Sexually Transmitted Infections Treatment Guidelines, 2021

Morbidity and Mortality Weekly Report

Recommendations and Reports / Vol. 70 / No. 4

July 23, 2021

Sexually Transmitted Infections Treatment

Guidelines, 2021

U.S. Department of Health and Human Services

Centers for Disease Control and Prevention

Recommendations and Reports

CONTENTS

Introduction.............................................................................................................1

Methods.....................................................................................................................1

Clinical Prevention Guidance.............................................................................2

STI Detection Among Special Populations................................................ 11

HIV Infection.......................................................................................................... 24

Diseases Characterized by Genital, Anal, or Perianal Ulcers................ 27

Syphilis.................................................................................................................... 39

Management of Persons Who Have a History of Penicillin Allergy... 56

Diseases Characterized by Urethritis and Cervicitis................................ 60

Chlamydial Infections........................................................................................ 65

Gonococcal Infections....................................................................................... 71

Mycoplasma genitalium..................................................................................... 80

Diseases Characterized by Vulvovaginal Itching, Burning, Irritation,

Odor, or Discharge............................................................................................ 82

Pelvic Inflammatory Disease........................................................................... 94

Epididymitis........................................................................................................... 98

Human Papillomavirus Infections...............................................................100

Viral Hepatitis......................................................................................................113

Proctitis, Proctocolitis, and Enteritis...........................................................124

Ectoparasitic Infections...................................................................................126

Sexual Assault and Abuse and STIs.............................................................128

References............................................................................................................135

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Recommendations and Reports

Sexually Transmitted Infections Treatment Guidelines, 2021

Kimberly A. Workowski, MD1,2; Laura H. Bachmann, MD1; Philip A. Chan, MD1,3; Christine M. Johnston, MD1,4; Christina A. Muzny, MD1,5;

Ina Park, MD1,6; Hilary Reno, MD1,7; Jonathan M. Zenilman, MD1,8; Gail A. Bolan, MD1

1Division of STD Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, CDC, Atlanta, Georgia; 2Emory University, Atlanta, Georgia;

3Brown University, Providence, Rhode Island; 4University of Washington, Seattle, Washington; 5University of Alabama at Birmingham, Birmingham, Alabama;

6University of California San Francisco, San Francisco, California; 7Washington University, St. Louis, Missouri; 8Johns Hopkins University, Baltimore, Maryland

Summary

These guidelines for the treatment of persons who have or are at risk for sexually transmitted infections (STIs) were updated by

CDC after consultation with professionals knowledgeable in the field of STIs who met in Atlanta, Georgia, June 11¨C14, 2019.

The information in this report updates the 2015 guidelines. These guidelines discuss 1) updated recommendations for treatment of

Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis; 2) addition of metronidazole to the recommended

treatment regimen for pelvic inflammatory disease; 3) alternative treatment options for bacterial vaginosis; 4) management of

Mycoplasma genitalium; 5) human papillomavirus vaccine recommendations and counseling messages; 6) expanded risk factors

for syphilis testing among pregnant women; 7) one-time testing for hepatitis C infection; 8) evaluation of men who have sex with

men after sexual assault; and 9) two-step testing for serologic diagnosis of genital herpes simplex virus. Physicians and other health

care providers can use these guidelines to assist in prevention and treatment of STIs.

Introduction

The term ¡°sexually transmitted infection¡± (STI) refers to

a pathogen that causes infection through sexual contact,

whereas the term ¡°sexually transmitted disease¡± (STD) refers

to a recognizable disease state that has developed from an

infection. Physicians and other health care providers have a

crucial role in preventing and treating STIs. These guidelines

are intended to assist with that effort. Although the guidelines

emphasize treatment, prevention strategies and diagnostic

recommendations also are discussed.

This report updates Sexually Transmitted Diseases Treatment

Guidelines, 2015 (1) and should be regarded as a source of

clinical guidance rather than prescriptive standards. Health care

providers should always consider the clinical circumstances of

each person in the context of local disease prevalence. These

guidelines are applicable to any patient care setting that serves

persons at risk for STIs, including family planning clinics,

HIV care clinics, correctional health care settings, private

physicians¡¯ offices, Federally Qualified Health Centers, clinics

for adolescent care, and other primary care facilities. These

guidelines are focused on treatment and counseling and do

not address other community services and interventions that

are essential to STI and HIV prevention efforts.

Corresponding preparer: Kimberly A. Workowski, MD, Division of

STD Prevention, National Center for HIV/AIDS, Viral Hepatitis,

STD, and TB Prevention, CDC. Telephone: 404-639-1898; Email:

kgw2@.

These STI treatment guidelines complement Recommendations

for Providing Quality Sexually Transmitted Diseases Clinical

Services, 2020 (2) regarding quality clinical services for STIs

in primary care and STD specialty care settings. This guidance

specifies operational determinants of quality services in various

clinical settings, describes on-site treatment and partner

services, and indicates when STI-related conditions should be

managed through consultation with or referral to a specialist.

Methods

These guidelines were developed by CDC staff who worked

with subject matter experts with expertise in STI clinical

management from other federal agencies, nongovernmental

academic and research institutions, and professional medical

organizations. CDC staff identified governmental and

nongovernmental subject matter experts on the basis of their

expertise and assisted them in developing questions to guide

individual literature reviews. CDC staff informed the subject

matter experts that they were being consulted to exchange

information and observations and to obtain their individual

input. All subject matter experts disclosed potential conflicts

of interest. STI Treatment Guidelines, 2021, Work Group

members are listed at the end of this report.

In 2018, CDC staff identified key questions about treatment

and clinical management to guide an update of the 2015

STD treatment guidelines (1). To answer these questions

and synthesize new information available since publication

of the 2015 guidelines, subject matter experts and CDC staff

US Department of Health and Human Services/Centers for Disease Control and Prevention

MMWR / July 23, 2021 / Vol. 70 / No. 4

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Recommendations and Reports

collaborated to conduct systematic literature reviews by using

an extensive MEDLINE database evidence-based approach for

each section of the 2015 guidelines (e.g., using English-language

published abstracts and peer reviewed journal articles). These

systematic reviews were focused on four principal outcomes

of STI therapy for each disease or infection: 1) treatment

of infection on the basis of microbiologic eradication;

2) alleviation of signs and symptoms; 3) prevention of sequelae;

and 4) prevention of transmission, including advantages (e.g.,

cost-effectiveness, single-dose formulations, and directly

observed therapy) and disadvantages (e.g., adverse effects)

of specific regimens. The outcome of the literature reviews

guided development of background materials, including tables

of evidence from peer-reviewed publications summarizing

the type of study (e.g., randomized controlled trial or case

series), study population and setting, treatments or other

interventions, outcome measures assessed, reported findings,

and weaknesses and biases in study design and analysis.

In June 2019, the subject matter experts presented their

assessments of the literature reviews at an in-person meeting

of governmental and nongovernmental participants. Each

key question was discussed and pertinent publications were

reviewed in terms of strengths, weaknesses, and relevance.

Participants evaluated the quality of evidence, provided their

input, and discussed findings in the context of the modified

rating system used by the U.S. Preventive Services Task Force

(USPSTF). The discussions were informal and not structured

to reach consensus. CDC staff also reviewed the publications

from other professional organizations, including the American

College of Obstetricians and Gynecologists (ACOG), USPSTF,

the American Cancer Society (ACS), the American Society

for Colposcopy and Cervical Pathology (ASCCP), and the

Advisory Committee on Immunization Practices (ACIP).

The discussion culminated in a list of participants¡¯ opinions

on all the key STI topic areas for consideration by CDC.

(More detailed descriptions of the key questions, search terms,

systematic search, evidence tables, and review process are

available at

default.htm).

CDC staff then independently reviewed the tables of evidence

prepared by the subject matter experts, individual comments

from the participants and professional organizations, and existing

guidelines from other organizations to determine whether

revisions to the 2015 STD treatment guidelines were warranted.

CDC staff ranked evidence as high, medium, and low on the

basis of each study¡¯s strengths and weaknesses according to the

USPSTF ratings (.

org/uspstf/us-preventive-services-task-force-ratings). CDC staff

then developed draft recommendations that were peer reviewed

by public health and clinical experts as defined by the Office of

2

MMWR / July 23, 2021 / Vol. 70 / No. 4

Management and Budget for influential scientific information.

A public webinar was held to provide an overview of the draft

recommendations and invite questions and comments on the

draft recommendations. The peer review comments, webinar,

questions, and responses were considered by CDC staff in

developing the final recommendations for the updated STI

treatment guidelines. Recommendations for HIV, hepatitis C,

cervical cancer screening, STI screening in pregnancy, human

papillomavirus (HPV) testing, and hepatitis A virus (HAV) and

hepatitis B virus (HBV) vaccination were developed after CDC

staff reviewed existing published recommendations. The Englishlanguage literature was searched periodically by CDC staff to

identify subsequently published articles warranting consideration.

Throughout this report, the evidence used as the basis for

specific recommendations is discussed briefly. Publication

of comprehensive, annotated discussions of such evidence

is planned in a supplemental issue of the journal Clinical

Infectious Diseases after publication of the treatment guidelines.

When more than one therapeutic regimen is recommended

and the listed regimens have similar efficacy and similar

rates of intolerance or toxicity, the recommendations are

listed alphabetically. If differences are specified, regimens are

prioritized on the basis of these differences. Recommended

regimens should be used primarily; alternative regimens can be

considered in instances of notable drug allergy or other medical

contraindications to the recommended regimens. Alternative

regimens are considered inferior to recommended regimens on

the basis of available evidence regarding the principal outcomes

and disadvantages of the regimens.

Clinical Prevention Guidance

Prevention and control of STIs are based on the following

five major strategies (3):

1. Accurate risk assessment and education and counseling

of persons at risk regarding ways to avoid STIs through

changes in sexual behaviors and use of recommended

prevention services

2. Pre-exposure vaccination for vaccine-preventable STIs

3. Identification of persons with an asymptomatic

infection and persons with symptoms associated with

an STI

4. Effective diagnosis, treatment, counseling, and followup of persons who are infected with an STI

5. Evaluation, treatment, and counseling of sex partners

of persons who are infected with an STI

US Department of Health and Human Services/Centers for Disease Control and Prevention

Recommendations and Reports

STI and HIV Infection Risk Assessment

Primary prevention of STIs includes assessment of behavioral

risk (i.e., assessing the sexual behaviors that can place persons

at risk for infection) and biologic risk (i.e., testing for risk

markers for STI and HIV acquisition or transmission). As part

of the clinical encounter, health care providers should routinely

obtain sexual histories from their patients and address risk

reduction as indicated in this report. Guidance for obtaining

a sexual history is available at the Division of STD Prevention

resource page (.

htm) and in the curriculum provided by the National Network

of STD Clinical Prevention Training Centers (.

). Effective interviewing and counseling skills,

characterized by respect, compassion, and a nonjudgmental

attitude toward all patients, are essential to obtaining a

thorough sexual history and delivering effective prevention

messages. Effective techniques for facilitating rapport with

patients include using open-ended questions (e.g., ¡°Tell me

about any new sex partners you¡¯ve had since your last visit¡± and

¡°What has your experience with using condoms been like?¡±);

understandable, nonjudgmental language (e.g., ¡°What gender

are your sex partners?¡±and ¡°Have you ever had a sore or scab

on your penis?¡±); and normalizing language (e.g., ¡°Some of my

patients have difficulty using a condom with every sex act. How

is it for you?¡±). The ¡°Five P¡¯s¡± approach to obtaining a sexual

history is one strategy for eliciting information about the key

areas of interest (Box 1). In addition, health care professionals

can consider assessing sexual history by asking patients such

questions as, ¡°Do you have any questions or concerns about

your sexual health?¡± Additional information about gaining

cultural competency when working with certain populations

(e.g., gay, bisexual, or other men who have sex with men

[MSM]; women who have sex with women [WSW] or with

women and men [WSWM]; or transgender men and women

or adolescents) is available in sections of these guidelines related

to these populations.

In addition to obtaining a behavioral risk assessment, a

comprehensive STI and HIV risk assessment should include

STI screening as recommended in these guidelines because

STIs are biologic markers of risk, particularly for HIV

acquisition and transmission among certain MSM. In most

clinical settings, STI screening is an essential and underused

component of an STI and HIV risk assessment. Persons

seeking treatment or evaluation for a particular STI should be

screened for HIV and other STIs as indicated by community

prevalence and individual risk factors (see Chlamydial

Infections; Gonococcal Infections; Syphilis). Persons should

be informed about all the tests for STIs they are receiving and

notified about tests for common STIs (e.g., genital herpes,

BOX 1. The Five P¡¯s approach for health care providers obtaining sexual histories: partners, practices, protection from sexually

transmitted infections, past history of sexually transmitted infections, and pregnancy intention

1. Partners

? ¡°Are you currently having sex of any kind?¡±

? ¡°What is the gender(s) of your partner(s)?¡±

2. Practices

? ¡°To understand any risks for sexually transmitted

infections (STIs), I need to ask more specific questions

about the kind of sex you have had recently.¡±

? ¡°What kind of sexual contact do you have or have you had?¡±

?? ¡°Do you have vaginal sex, meaning ¡®penis in vagina¡¯ sex?¡±

?? ¡°Do you have anal sex, meaning ¡®penis in rectum/anus¡¯

sex?¡±

?? ¡°Do you have oral sex, meaning ¡®mouth on penis/vagina¡¯?¡±

3. Protection from STIs

? ¡°Do you and your partner(s) discuss prevention of STIs

and human immunodeficiency virus (HIV)?¡±

? ¡°Do you and your partner(s) discuss getting tested?¡±

? For condoms:

?? ¡°What protection methods do you use? In what

situations do you use condoms?¡±

4. Past history of STIs

? ¡°Have you ever been tested for STIs and HIV?¡±

? ¡°Have you ever been diagnosed with an STI in the past?¡±

? ¡°Have any of your partners had an STI?¡±

Additional questions for identifying HIV and viral

hepatitis risk:

? ¡°Have you or any of your partner(s) ever injected drugs?¡±

? ¡°Is there anything about your sexual health that you

have questions about?¡±

5. Pregnancy intention

? ¡°Do you think you would like to have (more) children

in the future?¡±

? ¡°How important is it to you to prevent pregnancy

(until then)?¡±

? ¡°Are you or your partner using contraception or

practicing any form of birth control?¡±

? ¡°Would you like to talk about ways to prevent

pregnancy?¡±

US Department of Health and Human Services/Centers for Disease Control and Prevention

MMWR / July 23, 2021 / Vol. 70 / No. 4

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