Infection Treatment Other
Chlamydia

(chlamydia trachomatis)
2015 CDC recommendations
  • Up to 85 - 90% of infections are asymptomatic
  • Most commonly reported signs in women include cervical mucopurulent discharge and hypertrophic cervical ectopy (cervix swells and turns out). Other symptoms include dysuria, abnormal vaginal discharge, and postcoital bleeding.
  • Symptoms in men include urethral discharge, painful urination, and urethral itching [1]
  • For women, self- or clinician-collected vaginal swabs are the preferred sample type. A first catch urine sample is acceptable, but may miss up to 10% of infections.
  • For men, a first catch urine specimen is the preferred sample method
  • Oral and rectal swabs may be obtained in susceptible patients
  • Nucleic acid amplification tests (NAATs) are the recommended test method [3]
  • Patients should abstain from intercourse for 7 days after single-dose therapy or until the completion of a 7-day regimen [2]

Studies
  • Doxycycline vs azithromycin - A study published in the NEJM in 2015 compared doxycycline (100 mg BID for 7 days) to azithromycin (1 gram single dose) in 567 adolescents. In the per-protocol population, 155 subjects in each group received their assigned treatment. The primary outcome was treatment failure after 28 days. RESULTS: No patients in the doxycycline group had treatment failure. Five patients in the azithromycin group had treatment failure (3.2%). [Pubmed ID 26699167]

Infection Treatment Other
Genital warts 2015 CDC recommendations
  • Patient-applied treatments
    • Podofilox 0.5% (Condylox®) solution and gel - Apply twice daily for 3 consecutive days, then discontinue for 4 consecutive days. This one week cycle of treatment may be repeated until there is no visible wart tissue or for a maximum of four cycles. Safety and effectiveness of more than four treatment cycles has not been established. Apply to warts with the applicator tip or finger. Application on the surrounding normal tissue should be minimized. Treatment should be limited to 10 cm² or less of wart tissue and to no more than 0.5 g of the gel per day. Care should be taken to allow the gel to dry before allowing the return of opposing skin surfaces to their normal positions. Patients should be instructed to wash their hands thoroughly before and after each application. Solution comes in 3.5ml bottle. Gel comes in 3.5gm tube. ($$ - solution; $$$$ - gel)

    • Imiquimod 5% (Aldara®) cream - Apply 3 times per week to external genital/perianal warts. Continue until there is total clearance of the genital/perianal warts or for a maximum of 16 weeks. Apply prior to normal sleeping hours and leave on the skin for 6 -10 hours, then remove with mild soap and water. A thin layer of cream should be applied to the wart area and rubbed in until the cream is no longer visible. Local skin reactions at the treatment site are common. Comes in single use packet in boxes with 12 - 24 packets. ($$-$$$ for 12 packets)

    • Sinecatechins 15% (Veregen®) ointment - Apply three times per day to all external genital and perianal warts. Continue until complete clearance of all warts or a maximum of 16 weeks. Apply 0.5 cm strand of ointment to each wart using a finger, dabbing it on to ensure complete coverage and leaving a thin layer of the ointment on the warts. Patients should wash their hands before and after application. Local skin reactions are common. Comes in 15 and 30gm tube. ($$$$)

  • Provider-applied treatments
    • Cryotherapy with liquid nitrogen or cryoprobe - repeat applications every 1–2 weeks
    • Podophyllin resin 10%–25% in a compound tincture of benzoin
    • Trichloroacetic acid (TCA) or Bichloroacetic acid (BCA) 80%–90%
    • Surgical removal either by tangential scissor excision, tangential shave excision, curettage, or electrosurgery
  • 90% of genital warts are caused by HPV 6 or 11
  • Gardasil® vaccine protects against HPV 6 and 11
  • Genital warts typically occur around the introitus in women, under the foreskin of the uncircumcised penis, and on the shaft of the circumcised penis. They also can occur on the cervix, vagina, urethra, perineum, perianal skin, and scrotum. Intra-anal warts are observed predominantly in persons who have had receptive anal intercourse, but they can also occur in men and women who do not have a history of anal sexual contact.
  • If left untreated, genital warts might go away, stay the same, or grow in size or number
  • Women with genital warts do not need to get Pap tests more often than recommended
  • Genital warts are not associated with the development of anogenital cancers
  • It's unclear if treatment reduces the risk of transmitting HPV infection
  • Newborns born to women with genital warts can sometimes develop respiratory papillomatosis (warts of the larynx). This condition is very rare. It is unclear if cesarean section prevents respiratory papillomatosis, therefore, cesarean delivery should not be performed solely to prevent transmission of HPV infection to the newborn
  • Many persons with warts on the anal mucosa also have warts on the rectal mucosa and may need evaluation with anoscopy [2]

Infection Treatment Other
Gonorrhea

(neisseria gonorrhoeae)
2015 CDC recommendations
  • First line - cervical, urethral, and rectal
    • Ceftriaxone - 250 mg IM single dose +
      • Azithromycin* - 1000 mg single dose; OR
      • Doxycycline - 100 mg twice a day for 7 days ($-$$ for two meds)
      • *Azithromycin is preferred over doxycycline

  • Alternative treatments
    • Cefixime - 400 mg single dose +
      • Azithromycin* - 1000 mg single dose; OR
      • Doxycycline - 100 mg twice a day for 7 days ($$ for two meds)
      • *Azithromycin is preferred over doxycycline; test of cure in 1 week recommended with this regimen
    • Azithromycin - 2000 mg single dose +
  • In men, symptoms of urethral discharge and burning are typically present
  • In women, symptoms of vaginal discharge, burning with urination, and abnormal vaginal bleeding may be present. Women may also be asymptomatic.
  • Gonorrhea infections are often accompanied by chlamydia infections
  • For women, self- or clinician-collected vaginal swabs are the preferred sample type. A first catch urine sample is acceptable, but may miss up to 10% of infections.
  • For men, a first catch urine specimen is the preferred sample method
  • Nucleic acid amplification tests (NAATs) are the recommended test method [3]
  • Patients should abstain from intercourse for 7 days after single-dose therapy or until the completion of a 7-day regimen [2]

Infection Treatment Other
Genital herpes

(herpes simplex)
2015 CDC recommendations
  • Initial episode
    • Acyclovir
      • 400 mg 3 times a day for 7 - 10 days ($)
      • 200 mg 5 times a day for 7 - 10 days ($)
    • Famciclovir - 250 mg 3 times a day for 7 - 10 days ($)
    • Valacyclovir - 1000 mg twice a day for 7 - 10 days ($)

  • Recurrent episodes
    • Acyclovir
      • 400 mg 3 times a day for 5 days ($)
      • 800 mg twice a day for 5 days ($)
      • 800 mg 3 times a day for 2 days ($)
    • Famciclovir
      • 125 mg twice daily for 5 days ($)
      • 1000 mg twice daily for 1 day ($)
      • 500 mg once, followed by 250 mg twice daily for 2 days ($)
    • Valacyclovir
      • 500 mg twice daily for 3 days ($)
      • 1000 mg once daily for 5 days ($)

  • Suppressive therapy
    • Acyclovir - 400 mg twice daily ($)
    • Famciclovir - 250 mg twice daily ($$)
    • Valacyclovir - 500 - 1000 mg once daily (For patients with ≥ 10 episodes a year, 1000 mg a day is preferred) ($-$$)

Topical (not CDC recommended)
  • Epidemiology - Genital herpes is caused by herpes simplex virus (HSV). There are two types of herpes simplex virus, type 1 and type 2. HSV-1 causes herpes labialis (fever blisters) and genital herpes while HSV-2 only causes genital herpes. In the U.S., the prevalence of HSV-1 among persons 14 - 49 years is 54% and the prevalence of HSV-2 is 16%. [7,8]
  • Symptoms - Symptoms typically appear 4 - 7 days after exposure. Classic symptoms of HSV include clusters of vesicles on a red base that develop on the external genitalia and surrounding tissue. Lesions are often painful, itchy, and progress to ulcers and crusts that resolve over 2 - 3 weeks. In more severe cases, inguinal lymphadenopathy, fever, and malaise may develop. Atypical symptoms are common, and many infections go unrecognized due to mild or no symptoms. In one study, 74% of of genital HSV-1 infections were asymptomatic and 63% of HSV-2 infections were asymptomatic. Patients who are seropositive for HSV-1 are more likely to be asymptomatic when infected with HSV-2. [4,7,8]
  • Recurrence - After an initial outbreak of HSV-2, 70 - 90% of patients will have a recurrence within the first year with an overall average of 4 outbreaks in the first year. After an initial outbreak of HSV-1, 20 - 50% of patients will have a recurrence within a year with a median of 1.3 outbreaks in the first year. Recurrent outbreaks are often shorter (5 - 10 days) and less severe. Genital herpes is a lifelong infection. [7,8]
  • Transmission - Risk of transmission is greatest when sores are present, but may also occur when no sores are present. Asymptomatic viral shedding occurs on 10 - 30% of days in patients infected with HSV-2. Suppressive antiviral therapy has been shown to reduce the days with asymptomatic shedding to < 7%, and likewise, has also been shown to reduce the rate of transmission. Development of acyclovir-resistance with suppressive therapy is rare in immunocompetent patients. [8]
  • Diagnosis
    • Lesion testing - HSV DNA PCR testing is preferred. The sensitivity of PCR approaches 100% if vesicles or wet ulcers are present. Viral cultures have reduced sensitivity and are no longer recommended. [2,8]
    • Serological testing - Serum antibody testing (IgG, IgM) for HSV is available. IgM testing can detect recent infection, but it is not type-specific and may be positive during recurrent oral and genital episodes. IgG antibody testing is type-specific. After an initial infection, IgG antibodies may take from 3 weeks to 3 months to appear. Sensitivity of IgG testing for HSV-2 is 80 - 98% with a specificity of 93 - 97%. Sensitivity for HSV-1 is 69 - 98% with a specificity of 92 - 95%. [2,8]
  • Treatment - Antiviral therapy initiated within 24 hours of symptom onset reduces the overall length of symptoms by 1 - 2 days. In studies, suppressive therapy reduced the risk of recurrence from 80 - 85% to 25 - 30% over 4 months. [8]

Screening recommendations
  • The USPSTF recommends against screening for genital herpes in asymptomatic individuals including pregnant women [7]

Infection Treatment Other
Mycoplasma
genitalium

(M. genitalium)
2015 CDC recommendations
  • First line

  • Alternative treatments
    • Moxifloxacin - 400 mg once daily for 7, 10, or 14 days ($$-$$$)
  • M. genitalium was first discovered in 1980. It is not as widely known or understood as other STDs.
  • It is associated with urethral inflammation and burning in men. In women, it may be associated with vaginal discharge and cervicitis.
  • In studies, it accounts for 15 - 25% of nongonococcal urethritis
  • M. genitalium nucleic acid amplification tests (NAATs) for urine and swabs are available [2]

Infection Treatment Other
Syphilis

(Treponema pallidum)
2015 CDC recommendations
  • Primary and secondary syphilis

  • Early Latent syphilis

  • Latent syphilis

  • Tertiary syphilis

  • NOTE: Bicillin L-A® should be used, NOT Bicillin C-R® (benzathine-procaine)

  • Neurosyphilis
    • Aqueous crystalline penicillin G- 18–24 million units per day, administered as 3–4 million units IV every 4 hours or continuous infusion, for 10–14 days ($$$$)
    • Alternative:
      • Procaine penicillin 2.4 million units IM once daily + probenecid 500 mg orally four times a day, both for 10–14 days

  • Pen allergic
    • Primary and secondary syphilis
      • *Azithromycin - 2000 mg single dose ($)
      • Ceftriaxone - 1000 mg IM/IV daily for 10 - 14 days ($)
      • Doxycycline - 100 mg twice a day for 14 days ($)
      • Tetracycline - 500 mg four times a day for 14 days ($$$$)
      • * Azithromycin is a last resort; other treatments are preferred

    • Latent syphilis

    • Neurosyphilis
      • Ceftriaxone - 2000 mg IM/IV daily for 10 - 14 days ($)

    NOTE: - the effectiveness of these regimens has not been studied extensively

Other
  • Primary, secondary, early latent, latent syphilis
    • Amoxicillin - 1000 mg three times a day + probenecid 250 mg three times a day for 14 - 16 days (based on PMID 25829004)
TERMS AND DEFINITIONS

  • Primary syphilis - ulcer or chancre at infection site
  • Secondary syphilis - skin rash (frequently involves palms and soles), mucocutaneous lesions, fever, and lymphadenopathy
  • Early latent syphilis - no clinical symptoms with positive serology and known to have acquired syphilis within the past year
  • Latent syphilis - syphilis for > 1 year or unknown duration; no clinical symptoms with positive serology
  • Tertiary syphilis - cardiac disease and gummatous (granulomatous) lesions of skin, bone, and organs
  • Neurosyphilis - cranial nerve dysfunction, meningitis, stroke, acute or chronic altered mental status, loss of vibration sense, and auditory or ophthalmic abnormalities
  • RPR (Rapid Plasma Reagin) - nontreponemal test; detects reagin antibodies produced against cells damaged by T. pallidum; RPR is used to screen for syphilis; RPR will typically turn positive 4 - 6 weeks after initial infection; if positive, it is confirmed with a treponemal test; a fourfold change in RPR titer (ex. 1:16 to 1:4) is considered a clinically significant difference between two RPR tests; 15 - 41% of patients will continue to have a low RPR titer after treatment; RPR test can be positive in patients with antiphospholipid antibodies.

    • RPR has a specificity of 98% (93-99)
    • Reference [9]
    RPR sensitivity in syphilis stages
    Primary Secondary Latent Tertiary
    86% (77-100) 100% 98% (95-100) 73%
  • VDRL (Venereal Disease Research Laboratory) - nontreponemal test; detects reagin antibodies produced against cells damaged by T. pallidum; RPR is preferred over VDRL for screening; VDRL is still the gold standard for diagnosing neurosyphilis (CSF testing)
  • FTA-ABS (Fluorescent Treponemal Antibody Absorption) - treponemal test; detects antibodies to Treponema pallidum; not used to monitor disease activity; remains positive for life
  • TP-PA (Treponema Pallidum Particle Agglutination) - treponemal test; detects antibodies to Treponema pallidum; not used to monitor disease activity; remains positive for life
  • Jarisch-Herxheimer reaction - syndrome of fever, rash, malaise, headache, and myalgias that occurs within the first 24 hours of treatment of early syphilis with penicillin. Occurs in 10 - 35% of patients and is typically self-limited. [2,6,9,10]

FOLLOW-UP TESTING

  • Primary and secondary - perform RPR titer at 6 and 12 months. A fourfold decrease in baseline titer by 12 months is considered treatment success if no symptoms are present.
  • Latent - perform RPR titer at 6, 12, and 24 months. A fourfold decrease in baseline titer by 24 months is considered treatment success if no symptoms are present.
  • Neurosyphilis - recheck CSF every 6 months until normal [2,6]

SCREENING



Infection Treatment Other
Trichomoniasis

(T. vaginalis)
2015 CDC recommendations
  • Trichomoniasis is caused by the protozoan T. vaginalis
  • Symptoms in women include malodorous, yellow-green vaginal discharge and vulvar irritation. Many women are asymptomatic.
  • Symptoms in men include urethral inflammation, discharge, burning, and tingling. In studies, up to 77% of infected men are asymptomatic.
  • Trichomoniasis may be diagnosed by direct microscopic visualization of vaginal secretions, culture of vaginal or urethral (men) swabs, and through Nucleic Acid Amplification Tests (NAATs) on swabs and urine specimens
  • Wet-mount microscopy has low sensitivity (50 - 60%). NAATs like the APTIMA T. vaginalis assay are preferred. [2,5]