Cervicitis

Background

Cervicitis is an inflammation of the uterine cervix, characteristically diagnosed by: (1) a visible, purulent or mucopurulent endocervical exudate in the endocervical canal or on an endocervical swab specimen and/or (2) sustained, easily induced endocervical bleeding when a cotton swab is gently passed through the cervical os.^[1] A normal cervix is pictured below. (See Presentation.)

View Image

Normal cervix

Noninfectious cervicitis

Noninfectious cervicitis can be caused by the following:

• Local trauma - eg, cervical irritation caused by tampons, a cervical cap, the string from an intrauterine contraceptive device, a pessary, or a diaphragm
• Radiation
• Chemical irritation - eg, vaginal douches, latex exposure, or contraceptive creams
• Systemic inflammation - eg, Behçet syndrome
• Malignancy

Infectious cervicitis

The infectious etiologies of cervicitis, all of which are sexually transmitted infections (STIs), are significantly more common than the noninfectious causes. This article focuses on the infectious etiologies of cervicitis. (See Etiology.)

Infectious cervicitis may be caused by Chlamydia trachomatis (see the first image below), Neisseria gonorrhoeae, or herpes simplex virus (HSV) (see the second image below). In most cases of cervicitis, however, lab tests fail to isolate an organism; this is particularly true in women with low risk factors. (See Etiology and Workup.)^[1]

View Image

Signs of chlamydial cervicitis on speculum examination may include mucopurulent endocervical discharge and spontaneous or easily induced endocervical ....

View Image

Herpes simplex virus (HSV) cervicitis may involve the exocervix or endocervix, and it may be symptomatic or asymptomatic. Usually, the cervix appears ....

Trichomonas vaginalis, which, technically, causes vaginal infections, is commonly included in the discussion of cervicitis.

Because the female genital tract is contiguous from the vulva to the fallopian tubes, there is some overlap between vulvovaginitis and cervicitis; both conditions are commonly categorized as lower genital tract infections. Infections involving the endometrium and fallopian tubes are commonly categorized as upper genital tract infections and are not discussed in this article. (See DDx.)

• References

Etiology

The most common etiologies of cervicitis are infectious, with sexual transmission of organisms such as with C trachomatis and N gonorrhoeae being the primary means by which it is spread.^[1] Other etiologic organisms include Trichomonas vaginalis and herpes simplex virus (HSV), especially primary type 2 HSV.^[1]

Noninfectious causes of cervicitis include local trauma, radiation, chemical irritation, systemic inflammation, and malignancy. Limited data exist to suggest frequent douching, as well as Mycoplasma genitalium infection and bacterial vaginosis, as potential causes.^[1]

Risk factors

Risk factors for cervicitis include the following:

• Multiple sex partners
• Young age
• Single marital status
• Urban residence
• Low socioeconomic status
• Alcohol or drug use

Genetic predisposition, largely due to a variable host immune response, also plays an important role in the variability in infectious complications.^[2] Variants in the genes that regulate toll-like receptors (TLRs), an important component in the innate immune system, have been associated with an increased progression of C trachomatis infection to pelvic inflammatory disease (PID).^[3]

M genitalium

Although the role of M genitalium in PID is unclear, a study of 2378 British female students reported that this organism does not appear to be a significant etiologic agent for PID in this population (the incidence of PID was 3.9% over 12 mo in women with M genitalium infection vs 1.7% in noninfected women).^[4]

In a later study, however—a Swedish report on 5519 women at an outpatient gynecologic service—it was noted that M genitalium was a strong independent risk factor for PID and cervicitis, although there was a lower frequency of both conditions relative to women with C trachomatis infection.^[5] Further investigation is needed to determine the role of M genitalium in PID, infertility, and cervicitis.^[6]

A study by Dehon et al found a high prevalence of M. genitalium (7.4%) among the HIV-infected women and also found that chronic M. genitalium infection was associated with increased secretion of proinflammatory cytokines and marked inflammatory cervical infiltrates in the cervix with enrichment of HIV target cells. The study concluded that not only was M. genitalium implicated as an etiologic agent of cervicitis in HIV-infected women but that it also provided a potential mechanism for enhanced HIV transmission to an uninfected partner.^[7]

• References

Epidemiology

Occurrence in the United States

The Centers for Disease Control and Prevention (CDC) estimates that over 19 million new sexually transmitted infections (STIs) occur annually, almost half of them among persons aged 15-24 years.^[8] In addition to potentially severe health consequences, STIs pose a tremendous economic burden, with direct medical costs as high as $17 billion in a single year.^[8]

Trichomonas is the most common curable STI. Although an estimated 3.7 million people are infected (2.3 million in women ages 14-49 y), about 70% of these individuals are asymptomatic.^[9] About 7.4 million new cases occur each year in women and men.^[10]

Chlamydia, however, is the most frequently reported infectious disease in the US, with the majority of cases occurring in individuals aged 25 years or younger.^[11] The reported incidence of chlamydial infections has steadily increased over the past 2 decades, with 1.3 million cases reported in 2010.^[8] Although this increased incidence may reflect changes in screening efforts, many cases are not reported or are undiagnosed. More than 50% of sexually active young women are not screened annually, despite CDC recommendations.^[8]

Gonorrhea is the second most commonly reported infectious disease in the United States, with more than 300,000 cases reported in 2010.^[8] Annually, approximately 700,000 new gonococcal infections occur.^[12] Much like chlamydia, gonorrhea is believed to be underreported. In a study of 1469 emergency department patients diagnosed with cervicitis, Burnett et al found that 1.8% and 9.3% of patients with cervicitis were also positive for gonorrhea or chlamydia, respectively.^[13] Of a separate group of 343 patients with pelvic inflammatory disease (PID), 4.4% and 10% were positive for gonorrhea or chlamydia, respectively.^[13]

The annual rates of infection by herpes simplex virus (HSV) is difficult to estimate, because the vast majority of initial infections are asymptomatic or unrecognized. In addition, HSV infections are not required to be reported in the US.^[8]

The prevalence of HSV type 2 is about 16% (primarily among black women: 48%).^[14]

International occurrence

Worldwide, 448 million adults (ages 15-49 y) become infected with a curable STI (trichomoniasis, chlamydia, syphilis, or gonorrhea) every year.^[15] Other STIs are caused by various bacterial (chancroid, donovanosis) and viral (eg, human immunodeficiency virus [HIV], hepatitis B virus [HBV], cytomegalovirus [CMV]) pathogens, as well as by parasites (vaginal trichomoniasis, vulvovaginitis, balanoposthitis [men]).^[15]

Human papillomavirus

The prevalence of HPV, a cause of cervical cancer, varies roughly 20-fold internationally. In various studies, the seroprevalence of HSV-2 is higher in the United States (13-40%) than in Europe (7-16%) and is highest in Africa (30-40%).

Among the countries evaluated in a worldwide analysis, Spain had the lowest prevalence of HPV; only 1.4% of women in Spain tested positive for HPV.^[16] The highest prevalence of HPV was seen in sub-Saharan Africa; 26% of women in Nigeria tested positive for the virus. South America tended to have rates that were between those of Europe and sub-Saharan Africa, whereas rates in Asia varied widely (with the lowest rates in Hanoi, Vietnam, and the highest in India and Korea).^[16]

M genitalium

M genitalium infections have been implicated in cervicitis, PID, and female infertility.^{[5, 6]} A review of more than 27,000 women from 48 published reports found an overall global prevalence of 7.3% M genitalium urogenital infection in high-risk populations and 2.0% in low-risk populations.^[6] The investigators reported the prevalence of this agent in the general population as between that of C trachomatis and N gonorrhoeae. Furthermore, in 7 of 14 studies of lower tract inflammation, there was a positive association between M genitalium with urethritis, vaginal discharge, and microscopic evidence of cervicitis and/or mucopurulent discharge.^[6]

Race-, sex-, and age-related differences

No race predilection exists for cervicitis. Known risk factors include urban residence and low socioeconomic status.

Cervicitis can only be present in females. Male urethritis is more often symptomatic; therefore, diagnosis is usually made earlier in males than in females. Females with cervicitis are most often asymptomatic, so they do not seek evaluation or treatment as readily. Risk factors for cervicitis include age younger than 25 years, single marital status, and a new sexual partner within the past 6 weeks. Biologic (eg, postulated immaturity of the female reproductive tract) and behavioral factors (eg, greater number of partners, low awareness of acquired immunodeficiency syndrome [AIDS] and other STIs, and limited use of protection against STIs) are thought to contribute to this risk. Routine screening of sexually active adolescents and young adults is therefore recommended.

Routine chlamydia screening of sexually active women younger than 25 years is recommended by the US Preventive Services Task Force (USPSTF), American Cancer Society (ACS), American College of Obstetricians and Gynecologists (ACOG), American Society for Colposcopy and Cervical Pathology (ASCCP), and American Society for Clinical Pathology (ASCP) to prevent the consequences of untreated chlamydial infection (eg, PID, infertility, ectopic pregnancy, chronic pelvic pain).^{[17, 18, 19]} Fewer than half of young, sexually active females in the United States are screened for chlamydia.^[8]

• References

Prognosis

Gonorrhea, chlamydia, and trichomoniasis infections can be cured with antibiotic therapy, whereas antiviral therapy can reduce the number of herpes simplex virus (HSV) outbreaks, the duration of symptoms, and the severity of symptoms.

Complications from untreated infectious cervicitis depend on the pathogen. Untreated gonorrhea and chlamydia infections can lead pelvic inflammatory disease (PID), which can then result in infertility, chronic pelvic pain, and ectopic pregnancy. Other morbidity may include spontaneous abortion, premature rupture of membranes, and preterm delivery if infection is present during pregnancy.

Certain subtypes of HPV are linked with the development of cervical cancer. Untreated active HSV infections in the perinatal and neonatal period can cause mental retardation, blindness, low birth weight, stillbirth, meningitis, and death.

• References

Patient Education

Patients must understand that cervicitis is a preventable, sexually transmitted infection (STI) and that the most effective way to prevent the transmission of the infective agents that cause the disease is to avoid sexual intercourse with infected partners.

Ideally, both partners should be tested for common STIs, including human immunodeficiency virus, before initiating a sexual relationship. If the risk of infection is unknown by testing, then a condom should be used for all sexual acts. Condoms are available for men and women and have been proven to decrease the transmission of many STIs, including HIV, when used appropriately and consistently.

To avoid reinfection following cure, infected women must ensure that all of their sexual partners are treated for STIs.

For patient education resources, see the Women's Health Center and the Pregnancy Center, as well as Cervicitis, Pelvic Inflammatory Disease, Ectopic Pregnancy, Female Sexual Problems, and Pap Smear.

• References

History

Cervicitis is often asymptomatic in gonorrhea, chlamydia, and T vaginalis infections. When present, symptoms are often nonspecific and may include increased vaginal discharge, dysuria, urinary frequency, and intermenstrual or postcoital bleeding.^[1] If the infection has been long-standing, symptoms can include low abdominal or low back pain.

Most patients with herpes simplex virus (HSV) infection are asymptomatic. However, the first episode of genital herpes is frequently highly symptomatic and is marked by painful ulcerations associated with fever, myalgia, headache, and general malaise. Dysuria, vaginal discharge, and urethral discharge are also common symptoms. Recurrent outbreaks of HSV tend to be milder, but most patients have prodromal symptoms of itching or tingling, followed by the appearance of vesicles.

Because many causes of cervicitis are initially asymptomatic, ask all sexually active women for their complete gynecologic and sexual history at the initial evaluation and yearly thereafter.

In addition to the basic gynecologic history (eg, age of menarche, date of last menstrual period, gravida, para, pregnancy or delivery complications, date of last Papanicolaou test [Pap smear]), a complete sexual history is needed. This information includes the following:

• Number of recent and current partners (in the last 3 mo)
• Condom use
• Non-barrier contraception use
• Exchanging of sex for money or drugs
• Previous diagnoses of sexually transmitted infections (STIs)

A focused review of symptoms is recommended that asks about the following:

• Dyspareunia
• Vaginal discharge
• Genital skin lesions
• Abnormal vaginal bleeding
• Dysuria
• Genital burning
• Genital itching
• Genital malodor
• Lower abdominal or pelvic pain

• References

Physical Examination

The physical examination should include a general survey, an external inspection, and pelvic speculum and bimanual examinations. In certain patients, a rectal examination should be performed.

The physical examination is crucial to the evaluation and diagnosis of cervicitis, but it should not be limited to the pelvic region. An assessment for lymphadenopathy, skin lesions, oral lesions, joint redness or swelling, abdominal pain, and costovertebral angle tenderness can point to disseminated infection.

The pelvic examination must be performed in a competent and sensitive manner. The presence of a nursing assistant is advised to help with the examination and to act as a chaperone. Always explain to the patient what is going to be done before proceeding. Begin with a neutral touch on the patient's thigh and visually investigate the external genitalia in good lighting. Note any skin lesions (eg, warts, ulcers, vesicles, excoriations, erythema), inflammation of the Bartholin or Skene glands, or inguinal lymphadenopathy.

Speculum examination

Perform the speculum examination with water or gel lubrication (eg, Surgilube or K-Y jelly), and include direct visualization of the vaginal walls and cervix. Remember that normal vaginal secretions are nonadherent to the vaginal walls, clear to white in color, and nonodorous. Normal vaginal secretions have an acidic pH of less than 4.5. Vaginitis is present if the vaginal discharge is copious, colored, and malodorous, or if the pH is greater than 4.5.

Cervicitis is suspected if the cervix is erythematous, edematous, or easily friable. Classic mucopurulent cervicitis is present if thick, yellow-green pus is visible in the endocervical canal (the cervical os) or on an endocervical swab specimen. Laboratory specimens are collected for study at this point. Note cervical warts or ulcerations.

Bimanual examination

After the speculum is removed, a bimanual examination is performed to assess tenderness or enlargement of the cervix, uterus, and adnexa. Cervicitis or pelvic inflammatory disease (PID) is suspected if the patient has cervical motion tenderness (ie, if she experiences pain or tenderness while the examiner gently moves the cervix from side to side).

The following images depict a normal cervix, followed by images of cervicitis caused by various organisms.

View Image

Normal cervix

View Image

Cervix of a lactating woman without sexually transmitted infections. The patient had twice given birth vaginally.

View Image

Cervical cellularity (ectopy), which is often present in adolescents, allows for greater adherence of infectious organisms in the cervix. The risk of ....

View Image

Signs of chlamydial cervicitis on speculum examination may include mucopurulent endocervical discharge and spontaneous or easily induced endocervical ....

View Image

In women with gonococcal cervicitis, the cervix may show mucopurulent or purulent cervical discharge and easily induced cervical bleeding.

View Image

Herpes simplex virus (HSV) cervicitis may involve the exocervix or endocervix, and it may be symptomatic or asymptomatic. Usually, the cervix appears ....

View Image

T vaginalis can have a characteristic "frothy" gray or yellow-green vaginal discharge and pruritus. The occurrence of cervical petechiae, or "strawbe....

• References

Approach Considerations

The Centers for Disease Control and Prevention (CDC) recommends testing on self- or clinician-collected endocervical and vaginal swab specimens, as well as on urine specimens.^[11] Nucleic acid amplification testing (NAAT) is the most sensitive and specific for gonorrheal and chlamydial infections,^{[1, 11]} and it also allows for testing on the widest variety of specimen types.^[11]

There is an association between a finding of leukorrhea (>10 white blood cells [WBCs] under microscopic high-power field [HPF] examination of vaginal fluid) and cervical chlamydial and gonococcal infection.^[1] If the woman doesn’t have inflammatory vaginitis, leukorrhea may be a sensitive indicator of cervical inflammation with a high negative predictive value.^[1]

Note that although some experts believe the presence of elevated polymorphonuclear leukocytes on endocervical Gram stain is useful in diagnosing cervicitis, no standard criterion exists and it is generally unavailable in clinical settings. Moreover, the positive predictive value is low for C trachomatis and N gonorrhoeae.

Gonococcal cervical infection can be diagnosed from the presence of gram-negative intracellular diplococci (GNID) in endocervical fluid. However, only 50% of affected women have this finding.^[1]

If genital ulcer disease is observed, exclude the diagnosis of syphilis by serologic testing or consider performing a biopsy. Adolescents presenting with urinary symptoms should be tested for sexually transmitted and urinary tract infections. Adequate follow up should be established to ensure timely treatment.^[20]

In cases of suspected or documented treatment failure, perform culture and antimicrobial susceptibility testing.

Screening in high-risk populations

Women at risk for sexually transmitted infections (eg, women with multiple partners, sexually active women aged 25 years or younger [including adolescents], women with a history of previous sexually transmitted infections [STIs], and pregnant women) should be annually screened for gonorrhea and chlamydia. Such screening in this population has been proven to be cost effective.

HSV screening

General screening for herpes simplex virus (HSV) is not recommended, because no evidence demonstrates that serologic tests for HSV antibody improve health outcomes or symptoms or reduce disease transmission. However, in individuals whose sexual partners are known to be infected with HSV-2, screening can be offered.

• References

Identification of Infectious Agents

Because the causes of vulvovaginitis and cervicitis overlap, the initial diagnostic approaches to the 2 conditions are identical. Assess the appearance of vaginal secretions, measure the pH of the secretions, and perform microscopy with isotonic sodium chloride solution and 10% potassium hydroxide (KOH) along with a whiff test.

T vaginalis

Infection with T vaginalis usually produces a thin, purulent, frothy, and malodorous discharge and can cause vulvar erythema and edema. The cervix can be erythematous and may have punctate hemorrhages (ie, colpitis macularis or “strawberry cervix”).

The diagnosis is suggested if microscopy of cervical secretions reveals 10-30 leukocytes per oil immersion field. The diagnosis is confirmed by observation of the motile, flagellated protozoan on the normal saline wet mount under the microscope. However, note that trichomonads are observed under microscopy in only about 50% of cases (ie, low sensitivity); therefore, additional testing is recommended in symptomatic women with negative microscopy findings.^[1]

On cytology, Trichomonas is a pear-shaped extracellular organism with a pale nucleus and red granules in its cytoplasm (see the following image).

View Image

Pap stain, high power (under oil immersion), showing 2 pear-shaped structures representing Trichomonas. Small, pale nuclei and cytoplasmic granules ar....

Other tests for trichomoniasis in women include a nucleic acid probe test that evaluates for T vaginalis, Gardnerella vaginalis, and Candida albicans (available in about 45 min) in vaginal secretions^[21] and a test that uses an immunochromatographic capillary flow dipstick technology (available in about 10 min). However, despite the tendency toward greater sensitivity in these tests compared with those requiring wet mount preparation, there is the potential for false positives, particularly in areas with a low prevalence of disease.^[21]

Another sensitive and available technique for trichomoniasis is culture of vaginal secretions, generally used when the condition is suspected but not confirmed by microscopy.^[21] Liquid-based testing has enhanced sensitivity but also has the potential for false-positive results requiring other confirmatory tests. Techniques modified from detection of gonorrhea and chlamydia to detect trichomoniasis include a modified polymerase chain reaction (PCR) assay and transcription-mediated amplification.^[21]

C trachomatis and N gonorrhoeae

If cervicitis is suspected or mucopurulent cervicitis is observed, then cervical discharge is collected for culture and, optionally, for Gram stain. The microscopic finding of gram-negative intracellular diplococci has a sensitivity of 60% and a specificity of more than 90% for gonorrhea. The observation of more than 30 leukocytes per oil immersion field is highly suggestive of chlamydia and gonorrhea.

Although culture is still regarded as the criterion standard, many alternative techniques for the diagnosis of gonorrhea and chlamydia are available. They include enzyme immunoassay (EIA), direct fluorescent antibody [DFA] staining, DNA probe, and PCR assay.

Nucleic acid amplification tests (NAATs) are preferred over the other tests, because they are highly sensitive and specific for diagnosing gonococcal and chlamydial infections.^[1] NAATs can be performed on vaginal, cervical, and urine samples; the presence of 10 or more WBCs in vaginal fluid in the absence of trichomoniasis suggests endocervical inflammation from gonococcal or chlamydial infection.^[1]

The advantages of alternative techniques over conventional cultures include reduced turnaround time and lack of dependence on the complex and expensive systems needed to culture chlamydia and gonorrhea. Alternative techniques also possess the ability to detect both C trachomatis and N gonorrhoeae with the same sample. The main disadvantage of all the nonculture diagnostic techniques is the inability to assess microbial resistance. Nonetheless, many clinic- and hospital-based practices have already stopped using cultures and have switched to these alternative modalities.

Herpesvirus

If typical grouped vesicles mixed with small ulcers are observed, in addition to a typical history, the diagnosis of HSV infection can be made on clinical grounds alone. For atypical ulcers or first infection, attempt definitive diagnosis by culture.

However, although culture is considered the criterion standard for the diagnosis of herpes simplex, alternative techniques (eg, cytology, antigen detection, DNA probe) are also used. On cytology, HSV consists of cells with multinucleation, margination of chromatin, and nuclear molding. Nuclear inclusions may be appreciated (see the image below).

View Image

Papanicolaou (Pap) stain, high power, showing the Herpes simplex virus (HSV) infecting cells with multiple nuclei, intranuclear inclusions, and margin....

Serology currently has no role in the diagnosis of HSV infection, because of cross-reactivity between HSV types 1 and 2 in the assays. Newer, type-specific glycoprotein g1 and g2 serologic assays exist, but they are not yet for routine diagnostic use.

Human papillomavirus

If the patient has no gross lesions on the cervix and previously received adequate cervical cancer screening (negative cervical cytology within past 3 years or negative cytology and HPV testing within the past 5 years), no further testing for HPV is necessary. If the patient has not had screening for cervical cancer, she should be screened according to age-appropriate guidelines. The United States Preventive Services Task Force (USPSTF), American College of Obstetrics and Gynecology (ACOG), and American Cancer Society (ACS) recommend HPV testing combined with Pap testing every 5 years in women aged 30-65 years; however, the Pap test every 3 years alone for this age group is also acceptable.^{[17, 18, 19]} For women aged 21-29 years, Pap test screening for cervical cancer is recommended every 3 years. However, screening is not recommended in women younger than 21 years.^{[17, 18, 22]}

Women with abnormal cervical cancer screening results should be managed according to the American Society of Cytology and Cervical Pathology recommendations.^{[23, 24]}

• References

Approach Considerations

Admit women to the hospital if pelvic inflammatory disease [PID] is suspected and the patient is unable to take oral medications, is pregnant or immunocompromised, has failed prior outpatient therapy, has a tubo-ovarian abscess, or if the diagnosis is uncertain (e.g. appendicitis cannot be ruled out). If disseminated infection is suspected, intensive monitoring and parenteral medication are needed, as patients may quickly become unstable.

If the patient is unable to take oral medication because of intractable nausea, vomiting, or abdominal pain, then hospitalization for intravenous medication is warranted.

In most cases, test-of-cure is not necessary, because of the high efficacy of the medications used. In the case of persistent symptoms or pregnancy, follow-up testing is recommended.

• References

Antimicrobial Management

Treatment of all causes of cervicitis is medical and can be done presumptively (treatment with azithromycin or doxycycline) in infectious cases or with specific antibiotic treatment once the etiology is known; however, empiric treatment for cervicitis can also include coverage for gonorrhea if there is clinical suspicion for this condition.

Provide presumptive therapy to women at increased risk for chlamydial infection, particularly in cases in which follow-up is uncertain or in which a relatively insensitive diagnostic test is used instead of nucleic acid amplification testing (NAAT), as well as in patients who have been diagnosed with trichomoniasis and bacterial vaginosis.^[1]

Treatment must also include the patient's sexual partners to prevent reinfection. In addition, all [#TreatmentConsultations] sexual activity must cease for 7 days until the completion of therapy; that is: (1) after initiating treatment in the patient and (2) until the partner has also been treated.

Chlamydial cervicitis

The CDC recommends the following regimens for presumptive treatment of chlamydial cervicitis^[1] :

• Azithromycin 1 g oral (PO) in a single dose, OR
• Doxycycline 100 mg PO twice daily (bid) for 7 days

Effective alternative agents to azithromycin and doxycycline for the treatment of chlamidia include erythromycin, levofloxacin, and ofloxacin, as follows^{[1, 11]} :

• Erythromycin base 500 mg PO four times daily (qid) for 7 days, OR
• Erythromycin ethylsuccinate 800 mg PO qid for 7 days, OR
• Levofloxacin 500 mg PO daily (qd) for 7 days, OR
• Ofloxacin 300 mg PO bid for 7 days

These patients should also be treated concurrently for gonococcal infection in areas with high gonorrhea prevalence or if the individual’s personal risk is high.  In women who defer presumptive treatment, the need for therapy depends on the results of sensitive tests for chlamydia and gonorrhea.^[1]

Gonococcal cervicitis

For uncomplicated gonococcal infections of the cervix, the CDC updated their recommendations in August 2012, as follows^[25] :

• Ceftriaxone 250 mg administered intramuscularly (IM) in a single dose, PLUS
• Azithromycin 1 g PO in a single dose (preferred, owing to tetracycline resistance) or doxycycline 100 mg PO bid for 7 days

Alternatively, if ceftriaxone is not an option, the following regimens are recommended^[25] :

• Single-dose injectable cephalosporin regimens, PLUS
• Azithromycin 1 g PO in a single dose (preferred) or doxycycline 100 mg PO bid for 7 days, PLUS
• Test-of-cure in 1 week (with culture, including phenotypic antimicrobial susceptibility; if culture is unavailable, obtain NAAT)

If the patient has a severe cephalosporin allergy, azithromycin 2 g PO in a single dose plus test-of-cure in 1 week are recommended.^[25]

Trichomoniasis

The CDC recommends metronidazole 2 g PO in a single dose or tinidazole 2 g PO in a single dose for T vaginalis infections.^[21] Alternatively, metronidazole 500 mg PO bid for 7 days can be given.

Patients must avoid alcohol consumption during treatment with metronidazole or tinidazole, as well as for 24 hours after completion of metronidazole or 72 hours after completion of tinidazole.^[21] Topically applied antimicrobials are not as effective as the oral doses (eg, metronidazole) and should be avoided.

Lactating women who are administered metronidazole should withhold breastfeeding during treatment and for 12-24 hours after the last dose.^[21] Women treated with tinidazole should also withhold breastfeeding during treatment, as well as for 3 days after the last dose.

Evaluate male partners and treat them with either tinidazole in a single dose of 2 g PO or metronidazole 500 mg PO bid for 7 days.^[21]

Treatment during pregnancy

Do not treat pregnant women with doxycycline, ofloxacin, and levofloxacin.^[11] Pregnant women with chlamydial cervicitis may be treated with azithromycin as above or with amoxicillin 500 mg PO three times daily (tid) for 7 days. Erythromycin may be an alternative regimen, as follows^[11] :

• Erythromycin base 500 mg PO qid for 7 days, OR
• Erythromycin base 250 mg PO qid for 14 days, OR
• Erythromycin ethylsuccinate 800 mg PO qid for 7 days, OR
• Erythromycin ethylsuccinate 400 mg PO qid for 14 days

Pregnant women with gonococcal cervicitis should undergo the same treatment as nonpregnant women. In those who cannot tolerate a cephalosporin, consider azithromycin 2 g PO.^[12]

Pregnant women with trichomoniasis can be treated with 2 g metronidazole in a single dose at any stage of pregnancy.^[21] The safety of tinidazole in pregnant women has not been well evaluated.

Cervicitis and HIV coinfection

In women with concurrent cervicitis and HIV infection, the treatment regimen is the same as that for women not infected with HIV.^[1] It is essential for these women to receive treatment to reduce cervical HIV shedding, which is increased in cervicitis, and thus reduce the potential for HIV transmission to their sex partners.^[1]

In patients with trichomoniasis and HIV coinfection, the CDC recommends considering a multidose treatment regimen of metronidazole PO, as a study indicated the single dose of metronidazole 2 g PO was not as effective as 500 mg bid for 7 days.^[21]

Recurrent/persistent cervicitis

Aside from reevaluation for reexposure to a sexually transmitted infection (STI), there are currently no defined treatment options for women found to have recurrent and persistent cervicitis despite the exclusion of relapse/reinfection with a specific STI, the absence of bacterial vaginosis, and the evaluation and treatment of the patient’s sex partner(s).^[1] The efficacy of repeated or prolonged antibiotic therapy in these women is also unclear. Consider referring women with persistent symptoms clearly caused by cervicitis to gynecologic specialists.^[1]

Women with trichomoniasis, treatment failure using metronidazole 2 g single dose, and exclusion of reinfection should be treated with metronidazole 500 mg PO bid for 7 days.^[21] If retreatment is unsuccessful, consider tinidazole or metronidazole at 2 g PO for 5 days. If none of these treatment strategies are effective, consult with an infectious disease specialist to determine the susceptibility of the T vaginalis infection to metronidazole and tinidazole. The CDC also provides consultation (telephone: 404-718-4141; Web site: http://www.cdc.gov/std) and T vaginalis susceptibility testing.^[21]

Antimicrobial-resistant gonorrhea

Consult an infectious disease specialist for suspected treatment failure or for the management of patients infected with a microbial strain that has demonstrated in vitro resistance.^[12] Perform culture and susceptibility testing, retreat the patient with at least 250 mg of ceftriaxone intramuscular/intravenous (IM/IV), and treat the patient’s sex partners. In addition, notify the CDC through state and local public health authorities.^[12]

In April 2007, the CDC updated treatment guidelines for gonococcal infection and associated conditions (eg, pelvic inflammatory disease [PID]), owing to the ability of N gonorrhoeae to develop resistance to microbial therapies.^[26] The guidelines no longer recommended fluoroquinolone antibiotics to treat gonorrhea in the United States.

This change was based on analysis of new data from the CDC’s Gonococcal Isolate Surveillance Project (GISP). The GISP data showed that the proportion of fluoroquinolone-resistant gonorrhea (QRNG) cases in heterosexual men had reached 7.9% in 2010, a 13-fold increase from 0.6% in 2001.^{[26, 27]}

As a result of another update of the CDC’s treatment guidelines, in August 2012, oral cephalosporins are no longer recommended for gonococcal infections.^[25] Thus, cefixime at any dose is no longer a first-line treatment for such infections.^[25]

Treatment of gonorrhea is now limited to ceftriaxone 125 mg IM once as a single dose plus a second antibiotic. Fluoroquinolones may be an alternative treatment option for disseminated gonococcal infection if antimicrobial susceptibility can be documented.

For more information, see the CDC’s Antibiotic-Resistant Gonorrhea Web site, the Gonococcal Isolate Surveillance Project (GISP) Web site, or the May 18, 2012, video presentation, The Growing Threat of Multidrug Resistant Gonorrhea.

• References

Long-Term Monitoring

Follow up with women treated for cervicitis according to recommendations for the specific etiology to determine whether the condition has resolved.^[1] Routine test-of-cure (ie, repeat testing 3-4 wk following treatment completion) is not recommended following treatment, except in the following situations^{[1, 11]} :

• The patient is pregnant
• Symptoms persist
• Suspicion of reinfection exists
• There is questionable treatment compliance

Women with persistent symptoms following gonococcal or chlamydial infection should be reevaluated owing to the increased risk of reinfection within 6 months following treatment; ie, repeat testing should be performed 3-6 months after the initial treatment, whether or not a patient’s sex partner(s) underwent treatment.^[1] Women treated for trichomoniasis should also be rescreened at 3 months following treatment due to the high risk for reinfection.^[21]

• References

Medication Summary

Oral antibiotics effectively cure gonorrhea, chlamydia, and T vaginalis infections. Oral antivirals reduce the duration of symptoms, lesions, and viral shedding in the first and recurrent episodes of genital herpes infections. Initially, topical therapy is used for symptomatic genital wart removal. Other options include intralesional injection and surgery.

In April 2007, the CDC indicated that fluoroquinolone antibiotics were no longer recommended to treat gonorrhea in the United States.^[26] In August 2012, the CDC further revised treatment guidelines so that oral cephalosporins were no longer recommended as first-line therapy for gonococcal infections.^[25]

• References

Ceftriaxone (Rocephin)

• Dosing, Interactions, etc.

Clinical Context:  Ceftriaxone is first-line therapy for gonococcal cervicitis. This agent is a third-generation cephalosporin with broad-spectrum, gram-negative activity. Although it has lower efficacy against gram-positive organisms, ceftriaxone has higher efficacy against resistant organisms. Ceftriaxone arrests bacterial growth by binding to 1 or more penicillin-binding proteins.

• References

Cefixime (Suprax)

• Dosing, Interactions, etc.

Clinical Context:  Cefixime is a third-generation cephalosporin that is effective in treating gonorrhea. By binding to 1 or more of the penicillin-binding proteins, this drug arrests bacterial cell wall synthesis and inhibits bacterial growth. Cefixime is once again available in the United States.

As previously stated, however, as a result of an update of the CDC's treatment guidelines, in August 2012, oral cephalosporins are no longer recommended for gonococcal infections. Thus, cefixime is no longer considered to be a first-line treatment for gonorrhea.

• References

Spectinomycin (Trobicin)

Clinical Context:  Spectinomycin is an alternative regimen for the treatment of gonorrhea. This agent inhibits protein synthesis in bacterial cells. Its site of action is the 30S ribosomal subunit, and it is structurally different from related aminoglycosides. Use spectinomycin if the patient is allergic to penicillin and quinolones. Do not use spectinomycin if oropharyngeal gonorrhea is suspected.

• References

Azithromycin (Zithromax)

• Dosing, Interactions, etc.

Clinical Context:  Azithromycin is first-line therapy for chlamydia cervicitis. This drug is a semisynthetic macrolide antibiotic that is effective in treating chlamydia. Azithromycin also treats mild to moderate microbial infections.

• References

Doxycycline (Vibramycin)

• Dosing, Interactions, etc.

Clinical Context:  Doxycycline is a long-acting tetracycline derived from oxytetracycline. It inhibits protein synthesis and thus bacterial growth by binding to the 30S and possibly 50S ribosomal subunits of susceptible bacteria. This agent is effective in treating chlamydia.

• References

Erythromycin base (E-Mycin)

• Dosing, Interactions, etc.

Clinical Context:  Erythromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. This agent is an alternative therapy for chlamydial cervicitis.

• References

Erythromycin ethylsuccinate (E.E.S.)

• Dosing, Interactions, etc.

Clinical Context:  Erythromycin ethylsuccinate inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. This agent is an alternative regimen for chlamydial cervicitis.

• References

Metronidazole (Flagyl)

• Dosing, Interactions, etc.

Clinical Context:  Metronidazole is a synthetic antibacterial and antiprotozoal agent. This drug provides first-line therapy for T vaginalis infections.

• References

Levofloxacin (Levaquin)

• Dosing, Interactions, etc.

Clinical Context:  Levofloxacin inhibits DNA gyrase activity. This agent is an alternative treatment for chlamydial cervicitis.

• References

Ofloxacin (Floxin)

• Dosing, Interactions, etc.

Clinical Context:  Ofloxacin inhibits bacterial DNA gyrase, which in turn inhibits DNA replication, transcription, repair, recombination, and transposition, causing bacterial cell death. This agent is an alternative treatment for chlamydial cervicitis.

• References

Amoxicillin (Amoxil, Moxatag, Trimox)

• Dosing, Interactions, etc.

Clinical Context:  Amoxicillin interferes with synthesis of cell wall mucopeptides during active multiplication, resulting in bactericidal activity against susceptible bacteria. This agent is an alternative treatment for chlamydial cervicitis

• References

Class Summary

Antimicrobial therapy for cervicitis must be comprehensive and cover all likely pathogens in the context of this clinical setting.

• References

Acyclovir (Zovirax)

• Dosing, Interactions, etc.

Clinical Context:  Acyclovir is a synthetic purine nucleoside analogue that is indicated for genital herpes simplex virus (HSV) infections. For the first episode, begin treating within 6 days after the appearance of the first symptoms. If the episode represents a recurrence, begin treating during the prodrome or within 1 day after the onset of lesions. Suppression requires daily treatment for 1 year.

• References

Famciclovir (Famvir)

• Dosing, Interactions, etc.

Clinical Context:  Famciclovir is a prodrug for penciclovir (active moiety); this agent is indicated for genital HSV infections. For the first episode, begin treating within 6 days after the appearance of the first symptoms. For a recurrent attack, begin treating during the prodrome or within 1 day after the onset of lesions. Suppression requires daily treatment for 1 year.

• References

Valacyclovir (Valtrex)

• Dosing, Interactions, etc.

Clinical Context:  Valacyclovir is indicated for genital HSV infections. For the first episode, begin treating within 6 days after the appearance of the first symptoms. For a recurrent attack, begin treating during the prodrome or within 1 day after the onset of lesions. Suppression requires daily treatment for 1 year.

• References

Class Summary

Nucleoside analogues are initially phosphorylated by viral thymidine kinase to eventually form a nucleoside triphosphate. These molecules inhibit HSV polymerase with 30-50 times the potency of human alpha-DNA polymerase.

• References

Imiquimod (Aldara)

• Dosing, Interactions, etc.

Clinical Context:  Imiquimod is indicated for genital/perianal warts. This agent induces secretion of interferon alpha and other cytokines; however, its mechanism of action is unknown. Imiquimod may be more effective in women than in men.

• References

Podofilox (Condylox)

• Dosing, Interactions, etc.

Clinical Context:  Podofilox is a topical antimitotic that can be chemically synthesized or purified from the plant families Coniferae and Berberidaceae (eg, species of Juniperus and Podophyllum). Its exact mechanism of action is unknown.

• References

Fluorouracil topical (Carac, Efudex, Fluoroplex)

• Dosing, Interactions, etc.

Clinical Context:  Fluorouracil is a cycle-specific drug that has activity as a single agent; for many years, it has been combined with the biochemical modulator leucovorin. Fluorouracil has been shown to be effective in an adjuvant setting. A classic antimetabolite anticancer drug, it has a chemical structure similar to endogenous intermediates (the building blocks of DNA or RNA).

5-fluorouracil (5-FU) inhibits tumor cell growth through at least 3 different mechanisms that ultimately disrupt DNA synthesis or cellular viability. These effects depend on intracellular conversion of 5-FU into 5-FdUMP, 5-FUTP, and 5-FdUTP and are as following:

• References

Trichloroacetic acid topical (Tri-Chlor)

• Dosing, Interactions, etc.

Clinical Context:  Topical trichloroacetic acid cauterizes skin, keratin, and other tissues. Despite its causticity, this agent causes less local irritation and systemic toxicity than do other drugs in its class. However, the response to topical trichloroacetic acid is often incomplete, and recurrence occurs frequently.

• References

Class Summary

Topical skin products are indicated for genital/perianal warts.

• References

Tinidazole (Fasigyn, Tindamax)

• Dosing, Interactions, etc.

Clinical Context:  Tinidazole is indicated to treat trichomoniasis caused by T vaginalis in males and females. This agent is a 5-nitroimidazole derivative that is used for susceptible protozoal infections. The nitro group is reduced by the cell extract of Trichomonas. The free nitro radical generated is thought to be responsible for tinidazole's antiprotozoal activity against T vaginalis.

• References

Class Summary

Antiprotozoal agents are an alternative therapy for Trichomonas infections.

• References