SUPPLEMENT ARTICLE
Centers for Disease Control and Prevention
Sexually Transmitted Diseases Treatment
Guidelines
Kimberly A. Workowski
Department of Medicine, Division of Infectious Diseases, Emory University, Division of STD Prevention, National Center for HIV/AIDS, Viral Hepatitis, STD,
and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia
Sexually transmitted diseases (STDs) constitute an epi-
demic of tremendous magnitude, with an estimated
19.7 million persons acquiring a new STD each year
[1]. Reported disease rates underestimate the true bur-
den of infection because the majority of STDs are
asymptomatic and because of underreporting [2]. Sexu-
ally transmitted diseases have far-reaching public health
consequences on the sexual and reproductive health of
individuals, as well as the long-term health and health-
care costs to the community [3].
The accurate identification of STDs and the effective
clinical management of STDs represent an important
combined strategy necessary to improve reproductive
health and human immunodeficiency virus (HIV) pre-
vention efforts [4]. This is especially relevant to women,
adolescents, and infants, as untreated infections fre-
quently result in severe, long-term complications, includ-
ing facilitation of HIV infection, tubal infertility, adverse
pregnancy outcomes, and cancer [5–7]. For >30 years,
the Centers for Disease Control and Prevention’s (CDC)
publication of national guidelines for management of
STDs has assisted clinicians with effective guidance on
the delivery of optimal STD care. The CDC STD treat-
ment guidelines are the most widely referenced and au-
thoritative source of information on STD treatment and
prevention strategies for clinicians who evaluate persons
with STDs or those at risk for STDs.
The 2015 guidelines for the treatment of STDs
were developed in consultation with an independent
Correspondence: Kimberly A. Workowski, MD, FACP, FIDSA, CDC/OID/NCHHSTP/
DSTDP/PDQIB, 1600 Clifton Rd, NE, Mailstop MS E-27, Atlanta, GA 30329-4027
(kgw2@cdc.gov).
Clinical Infectious Diseases® 2015;61(S8):S759–62
© Crown copyright 2015.
DOI: 10.1093/cid/civ771
Downloaded from http://cid.oxfordjournals.org/ at University of Nebraska-Lincoln Libraries on November 30, 2015
workgroup selected on the basis of their expertise in
the clinical management of STDs [8]. A systematic re-
view was performed using a Medline database evidence-
based approach focusing on peer-reviewed journal articles
and abstracts that became available after the publication
of the 2010 STD treatment guidelines. The outcome of
this literature review informed development of tables of
evidence that summarized the type of study (eg, rando-
mized controlled trial or case series), study population
and setting, treatment or other interventions, outcome
measures assessed, reported findings, and weaknesses
and biases in study design and analysis (available at
www.cdc.gov/std/tg2015/evidence.htm). This report
contains 10 background articles that contain more com-
prehensive discussions of the evidence used as the basis
for specific recommendations contained in the 2015
STD treatment guidelines. The specific background
manuscripts in this supplement include comprehensive
discussion regarding the prevention, evaluation, and
management of various sexually transmitted infections
(STIs) and syndromes that have important implications
for clinical practice.
Nongonococcal urethritis (NGU) is a common syn-
drome encountered in clinical practice and is associated
with numerous etiologic agents, including Chlamydia
trachomatis, Mycoplasma genitalium, Trichomonas vag-
inalis, herpes simplex virus, and adenovirus [9–11].
Studies on the role of Ureaplasma have been inconsis-
tent [12, 13], whereas uncultured or fastidious organ-
isms found in bacterial vaginosis have been associated
with urethritis [14]. The spectrum of pathogens may
differ between heterosexual men and men who have
sex with men, as some studies suggest that sexual pref-
erence and associated sexual practices may have clinical
relevance [15, 16]. However, in a significant proportion
CDC STD Treatment Guidelines • CID 2015:61 (Suppl 8) • S759
of instances, no pathogen can be identified. Current research is
investigating male genitourinary microbiomes and the role of
complex microbial communities related to urethritis [17]. The
urethral Gram stain has been utilized as the point-of-care test to
diagnose urethritis in many healthcare settings. However, based
on several studies (dependent on the sampling technique), a
threshold of ≥2 white blood cells per high-power field should
be considered to diagnose NGU in high-risk settings [18, 19]. Due
to the various organisms associated with NGU and the lack of
diagnostic tools for some organisms, treatment challenges re-
main, especially in men with recurrent urethritis.
Acute epididymitis is a clinical syndrome consisting of pain,
swelling, and inflammation of the epididymis that lasts <6
weeks. Sexually transmitted acute epididymitis usually is accom-
panied by urethritis, which frequently is asymptomatic. Among
sexually active men aged <35 years, acute epididymitis is most
frequently caused by C. trachomatis or N. gonorrhoeae [20].
Acute epididymitis caused by sexually transmitted enteric or-
ganisms (eg, Escherichia coli) also occurs among men who are
the insertive partner during anal intercourse. All suspected
cases of acute epididymitis should be tested for C. trachomatis
and for N. gonorrhoeae by nucleic acid amplification tests
(NAATs). Urine bacterial culture might have a higher yield in
men with sexually transmitted enteric infections and in older
men with acute epididymitis caused by genitourinary bacteriu-
ria. Selection of presumptive therapy is based on risk for chla-
mydia and gonorrhea and/or enteric organisms.
Chlamydia trachomatis infection is the most frequently re-
ported bacterial STI in the United States [2]. Asymptomatic in-
fection is common, and providers rely on screening tests for
diagnosis. Annual screening of all sexually active women aged
<25 years is recommended, as is screening of older women at
increased risk for infection (eg, those who have a new sex part-
ner, >1 sex partner, a sex partner with concurrent partners, or a
sex partner who has an STI) [21]. Reproductive health benefits
of screening demonstrate reduced rates of pelvic inflammatory
disease (PID) [22, 23]. There is insufficient evidence to recom-
mend routine screening for C. trachomatis in sexually active
young men, based on feasibility, efficacy, and cost-effectiveness;
however, screening should be considered in high-prevalence
areas, such as adolescent clinics, correctional facilities, and
STD clinics [24]. Either azithromycin or doxycycline is recom-
mended for chlamydial infection; however, recent retrospective
studies have raised concerns about the efficacy of azithromycin
for rectal C. trachomatis infection [25, 26].
Neisseria gonorrhoeae has progressively developed resistance
to each of the antimicrobials previously recommended for treat-
ment, and current antimicrobial options are severely limited.
Dual treatment has been recommended for gonorrhea treat-
ment to improve treatment efficacy and potentially slow the
emergence and spread of resistance to cephalosporins. Dual
S760 • CID 2015:61 (Suppl 8) • Workowski
treatment with ceftriaxone 250 mg intramuscularly and azithro-
mycin 1 g orally is recommended for the treatment of uncom-
plicated gonorrhea of the urethra, cervix, rectum, or pharynx.
Two new dual treatment regimens (gemifloxacin 320 mg orally
as a single dose and azithromycin 2 g orally as a single dose, or
gentamicin 240 mg intramuscularly as a single dose and azi-
thromycin 2 g orally as a single dose) may be considered as al-
ternative treatment options; however, gastrointestinal adverse
events may limit their use [27]. Due the high prevalence of tet-
racycline resistance in the United States, doxycycline is no lon-
ger recommended as a second antimicrobial in either the
recommended or alternative dual treatment regimen [2].
Novel antimicrobials or new combinations of antimicrobials
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for the treatment of gonorrhea are urgently needed.
Mycoplasma genitalium is associated with an increased risk
of NGU among men [28] and a 2- to 2.5-fold increase in the
risk of cervicitis, PID, infertility, and preterm delivery in
women [29]. There has been an increasing awareness of the sig-
nificant challenges associated with the detection and treatment
of this pathogen. Several randomized trials have demonstrated
poor efficacy of doxycycline and declining efficacy of single-
dose azithromycin therapy [10, 11, 30]. The most effective re-
maining therapeutic is moxifloxacin, but treatment failures
and resistance are emerging [31, 32].
Rates of primary and secondary syphilis have increased sig-
nificantly in the last several years and represent the highest re-
corded rates since 1995 [2]. Reinfection rates, particularly in
men who have sex with men, are high, and screening strategies
for repeat syphilis infection and HIV acquisition are warranted
[33–35]. Invasion of the cerebrospinal fluid (CSF) by Trepone-
ma pallidum accompanied by laboratory abnormalities is com-
mon among adults who have primary or secondary syphilis
[36]. However, unless clinical signs or symptoms of neurologic
or ophthalmic involvement are present, routine CSF analysis is
not recommended for persons who have primary or secondary
syphilis. Penicillin G remains the antimicrobial of choice re-
gardless of stage of infection. There are no convincing data to
support enhanced or prolonged therapy in treating syphilis in
persons with HIV infection [37–39]. Serologic response to treat-
ment appears to be associated with several factors, including the
stage of syphilis (earlier stages are more likely to decline 4-fold)
and initial nontreponemal antibody titers (lower titers are less
likely to decline 4-fold) [40].
Trichomonas vaginalis is the most prevalent nonviral STI in
the United States [1]. Screening might be considered for persons
receiving care in high-prevalence settings and for asymptomatic
persons at high risk for infection; however, data are lacking on
whether screening and treatment for asymptomatic infection re-
duces adverse health events or community burden of infection
[8]. Routine screening of asymptomatic women with HIV infec-
tion for T. vaginalis is recommended because of the adverse
events associated with asymptomatic trichomoniasis and HIV
infection [41, 42]. Diagnostic testing for T. vaginalis is recom-
mended in women seeking care for vaginal discharge. NAATs
are now available for detection of T. vaginalis, and these assays
can detect a prevalence 3- to 5-fold higher than using wet
mount for vaginal infections [43, 44]. The nitroimidazoles are
the only class of antimicrobials known to be effective against
T. vaginalis infections. Because there is a high rate of reinfection
among women treated for trichomoniasis, retesting is recom-
mended within 3 months following treatment [45]. Persistent
infection caused by antimicrobial-resistant T. vaginalis or
other causes should be distinguished from the possibility of re-
infection from an untreated sex partner. Persistent infection
may be due to antimicrobial resistance, which can occur in
4%–10% of cases of vaginal trichomoniasis [46, 47].
Most sexually active persons become infected with human
papillomavirus (HPV) at least once in their lifetime [1, 48]. Pre-
exposure vaccination is one of the most effective methods for
preventing transmission of HPV. The Advisory Committee on
Immunization Practices has specific recommendations for rou-
tine HPV vaccination [49]. Appropriate infection control prac-
tices, per the National Institute of Occupational Safety and
Health, is recommended to prevent possible transmission to
healthcare workers who treat anogenital warts, oral warts, and
anogenital intraepithelial neoplasias with laser or electrosurgical
procedures (http://www.cdc.gov/niosh/docs/hazardcontrol/
hc11.html). Podophyllin resin is no longer a recommended reg-
imen as there are safer regimens available, and severe systemic
toxicity, including death and fetal loss, has been reported when
podophyllin resin was applied longer than recommended or ap-
plied to friable tissue [50, 51].
Identification or prevention of STIs is important in the evalu-
ation of survivors of sexual assault. Trichomoniasis, gonorrhea,
and chlamydia are the most frequently diagnosed infections in
females who have been sexually assaulted [52, 53]. The decision
to obtain genital or other specimens for STD diagnosis should be
made on an individual basis; however, compliance with follow-
up visits is poor after sexual assault, and routine presumptive
treatment afterward is recommended (gonorrhea, chlamydia,
and trichomonas). Postexposure hepatitis B vaccination, if the
hepatitis status of the assailant is unknown and the survivor
has not been previously vaccinated [54], and HPV vaccination
are also recommended for survivors [49].
The manuscripts in this supplement provide important in-
formation that enhances the guidance provided in the CDC
STD treatment guidelines. The guidance provided continues
to evolve, reflecting advances in basic and clinical research,
emerging antimicrobial resistance, and changing sexual and
healthcare behaviors. Utilization of new, more effective treat-
ment regimens, highly sensitive tests for screening for asymp-
tomatic infection, improvements in counseling of patients and
their sexual partners, and new vaccines for sexually transmitted
pathogens are crucial to achieve the broader public health goals
of improving sexual and reproductive health.
Notes
Disclaimer. The findings and conclusions in this report are those of the
authors and do not necessarily represent the views of the Centers for Disease
Control and Prevention (CDC).
Supplement sponsorship. This article appears as part of the supplement
“Evidence Papers for the CDC Sexually Transmitted Diseases Treatment
Guidelines,” sponsored by the Centers for Disease Control and Prevention.
Potential conflict of interest. Author certifies no potential conflicts of
interest.
The author has submitted the ICMJE Form for Disclosure of Potential
Conflicts of Interest. Conflicts that the editors consider relevant to the con-
Downloaded from http://cid.oxfordjournals.org/ at University of Nebraska-Lincoln Libraries on November 30, 2015
tent of the manuscript have been disclosed.
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