2021 STI Treatment Guidelines Webinar Questions and Answers

1. Is the expectation for jurisdictions to wait to make these treatment changes until the official 2021 guidelines are released (with the exception of gonorrhea [GC])? When will updated treatment guidelines be available to refer to publicly? Should clinicians change practice now or await formal release of these recommendations?

Answer: Treatment recommendations for uncomplicated gonorrhea in adolescents and adults were updated in a Morbidity and Mortality Weekly Report (MMWR) special policy note published December 17, 2020, entitled, “Update to CDC’s Treatment Guidelines for Gonococcal Infection, 2020.” The published GC treatment recommendations should be implemented now. Additional recommendations will be available in 2021 when the comprehensive 2021 STI Treatment Guidelines (STI Treatment Guidelines) document is published.

2. Would CDC consider releasing recommendations on a rolling basis (like the GC recommendations released in December 2020)?

 Answer: Additional formats for timely publication of these important guidelines are being considered.

3. Will preferred terminology be “STI” [sexually transmitted infection] or “STD” [sexually transmitted disease], or will they be considered equivalent?

Answer: STI refers to an organism acquired via sexual contact. STD is a disease state, which develops as a result of an STI. The terminology has been debated within the field and there is no clear preference in all instances. For the purposes of the 2021 STI Treatment Guidelines, STI will be the terminology used, as the Guidelines recognizes the asymptomatic nature of many infections.

4. How were the peer reviewers of the guidelines selected?

Answer:  Peer reviewers were selected based on expertise in the clinical management and treatment of HIV, STD and viral hepatitis; expertise in STD prevention for men who have sex with men (MSM) and heterosexual women and men in the United Stated (U.S.); and with backgrounds in public health, obstetrics and gynecology, internal medicine, pediatrics, and adolescent medicine.

5. Given the continued nationwide rise in all the major STIs, what are we doing wrong? What, if anything, are we sure we are doing correctly?

Answer: The U.S. is facing unprecedented challenges with STIs. Rates continue their historic climb, contributing to myriad adverse health effects, including infant death and increased risk of HIV acquisition. A range of factors can reduce access to care, including poverty, stigma, and unstable housing. Research also indicates that condom use is declining among vulnerable groups, including young people and gay and bisexual men. Infrastructure issues challenge prevention efforts, including STD clinic closures, reduced screening, and reduced patient follow-up and linkage to care services. Disparities and health inequities among racial, ethnic, and sexual minorities create additional barriers to obtaining adequate care and treatment. The COVID-19 pandemic has compounded many of these challenges, exacerbating pre-existing racial and ethnic disparities in healthcare and prevention access, and straining our public health infrastructure.

Quality STI prevention, which includes effective screening and treatment, remains the cornerstone of protecting the health and wellness of Americans. The STI Treatment Guidelines will continue to facilitate that work, leveraging the latest available science and research to give healthcare providers the information they need to address five major strategies for STI prevention and control including accurate risk assessment, education and counseling of persons at risk for STIs; pre-exposure vaccination for vaccine preventable STIs; identification of asymptomatically infected persons and persons with STI-associated symptoms; effective diagnosis, treatment, counseling, and follow-up of infected persons; and evaluation, treatment, and counseling of sex partners of persons infected with an STI. The STI Treatment Guidelines can be used alongside the Recommendations for Providing Quality Sexually Transmitted Diseases Clinical Services, which provides guidance regarding quality clinical services for STIs in primary care and sexually transmitted disease (STD) specialty care settings.

Simultaneously, the Department of Health and Human Services’ (HHS)  Sexually Transmitted Infections National Strategic Planpdf iconexternal icon (STI Plan), a five-year plan that aims to reverse the recent dramatic rise in STIs in the U.S. (https://www.hhs.gov/programs/topic-sites/sexually-transmitted-infections/plan-overview/index.htmlexternal icon), is working to set a vision as well as goals, objectives, strategies, and measurable targets to respond to the STI epidemic. And the STI Treatment Guidelines will be an important piece of CDC’s role in that Plan.

1. Polymerase chain reaction (PCR) and Nucleic Acid Amplification Test (NAAT) are used interchangeably. Recommend use of NAAT as there are several amplification methods being used in Federal Drug Administration (FDA)-cleared and approved assays.

Answer: NAAT is used in the document to define molecular testing throughout the document.

2. Was rapid diagnosis considered or discussed for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (GC), and/or Mycoplasma genitalium (MG)?

Answer: Point-of-care NAATs are discussed in the document for CT and GC. There will be a diagnostics subsection in the trichomonas section that addresses rapid testing. There are no commercially available rapid NAAT tests for MG.

3. Neither the CT nor GC sections mention opt-out screening as an approach to increase uptake and adherence to CT/GC screening despite opt-out being encouraged as part of the STI National Strategic Plan. Will the STI management guidelines include an update encouraging the use of opt-out strategies? Do the guidelines also recommend opt-out testing for adolescents 15 – 24? Are there additional studies to support the recommendation for extragenital testing in adolescents?

Answer: Recommendations for GC and CT screening are based on national United States Preventive Services Task Force (USPSTF) guidance. The national strategic guidance can be adapted to local epidemiology. Providers may consider opt-out chlamydia and gonorrhea screening for female adolescents and young adults during clinical encounters.

4. Wording should be external and internal condoms in the prevention section.

Answer: The guidelines discuss both external and internal condoms as STI prevention methods.

5. Can you talk more about the shared decision-making recommendation for the human papilloma virus (HPV) vaccine for persons 27 – 45 years?

Answer: Specific recommendations on HPV vaccination for persons 27 – 45 years is per Advisory Committee on Immunization Practices (ACIP) guidance.

6. With the unveiling of the STI Plan, there has already been some push back from organizations that the language focused on binary gender identities (rather than body parts), which they found to be alienating to transgender or gender non-conforming patients. How can we make sure the 2021 STI Treatment Guidelines are friendly to all populations?

Answer: The 2021 STI Guidelines will discuss this topic under the transgender and gender diverse population section of the document.

7. For sexual assault in children, can herpes simplex virus (HSV) PCR be used?

Answer: Because HSV can be indicative of sexual abuse, specimens should be obtained from all vesicular or ulcerative genital or perianal lesions and sent for NAAT or viral culture.

8. Will the guidelines mention self-testing for STIs in men who have sex with men (MSM)?

Answer:  Discussion of rectal and pharyngeal testing (provider or self-collected) will be discussed for MSM who report exposure at these sites.

9. Although there are studies documenting increased efficacy of doxycycline (doxy) compared to azithromycin for CT, why is the expedited partner therapy (EPT) recommendation recommending doxy in the co-treatment part of GC EPT. Is doxy 100 bid x7 recommended for CT EPT alone? Or only if in combination with cefixime for GC when CT not excluded? Are there suggestions for evaluating concerns of adherence for EPT partners and the 7-day course of treatment for doxy?

Answer: The recent updated MMWR GC treatment recommendations document the rationale for change in gonorrhea treatment recommendations including antimicrobial stewardship, pharmacokinetic and pharmacodynamics considerations, and changes in azithromycin susceptibility. Concurrent CT treatment for GC EPT is recommended only in instances where CT infection was not excluded in the patient. There is discussion about adherence and antimicrobial selection in the CT section of the 2021 STI Treatment Guidelines.

10. We have a swab shortage and we’re supposed to do test of cure for every pharyngeal GC infection. What about prioritization of tests in MSM for example where positivity of urine test in asymptomatic screening is so low?

Answer: CDC has provided guidancepdf icon for prioritizing STI tests if test kits are in short supply.

1. What is the guidelines stance on yearly anal pap for anal cancer if anoscopy is available? In that case digital rectal exam (DRE) still the preferred screening tool?

Answer: The guidelines discuss inquiring about anal cancer risk in specific populations to guide management.  A digital anorectal examination should be performed to detect early anal cancer in persons with HIV and men who have sex with men without HIV with a history of receptive anal intercourse. However, there is limited data to define the age at which to initiate screening or optimal screening intervals. Other screening methods will be discussed in the section on anal cancer screening.

1. What will be gold standard for BV diagnosis? Will Becton Dickson (BD) Affirm/DNA Probe continued to be recommended for BV, vulvovaginal candidiasis (VVC), and trichomoniasis diagnoses? As far as BV, is DNA probe technology still within the diagnostic guidelines?

Answer: BV can be diagnosed by the use of clinical criteria (Amsel’s Diagnostic Criteria) or by determining the Nugent score from a vaginal Gram stain. In addition to Amsel criteria, there are several tests which are discussed in the guidelines including point-of-care (POC) tests, and nucleic acid amplification tests for BV diagnosis.

1. The changes to cervical screening are based on limited data with understudy of racial/ethnic populations. Suggest further studies to understand the use of these screening models on underserved race/ethnic populations.

Answer: The 2021 STI Treatment Guidelines cites national guidance for cervical cancer screening and will include a table that outlines screening test options and intervals, including the most recent guidance from the United States Preventative Services Task Force (2018), American College of Obstetricians and Gynecologists (2016), American Cancer Society (2020), and the Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV (2021).

1. There are concerns about compliance in adolescents with the longer treatments using doxycycline instead of azithromycin. Compliance with doxycycline 100 mg BID (twice daily) for 7 days is a challenge for compliance among our patients. Doxycycline might pose multiple issues, especially for adolescents: taking the med at home with parent(s), insurance issues, not directly observed therapy (DOT), etc. What are the recommendations for rectal CT management in women? Will a test of cure will be recommended for CT when the alternative regimen (1g azithromycin) is used? Is doxycycline preferred over azithromycin for asymptomatic contacts?

Answer: Doxycycline is efficacious for CT infection of the urogenital, rectal, and oropharyngeal sites. Although azithromycin maintains high efficacy for urogenital CT infection in women, there is concern about the effectiveness of azithromycin for concomitant rectal CT infection, which may occur commonly in women and cannot be predicted by reported sexual activity. Inadequately treated rectal CT infection in women who have urogenital CT could increase the risk of transmission and could put women at risk for urogenital CT infection through autoinoculation from the anorectal site. When nonadherence to doxycycline regimen is a significant concern, azithromycin 1g would be an alternative treatment option but may require post treatment evaluation and testing, especially for persons with rectal infection. There is further discussion about antimicrobial selection in the CT section of the 2021 STI Treatment Guidelines.

1. Herpes serology is recommended for herpes simplex virus (HSV-2) positive partners. If positive, is treatment recommended if partner is asymptomatic?

Answer: Asymptomatic persons who receive a diagnosis of HSV-2 by type-specific serologic testing should receive education about the symptoms of genital herpes infection. For persons with serological evidence of HSV-2 without symptomatic recurrences, neither episodic nor suppressive therapy are indicated for prevention of recurrences.

2. Would you elaborate on how serologic two-step testing for HSV-2 goes beyond what’s in the current guidelines re: confirmatory testing with low-positive index values?

Answer: Due to the poor specificity of the most commonly used test (HerpeSelect HSV-2 EIA) at low index values, a confirmatory test with a second method (Biokit or Western Blot) should be performed prior to test interpretation. The use of confirmatory testing with the Biokit or the Western blot assays have been shown to improve the accuracy of HSV-2 serologic testing.

1. Regarding the administration of 500 mg of Ceftriaxone — should that be reconstituted in 1 ml or 2 ml of lidocaine?

Answer: Specific practices regarding use of lidocaine with ceftriaxone is based on local administration practices.

2. Can you provide more details on expedited partner therapy (EPT) given the changes in GC management—especially about needing added warnings/counseling for EPT that would include doxycycline vs azithromycin?

Answer: Gonococcal EPT is based on specific state law and the recommended regimen is based on whether or not concurrent chlamydial infection has been excluded in the patient. Specific counseling should be based on specific antimicrobial educational materials developed and provided locally.

3. Clarify the past use of dual therapy for GC.

Answer: Please refer to the recent Morbidity and Mortality Weekly Report (MMWR) special policy note published December 17, 2020, entitled, “Update to CDC’s Treatment Guidelines for Gonococcal Infection, 2020” concerning the rationale for past dual therapy, which might have mitigated emergence of reduced susceptibility to ceftriaxone.

4. Why gentamicin plus azithromycin and not gentamicin plus doxycycline? What happened to gemifloxacin 320 mg as an alternative treatment for GC?

Answer: The use of gentamicin 240mg IM plus azithromycin 2g orally as an alternative treatment was based on a clinical trial that demonstrated effectiveness for urogenital GC. Gentamicin plus doxycycline has not been studied in a clinical trial. Gemifloxacin plus azithromycin has been studied but is no longer recommended as an alternative regimen because of limited availability, cost, and antimicrobial stewardship concerns.

5. If GyrA testing becomes Federal Drug Administration (FDA)-cleared as a point of care testing (POCT), why not treat symptomatic or asymptomatic with ciprofloxacin?

Answer: GyrA testing is not currently FDA-cleared for use in gonococcal infection. Once FDA-cleared, there are scenarios where ciprofloxacin may be able to be administered, which is discussed in the guidelines.

6. For recurrent GC, why are culture and nucleic acid amplification tests (NAAT) both recommended? For oral GC, what is the time frame for test of cure?

Answer: NAAT is more sensitive than culture, but antimicrobial susceptibility testing can be performed on culture. A test-of-cure should be obtained 7–14 days after treatment; culture is the recommended test, preferably with simultaneous NAAT with antimicrobial susceptibility testing if N gonorrhoeae is isolated.

7. Should we still use azithromycin for disseminate gonococcal infection (DGI)?

Answer: The released “Update to CDC’s Treatment Guidelines for Gonococcal Infection, 2020” made treatment recommendations for uncomplicated GC in adults and adolescents and has completed the CDC review process. The 2021 STI Treatment Guidelines, including sections that include treatment of complicated gonococcal infections, addresses this question.

1. What is the recommendation if patients do not have insurance and moxifloxacin treatment would not be possible?

Answer: The 2021 STI Treatment Guidelines discuss treatment recommendations and alternative regimens based on resistance guided therapy and treatment options if moxifloxacin treatment is not possible.

1. Will PID treatment include 500mg ceftriaxone + 100mg twice daily (BID) doxycycline x 7d + 500mg BID metronidazole x7?

Answer: Draft PID treatment recommendations include ceftriaxone, doxycycline, and metronidazole.

1. Are there any specific recommendations for who should be screened for syphilis? Who is considered “at risk”?

Answer: The guidelines reference various national guidelines that address syphilis screening in specific populations including; pregnant women, men who have sex with men, and persons with HIV infection. The national guidelines are from the United States Preventative Services Task Force, American College of Obstetrics and Gynecology, and the Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV Infection.

2. Will there be better clarification of pregnant women being treated for syphilis (three-shot series) concerning restarting the series if the dose is given on day 7 vs day 8?

Answer: Optimal interval between doses is 7 days for pregnant women. Missed doses beyond 9 days between doses are not acceptable for pregnant women receiving therapy for late latent syphilis. If a pregnant woman does not return for the next dose on day 7, then every effort available should be made to contact her and link her to immediate treatment within 2 days to avoid retreatment. Pregnant women who miss a dose of therapy must repeat the full course of therapy.

3. Is Doxycycline no longer a recommended alternative for syphilis infections? Can ceftriaxone 1g be given intramuscularly (IM) alternatively for syphilis treatment?

Answer: Data to support use of alternatives to penicillin in treating syphilis are limited and only penicillin should be used to treat syphilis during pregnancy. Both doxycycline and ceftriaxone intravenous or IM are alternative treatments as noted in previously published guidelines.

4. Is the atypical painful presentation for primary syphilis only? What are the implications for STI surveillance reporting?

Answer: Primary or secondary syphilis can present with multiple, atypical, or painful lesions. There are no changes in surveillance. Reporting is based on clinical staging, not painful lesions.

5. Explain why some clients will always have a reactive rapid plasma reagin (RPR) and/or the treponema pallidum particle agglutination assay (TPPA) even after treatment and others convert back to non-reactive.

Answer: Serologic response to syphilis treatment can be affected by syphilis stage, patient age, and initial titer. The 2021 STI Treatment Guidelines will include detailed management scenarios.

6. For a patient with syphilis and only conjunctivitis, is a lumbar puncture (LP) recommended and/or empiric treatment for ocular syphilis?

Answer: There will be an expanded discussion on indications for cerebrospinal fluid (CSF) evaluation in persons with syphilis in the 2021 STI Treatment Guidelines.

1. What is the official screening recommendation for Trichomonas?

Answer: Diagnostic testing for T. vaginalis should be performed in women seeking care for vaginal discharge. Screening can be considered for persons in high-prevalence settings and for asymptomatic women at high risk for infection. Screening women with HIV infection for trichomonas is recommended.

2. Is the CDC recommending expedited partner therapy (EPT) for trichomonas? How can I get treatment for trichomonas for partners?

Answer: There is no change from previous guidance which states that EPT might have a role in partner management. A specific section of the guidelines will address partner treatment.

1. In reference to STD registered nurses (RN) who cannot give any medications to be taken out of the clinic (i.e., doxycycline x 7 days), how will they provide syndromic treatment for empiric gonorrhea (GC) & Chlamydia trachomatis (CT) before results return? Would you recommended in a high sexually transmitted infection (STI) prevalence area and concern for follow-up, would you treat for empiric urethritis and cervicitis before test results come back?

2. In our STD clinic, M genitalium (MG) is more common in urethritis than CT. Why not screen for MG at the same time as GC and CT? Why not recommend MG testing for all initial urethritis and cervicitis cases?

3. In the persistent urethritis section, azithromycin “z-pack” is recommended a second regimen?

Answer (for all three): Treatment should be pathogen-based but diagnostic information might not be immediately available. Presumptive treatment should be initiated at initial non gonococcal urethritis (NGU) diagnosis. If symptoms persist after therapy completion, objective documentation of urethritis and MG and T. vaginalis (in men who only have sex with women) testing is recommended. For treatment of MG, resistance guided therapy is recommended. As part of this approach, doxycycline is provided as initial empiric therapy that reduces the organism load and facilitates organism clearance followed by high-dose azithromycin for macrolide-sensitive MG infections or moxifloxacin for macrolide-resistant infections.

1. What is the specificity of albicans polymerase chain reaction (PCR) in diagnosis of vulvovaginal candidiasis (VVC)?

Answer: The majority of PCR tests for yeast are not Federal Drug Administration (FDA)-cleared, and providers who use these tests should be familiar with the performance characteristics of the specific test used.

2. Why did you choose not to provide guidance on Aerobic Vaginitis?

Answer: There is no guidance on aerobic vaginitis included in the treatment guidelines, as there is no data that aerobic vaginitis is sexually transmissible.