History of Present Illness

A 28-year-old, gravida 0, presents due to worsening of dysuria, dyspareunia, and purulent vaginal discharge that started three weeks ago after being sexually active with a new male partner. She initially thought the vaginal irritation and discharge were due to yeast infection. However, after using an over-the-counter medication to treat the yeast infection, the symptoms worsened. She denies other medical conditions. She is currently using oral contraception for birth control, and she did not use condoms when they had intercourse. She denies any past surgical history. Her family history is notable for hypertension on her mother’s side. She drinks alcohol occasionally and denies tobacco or illicit drug use. She reports that she developed a diffuse rash and itching immediately after taking oral metronidazole last year.

Physical Examination

General appearance

Well-developed, well-nourished woman, mildly anxious, but otherwise in no acute distress, alert and oriented

Temperature

98.6°F (37°C)

Pulse

70 beats/min

Blood pressure

110/80 mmHg

Respirations

18 breaths/min

Abdomen

Thin, soft, non-tender, non-distended, no guarding, no rebound, mild suprapubic tenderness

External genitalia

Unremarkable

Vagina

Mucosa mildly erythematous, moderate amount of thin green-yellow, frothy discharge

Cervix

Punctate hemorrhages

Uterus

Anteverted, small, mobile, normal size, non-tender on bimanual examination

Adnexa

No masses, non-tender

Urine pregnancy test

Negative

Urinalysis

Negative

Wet mount

Numerous trichomonads, no candida or clue cells

GC/CT

Negative

HIV

Negative

How Would You Manage This Patient?

This patient presents with classic symptoms of trichomonas infection, which include green-yellow frothy discharge, dyspareunia, pruritus, and dysuria. This was most likely transmitted from her new male partner. It is important after diagnosis of a trichomonas infection for patients to be screened for other sexually transmitted infections, since these frequently coexist. Her tests for gonorrhea, chlamydia, and HIV were all negative.

The Centers for Disease Control and Prevention recommendations for treatment of trichomonas infection are for metronidazole 2 g orally or tinidazole 2 g orally in a single dose [1]. Nitromidazoles are the only family of anti-protazoal medications that have been shown to be effective in treating trichomonas. Because of this patient’s history of metronidazole allergy, she was referred to a specialist (an allergist/immunologist) for metronidazole desensitization. The patient was counseled on the use of barrier protection, on the need for her partner to be treated, and to abstain from intercourse until both are treated and symptoms resolved. She was instructed to return in three months to be rescreened due to the high rate of reinfection among women treated for trichomoniasis.

Trichmonas Infection with Metronidazole Allergy

Trichomonas vaginalis (T. vaginalis), along with bacterial vaginosis and vulvovaginal candidiasis, is one of the three most common causes of vaginitis among reproductively aged women and the most common nonviral sexually transmitted infection in the United States. While not a reportable sexually transmitted infection, the annual incidence is estimated to be 7.4 million cases in the United States, with an overall prevalence of 3.1 percent [1]. There are significant differences in prevalence between non-Hispanic black women (13.5 percent) compared to non-Hispanic white women (1.2 percent) [2, 3].

T. vaginalis is a flagellated protozoan most commonly transmitted from men to women through penile-vaginal intercourse. Women can acquire the infection from other women, and it is only rarely transmitted between men. Trichomonas favors the squamous epithelium of the female lower genitourinary tract, affecting mainly the vagina, urethra, and paraurethral glands. Less common sites include the cervix, bladder, and Bartholin glands. Humans are the only natural host [4, 5].

Women are most commonly asymptomatic (50 percent) and may remain so for as long as three months. The most common symptom is a purulent, malodorous discharge, which may be associated with pruritus, irritation, dysuria, lower abdominal pain, increased frequency of urination, dyspareunia, or postcoital bleeding. Green, frothy, malodorous discharge is seen on examination in approximately 30 percent of symptomatic women. A minority of patients will have punctate hemorrhages on the vagina and cervix, known as “strawberry cervix.” Pain with bimanual examination may or may not be present. Complications of the infection are rare, and may include urethritis, cystitis, cervical neoplasia, posthysterectomy cuff cellulitis or abscess, pelvic inflammatory disease, HIV infection, and infertility. Pregnancy-related complications may also occur [1, 2].

Saline microscopy may be used to diagnose infection via direct visualization of motile trichomonads, and is commonly used due to ease and low cost. However, microscopy has a sensitivity of only 55–60 percent [1]. To diagnose the infection with microscopy, a sample of vaginal discharge is mixed with one to two drops of 0.9 percent normal saline solution at room temperature on a glass slide. A cover slip is placed over the mixture and examined under low and high power. Trichomonads may remain motile for 10–20 minutes outside of their natural human host. Vaginal pH is nondiagnostic, but typically elevated >4.5. One may also see an increased number of neutrophils.

Nucleic acid amplification tests (NAATs) have become the gold standard for diagnosing trichomonas infection due to high sensitivity and specificity. NAATs detect RNA by transcription-mediated amplification. Multiple assays are available. The Aptima T. vaginalis assay uses vaginal swab or urine specimens and has a sensitivity and specificity as high as 95–100 percent. If available, the “inPouch” T. vaginalis culture system has high sensitivity and takes <3 days to report. Rapid antigen and DNA hybridization probes have been found to have high sensitivity and specificity; results are obtained the same day, and have been approved by the Food and Drug Administration (FDA) for women [1, 5, 6]. The OSOM trichomonas rapid test is an antigen-detecting test that gives results in 10 minutes. The Affirm VP III is a DNA hybridization probe test that also evaluates for bacterial vaginitis and candida albicans. These methods are particularly useful in areas of high prevalence [5]. Culture was once considered gold standard for the diagnosis of T. vaginalis, but turnaround time for results may take up to one week to obtain. T. vaginalis cultures still have a role in situations where there are concerns for infection, but trichomonads are not seen on microscopy and NAAT is unavailable [1, 5].

Incidental findings of trichomonads may be reported on cervical cancer screening reports. Liquid-based cytology has a high specificity with a low false positive rate (and a low sensitivity), making it reasonable to offer as treatment to patients. In contrast, conventional Papanicalaou smears have higher false positive rates compared to liquid-based cervical cytology and therefore treatment should be withheld on asymptomatic women until evaluation is completed by wet mount, NAAT, culture, or rapid test [6]. Asymptomatic screening for T. vaginalis should be performed in all HIV-positive women annually and at their initial prenatal visits, and may be considered in individuals at high risk for infection (new or multiple partners, history of STI, illicit drug use, sex workers) [1]. Treatment of T. vaginalis infections reduces symptoms, transmission, and adverse outcomes in HIV-positive women.

Nitroimidazoles, which include metronidazole and tinidazole, are the only class of medications known to effectively treat T. vaginalis infections, are FDA approved for oral and parenteral treatment, and should be utilized in both asymptomatic and symptomatic women. To reduce the incidence of a disulfiram-like reaction, patients should be instructed to avoid alcohol (for 24 hours after completing metronidazole and 72 hours after tinidazole).Typically, a 2 g single oral dose of metronidazole or tinidazole is recommended due to ease of use, better compliance, and shorter period of alcohol avoidance. Alternatively, metronidazole 500 mg orally twice daily for seven days may be prescribed if the higher dose is not tolerated or if compliance is not a concern. Cure rates are comparable; however, tinidazole is associated with decreased gastrointestinal side effects but at higher cost. Metronidazole gel is not recommended because it does not reach therapeutic drug levels in anatomic locations that can act as reservoirs, such as the Bartholin and Skene’s glands, urethra, and periurethral glands. Both partners should be instructed to abstain from intercourse until seven days after antibiotic completion. Patients should also be screened for other STIs, including gonorrhea, chlamydia, and HIV. Because of high rates of reinfection, retesting within three months following initial treatment is recommended. Testing with NAAT can be conducted as soon as two weeks after treatment [1, 5].

Metronidazole Allergy

Adverse IgE-mediated allergic reactions to metronidazole are rare, but can include flushing, urticaria, fever, angioedema, and anaphylactic shock [7]. Due to their similar molecular structures, and thus high likelihood of hypersensivity reaction, tinidazole is not a recommended alternative to metronidazole. This overlap has been noted in case reports; however, data are still lacking. Alternative intravaginal treatments, such as betadine douche, paromomycin, clotrimazole, furazolidone, and acetersol, are not effective or are associated with adverse reactions, and so are not recommended. While intravaginal paromomycin was noted to successfully treat 25 percent of women, it was associated with ulceration of the vaginal mucosa [6]. Clotrimazole was found to only be 11 percent successful in eradicating infection, according to a recent multicenter trial [6]. Given this, nitromidazoles are the best options for treatment [7–9].

Patients with an IgE-mediated-type allergy to nitromidazoles should have metronidazole desensitization according to published regimens and in consultation with an allergy specialist [1]. Oral and intravenous dosing protocols have been used with 100 percent effectiveness [7]. Desensitization is the process of reintroducing a medication to which an individual has had an allergic response in order to allow for temporary tolerance. Once the medication is discontinued, the hypersensitivity to the medication returns. An allergist/immunologist should conduct the process, which may occur in either an inpatient or outpatient setting. After confirmation of the allergic reaction with skin testing, the total dose of medication is divided into very small dilutions. The medication is then delivered over a period of time, typically 15 minutes. The dose is doubled with each step until a full therapeutic dose has been delivered. By administering the medication in this manner, the immune system is inhibited. If a reaction is observed, the medication is held and symptoms are treated, and then the protocol is reinitiated. While no standard protocol has been developed for the class of nitromidazoles, both oral and IV metronidazole desensitization regimens have been used with 100 percent success in the management of trichomonas infections [7]. Desensitization is not a permanent cure for the drug allergy and the nitromidazoles should be avoided after treatment is completed and must be performed again if the drug is required for treatment in the future.

Key Points

• 
  

  Adverse IgE-mediated allergic reactions to metronidazole are rare, but can include flushing, urticaria, fever, angioedema, and anaphylactic shock.

  
  
• 
  

  Due to their similar molecular structures, and thus high likelihood of hypersensivity reaction, tinidazole is not a recommended alternative to metronidazole.

  
  
• 
  

  There are currently no safe and effective alternatives to metronidazole and tinidazole, and therefore desensitization according to published regimens and in consultation with an allergy specialist is recommended.

  
  
• 
  

  Desensitization is the process of reintroducing a medication to which an individual has had an allergic response in order to allow for temporary tolerance. Once the medication is discontinued, the hypersensitivity to the medication returns.

  
  
• 
  

  Both oral and IV metronidazole desensitization regimens have been used with 100 percent success in the management of trichomonas infections.

History of Present Illness

A 24-year-old nulliparous female presents to the office complaining of vaginal discharge for the past week. She also reports vaginal spotting after intercourse. Her last menstrual period was one week ago. The patient denies abdominal pain, fever, or chills. Her past medical and surgical history is negative. The patient is heterosexual and is not in a committed relationship. She denies any prior history of sexually transmitted infections. She reports having had three sexual partners within the last year and sporadic condom use. Her most recent intercourse was two weeks ago and was with a new partner. Her family history is noncontributory. The patient has no known drug allergies and does not take any regular medications.

Physical Examination

General appearance

Well-developed, well-nourished woman in no apparent distress. She is alert and oriented.

Temperature

37.0°C

Pulse

80 beats/min

Blood pressure

110/72 mmHg

Respiratory rate

16 breaths/min

Height

65 inches

Weight

120 lb

Abdomen

Thin, soft, non-tender, non-distended, no guarding, no rebound

External genitalia

Unremarkable

Vagina

No abnormalities

Cervix

Mucopurulent discharge at the external os, cervix bleeds easily when touched with a cotton swab, no cervical motion tenderness

Uterus

Anteverted, mobile, non-tender

Adnexa

No masses or tenderness

Urine pregnancy test

Negative

Wet prep

Many leukocytes, no clue cells or trichomonads

How Would You Manage This Patient?

Based on the patient’s clinical presentation with mucopurulent cervical discharge and endocervical bleeding (friability) with gentle touch, this patient has acute cervicitis. There is no foreign body in the vagina, and the non-tender uterus and adnexae exclude pelvic inflammatory disease. To distinguish infectious from noninfectious acute cervicitis, the evaluation includes a swab of the discharge for microscopy (wet prep) and vaginal pH to identify bacterial vaginosis and trichomonas, and nucleic acid amplification test (NAAT) for chlamydia, gonorrhea, and trichomonas (if the wet prep is negative for trichomonas).

The patient was managed empirically with antibiotic therapy at the time of initial evaluation, without waiting for results of laboratory tests. In a 24-year-old, the empiric treatment regimen for cervicitis should include coverage of chlamydia at a minimum, as the prevalence in women ≤25 years old is high. This patient also has other risk factors, including more than one sexual partner and inconsistent use of condoms. Therefore, she was also treated empirically for gonorrhea, with ceftriaxone 250 mg IM in a single dose plus azithromycin 1 g orally in a single dose in the office the day she was evaluated. The patient was also offered testing for HIV and syphilis. In addition, the patient should receive counseling about prevention of STIs, including a description of high-risk behaviors and education about prevention methods. All partners for the past 60 days should be referred for evaluation and treatment. The patient should be given follow-up to ensure that the cervicitis has resolved.

Cervicitis

Acute cervicitis is an inflammation of the columnar epithelial cells of the endocervical glands and can also affect the squamous epithelium of the ectocervix. It may be due to an infectious or noninfectious etiology. Chlamydia and gonorrhea are the most common organisms identified, with chlamydia cervicitis the most common. It is important to note that a large proportion of women with chlamydia and gonorrhea are asymptomatic and do not develop mucopurulent cervicitis [1]. Cervicitis can also be caused by Trichomonas vaginalis, bacterial vaginosis, or genital herpes (particularly primary herpes simplex virus-2 infection). Noninfectious cervicitis may be caused by retained foreign bodies (condoms, tampons) or chemical irritation from latex, vaginal douches, or contraceptive creams. Risk factors for cervicitis include women ≤ 25 years of age, history of sexually transmitted infections, new or multiple sexual partners, lack of barrier protection, drug use, and commercial sex work.

Patients often present with vaginal discharge, postcoital spotting, or intermenstrual bleeding. Some patients are asymptomatic. Cervicitis is diagnosed on physical examination by the presence of a mucopurulent discharge visualized at the external os or endocervical bleeding that is present with gentle manipulation of the os. It is important to determine if the patient has associated upper genital tract symptoms such as pelvic pain, cervical motion tenderness, abdominal pain, or fever that would suggest pelvic inflammatory disease. This will guide treatment options.

Testing for infectious causes of cervicitis includes a swab of the discharge for microscopy and vaginal pH to test for bacterial vaginosis and trichomonas, as well as NAAT testing for chlamydia and gonorrhea. Because sensitivity of microscopy to detect trichomonas is only approximately 50 percent, women with cervicitis and negative wet preps should also be tested for trichomonas by NAAT, which has a sensitivity of at least 95 percent and can be performed on the same swab used for chlamydia and gonorrhea testing [2].

Most women with mucopurulent cervicitis should be treated empirically at the time of initial evaluation with antibiotics even before the results of diagnostic tests are available. For some low-risk patients, treatment can be deferred until the results are available. The Centers for Disease Control and Prevention (CDC) guidelines for treating cervicitis recommend antibiotic coverage for chlamydia at a minimum [2]. For women at higher risk, treatment should also add coverage for gonorrhea. There is no strict definition of which patients are defined as high risk, and clinicians should consider risk factors such as age ≤25 years old (the prevalence is highest in this age group), local prevalence of gonorrhea, previous chlamydial or gonorrhea infection in the prior months, new or more than one sexual partner, and inconsistent use of condoms in making this decision. If reliable patient follow-up of test results is a concern, it is also reasonable to treat empirically for both chlamydia and gonorrhea. Empiric therapy for acute cervicitis includes azithromycin 1 g orally in a single dose or doxycycline 100 mg orally twice a day for seven days [2].

Neisseria gonorrhoeae is a gram-negative coccobacillus that invades the columnar cells of the endocervix. There are an estimated 820,000 new infections each year in the United States and it is the second most common reported communicable disease [2]. Gonococcal infections are frequently asymptomatic in women. Annual screening is recommended in women ≤ 25 years old and in older women who are at risk for infection. NAATs have replaced cultures in most laboratories to diagnose gonococcal infections. Samples can be obtained from the vagina, the endocervix, or urine. In 2007, there was an emergence of fluoroquinolone-resistant N. gonorrhoeae. This prompted the CDC to change its recommendation of fluoroquinolones for the treatment of gonorrhea. In order to prevent the development of resistance to cephalosporins, the CDC recommends dual therapy first-line treatment of gonorrhea with ceftriaxone (250 mg, single IM dose) and azithromycin (1 g, single oral dose), regardless of the results of chlamydia testing. These treatments should be administered together on the same day. If ceftriaxone is not available, an alternative is cefixime 400 mg orally in a single dose plus azithromycin 1 g orally in a single dose, but this should be second line due to concerns about decreased susceptibility of the organism for orally delivered antibiotics [2].

Chlamydial infection is the most frequently reported infectious disease in the United States, and its prevalence is highest in persons ≤ 24 years [2]. Chlamydia trachomatis is an obligate intracellular parasite that can cause columnar epithelial infection. As with gonorrhea, infection is usually asymptomatic and screening is recommended annually for women ≤ 25 years old and for older women who are at risk for infection (new partner, more than one partner, a partner with concurrent partners, or partner with sexually transmitted infection). Diagnosis is made using NAAT on vaginal, endocervical, or urine specimens.

First-line treatment for chlamydial infection is azithromycin 1 g orally in a single dose or doxycycline 100 mg orally twice a day for seven days. There appears to be comparable efficacy between these regimens. Alternatives for patients with allergies or adverse reactions to these drugs include erythromycin base 500 mg orally four times a day for seven days, levofloxacin 500 mg orally once daily for seven days, and ofloxacin 300 mg orally twice daily for seven days [2]. Posttreatment infections are generally not from therapeutic failure, but are from reinfection caused by partners not receiving treatment or sexual activity with a new infected partner. Therefore, test-of-cure to detect therapeutic failure is not indicated, and retesting less than three weeks after treatment with NAAT may result in false positives because the continued presence of nonviable organisms. Women who have been treated for chlamydia should follow up three months after treatment to be tested for reinfection [2].

Trichomoniasis is one of the most common sexually transmitted infections in the United States, affecting an estimated 3.7 million persons [2]. Trichomonas vaginalis is a single-cell, anaerobic, flagellated protozoan. Infection is characterized by a discharge that is often foul-smelling, thin, and yellow or green. Inflammation of the cervix, resulting in subepithelial hemorrhages (strawberry cervix), is commonly noted. Diagnosis is made by microscopic identification of the mobile parasites. Treatment consists of metronidazole in a 2 g, single oral dose, or tinidazole in a 2 g, single oral dose. For patients who cannot tolerate 2 g at once, an alternative is metronidazole 500 mg orally twice daily for seven days. Options are limited for patients with allergy to metronidazole and tinidazole, and referral for desensitization is recommended [2].

Bacterial vaginosis is a clinical syndrome resulting from changes in the vaginal flora, including an overabundance of anaerobic bacteria along with a decrease of the normal lactobacillus species. Risk factors include oral sex, douching, black race, cigarette smoking, sex during menses, intrauterine device, early age of sexual intercourse, new or multiple sexual partners, and sexual activity with other women [3]. The most common symptom is a nonirritating, malodorous discharge. Clinical diagnosis can be made using Amsel’s criteria, which requires three of the following signs or symptoms to be present:

1. 
   

   (1) homogenous, white discharge

   
   
2. 
   

   (2) clue cells on microscopic evaluation

   
   
3. 
   

   (3) vaginal pH >4.5

   
   
4. 
   

   (4) fishy odor after addition of 10 percent KOH (whiff test) [2]

Alternatively, the diagnosis can be made with a gram stain.

First-line treatment regimens for bacterial vaginosis include metronidazole 500 mg, orally twice a day for seven days, or gel 0.75 percent, 5 g, intravaginally, once a day for five days; or clindamycin intravaginal cream 2 percent, 5 g, intravaginally at bedtime for seven days. Patients taking metronidazole should be instructed to avoid alcohol during treatment and for 24 hours after completion of treatment with metronidazole to avoid a disulfiam-like reaction [2]. The data on the performance of alternative regimens are limited, but options include tinidazole 2 g orally once daily for two days or 1 g orally once daily for five days, or clindamycin 300 mg orally twice daily for seven days or 100 mg ovules intravaginally once at bedtime for three days. Patients should be warned that clindamycin ovules use an oleaginous base that can weaken condoms and diaphragms, so these should not be used within 72 hours following treatment with clindamycin ovules.

Sexual partners of women with chlamydia, gonorrhea, or trichomoniasis should be treated for the infection for which the woman received treatment. Patients and their sex partners should be advised to abstain from sexual intercourse until seven days after a single-dose regimen or after completion of a seven-day regimen. All patients should be offered counseling and testing for HIV and syphilis. Repeat testing three to six months after a diagnosis of either chlamydia or gonorrhea is recommended, due to high rates of recurrent infection [2].

Key Teaching Points

• 
  

  Cervicitis is defined as presence of a mucopurulent discharge from the endocervical os or the presence of endocervical bleeding/friability.

  
  
• 
  

  The two most common infectious etiologies of mucopurulent cervical discharge are chlamydia and gonorrhea.

  
  
• 
  

  Cervicitis should be treated empirically, before results of chlamydia and gonorrhea are available. At a minimum, antibiotic treatment should be for chlamydia with azithromycin 1 gram × 1. For higher-risk patients, treatment includes azithromycin 1 g PO × 1 dose or doxycycline 100 mg PO BID × seven days.

  
  
• 
  

  Women should follow up in three months to be tested for reinfection.

History of Present Illness

A 27-year-old, gravida 0, woman presents to the office complaining of vaginal discharge. She has been sexually active since age 18, and she has been with her current partner for about three months. She reports she was seen at an urgent care center about one month ago with a similar complaint and diagnosed with trichomonas and treated with a single dose of 2 g oral metronidazole. The patient is uncertain if her partner was ever tested or treated, although she did tell him that she had an infection. She reports that she has had unprotected intercourse with her partner since being treated.

Physical Examination

General appearance

Well-developed, well-nourished, alert and oriented

Temperature

37.0°C

Pulse

76 beats/min

Blood pressure

114/70 mmHg

Height

65 inches

Weight

130 lb

BMI

21.6 kg/m2

Abdomen

Thin, soft, non-tender, non-distended, no guarding, no rebound

External genitalia

Unremarkable

Vagina

Erythema of mucosa with green, frothy, malodorous discharge noted in vault

Cervix

Nulliparous, has punctate hemorrhages with a “strawberry cervix” appearance, no cervical motion tenderness

Uterus

Anteverted, mobile, normal size, non-tender

Adnexa

No masses, non-tender bilaterally

Laboratory

Wet mount with motile trichomonads, increase in white blood cells noted on saline microscopy; p. 5

How Would You Manage This Patient?

The patient is diagnosed with trichomonas vaginitis, most likely from reinfection, since her partner was not treated. The patient is counseled regarding her diagnosis and the risk of other sexually transmitted infections (STIs). Safe sex practices for prevention of STIs are reviewed with the patient. She is screened for gonorrhea, chlamydia, HIV, and syphilis at the time of her evaluation. She is treated with single-dose therapy with 2 g oral metronidazole. She is instructed to notify her sexual partners for the past two months to seek evaluation and treatment and to avoid intercourse for one week after both she and her partner have completed therapy.

The patient asks if she can be given a prescription today for her partner to be treated. Given this patient’s history of prior treatment, the patient was likely reinfected by an untreated sexual partner. The patient is questioned regarding barriers to her partner obtaining evaluation and treatment. She did not indicate any limitations to this access. In the absence of any barriers, EPT (expedited partner therapy) is not performed, and the patient is given the information for the city STI clinic for her partner.

Expedited Partner Therapy

To ensure adequate treatment, patients with STIs need to avoid reinfection by untreated sexual partners. Ideally, partner treatment should occur through clinical evaluation in a health-care setting. In the United States, partner notification and referral to treatment are most commonly performed by the patient. However, this method has been unsuccessful in ensuring treatment of sexual partners. In order to improve prevention and control the spread of STIs, particularly given the problems untreated STIs can cause young women with future fertility and chronic pain, partner management with EPT has been recommended [1–5]. EPT is the practice of treating the sexual partners of patients diagnosed with STIs without medical evaluation or counseling. Typically, EPT is performed through patient-delivered partner therapy, in which medication is provided by clinicians through direct dosing or prescription to the patient that includes treatment of both the patient and her partner.

Currently, only EPT for treating gonorrhea and chlamydia have data supporting its use [1]. The Centers for Disease Control and Prevention (CDC) sponsored four randomized controlled trials between 2000 and 2004 to compare EPT with standard partner management approaches and also assess behavioral predictors of treatment and reinfection. These trials demonstrated an approximately 20 percent reduction in recurrent infections among patients with chlamydia infections and a 60 percent or better reduction rate among patients with gonorrhea infections. The studies also noted increased notification and treatment of sexual partners and decreased rates of unprotected intercourse with EPT. In conjunction with the findings of two expert consultations convened in 2004 and 2005, the CDC issued a report in February 2006 supporting the use of EPT as an option for the management of heterosexual sex partners with gonorrhea or chlamydia infection.

The 2006 CDC recommendations state that EPT is at least equivalent to, if not better than, standard patient partner management in preventing recurrent or persistent gonorrhea or chlamydial infection. The CDC concluded that EPT can be used to treat the male sex partners of females infected with gonorrhea and chlamydia when other management strategies are not practical or successful. EPT can also be used to treat the female partners of male patients infected with gonorrhea and chlamydia when other management strategies are similarly deemed impractical or unsuccessful, with the understanding that female recipients of EPT are strongly encouraged to seek medical attention – particularly in cases of patients exhibiting symptoms of acute pelvic inflammatory disease, such as abdominal or pelvic pain.

In 2012, due to concern over increasing resistance of gonorrhea to oral cefixime and possible treatment failures, the CDC updated its gonorrhea treatment recommendations [2, 3]. The current CDC-recommended treatment for uncomplicated gonorrhea infections is combination therapy with a single intramuscular dose of ceftriaxone 250 mg plus a single dose of azithromycin 1 g orally. Given that the treatment regimen involves an injection, the potential use of EPT is limited in the treatment of gonorrhea. The current recommendation is for the patient’s sexual partners to be evaluated and treated with ceftriaxone and azithromycin; however, the CDC still approves the use of EPT in cases where the provider is concerned for timely evaluation and treatment of the partner. In such cases, oral cefixime and azithromycin can still be considered.

Historically, EPT is believed to have been widely employed in the treatment of the partners of women with trichomonas. Currently, there is not sufficient evidence to support the use of EPT for the treatment of trichomoniasis [1]. EPT is not routinely recommended for treatment of female patients with trichomoniasis due to the high risk of STI comorbidity in sex partners. Undiagnosed gonorrhea and chlamydia infection are common in the partners of women with trichomoniasis. The CDC advises the use of EPT for trichomonal infection with caution only in selective cases where other strategies again are impractical or unsuccessful.

The CDC 2006 statement also notes that EPT is not suggested for use in the treatment of patients with syphilis [1]. Treatment of syphilis frequently requires injection, as penicillin is the current recommended therapy. Concern for penicillin allergy and anaphylaxis limits its use for EPT when compared to cephalosporins and macrolides used to treat gonorrhea or chlamydia. Typically, partner notification services are also available at state and local health departments for syphilis infections through mandatory notification requirements.

Studies evaluating EPT use are largely limited to heterosexual adults, although EPT can be used for other populations. The CDC advises that EPT should not be used in gonorrhea and chlamydial infection in men who have sex with men due to the high risk of comorbidity, particularly undiagnosed HIV, in partners. There is no specific statement regarding the use of EPT in homosexual women. No data exist to demonstrate the efficacy or role of EPT among women who have sex with women. However, the American College of Obstetricians and Gynecologists (ACOG) states that EPT may be an appropriate management option for same-sex partners of female patients [4].

The ACOG has endorsed the use of EPT for a patient’s partners who are unable or unwilling to seek medical care as a method of preventing gonorrhea and chlamydial reinfection [4]. EPT has also been supported by other medical professional organizations, including the Society for Adolescent Medicine and the American Academy of Family Physicians [5]. Guidelines have been published for the practice of EPT by the CDC, as well as several state health departments [1–3].

Use of EPT includes education of the patient for her partner. This education should include the indication for the partner treatment, instructions for administration, and warnings regarding adverse reactions. It should also include STI counseling with the recommendation for referral to a local testing center for a full STI evaluation. Furthermore, instructions should include abstinence from intercourse for seven days after treatment.

EPT is recommended for all sexual partners in the last 60 days [1]. Additionally, it is important for providers to assess the risk of intimate partner violence with partner notification. EPT is not recommended in situations of suspected child abuse, sexual assault, or other situations in which the patient’s safety may be compromised [4].

EPT has not been studied in pregnant women in isolated trials. Pregnancy may be a key time to implement EPT given the potential adverse effects of infection with gonorrhea and chlamydia on the pregnancy and on neonatal health. Conversely, there may be less need for EPT in pregnancy; traditional partner treatment may be more successful due to increased access to care for pregnant women, as well as a desire of the patient and partner to protect the health of the fetus. EPT may be important in adolescents, but is not well studied. Rates of gonorrhea and chlamydia infection in female adolescents are much higher than in other age groups.

The legal status of EPT has not always been certain, resulting in a large barrier to the use of EPT. While no specific rule of law prohibited the use of EPT, EPT use can be prevented indirectly through licensing, public health, or prescription drug laws that require examination of patients or direct patient–physician relationships as specific requirements for a pharmacist to dispense drugs. To help clarify the legal framework to allow state and local programs to institute EPT in their areas, the CDC developed a website in conjunction with the Center for Law and the Public’s Health that contains state information [6]. Included are the key legal provisions in six areas that were found to relate to EPT implementation for each state; a final conclusion indicates whether EPT is supported legally in that jurisdiction. As of December 2016, EPT is permissible in 38 states, potentially allowable in eight states, and prohibited in four states. The website can be accessed at www.cdc.gov/std/ept/legal for further information. Of note, variation exists by state as to which diseases may be treated with EPT. For example, in New York, EPT can only be used to treat chlamydia.