eMedicine Specialties > Obstetrics and Gynecology > Infections

Cervicitis

Arthur T Ollendorff, MD, Associate Professor of Clinical Obstetrics and Gynecology, Residency Program Director, Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine; Chief of Gynecology, Veterans Affairs Medical Center, Cincinnati

Updated: Aug 3, 2009

Introduction

Background

Cervicitis is an inflammation of the uterine cervix. Infectious cervicitis might be caused by Chlamydia trachomatis, Neisseria gonorrhoeae, herpes simplex virus (HSV), or human papillomavirus (HPV). Trichomonas vaginalis, technically a vaginal infection, is commonly discussed when discussing cervicitis. Noninfectious cervicitis might be caused by local trauma, radiation, or malignancy. The infectious etiologies are significantly more common than the noninfectious causes, and all possible infectious causes of cervicitis are sexually transmitted infections (STIs). This article focuses on the infectious etiologies of cervicitis.

Pathophysiology

Because the female genital tract is contiguous from the vulva to the fallopian tubes, there is some overlap between vulvovaginitis and cervicitis. Vulvovaginitis and cervicitis 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.

Frequency

United States

The Centers for Disease Control and Prevention (CDC) estimates that over 19 million STI infections occur annually, almost half of them among those aged 15-24 years. In addition to potentially severe health consequences, STIs pose a tremendous economic burden, with direct medical costs as high as $16 billion in a single year.

Trichomonas is the most common curable STI in young, sexually active women. An estimated 7.4 million new cases occur each year in women and men. In 2007, 1.1 million chlamydial infections were reported to the CDC, up from 877,478 cases reported in 2003.¹ Because many cases are not reported or even diagnosed, 2.8 million new cases of chlamydia are actually estimated to occur each year. Gonorrhea is the second most commonly reported infectious disease in the United States, with 355,991 cases reported in 2007.¹ Much like chlamydia, gonorrhea is believed to be underreported.

The annual rates of infection by HSV and HPV are difficult to estimate because the vast majority of initial infections are asymptomatic or unrecognized.¹ In the United States, seroprevalence studies show that 22% of adults have HSV type 2 antibodies; currently, over 500,000 new cases of genital herpes are believed to occur annually. Approximately 20 million people are currently infected with HPV. At least 50% of sexually active men and women acquire a genital HPV infection at some point in their lives. By age 50 years, at least 80% of women will have acquired a genital HPV infection. About 6.2 million Americans get a new genital HPV infection each year.

International

Worldwide, more than 400 million adults become infected with an STI every year. Four STIs that are spread primarily through sexual contact are completely curable—trichomoniasis, chlamydia, syphilis, and gonorrhea. These infections account for 340 million STI infections, or about 80% of the worldwide total. Approximately 9% of all persons aged 15-44 years in North America contract 1 of these STIs annually, but the rate rises to 25% in sub-Saharan Africa.

Worldwide, over 170 million cases of trichomoniasis are reported each year. Infection rates have been reported as high as 67% in Mongolia in 1988, 40-60% in Africa, and 40% in indigenous Australians older than 40 years.

Chlamydia is the next most common STI, with approximately 92 million cases a year. Prevalence of chlamydia varies enormously across the world. In the 1990s, rates among pregnant women in Europe ranged from 2.7% in Italy to 8.0% in Iceland, while studies in South America found rates of 1.9% among teenagers in Chile and 2.1% among pregnant women in Brazil. In Asia, rates among pregnant women tend to be much higher: up to 17% in India and 26% in rural Papua New Guinea. In Africa, studies of pregnant women have revealed rates from 6% in Tanzania to 13% in Cape Verde.

HPV, HSV, and gonorrhea each account for roughly 20-60 million cases of STIs per year.

The prevalence of HPV, a cause of cervical cancer, varies roughly 20-fold internationally. An analysis of worldwide prevalence was published in 2005.² Among the countries evaluated, Spain had the lowest prevalence of HPV; only 1.4% of women in Spain tested positive for HPV. The highest prevalence of HPV was seen in sub-Saharan Africa; 26% of the women in Nigeria tested positive for HPV. South America tended to have rates that were in between those of Europe and sub-Saharan Africa, while rates in Asia varied widely (with the lowest rates in Hanoi, Vietnam, and the highest in India and Korea).

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%).

Studies of pregnant women in Africa have found rates for gonorrhea ranging from 0.02% in Gabon to 3.1% in Central African Republic and 7.8% in South Africa. In the Western Pacific in the 1990s, the highest prevalence rates (>3%) were in Cambodia and Papua New Guinea. Other areas such as China, Vietnam, and the Philippines had rates of 1% or less. Between 1995 and 1999, a significant increase in gonorrhea incidence occurred in Eastern Europe, with the highest rates in Estonia, Russia, and Belarus.

Mortality/Morbidity

Complications from untreated infectious cervicitis depend on the pathogen. Morbidity includes pelvic inflammatory disease (PID), infertility, ectopic pregnancy, chronic pelvic pain, spontaneous abortion, cervical cancer, premature rupture of membranes, and preterm delivery. Perinatal and neonatal infections can cause mental retardation, blindness, low birth weight, stillbirth, meningitis, and death. The social stigma is strong and might expose women to verbal, emotional, or physical abuse from others, particularly male partners.

Race

No racial predilection exists. Known risk factors include urban residence and low socioeconomic status.

Sex

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.

Age

Age younger than 25 years, single marital status, and a new sexual partner within the past 6 weeks are risk factors for cervicitis. Both biological (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 young women is recommended by the US Preventive Services Task Force to prevent consequences of untreated chlamydial infection (eg, pelvic inflammatory disease, infertility, ectopic pregnancy, chronic pelvic pain). Fewer than half of young, sexually active females in the United States are screened for chlamydia, according to the Morbidity and Mortality Weekly Report (MMWR). Nationally, the annual screening rate increased from 25.3% in 2000 to 43.6% in 2006, and then decreased slightly to 41.6% in 2007.¹

Clinical

History

• Gonorrhea, chlamydia, and T vaginalis infections are often asymptomatic. When present, symptoms are often nonspecific. Symptoms include increased vaginal discharge, dysuria, urinary frequency, and intermenstrual or postcoital bleeding. If the infection has been long standing, symptoms can include low abdominal or low back pain.
• Infection with HPV is frequently asymptomatic because the genital warts are often flat and internal. When the warts are raised and on the labia, perineum, or perianal area, they are called condylomata acuminata and are easily visible.
• Similarly, most patients with HSV infection are asymptomatic. However, first episode 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 number of recent and current partners (in the last 3 months), condom use, nonbarrier contraception use, exchanging of sex for money or drugs, and previous diagnoses of STIs. A focused review of symptoms that asks about dyspareunia, vaginal discharge, genital skin lesions, abnormal vaginal bleeding, dysuria, genital burning, genital itching, genital malodor, and lower abdominal or pelvic pain is recommended.
• In high-risk populations (eg, women with multiple partners, adolescents, women with a history of previous STIs, pregnant women), screen for gonorrhea, chlamydia, and T vaginalis infections. Screening in this population has been proven to be cost effective. Screening can be performed annually in conjunction with the Pap smear. Pap smears are not an effective screening test for STIs, vaginitis, or cervicitis; however, a significant proportion of abnormal Pap smear results indicate subclinical HPV.
• New primary cervical screening guidelines from both the American Cancer Society (ACS) and the American College of Obstetricians and Gynecologists (ACOG) include the option to screen women aged 30 years and older with an HPV test plus cervical cytology.
• Persistent infection with oncogenic HPV is the primary cause of cervical cancer and its precursor lesions. Therefore, testing for HPV can detect cervical cancer risk at an early stage. However, the usefulness of the HPV DNA test result is dependent on the age of women being screened. In women younger than age 25, HPV infection is common but mostly transient and not associated with cervical cancer risk. Therefore, HPV screening is not recommended for women younger than age 25. In contrast, in women older than age 30, a positive HPV DNA test result is mostly indicative of persistent infection, and no more than 5% tend to have a positive test result. Also, about 95% of cervical cancers occur in this age group. Therefore, finding HPV infection in this age group is considered significant regardless of Papanicolaou test results, as this is known to be associated with an increased risk of cervical cancer.
• The application of the HPV DNA test as an adjunct test in Atypical Squamous Cells of Unknown Significance (ASC-US) triage has been well established.³ ASC-US Papanicolaou tests account for nearly two thirds of all Papanicolaou test abnormalities reported, but, in most patients this is not a predictor of cervical cancer risk. However, 5-17% in this group could have underlying HSIL and hence the indication for further follow-up. In this context, the HPV DNA test can identify women who are at risk for cervical cancer and allow for close surveillance of those testing HPV positive.
• General screening for HSV is not recommended because no evidence demonstrates that serological tests for HSV antibody improves health outcomes or symptoms or reduces transmission of disease. However, in individuals in partnerships with individuals infected with HSV-2, screening can be offered.

Physical

The physical examination should include a general survey; 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 do not limit the examination to the pelvic region. A survey 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. A nursing assistant can help the examiner and act as chaperone. Always explain to the patient what is going to be done before proceeding. Begin with a neutral touch on the patient's thigh.
  • The pelvic examination begins by visually investigating 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.
  • 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.
  • After the speculum is removed, the 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, she experiences pain or tenderness while the examiner gently moves the cervix from side to side.

Causes

All of the infectious etiologies of cervicitis are STIs. Risk factors include multiple sex partners, young age, single marital status, urban residence, low socioeconomic status, and alcohol or drug use.

Differential Diagnoses

Other Problems to Be Considered

Retained foreign body (eg, tampon, condom)

Workup

Laboratory Studies

• Because the causes of vulvovaginitis and cervicitis overlap, the initial diagnostic approaches to vulvovaginitis and cervicitis are identical. Appearance of vaginal secretions is assessed, pH of the secretions is measured, and microscopy with isotonic sodium chloride solution and 10% potassium hydroxide (KOH) is performed along with a whiff test.
• 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, 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.
• 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, direct fluorescent antibody staining, DNA probe, and polymerase chain reaction (PCR).
  • The advantages over conventional cultures include reduced turnaround time and lack of dependence on the complex and expensive systems needed to culture chlamydia and gonorrhea. It also possesses the ability to detect both organisms 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 techniques.
• If genital ulcer disease is observed, exclude the diagnosis of syphilis by serologic testing or consider performing a biopsy.
• 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. Although culture is considered the criterion standard, alternative techniques (eg, cytology, antigen detection, DNA probe) are used. Serology currently has no role because of cross-reactivity between 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.
• If genital warts are noted, subclinical lesions can be identified after applying a 3-5% solution of acetic acid and performing magnification with colposcopy.
• While there have been more than 80 types of HPV identified, types 16, 18, 31, 33, 35, 45, 51, and 56 are associated with higher oncogenic risks, particularly cervical cancer. Currently, the United States Preventive Services Task Force (USPSTF) believes insufficient evidence exists to recommend HPV testing in women older than age 30 as an adjunct to Papanicolaou testing.⁴ However, the American College of Obstetrics and Gynecology (ACOG) and American Cancer Society (ACS) state that HPV testing can be a routine option for these women with the appropriate guidance from their health care provider.

Treatment

Medical Care

Treatment of all causes of cervicitis is medical. Treatment must include the patient's sexual partners to prevent reinfection. Treatment for infectious causes of cervicitis can be done presumptively (treatment with azithromycin or doxycycline) or with specific antibiotic treatment once the etiology is known.

Activity

• No sexual activity for 7 days after initiating treatment
• No sexual activity until partner has been treated

Medication

Oral antibiotics effectively cure gonorrhea, chlamydia, and T vaginalis infections. Oral antivirals reduce 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 Centers for Disease Control and Prevention (CDC) updated treatment guidelines for gonococcal infection and associated conditions.⁵ Fluoroquinolone antibiotics are no longer recommended to treat gonorrhea in the United States. The recommendation was based on analysis of new data from the CDC’s Gonococcal Isolate Surveillance Project (GISP). The data from GISP showed the proportion of fluoroquinolone-resistant gonorrhea (QRNG) cases in heterosexual men reached 6.7%, an 11-fold increase from 0.6% in 2001. The data were published in the April 13, 2007 issue of the Morbidity and Mortality Weekly Report. This limits treatment of gonorrhea to drugs in the cephalosporin class (eg, ceftriaxone 125 mg IM once as a single dose). 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 or Updated Gonococcal treatment recommendations (April 2007).

Antibiotics

Therapy must be comprehensive and cover all likely pathogens in the context of this clinical setting.

Ceftriaxone (Rocephin)

First-line therapy for gonococcal cervicitis. Third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin-binding proteins.

Dosing

Adult

125 mg IM once

Pediatric

Administer as in adults

Interactions

Probenecid may increase levels; coadministration with ethacrynic acid, furosemide, and/or aminoglycosides may increase nephrotoxicity

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Partner(s) must be treated; adjust dose in renal impairment; caution in allergy to penicillin; if chlamydia testing results are not available, also treat for chlamydia because 20-40% of patients with gonorrhea are co-infected

Cefixime (Suprax)

Third-generation cephalosporin effective in treating gonorrhea. By binding to one or more of the penicillin-binding proteins, it arrests bacterial cell wall synthesis and inhibits bacterial growth. This medication is once again available in the United States.

Dosing

Adult

400 mg PO once

Pediatric

<45 kg: Not established
>45 kg: Administer as in adults

Interactions

Coadministration of aminoglycosides increase nephrotoxicity; probenecid may increase effects; false-positive Clinitest results

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Partner must be treated; adjust dose in renal impairment; colitis may occur

Spectinomycin (Trobicin)

Inhibits protein synthesis in bacterial cells. Site of action is 30S ribosomal subunit and is structurally different from related aminoglycosides. Use if allergic to penicillin and quinolones. Alternative regimen for treatment of gonorrhea. Do not use if oropharyngeal gonorrhea is suspected.

Dosing

Adult

2 g IM once

Pediatric

<45 kg: 40 mg/kg IM once
>45 kg: Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Partner must be treated; benzyl alcohol used as a diluent is associated with fatal gasping syndrome in infants

Azithromycin (Zithromax)

First-line therapy for chlamydia cervicitis. Semisynthetic macrolide antibiotic effective in treating chlamydia. Treats mild-to-moderate microbial infections.

Dosing

Adult

1 g PO once

Pediatric

<6 months: Not established
>6 months: Administer as in adults

Interactions

May increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine

Contraindications

Documented hypersensitivity; hepatic impairment; use of pimozide

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Partner must be treated; bacterial or fungal overgrowth may result with prolonged antibiotic use; may increase hepatic enzymes and cholestatic jaundice; caution in patients with impaired hepatic function, prolonged QT intervals, or pneumonia; caution in patients who are hospitalized, elderly, or debilitated

Doxycycline (Vibramycin)

Long-acting tetracycline derived from oxytetracycline. Effective in treating chlamydia. Inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.

Dosing

Adult

100 mg PO bid for 7 d

Pediatric

<8 years: Not recommended
>8 years: Administer as in adults

Interactions

Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of PO contraceptives, causing breakthrough bleeding and increased risk of pregnancy

Contraindications

Documented hypersensitivity; children <8 y; severe hepatic impairment

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Partner must be treated; if pregnant, use erythromycin; photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (ie, last half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines

Erythromycin base (E-Mycin)

Inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Alternative therapy for chlamydia cervicitis.

Dosing

Adult

500 mg PO bid for 7 d

Pediatric

<12 years: Not established
>12 years: Administer as in adults

Interactions

Decrease clearance of alfentanil, bromocriptine, carbamazepine, cyclosporine, digoxin, disopyramide, ergot alkaloids, methylprednisolone, protease inhibitor, theophylline, and triazolam; increases anticoagulant effect of warfarin; decreases metabolism of vinblastine; serum levels increased by protease inhibitors, increased levels and rhabdomyolysis with use of lovastatin and simvastatin

Contraindications

Documented hypersensitivity; hepatic dysfunction; current use of pimozide

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Partner must be treated; estolate formulation may cause cholestatic jaundice; adverse GI effects are common (administer doses pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occur

Erythromycin ethylsuccinate (E.E.S.)

Inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Alternative regimen for chlamydia cervicitis.

Dosing

Adult

800 mg PO qid for 7 d

Pediatric

<12 years: Not established
>12 years: Administer as in adults

Interactions

Decrease clearance of alfentanil, bromocriptine, carbamazepine, cyclosporine, digoxin, disopyramide, ergot alkaloids, methylprednisolone, protease inhibitor, theophylline, and triazolam; increases anticoagulant effect of warfarin; decreases metabolism of vinblastine; serum levels increased by protease inhibitors, increased levels and rhabdomyolysis with use of lovastatin and simvastatin

Contraindications

Documented hypersensitivity; hepatic dysfunction; current use of pimozide

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Partner must be treated; caution in liver disease; discontinue if GI distress, malaise, or fever occurs

Metronidazole (Flagyl)

Synthetic antibacterial and antiprotozoal agent. First-line therapy for T vaginalis infections.

Dosing

Adult

2 g PO once; alternatively, 500 mg PO bid for 7 d

Pediatric

<1 year: 10-30 mg/kg/d PO for 5-8 d
<12 years: 15 mg/kg/d PO in 3 divided doses for 7-10 d
>12 years: Administer as in adults

Interactions

Avoid alcohol for 7 d (disulfiramlike reaction); effect decreased by phenobarbital and phenytoin; increases PT with warfarin; increases toxicity/serum level of lithium; serum level increased by cimetidine

Contraindications

Documented hypersensitivity; controversy exists about treatment during first trimester (category D) despite no proof of harm, some suggest waiting until second trimester to treat using 2 g PO x 1 or 500 mg PO bid for 7 d

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Partner must be treated; adjust dose in hepatic disease; monitor for seizures and development of peripheral neuropathy

Antivirals

Nucleoside analogs 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.

Acyclovir (Zovirax)

Synthetic purine nucleoside analog indicated for genital HSV infections. First episode, begin treating within 6 d after appearance of first symptoms. If recurrent attack, begin treating during prodrome or within 1 d after onset of lesions. Suppression requires daily treatment for 1 y.

Dosing

Adult

First episode: 400 mg PO tid for 7-10 d; alternatively 200 mg PO 5 times qd for 7-10 d
Recurrent attack: 200 mg PO 5 times qd for 5 d; alternatively 400 mg PO tid for 5 d or 800 mg PO bid for 5 d
Suppression: 400 mg PO bid for 1 y

Pediatric

First episode: 400 mg PO tid for 7-10 d; not to exceed 80 mg/kg/d
Recurrent attack: 400 mg PO tid for 5 d; alternatively, 800 mg PO bid for 5 d; not to exceed 80 mg/kg/d
>12 years: Administer as in adults

Interactions

Probenecid and zidovudine increase adverse CNS effects

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Register pregnant patients on acyclovir at 1-800-722-9292; caution in renal failure or coadministration of nephrotoxic drugs

Famciclovir (Famvir)

Prodrug for penciclovir (active moiety) indicated for genital HSV infections. For first episode, begin treating within 6 d after appearance of first symptoms. For recurrent attack, begin treating during prodrome or within 1 d after onset of lesions. Suppression requires daily treatment for 1 y.

Dosing

Adult

First episode: 250 mg PO tid for 7-10 d
Recurrent attack: 125 mg PO bid for 5 d
Suppression: 250 mg PO bid for 1 y

Pediatric

Not established

Interactions

Cimetidine and probenecid increase toxicity/serum level of penciclovir; increases digoxin level

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Register pregnant patients at 1-800-722-9292; caution in renal failure or coadministration of nephrotoxic drugs

Valacyclovir (Valtrex)

Indicated for genital HSV infections. For first episode, begin treating within 6 d after appearance of first symptoms. For recurrent attack, begin treating during prodrome or within 1 d after onset of lesions. Suppression requires daily treatment for 1 y.

Dosing

Adult

First episode: 1 g PO bid for 7-10 d
Recurrent attack: 500 mg PO bid for 5 d
Suppression: 1 g PO qd for 1 y; alternatively, 500 mg PO qd for 1 y or 250 mg PO bid for 1 y

Pediatric

<12 years: Not established
>12 years: Administer as in adults

Interactions

Cimetidine/probenecid decrease conversion rate to acyclovir

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Register pregnant patients at 1-800-722-9292; monitor patients who are immunocompromised for thrombotic thrombocytopenic purpura/hemolytic uremic syndrome; adjust dose in renal impairment

Topical skin products

Indicated for genital/perianal warts.

Imiquimod (Aldara)

Indicated for genital/perianal warts. Induces secretion of interferon alpha and other cytokines; mechanism of action are unknown. May be more effective in women than in men.

Dosing

Adult

Apply to warts qhs 3 times/wk for up to 16 wk, rinse treatment area with soap and water 6-10 h after application

Pediatric

<12 years: Not established
>12 years: Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

In pregnancy, most lesions may be treated postpartally; however, consideration may be given to using topical liquid nitrogen qwk or surgical treatments (eg, excision, electrocauterization, laser vaporization); avoid contact with genital mucous membranes; burning, pain, inflammation, erosion, and pruritus have occurred

Podofilox (Condylox)

Topical antimitotic which can be chemically synthesized or purified from plant families Coniferae and Berberidaceae (eg, species of Juniperus and Podophyllum). Exact mechanism of action is unknown.

Dosing

Adult

Apply bid for 3 d, no therapy for 4 d, then repeat up to 4 cycles

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Avoid contact with eyes; if eye contact, immediately flush eye with copious quantities of water and seek medical advice; not for use on mucous membranes of genital area including urethra, rectum and vagina; do not exceed frequency of application or duration of usage

Fluorouracil (Carac, Efudex, Fluoroplex)

Cycle-specific agent that has activity as single agent and has for many years been combined with biochemical modulator leucovorin. Shown to be effective in adjuvant setting. Classic antimetabolite anticancer drug with chemical structure similar to endogenous intermediates or building blocks of DNA or RNA synthesis. 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. 5-FdUMP inhibits thymidylate synthase (key enzyme in DNA synthesis). 5-FUTP is incorporated into RNA and interferes with RNA processing, and 5-FdUTP is incorporated into DNA, leading to cytotoxic DNA strandbreaks.

Dosing

Adult

Apply daily, may use an applicator for urethral warts

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity; potentially serious infections

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Inflammatory reactions may occur with use of occlusive dressings; porous gauze dressing may be applied for cosmetic reasons without increase in reaction; patients should expect inflammatory reaction with crusting

Trichloroacetic acid (Tri-Chlor)

Cauterizes skin, keratin, and other tissues. Although caustic, causes less local irritation and systemic toxicity than others in the same class. However, response is often incomplete and recurrence occurs frequently.

Dosing

Adult

Apply to warts and powder with talc or sodium bicarbonate (baking soda) to remove unreacted acid; may repeat weekly

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity; not for use on premalignant or malignant lesions

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

External use only; restrict use to treatment areas only

Antiprotozoal

Alternative therapy for trichomonas infections.

Tinidazole (Fasigyn, Tindamax)

5-nitroimidazole derivative used for susceptible protozoal infections. Nitro group is reduced by cell extract of Trichomonas. The free nitro radical generated is thought to be responsible for antiprotozoal activity against T vaginalis. Indicated to treat trichomoniasis caused by T vaginalis in both males and females.

Dosing

Adult

Individual and sexual partner: 2 g PO once with food

Pediatric

<3 years: Not established
>3 years: 50 mg/kg PO qd for 3 d with food, not to exceed 2 g/dose

Interactions

Limited data exist; interaction information based on experience with other nitroimidazole derivatives (ie, metronidazole); may prolong PT when coadministered with warfarin; avoid alcoholic beverages and preparations containing ethanol or propylene glycol during and 3 d following administration (may cause disulfiramlike reaction); may increase serum levels of lithium, phenytoin, cyclosporine, tacrolimus, and fluorouracil; CYP450 inducers (eg, phenobarbital, rifampin, phenytoin) may increase elimination; CYP450 inhibitors (eg, cimetidine, ketoconazole) may decrease elimination; concurrent administration with cholestyramine may decrease oral bioavailability; oxytetracycline may antagonize effect

Contraindications

Documented hypersensitivity; first trimester of pregnancy; breastfeeding women (recommend interruption during therapy and for 3 d following last dose)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

X - Contraindicated; benefit does not outweigh risk

Precautions

Caution in blood dyscrasias, organic neurological dysfunction, late trimesters of pregnancy, seizure disorders, and hepatic and renal impairment
Carcinogenicity has been observed in mice and rats treated chronically with metronidazole (another nitroimidazole), although not observed with tinidazole, use cautiously; may cause metallic/bitter taste, nausea, anorexia, vomiting, weakness, fatigue, dizziness, or headache; if administered on day of hemodialysis, administer additional dose equivalent to one-half of recommended dose following dialysis

Follow-up

Further Inpatient Care

• Admit to hospital if disseminated infection (ie, PID) is suspected, if the diagnosis is uncertain, or if the patient is unable to take oral medications.
  • If disseminated infection is suspected, then patients can quickly become unstable. These patients need intensive monitoring and parenteral medication.
  • If the diagnosis is uncertain, and competing diagnoses cannot be reliably excluded (eg, appendicitis, ectopic pregnancy), then further testing and monitoring is indicated.
• If the patient is unable to take oral medication because of intractable nausea, vomiting, or abdominal pain, then hospitalization for intravenous medication is warranted.

Further Outpatient Care

• In high-risk patients, consider screening for HIV, syphilis, and hepatitis B.
• In most cases, a 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.

Deterrence/Prevention

• The most effective way to prevent the transmission of the infective agents that cause cervicitis is to avoid sexual intercourse with infected partners. Ideally, both partners should be tested for common STDs, including HIV, before initiating a sexual relationship. If the risk of infection is unknown by testing, then use a condom for all sexual acts. Condoms are available for men and women and have been proven to decrease the transmission of many STDs, including HIV, when used appropriately and consistently.

Complications

• Untreated gonorrhea and chlamydia infections can lead to PID, which can then lead to infertility, chronic pelvic pain, and ectopic pregnancy. Certain subtypes of HPV are linked with the development of cervical cancer. Severe cases of condyloma may obstruct the birth canal during pregnancy, resulting in the need for cesarean section. Untreated active HSV infections can cause significant perinatal and neonatal complications such as mental retardation, blindness, meningitis, and death.

Prognosis

• Gonorrhea, chlamydia, and T vaginalis infections can be cured with antibiotic therapy.
• The number of HSV outbreaks, the duration of symptoms, and the severity of symptoms can be reduced with antiviral therapy.
• External genital warts caused by infection with HPV can be controlled but not always eradicated by topical therapy and surgical therapy.

Patient Education

• Patients must understand that their infection is a preventable STD. They must ensure that all their sexual partners are also treated, or they will become reinfected. Proper use of condoms reduces the risk of infection.
• For excellent patient education resources, visit eMedicine's Women's Health Center, Pregnancy and Reproduction Center. Also, see eMedicine's patient education articles Cervicitis, Ectopic Pregnancy, Female Sexual Problems, and Pap Smear.

Miscellaneous

Medicolegal Pitfalls

• In women of childbearing age, always perform a urine pregnancy test before prescribing any medication.
• Failure to adequately screen for sexually transmitted infections (STIs) in patients who present with symptoms of an STI.

Special Concerns

• Be aware of local and state regulations regarding reporting of STIs.
• In a young adolescent or child, suspect abuse and notify the proper authorities.

References

1. Centers for Disease Control and Prevention. Chlamydia screening among sexually active young females enrollees of health plans - United States, 2000-2007. MMWR Weekly. April 17, 2009;58(14):362-365. [Full Text].

2. Clifford GM, Gallus S, Herrero R, Munoz N, Snijders PJ, Vaccarella S. Worldwide distribution of human papillomavirus types in cytologically normal women in the International Agency for Research on Cancer HPV prevalence surveys: a pooled analysis. Lancet. Sep 17-23 2005;366(9490):991-8. [Medline].

3. Wright TC Jr, Schiffman M, Solomon D, Cox JT, Garcia F, Goldie S. Interim guidance for the use of human papillomavirus DNA testing as an adjunct to cervical cytology for screening. Obstet Gynecol. Feb 2004;103(2):304-9. [Medline].

4. Goldie SJ, Kim JJ, Wright TC. Cost-effectiveness of human papillomavirus DNA testing for cervical cancer screening in women aged 30 years or more. Obstet Gynecol. Apr 2004;103(4):619-31. [Medline].

5. CDC. Update to CDC's sexually transmitted diseases treatment guidelines, 2006: fluoroquinolones no longer recommended for treatment of gonococcal infections. MMWR Morb Mortal Wkly Rep. Apr 13 2007;56(14):332-6. [Medline]. [Full Text].

6. American College of Obstetricians and Gynecologists. Cervical Cytology and Screening. August 2003. ACOG Practice Bulletin.

7. Anderson JR. Genital tract infections in women. Med Clin North Am. Nov 1995;79(6):1271-98. [Medline].

8. CDC, Workowski KA, Berman SM. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. Aug 4 2006;55(RR-11):1-94. [Medline]. [Full Text].

9. Griffith WF, Stuart GS, Gluck KL, Heartwell SF. Vaginal speculum lubrication and its effects on cervical cytology and microbiology. Contraception. Jul 2005;72(1):60-4. [Medline].

10. Katz VL, Lentz GM, Lobo RA, Gershenson DM. Comprehensive Gynecology. 5^th ed. Mosby; 2007:598-600.

11. Low N, Cowan F. Genital chlamydial infection. Clin Evid. Jun 2003;(9):1721-8. [Medline]. [Full Text].

12. Schiffman M, Khan MJ, Solomon D, Herrero R, Wacholder S, Hildesheim A. A study of the impact of adding HPV types to cervical cancer screening and triage tests. J Natl Cancer Inst. Jan 19 2005;97(2):147-50. [Medline].

13. Sexually Transmitted Disease Surveillance 2007. Centers for Disease Control and Prevention; December 2008. [Full Text].

14. Soper DE. Sexually transmitted disease & pelvic inflammatory disease. Primary Care of Women. 1995:339-347.

15. World Health Organization. Sexually Transmitted Infections. October 2007. WHO Fact Sheet. [Full Text].

Keywords

cervicitis, female lower genital tract infections, mucopurulent cervicitis, sexually transmitted diseases, STDs, vulvovaginitis, Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, human papillomavirus, HPV, herpes simplex virus, HSV, pelvic inflammatory disease, PID, infertility, ectopic pregnancy, spontaneous abortion, cervical cancer, preterm delivery, condylomata acuminata, Papanicolaou test, Pap smear

Contributor Information and Disclosures

Author

Arthur T Ollendorff, MD, Associate Professor of Clinical Obstetrics and Gynecology, Residency Program Director, Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine; Chief of Gynecology, Veterans Affairs Medical Center, Cincinnati
Arthur T Ollendorff, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists and American Public Health Association
Disclosure: Nothing to disclose.

Medical Editor

Jeffrey B Garris, MD, Chief, Assistant Professor, Department of Obstetrics and Gynecology, Division of Urogynecology and Reconstructive Pelvic Surgery, Tulane University School of Medicine
Jeffrey B Garris, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, American Medical Association, American Urological Association, Association of Professors of Gynecology and Obstetrics, Louisiana State Medical Society, Royal Society of Medicine, and Sigma Xi
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

A David Barnes, MD, PhD, MPH, FACOG, Consulting Staff, Department of Obstetrics and Gynecology, Mammoth Hospital (Mammoth Lakes, California), Pioneer Valley Hospital (Salt Lake City, Utah), Warren General Hospital (Warren, Pennsylvania), and Mountain West Hospital (Tooele, Utah)
A David Barnes, MD, PhD, MPH, FACOG is a member of the following medical societies: American College of Forensic Examiners, American College of Obstetricians and Gynecologists, American Medical Association, Association of Military Surgeons of the US, and Utah Medical Association
Disclosure: Nothing to disclose.

CME Editor

Frederick B Gaupp, MD, Consulting Staff, Department of Family Practice, Hancock Medical Center
Frederick B Gaupp, MD is a member of the following medical societies: American Academy of Family Physicians
Disclosure: Nothing to disclose.

Chief Editor

Michel E Rivlin, MD, Professor, Coordinator of Quality Assurance/Quality Improvement, Department of Obstetrics and Gynecology, University of Mississippi School of Medicine
Michel E Rivlin, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Medical Association, Mississippi State Medical Association, and Royal College of Surgeons of Edinburgh
Disclosure: Nothing to disclose.

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