Clinical Infectious Diseases
SUPPLEMENT ARTICLE
Centers for Disease Control and Prevention’s Sexually
Transmitted Diseases Infection Guidelines
Kimberly A. Workowski1,2 and Laura H. Bachmann1
1
Division of STD Prevention, National Center for HIV, Viral Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA; and 2Department of Medicine,
Emory University, Atlanta, Georgia, USA
Sexually transmitted infections (STIs) constitute an epidemic
of tremendous magnitude, with an estimated 27 million per-
sons acquiring a new STI in 2018 at a cost of $16 billion [1,
2]. Reported disease rates underestimate the true burden of
infection because the majority of STIs are asymptomatic and
underreported [3]. STIs have far-reaching public health conse-
quences on the sexual and reproductive health of individuals, as
well as long-term healthcare costs to the community [2]. Due
to the dramatic increase in reportable STI rates with resultant
reproductive health consequences, an STI National Strategic
Plan (https://www.hhs.gov/sites/default/files/STI-National-
Strategic-Plan-2021-2025.pdf) was developed with actionable
goals, objectives, and strategies for prevention that focus on 4
of the STIs with the highest morbidity rates (chlamydia, gon-
orrhea, syphilis, and human papillomavirus), though most of
the components of the plan are applicable to other STIs (herpes
simplex virus, trichomoniasis, Mycoplasma genitalium).
The accurate identification of STIs and their effective clinical
management represent an important combined strategy nec-
essary to improve reproductive and sexual health and human
immunodeficiency virus (HIV) prevention efforts. Untreated
infections may result in severe, long-term complications, in-
cluding facilitation of HIV infection, tubal infertility, chronic
pelvic pain, adverse pregnancy outcomes, and cancer. For the
past 40 years, Centers for Disease Control and Prevention’s
(CDC’s) publication of comprehensive national guidelines
for STI management has assisted clinicians with recom-
mendations on the delivery of optimal STI care. The CDC STI
Treatment Guidelines are the most widely referenced and au-
thoritative source of information on STI treatment and preven-
tion strategies for clinicians who evaluate persons with STIs or
those at risk for STIs [4]. The Recommendations for Providing
Quality Sexually Transmitted Diseases Clinical Services 2020
document can complement the STI treatment guidelines by
Correspondence: Kimberly A. Workowski, Centers for Disease Control and Prevention, 1600
Clifton Road NE, MS 12-2, Atlanta, GA 30329 (kgw2@cdc.gov).
Clinical Infectious Diseases®  2022;74(S2):S89–94
Published by Oxford University Press for the Infectious Diseases Society of America 2022. This
work is written by (a) US Government employee(s) and is in the public domain in the US.
https://doi.org/10.1093/cid/ciab1055
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providing recommendations for the implementation of quality
STI services in primary and specialized care clinical settings
[5].
The 2021 STI Treatment Guidelines were developed by CDC
staff who worked with subject matter experts in STI clinical
management from other federal agencies, nongovernmental
academic and research institutions, and professional medical
organizations. CDC staff assisted governmental and nongov-
ernmental subject matter experts in developing questions to
guide individual literature reviews. An evidence-based system-
atic review was performed focusing on peer-reviewed journal
articles and abstracts that were available since publication of the
previous treatment guidelines, published in 2015. Evidence ta-
bles were developed from systematic reviews that summarized
the study type, population, and setting; treatment regimens or
other interventions; outcome measures; and potential limita-
tions to the reported findings. This report includes 10 back-
ground papers that describe updated guidance on STI diagnosis
and management that forms the basis for the new recommenda-
tions in the 2021 CDC STI Treatment Guidelines. Current ad-
vances and controversies described in this supplement include
discussion regarding STI prevention, evaluation, and manage-
ment; STI-related syndromes; and populations that have impor-
tant implications for clinical practice.
NEISSERIA GONORRHOEAE
In the United States, 616 392 new Neisseria gonorrhoeae infec-
tions occurred in 2019, accounting for the second most common
notifiable condition for that year [3]. Annual screening for
N. gonorrhoeae infection is recommended for all sexually ac-
tive women aged <25 years and for older women at increased
risk for infection (eg, those aged ≥25 years who have a new sex
partner, more than 1 sex partner, a sex partner with concur-
rent partners, or a sex partner who has an STI) [6]. Preventive
screening for men who have sex with men (MSM) is recom-
mended at anatomic sites of exposure at least annually and
more frequently, every 3–6 months, if risk behaviors persist or
if they or their sex partners have multiple partners [4]. Effective
treatment can prevent complications and transmission, but N.
Sexually Transmitted Infections • CID 2022:74 (Suppl 2) • S89
gonorrhoeae’s ability to develop antimicrobial resistance influ-
ences treatment recommendations and complicates control [7].
Important factors that were considered in the development of
optimal treatment recommendations included trends in gon-
ococcal antimicrobial susceptibility (azithromycin, cephalo-
sporins), influence of antimicrobials on the microbiome and
other pathogens, and variability in antimicrobial pharmacoki-
netic and pharmacodynamic characteristics [8]. Ceftriaxone
500 mg intramuscularly (average-weight adult) achieves suffi-
ciently high serum levels for an adequate duration to eradicate
efficacy for urogenital C. trachomatis infection among women
[13], concern exists regarding effectiveness of azithromycin for
concomitant rectal C. trachomatis infection, which can occur
commonly among women and cannot be predicted by reported
sexual activity [14].
SYPHILIS
Syphilis continues to be an important concern due to ongoing
epidemics occurring among MSM and heterosexuals (related to

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substance misuse) [3, 15, 16]. In 2019, 129 813 cases of all stages
infection, even with differences in pharmacokinetic variability.
of syphilis were reported, including 38 992 cases of primary and
Due to the frequency of gonococcal pharyngeal infection and
secondary syphilis, resulting in a 74% increase in rates since
the complexity of antimicrobial pharmacokinetics, a test of cure
2015 [3]. The US Preventive Services Task Force recommends
is recommended for persons with pharyngeal gonorrhea to en-
screening for syphilis in persons who are at increased risk for
sure eradication and detect treatment failure. Ongoing global
infection (MSM, persons living with HIV, persons with a his-
gonococcal surveillance of antimicrobial resistance patterns
tory of incarceration or commercial sex work, persons living
and prompt recognition of potential treatment failure are essen-
in areas of increased syphilis prevalence, and males aged <29
tial components to prevention and control efforts.
years) [17]. Long-acting preparations of penicillin remain the
treatment of choice for all stages of syphilis. Previous studies
CHLAMYDIA TRACHOMATIS examining extended use of antimicrobials for early syphilis
have not demonstrated differences in long-term clinical or se-
Chlamydia trachomatis infection is the most common bac-
rologic outcomes [18-20]. An ongoing randomized clinical trial
terial STI in the United States, with 1  808  703 reported cases
(NCT03637660) is examining the serologic and clinical re-
in 2019 [3]. Reported rates of chlamydial infections have in-
sponse to an extended penicillin regimen in persons with early
creased over the past decade, reflecting expansion of chla-
syphilis regardless of HIV status. Alternatives to penicillin in
mydial screening with sensitive nucleic acid amplification tests,
treating primary and secondary syphilis in nonpregnant per-
improvements in information systems used for reporting, and
sons are limited, especially in persons living with HIV. Central
quite likely increased transmission. Multiple sequelae can re-
nervous system involvement can occur during any stage of
sult from C. trachomatis infection among women, the most
syphilis, and cerebrospinal fluid (CSF) laboratory abnormal-
serious of which include pelvic inflammatory disease, ectopic
ities are common among persons with early syphilis, even in the
pregnancy, and infertility. Annual chlamydial screening is re-
absence of clinical neurologic findings. No evidence exists to
commended for all sexually active women aged <25 years and
support variation from recommended management for syphilis
among older women with risk factors (eg, those who have a new
at any stage for persons without clinical neurologic findings, ex-
sex partner or multiple sex partners), as most infections are
cept during evaluation of tertiary syphilis. Data from 2 studies
asymptomatic [6]. The primary focus of chlamydia screening
indicate that among immunocompetent persons and persons
is to detect and treat chlamydia, prevent complications, and
living with HIV who are on effective, antiretroviral therapy,
provide treatment for partners. Targeted chlamydia screening
normalization of the serum rapid plasma reagin titer predicts
for heterosexual men should be considered when prevalence
normalization of abnormal CSF parameters after neurosyphilis
is high, resources permit, and such screening does not hinder
treatment [21, 22]. Therefore, repeated CSF examinations are
chlamydia screening efforts for women. Screening for ure-
unnecessary for persons not living with HIV infection or per-
thral and rectal C. trachomatis infection should be performed
sons living with HIV who are on antivirals and who exhibit se-
at least annually among men who report sexual activity with
rologic and clinical response to syphilis after treatment.
men and more frequently, every 3–6 months, if risk behaviors
persist or if they or their sex partners have multiple partners.
GENITAL HERPES
Optimal chlamydial treatment can prevent adverse reproduc-
tive health complications and continued sexual transmission. Genital herpes is a chronic viral infection with most recurrent
Available evidence supports that doxycycline is efficacious for genital herpes caused by herpes simplex virus type 2 (HSV-2)
C. trachomatis infections of urogenital, rectal, and oropharyn- [23]. However, an increasing proportion of anogenital her-
geal sites [4, 9, 10]. Two recent randomized clinical trials dem- petic infections have been attributed to HSV type 1, which is
onstrated superiority in treatment efficacy in men treated for especially prominent among young women and MSM [24, 25].
asymptomatic rectal infection with doxycycline compared with Clinical diagnosis of genital herpes can be difficult because le-
azithromycin [11, 12]. Although azithromycin maintains high sions are often absent during evaluation. If genital lesions are

S90 • CID 2022:74 (Suppl 2) • Workowski and Bachmann

present, clinical diagnosis of genital herpes should be con-
firmed by type-specific virologic testing from the lesion by
nucleic acid amplification test or culture. Type-specific HSV-2
serologic tests can be used to aid in the diagnosis of herpes sim-
plex infection in the following scenarios: recurrent or atypical
genital symptoms or lesions with a negative herpes simplex nu-
cleic acid amplification test or culture, a clinical diagnosis of
genital herpes without laboratory confirmation, and a partner
with genital herpes. However, there are limitations to herpes
type-specific serologic testing, as the available HSV-2 sero-
logic tests lack specificity. The 2021 guidelines provide insights
into an optimal strategy for using serologic assays to diagnose
HSV. The test characteristics are highly dependent on the index
value, with index values of 1.1–2.9 having only 39.8% spec-
ificity, and index values of ≥3.0 having 78.6% specificity [26].
Serologic diagnosis of HSV-2 should ideally be performed only
if patients and providers are aware of the assay limitations, and
low positive results (index value <3.0) should be confirmed
with a second assay using a different glycoprotein G2 antigen.
Because of the poor specificity of commercially available type-
specific enzyme immunoassays, particularly with low index
values (<3.0), a confirmatory test (Biokit or Western blot) with
a second method should be performed before test interpreta-
tion. Use of confirmatory testing with the Biokit or the Western
blot assays have been reported to improve accuracy of HSV-2
serologic testing [27, 28]. Systemic antiviral drugs can partially
control the signs and symptoms of genital herpes when used to
treat first clinical and recurrent episodes or when used as daily
suppressive therapy. However, these drugs neither eradicate la-
tent virus nor affect the frequency or severity of recurrences
after the drug is discontinued. Several antiviral medications
provide clinical benefit for genital herpes, including acyclovir,
valacyclovir, and famciclovir. If lesions persist or recur in a pa-
tient receiving antiviral treatment, acyclovir resistance should
be suspected and a viral culture should be obtained for pheno-
typic sensitivity testing. Foscarnet and cidofovir (intravenous or
topical) are options for acyclovir-resistant herpes; additionally,
a clinical trial is evaluating a novel helicase-primase inhibitor in
immunocompromised persons (NCT03073967).
BACTERIAL VAGINOSIS
Bacterial vaginosis (BV) is a vaginal dysbiosis that results from
replacement of normal hydrogen peroxide and lactic acid–pro-
ducing Lactobacillus species in the vagina with high concentra-
tions of anaerobic bacteria (eg, Gardnerella vaginalis, Prevotella
species, Mobiluncus species, Atopobium vaginae, BV-associated
bacteria). Bacterial vaginosis is associated with adverse birth
outcomes, gynecologic sequelae, and increased risk of HIV and
STI acquisition [29-31]. Established benefits of therapy among
nonpregnant women are to relieve vaginal symptoms and signs
of infection. Other potential benefits include reduction in the
risk for acquiring HIV and STIs. There are no data that di-
rectly compare the efficacy of oral and topical regimens for
treatment. Several additional alternative single-dose regimens
are now available, including seconidazole, metronidazole 1.3%
vaginal gel, and Clindesse 2% vaginal cream. There are limited
data regarding optimal management strategies for women with
persistent or recurrent BV. A polymicrobial biofilm on vaginal
epithelial cells likely influences poor treatment outcomes [32].
A phase 2 study is currently underway to determine the efficacy
of a biofilm-disrupting regimen in women with recurrent bac-
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terial vaginosis administered after treatment with oral metroni-
dazole (NCT03930745).
TRICHOMONIASIS
Trichomoniasis is the most prevalent nonviral STI, with an esti-
mated 2.1 million prevalent and 3.5 million incident infections
in the United States in 2018 [1].The majority of persons who have
trichomoniasis either have minimal or no genital symptoms,
and untreated infections can last months to years. Trichomonas
vaginalis can cause reproductive morbidity, including risk of
preterm birth, premature rupture of membranes, infants who
are small for gestational age, and increased risk of HIV acquisi-
tion [33, 34]. Diagnostic testing for T. vaginalis should be per-
formed for women seeking care for vaginal discharge. Annual
screening might be considered for persons in high-prevalence
settings (eg, sexually transmitted disease clinics) and women
at high risk for infection (eg, multiple sex partners, transac-
tional sex, drug misuse, or a history of STIs or incarceration).
However, it is not known whether screening for trichomoni-
asis in high-prevalence settings influences subsequent adverse
outcomes. Routine annual screening of asymptomatic women
living with HIV is recommended. The nitroimidazoles are the
only class of medications with demonstrated efficacy against T.
vaginalis infections. New trichomonas treatment recommenda-
tions for women are based on a randomized, controlled clin-
ical trial that demonstrated that multidose metronidazole was
more effective in trichomonas eradication at 1 month compared
with single-dose therapy [35]. There are no published random-
ized trials comparing single or multidose regimens among
men. Nitroimidazole resistance can occur in 4%–10% of cases
of vaginal trichomoniasis [36, 37]. In persons who experience
persistent infection not due to reinfection, resistance testing
can be performed (https://www.cdc.gov/laboratory/specimen-
submission/detail.html?CDCTestCode=CDC-10239).
VULVOVAGINAL CANDIDIASIS
Vulvovaginal candidiasis (VVC) is a common etiology of vag-
inal discharge and affects the majority of women at least once
during their life [38]. The diagnosis can be made in a woman
who has signs and symptoms of vaginitis when either a wet prep-
aration (saline, 10% potassium hydroxide) of vaginal discharge
Sexually Transmitted Infections • CID 2022:74 (Suppl 2) • S91
demonstrates budding yeasts, hyphae, or pseudohyphae or when
a culture or other test yields a positive result for a yeast species.
VVC can be classified as either uncomplicated or complicated
depending on such factors as severity of infection, yeast species,
and underlying immune compromising conditions. Short-course
topical formulations or single-dose azole effectively treat uncom-
plicated VVC. Only topical azole therapies are recommended for
use among pregnant women, as additional evidence of an associ-
ation between oral azole and spontaneous abortion or congenital
anomalies has been shown since the 2015 guidelines [39, 40]. A
recently approved novel oral antifungal, ibrexafungerp, which is
a semisynthetic triterpenoid antifungal glucan synthase inhib-
itor, has demonstrated lower recurrence rates compared with
fluconazole at 120 days in one study [41], and several other com-
pounds are under investigation for VVC [42, 43].
ENTERIC PATHOGENS
Sexual transmission of enteric pathogens should be considered
when evaluating MSM for enteritis or protocolitis. Sexual
transmission of enteric pathogens through direct (rimming)
or indirect (fisting or fingering) oral–anal contact during sex
may facilitate person-to-person transmission of enteric patho-
gens. There have been sporadic outbreaks of enteric patho-
gens among MSM, including Shigella sonnei, Shigella flexneri,
Campylobacter jejuni, Campylobacter coli, and Escherichia coli
[44-47]. Specific behaviors associated with sexually transmitted
enteric infections among MSM involve recreational drug use
(ie, using crystal methamphetamine, gamma-butyrolactone,
or mephedrone before or during sex), condomless sex, group
sex, fisting, and use of sex toys [48, 49]. Antimicrobial-resistant
pathogens, particularly Shigella and Campylobacter, among
MSM sexual networks have been described [46, 50].
HUMAN PAPILLOMAVIRUS
Persistent oncogenic human papillomavirus (HPV) infection is
the strongest risk factor for development of HPV-attributable
precancers and cancers [51]. Anal cancer incidence is higher
among certain populations including MSM living with HIV,
men or women living with HIV, and MSM not living with HIV
infection [52, 53]. The risk of anal cancer should be discussed
with patients in these populations to guide management. Anal
cancer is often preceded by an anal high-grade intraepithelial
lesion (HSIL); however, more evidence is needed on the nat-
ural history of the HSIL to identify predictors of progres-
sion, the optimal screening methods, and safety and response
to treatments. A digital anogenital exam to detect early anal
cancer should be performed in persons living with HIV and
MSM not living with HIV with a history of receptive anal in-
tercourse, per existing guidance [54, 55]. However, there is
limited data on the optimal age or intervals for a digital an-
orectal exam. Some clinical centers perform anal cytology to
S92 • CID 2022:74 (Suppl 2) • Workowski and Bachmann
screen for anal cancer among populations at high risk followed
by high-resolution anoscopy for those with abnormal cytologic
results. However, there are limited outcome data that show that
use of high-resolution anoscopy affects anal cancer incidence
or morbidity. A clinical trial investigating whether treatment
of HSIL was effective in reducing the incidence of anal cancer
among persons living with HIV that was recently halted indi-
cated that removal of anal high-grade squamous intraepithelial
lesions reduced the risk of progression to anal cancer (https://
anchorstudy.org/sites/default/files/newsletters/anchor_press_
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release_07oct2021.pdf).
STI SCREENING IN CORRECTIONS
STIs are common among persons entering correctional facil-
ities [3]. The utility of STI screening and treatment services in
correctional settings has been demonstrated in jails, prisons,
and juvenile detention centers [56, 57]. STI screening should
be conducted at intake and offered in an opt-out manner in
correctional facilities for gonorrhea/chlamydia among women
aged ≤35 and men aged < 30 years, trichomonas in women
aged ≤35 (new recommendation), HIV status, and syph-
ilis based on community and institutional prevalence of early
syphilis. All persons housed in juvenile and adult correctional
facil­ities should be screened at entry for hepatitis B and C.
Vaccination for HBV should be offered if the person is suscep-
tible. Unvaccinated persons in outbreak settings who are at risk
for HAV infection or at risk for severe disease should be vac-
cinated. The high prevalence of STIs in correctional facilities
and the strong association between incarceration rates and STIs
support continued STI screening in these settings.
Healthcare providers can assist in the prevention of STIs
through education and counseling of persons at risk, screening
for asymptomatic infection, performing recommended diag-
nostic testing and treatment for persons and their sex part-
ners, and administering preexposure vaccination of persons at
risk for a vaccine-preventable STI. The publication of national
guidelines for management of STIs provides the clinical guid-
ance necessary to deliver optimal care in both the public and
private sectors. STI treatment recommendations will continue
to evolve, reflecting advances in basic and clinical research,
emerging antimicrobial resistance, and changing sexual and
healthcare behaviors. Use of new, more effective treatment re-
gimens, highly sensitive tests for screening for asymptomatic
infection, improvements in counseling of patients and their
sexual partners, and new vaccines for sexually transmitted
pathogens are crucial to achieving the broader public health
goals of improving sexual and reproductive health.
Notes
Disclaimer. The findings and conclusions presented here are those of
the authors and do not necessarily represent the views of the Centers for
Disease Control and Prevention.
 Supplement sponsorship. This supplement is sponsored by The Centers
for Disease Control and Prevention.
Potential conflicts of interest. L. B. reports book royalties from Springer-
Verlag. The remaining author: No reported conflicts of interest. All authors
have submitted the ICMJE Form for Disclosure of Potential Conflicts of
Interest. Conflicts that the editors consider relevant to the content of the
manuscript have been disclosed.
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