexistent neoplasm. The discharge has a pH of 4.7 or higher. A simple evaluation of the epithelial cells using a saline wet-mount preparation or Papanicolaou (Pap) smear confirms the diagnosis, with immature basal cells and parabasal cells replacing superficial vaginal epithelial cells.
The treatment of choice is topical estrogen available in vaginal creams, suppositories, or rings. If systemic hormonal treatment is desirable, oral tablets, transdermal patches, sprays, and gels are available. Aerobic cultures for predominant microorganisms should be obtained in refractory cases and when infection is suspected.
When a mother states there is discharge on the baby’s diaper or the child has vulvar itching, infection, or a bloody vaginal discharge, a foreign body should be suspected in addition to sexual abuse. In adults, forgotten or lost tampons, diaphragms, or condoms may be the cause of vaginitis. With removal of the foreign body and vaginal application of some form of sulfa cream (or estrogen cream in children), rapid improvement usually occurs.
Other Common Sexually Transmitted Infections
Genital herpes is the most prevalent STI in the United States, with an estimated 50 million adults infected (active or latent) with herpes simplex virus (HSV) and about 1.5 million new cases occurring every year. It is a chronic lifelong viral infection with the potential for rare to frequent recurrences. This infection may have devastating emotional and social consequences. Unfortunately, only 10% to 20% of infected persons know that they are infected, and 70% of transmissions are from asymptomatic viral shedding from infected partners with no visible lesions. Individuals who are infected with HSV are at increased risk for acquiring and transmitting HIV.
HSV has two serotypes, HSV-1 and HSV-2. HSV-1 is most commonly associated with oral lesions (cold sores), but about 30% of primary genital herpes is due to HSV-1. HSV-2 is the cause of 70% of primary genital herpes and 95% of recurrent genital herpes. The frequency of recurrences is much higher after a primary infection with HSV-2 than HSV-1. The virus enters the body through mucosa or microabrasions in the skin and follows the sensory nerves to the dorsal spinal ganglion, where it remains dormant until reactivated. Transmission occurs through intimate genital, oral, or anal contact. An infected mother can transmit the virus to her infant during delivery resulting in significant fetal mortality and morbidity. Regular condom use decreases transmission by about 50%, especially from men to women.
Primary genital herpes infection occurs when the infected person has no HSV-2 or HSV-1 antibodies. The usual clinical presentation is multiple, bilateral, and painful anogenital vesicles or ulcers with an erythematous base. Systemic symptoms may also be present, such as fever, headache, malaise, and lymphadenopathy. Acute cervicitis may be present. The lesions heal without scarring in 14 to 21 days.
Recurrent genital herpes infection occurs when the infected person has HSV antibodies to the same serotype. The lesions are fewer, unilateral, and less painful. Systemic symptoms and lymphadenopathy are rare. The lesions heal without scarring in 5 to 7 days in immunocompetent individuals.
Laboratory tests that are used to confirm the diagnosis include (1) viral culture that requires live cells from a lesion, which is expensive, time-consuming, and has a relatively low sensitivity (50% to 80%); (2) PCR, which is expensive and very accurate, is very useful for testing cerebrospinal fluid, but is not used routinely on genital lesions; and (3) type-specific serologic tests for HSV-1 and HSV-2 antibodies. These are highly sensitive and specific tests that can identify infected individuals who are asymptomatic.
The goals of treatment for genital herpes are symptom relief, acceleration of lesion healing, and a decrease in frequency of recurrences. Education and supportive counseling are also important. The antiviral agents (acyclovir, famciclovir, and valacyclovir) are safe and effective for treating primary and episodic outbreaks and for providing suppressive therapy for patients with chronic disease. No treatment can eradicate the latent virus from the dorsal ganglia of the spinal cord. Work is underway to develop an HSV vaccine.
HUMAN PAPILLOMAVIRUs (HPV)
Genital HPV is a common viral STI with an estimated 20 million infected persons in the United States and 5 million new cases every year. It is believed that about 75% of sexually active adults will be infected sometime in their life. Most HPV cases are latent infections with no visible lesions and are only diagnosed by DNA hybridization testing performed in the evaluation of an abnormal Pap smear. Subclinical infections have lesions that are only visible during colposcopy. Clinical infections are characterized by readily visible “warty” growths called condylomata acuminata on the vulva, vagina, cervix, urethra, and perianal area.
There are about 1 million new cases of these external genital (venereal) warts every year in the United States. HPV infection usually clears spontaneously within 2 years, but recurrences are common. There are about 200 HPV subtypes. Some have been strongly associated with genital neoplasia and cancers, especially cervical (see Chapter 38). Biopsies of atypical or persistent lesions are needed to rule out neoplastic disease. Because these growths may also mimic condylomata lata, syphilis must be excluded if the lesions are atypical or do not respond to treatment. Transmission of HPV can occur even when there are no visible lesions. Regular condom use may provide some degree of protection. During pregnancy, condylomata may increase in number and size, but transmission from mother to infant is rare.
An HPV-like particle vaccine (Gardasil) is now available that protects against four HPV serotypes (6, 8, 16, and 18), which together are responsible for 70% of cervical cancers and 90% of genital warts. This vaccine was licensed in 2006 for use in females aged 9 to 26 years. Another vaccine against HPV types 16 and 18 only (Cervarix) may be available soon (from 2008). These vaccines are highly effective (>95%) in women who have not been exposed to these HPV types.
The reasons for treating genital warts are to relieve symptoms (pain and bleeding) and to ameliorate psychological and cosmetic concerns of the patient. Multiple therapeutic modalities are available, and all are comparable. Provider-applied topical therapies include (1) podophyllin resin 10% to 25% in tincture of benzoin and (2) trichloroacetic acid (TCA) or bichloracetic acid (BCA) 80% to 90%. Patient-applied topical therapies include (1) podofilox 0.5% solution or gel and (2) imiquimod 5% cream. Surgical therapies include (1) cryotherapy, (2) surgical excision, (3) electrocautery, (4) laser vaporization, and (5) intralesional interferon. Podophyllin, podofilox, and imiquimod should not be used during pregnancy.
Chlamydia has the highest incidence of any bacterial STI in the United States, with 3 million new cases every year. Most cases (75%) are found in individuals who are younger than 25 years, and about half of cases are in adolescents.
Chlamydia trachomatis is an obligate intracellular bacteria that grows in vitro only in tissue culture. It can infect the columnar epithelium of the endocervix, urethra, endometrium, fallopian tubes, and rectum. This organism can persist for long periods in an asymptomatic carrier state. There is no vaccine available, and even though chlamydia antibodies are produced, they do not protect against reinfection. Because about 70% of infected females and 50% of infected males have no symptoms, it is very difficult to diagnose and treat this “hidden” infection. In those cases in which symptoms are present, the clinical manifestations of lower genital tract chlamydia infection are (1) mucopurulent cervicitis or mucopus, which is a yellow discharge coming from a swollen, red, friable cervix that bleeds easily (see Figure 22-3), and (2) acute urethritis with dysuria but minimal frequency and urgency and a negative urine culture.
Various laboratory tests are used to confirm the diagnosis of chlamydia: (1) tissue culture, which requires live cells and is expensive; (2) antigen tests, which are inexpensive and rapid with a high sensitivity and specificity; and (3) DNA hybridization tests and nucleic acid amplification tests (PCR and ligase chain reaction), which are rapid and very accurate. These newer DNA amplification tests can be done on urine specimens as well as cervical swabs and therefore they are very convenient for screening purposes. Selective screening should be performed at least annually on all sexually active females younger than 26 years and all women with risk factors (e.g., unmarried, multiple partners, inconsistent use of barrier contraception, previous history of any STI, and all pregnant women). It is estimated that 30% of untreated chlamydial cervicitis will progress to PID. Aggressive screening and appropriate early treatment have been shown to decrease the incidence of PID. Screening may also be performed after partner change or for any concern.
General treatment guidelines for lower genital tract chlamydial infection include the following: (1) presumptive treatment with appropriate antibiotics (e.g., azithromycin, 1 g orally in a single dose, or doxycycline, 100 mg twice a day for 7 days); (2) treatment of all sexual contacts within the past 60 days before diagnosis; (3) testing for other STIs, including gonorrhea, syphilis, hepatitis B, and HIV; and (4) abstinence from sexual contact for 7 days after last partner has started antibiotic therapy. Test of cure is not necessary; however, rescreening in 3 to 4 months to check for reinfection is recommended.
Chlamydial infection during pregnancy can cause adverse outcomes for both mother and infant. These include preterm labor, chorioamnionitis, and postpartum endometritis. Intrapartum transmission to the infant can cause neonatal conjunctivitis and pneumonia.
N. gonorrhoeae is the second most common bacterial STI in the United States, with 600,000 new cases annually. The organism is a gram-negative diplococcus, and it infects the same columnar epithelium as chlamydia. Additionally, it can infect the pharynx in about 10% of the cases. It can also survive in the host as an asymptomatic carrier. There is no vaccine available, and no immunity is conferred even though antibodies are produced.
Most infected women, but as few as 5% of infected men, have no symptoms. If symptoms are present, the clinical manifestations of lower genital tract gonococcal infections are the same as for chlamydia and include mucopurulent cervicitis, which involves a swollen, red, friable cervix; contact bleeding; and acute urethritis, producing dysuria with minimal frequency and urgency and usually a negative urine culture.
Laboratory tests that can be used to confirm the diagnosis include Gram stain of the discharge or cervix, which is rapid and inexpensive. The presence of gram-negative diplococci in the leukocytes is very sensitive in men; however, in women, the sensitivity is only 50%. Thayer-Martin or Transgrow media culture is inexpensive but takes longer with a sensitivity of 90% and a specificity of 97%. DNA hybridization test is inexpensive and rapid, with a high sensitivity and specificity, and nucleic acid amplification tests (PCR and ligase chain reaction [LCR]) are more expensive and rapid with high sensitivity and specificity. These tests can be done on urine or cervical swabs. Because most women with gonococcal cervical infection are asymptomatic, selective screening of high-risk persons is essential in attempting to control the progression and spread of this disease. About 15% of untreated gonococcal cervical infections progress to PID.
Resistant strains of gonorrhea include penicillinase-producing N. gonorrhoeae, chromosomal mediated–resistant N. gonorrhoeae, tetracycline-resistant N. gonorrhoeae, and quinolone-resistant N. gonorrhoeae. A Centers for Disease Control and Prevention (CDC) update (April 2007) recommends that quinolones no longer be used for the treatment of gonococcal infections due to significant resistance.
General treatment guidelines for lower genital tract gonococcal infection include (1) treatment with appropriate antibiotics (e.g., cefixime, 400 mg orally in a single dose, or ceftriaxone 125 mg intramuscularly in a single dose); (2) simultaneous treatment for chlamydia (i.e., 1 g of azithromycin orally in a single dose is indicated because 20% to 40% of gonococcal cervical infections also have chlamydia); (3) treatment of all sexual contacts within the 60 days before diagnosis; (4) abstinence from sexual activity for 7 days after the start of antibiotic therapy; (5) testing for other STIs, including chlamydia, syphilis, hepatitis B, and HIV. Test of cure is not necessary; however, rescreening in 3 to 4 months to check for reinfection may be helpful.
Gonococcal infection during pregnancy can cause adverse outcomes for both the mother and infant. These include preterm labor and delivery, chorioamnionitis, and postpartum endometritis. Intrapartum transmission to the infant can cause neonatal conjunctivitis (ophthalmia neonatorum).
Pelvic Inflammatory Disease
PID is a morbid and costly sexually transmitted bacterial upper reproductive tract infection affecting nonpregnant and occasionally pregnant women. Studies demonstrate the importance of pathogenic lower reproductive tract microorganisms ascending from the endocervix to mediate endometritis, salpingitis, and sometimes peritonitis.
EPIDEMIOLOGY AND PATHOGENESIS
More than 10% of reproductive-aged women report a history of PID. PID is an expensive public health problem. It has been estimated that the direct costs of treating PID in the United States exceed $6 billion annually. These costs do not include the indirect costs of treating sequelae such as infertility, ectopic pregnancy, and preterm birth.
The most important single-agent causes of PID include C. trachomatis, N. gonorrhoeae, and genital mycoplasmas (M. hominis, U. urealyticum, and Mycoplasma genitalium). Each of these is an STI with inoculation occurring most commonly during intercourse. M. hominis, U. urealyticum, and M. genitalium are widely recognized causes of nongonococcal urethritis in males and females. Both C. trachomatis and N. gonorrhoeae have well-defined molecular virulence factors that mediate genital attachment and cell damage. Unlike gonorrhea, which occurs more frequently within inner-city and minority populations, chlamydial infections are broadly distributed among most racial, ethnic, and economic groups.
PID develops in 15% to 30% of women with inadequately treated gonococcal or chlamydial cervicitis. There are an estimated 3 million chlamydial genital infections yearly in the United States. The highest rates of chlamydial cervicitis occur in sexually active adolescents and young adults between the ages of 20 and 25 years. The largely asymptomatic nature of chlamydial cervicitis in women and urethritis in men makes routine screening and treatment for chlamydia necessary for the prevention of PID.
The most common microbial isolates recovered from patients at laparoscopy or at drainage of pelvic abscesses are endogenous lower reproductive tract or gastrointestinal microflora, including E. coli, Bacteroides and Prevotella species, G. vaginalis, and anaerobic streptococci. These common sexually transmitted and endogenous agents should be covered during antibiotic treatment for PID.
The sequelae of PID are much more common, morbid, and costly than previously recognized. A seminal study of PID was performed in Lund, Sweden, where 2500 women with PID were followed from 1960 to 1984. Women with clinical PID were 6 times more likely to have an ectopic pregnancy and 14 times more likely to have tubal factor infertility than women without PID. Women with a history of PID were 6 to 10 times more likely than healthy controls to have the diagnosis of endometritis, suffer from chronic pelvic pain, or require a hysterectomy. Women with prior salpingitis are at increased risk for premature labor.
Women with symptomatic PID commonly have lower abdominal pain and tenderness (especially when walking or during coitus), abnormal vaginal discharge, chills, and fever. Less common symptoms include irregular vaginal bleeding, dysuria, nausea, and vomiting. No specific combination of symptoms is consistently associated with PID. Some women are asymptomatic.
Clinical signs in women with laparoscopically confirmed PID most frequently include lower abdominal tenderness, with or without rebound tenderness; uterine and adnexal tenderness to palpation and motion; and findings of mucopurulent cervicitis (Figure 22-6). Fever is the least common finding. A pregnancy test should be performed when symptoms or signs of pregnancy are present.
FIGURE 22-6 Uterine cervix at the time of speculum examination with mucopus protruding from the os.
Nucleic acid, antigenic, or culture tests should be done to detect chlamydial and gonococcal infections. Confirmatory laboratory evidence includes leukocytosis, increased erythrocyte sedimentation rate, or C-reactive protein level, and microscopic or leukocyte esterase test evidence of purulent cervical discharge (mucopus). Pelvic ultrasonic studies may show enlarged, tender fallopian tubes as well as cul-de-sac fluid.
Laparoscopy is no longer considered clinically necessary for diagnosis of PID or tubo-ovarian abscess (TOA) because it is invasive and costly, and safer, effective antimicrobial regimens are now available for empiric use. Laparoscopy is generally not performed unless differentiation from other processes (e.g., appendicitis) is required.
PID should be diagnosed and treated empirically in sexually active young women and women with risk factors who have uterine and adnexal or cervical motion tenderness. The CDC cautions that PID is unlikely if the patient does not have a mucopurulent cervical discharge (see Figure 22-6) or white blood cells on vaginal wet mount. Abnormal findings that make the diagnosis more secure include fever, elevated erythrocyte sedimentation rate, elevated C-reactive protein, and documented cervical infection with gonorrhea or chlamydia.
Therapeutic goals for treating PID are elimination of reproductive tract infection and inflammation, improvement of symptoms and physical findings, prevention or minimization of long-term sequelae, and eradication of causal agents from the patient and her sexual partner.
Empiric antibiotic regimens should be aimed at treating likely causative agents, that is, N. gonorrhoeae, C. trachomatis, genital mycoplasmas, and BV-associated endogenous microflora. The latter include anaerobic (Bacteroides and Prevotella species and anaerobic streptococci) as well as aerobic organisms (G. vaginalis, E. coli, and facultative streptococci). Except for N. gonorrhoeae and some anaerobes, resistance is not yet a clinical problem.
The need for hospitalization is an important treatment decision (Box 22-1). Women with severe infections or an inability to take and absorb oral antibiotics (nausea, vomiting, possible peritonitis, and ileus) should be hospitalized and treated until clinical improvement is evident. Similarly, women with a questionable diagnosis, pregnancy, or unreliability, should be admitted initially and treated with parenteral agents to ensure compliance and treatment efficacy, as should those who fail to respond to outpatient therapy.
BOX 22-1 Pelvic Inflammatory Disease: Clinical Criteria for Hospitalization and Parenteral Treatment
1. Surgical emergencies (e.g., appendicitis) not ruled out
2. Pregnancy (decrease fetal wastage from preterm birth)
3. Failed oral treatment (no improvement with short-term treatment)
4. Compliance questionable (i.e., patient unable to follow or tolerate outpatient regimen)
5. Severe illness (toxicity: nausea, vomiting, high fever)
6. Tubo-ovarian abscess shown or suspected
Table 22-2 lists antibiotic regimens for inpatient and outpatient management, as recommended by the CDC. Other recommended and alternative treatments are listed on their website, http://www.cdc.gov.
TABLE 22-2 CENTERS FOR DISEASE CONTROL AND PREVENTION RECOMMENDED TREATMENTS FOR PELVIC INFLAMMATORY DISEASE, 2006∗
Cefoxitin, 2 g IV q6hr
Cefotetan, 2 g IV q12hr
Doxycycline, 100 mg IV q12hr until improved, followed by doxycycline, 100 mg orally twice daily, to complete 14 days
Clindamycin, 900 mg IV q8hr
Gentamicin, 2 mg/kg IV once, followed by 1.5 mg/kg IV q8hr until improved, followed by doxycycline, 100 mg orally bid, to complete 14 days
Ceftriaxone, 250 mg IM in a single dose, plus doxycycline, 100 mg twice daily, to complete 14 days
with or without
Metronidazole, 500 mg orally twice daily for 14 days
Cefoxitin, 2 g IM single dose, and probenecid, 1 g orally,
Doxycycline, 100 mg twice daily, to complete 14 days
with or without
Metronidazole, 500 mg orally twice daily for 14 days
IM, intramuscularly; IV, intravenously.
∗ See Centers for Disease Control and Prevention website for verification of latest recommended dose and a more complete list of alternative treatments at http://www.cdc.gov.
Outpatient treatments may be selected for most women, who will return promptly if no improvement is seen within 24 to 48 hours and who are likely to be compliant. Direct observation of initial oral treatment is preferred.
Patients should be reevaluated 3 to 4 weeks after treatment. Pelvic examination should be done at that time to ensure adequacy of treatment. Counseling regarding preventative strategies for STIs and HIV infection, as well as contraceptive advice, should be repeated at the follow-up visit.
Developments in diagnostic testing and the use of single-dose antibiotic treatments for gonococcal and chlamydial infections, trichomoniasis, and BV have led to new opportunities to prevent PID. The practice of routine screening for and treatment and prevention of chlamydial infections has dramatically reduced rates of PID in the United States.
Use of sensitive and specific nucleic acid diagnostic techniques such as PCR and LCR for common STIs allows for relatively inexpensive screening and diagnosis in both high- and low-prevalence populations.Although direct cervical or urethral sampling is preferable, both females and males may now submit either urine samples or self-collected swabs for accurate and inexpensive nucleic acid–based testing. Use of urine-based testing greatly facilitates identification of infected asymptomatic carriers.
Single-dose regimens, such as azithromycin, 1 g orally (for chlamydial infections), and cefixime, 400 mg, or intramuscular ceftriaxone, 125 mg, simplify treatment and ensure greater compliance. Directly observed therapy also ensures compliance.
To minimize the risk for reinfection, partners for the past 60 days should be identified, diagnosed, and given specific treatment or treated empirically for both chlamydial infection and gonorrhea.Most infected male partners are asymptomatic. This practice should minimize recurrence and reinfection that can lead to permanent adhesions (Figure 22-7).
FIGURE 22-7 View of agglutinated adhesions of the female reproductive organs at the time of laparotomy typical of recurrent episodes of pelvic inflammatory disease.
Other Clinical Issues Related to STIs
INTRAUTERINE DEVICE USE
Studies are reassuring with respect to a lack of an association between PID and IUD use. However, these devices are intended only for couples who are in stable, mutually monogamous relationships. It is prudent, however, to screen patients for common STIs and to treat for BV before insertion to minimize the risk for endometrial contamination.
TUBO-OVARIAN ABSCESs (TOA)
TOA involving fallopian tubes, ovaries, bowel, and possibly other pelvic structures is a potentially lethal complication of PID. Inflammatory complexes also represent severe infection but do not contain significant amounts of pus and are more easily treated with antibiotics.
TOAs occur in about 10% of women hospitalized for PID. A TOA in the course of the initial episode of PID represents severe infection in which the host is unable to localize tissue damage. Some TOAs are caused by reactivation of past infection or repeated infections, whereas others may occur as a result of postpartum or postoperative infections.
Rupture of a TOA causes spreading peritonitis, which can be rapidly lethal in the absence of expeditious surgical drainage, antimicrobial treatment, and systemic vital organ support. TOAs may cause considerable long-term morbidity from irreversible tubal and ovarian damage, with subsequent infertility, chronic pain, and gonadal failure. Rarely, death results from uncontrolled sepsis. Figure 22-8 shows a gross postoperative specimen of a uterus with bilateral TOAs.
FIGURE 22-8 Gross appearance of bilateral tubo-ovarian abscesses.
(From Kumar V, et al: Robbins and Cotran Pathologic Basis of Disease, 7th ed. Philadelphia, Saunders, 2005.)
A TOA is distinguished from uncomplicated endometritis or salpingitis by the presence of a tender inflammatory adnexal mass. Confirmation of the diagnosis may require the use of imaging techniques such as ultrasonography, computed tomography, or magnetic resonance imaging, as depicted in Figure 22-9. Drainage of a TOA under ultrasonic guidance can be both diagnostic and therapeutic. Laparotomy or laparoscopy may be required to distinguish TOAs from inflammatory complexes, twisted or infected adnexal structures, or pelvic abscesses from other sources (e.g., appendicitis or diverticulitis). If there is doubt regarding the diagnosis, laparoscopy should be performed promptly. If laparoscopy or laparotomy is performed, the TOA or pyosalpinx should be drained (extraperitoneally if possible), followed by copious irrigation.
FIGURE 22-9 Pelvic magnetic resonance imaging of a patient with tubo-ovarian abscesses.
Broad-spectrum intravenous antibiotic treatment, including coverage for endogenous pelvic microorganisms (E. coli, B. fragilis, and aerobic and anaerobic cocci) and N. gonorrhoeae, should be started promptly after obtaining microbiologic tests from the cervix. Intensive antibiotic treatment for TOAs should consist of broad coverage, multiagent regimens.
Such regimens are associated with curative response rates of about 85%. Some meta-analyses have found improved results if clindamycin is included in a multiagent regimen. Empiric oral antibiotic treatment such as oral doxycycline (100 mg twice daily), amoxicillin-clavulanic acid (250 mg 3 times a day), or metronidazole (500 mg twice a day) is traditionally given for at least 7 days after response to parenteral treatment.
In the face of clinical deterioration or the absence of obvious clinical improvement after 24 to 48 hours of antibiotic treatment, other modalities should be used. Aspiration using vaginal, abdominal, or rectal ultrasonic guidance should be considered initially. When uterine and ovarian preservation is a goal, drainage of the abscess, possibly combined with salpingectomy, may be required. Total abdominal hysterectomy and bilateral salpingo-oophorectomy may be necessary in refractory cases, usually by a laparotomy.
LESS COMMON SEXUALLY TRANSMITTED INFECTIONS AND INFESTATION
Chancroid is caused by Haemophilus ducreyi. The lesions, called soft chancres, are painful and are usually accompanied by pelvic adenopathy. Diagnosis is made clinically and confirmed with cultures. Treatment is with azithromycin, 1 g orally in a single dose, or ceftriaxone, 250 mg intramuscularly in a single dose.
Granuloma inguinale (donovanosis) is caused by Calymmatobacterium granulomatis. The lesions are red and raised. Treatment is with doxycycline, 100 mg twice a day for a minimum of 3 weeks.
Lymphogranuloma venereum is caused by C. trachomatis. Vesicles progress to bubo formation. A complement fixation test is available for diagnosis. Treatment is with doxycycline, 100 mg twice a day for at least 3 weeks.
Molluscum contagiosum is caused by Poxviridae. The raised papules with waxy cores are desiccated or treated with cryotherapy or topical imiquimod.
Syphilis is relatively uncommon in the United States. It is particularly important, however, for the obstetrician to recognize this infection in the pregnant patient (see Chapter 16) or in the patient who may become pregnant. Syphilis is caused by Treponema pallidum. Treatment is with parenteral (intramuscular) benzathine penicillin G.
Pediculosis pubis is caused by the crab louse Phthirus pediculosis, a millimeter-sized insect that infests the pubic area. Treatment is with permethrin 1% crème rinse.
Scabies is caused by a microscopic mite, Sarcoptes scabiei. Infestation is common and found worldwide. Treatment is with permethrin 5% crème or ivermectin.
HIV/AIDS AND REPRODUCTIVE-TRACT INFECTIONS IN WOMEN
Lower and upper reproductive tract infections may increase HIV risk in multiple ways. The presence of vaginal, cervical, and endometrial infection may amplify both the susceptibility to HIV infection and its transmission to sexual partners. Both ulcer- and non–ulcer-causing STIs appear to increase the susceptibility to HIV by damaging host defenses or increasing the number and efficiency of HIV viral receptors. Conversely, genital tract inflammation increases local release of HIV virus, which potentiates transmission to sexual partners and vaginally delivered babies. Screening for and treatment of STIs provides an opportunity to reduce the risks for HIV acquisition and transmission.
Centers for Disease Control and Prevention: Sexually transmitted diseases: Treatment guidelines. MMWR Morb Mortal Wkly Rep 55:1-92, 2006. Updates and ordering available online at: http://www2.cdc.gov/nchstp_od/piweb/stdorderform.asp or by telephone at 404-639-3311.
McClelland R.S. Trichomonas vaginalis infection: Can we afford to do nothing? J Infect Dis. 2008;197:487-489.
Paavonen J., Lehtinen M. Introducing human papillomavirus vaccines: Questions remain. Ann Med. 2008;40:162-166.
U.S. Preventive Services Task Force (USPSTF). Recommendations for human immunodeficiency virus (HIV) of adults and adolescents in healthcare settings. Am Fam Physician. 2008;77:819-824.
Vanvranken M. Prevention and treatment of sexually transmitted diseases. Am Fam Physician. 2007;76:1827-1832.