Centers for Disease Control and Prevention Sexually Transmitted Diseases Treatment Guidelines

Sexually transmitted diseases (STDs) constitute an epidemic of tremendous magnitude, with an estimated 19.7 million persons acquiring a new STD each year [1]. Reported disease rates underestimate the true burden of infection because the majority of STDs are asymptomatic and because of underreporting [2]. Sexually transmitted diseases have far-reaching public health consequences on the sexual and reproductive health of individuals, as well as the long-term health and healthcare 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) prevention efforts [4]. This is especially relevant to women, adolescents, and infants, as untreated infections frequently result in severe, long-term complications, including 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 treatment guidelines are the most widely referenced and authoritative 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 workgroup selected on the basis of their expertise in the clinical management of STDs [8]. A systematic review 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, randomized 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 comprehensive 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 syndrome encountered in clinical practice and is associated with numerous etiologic agents, including Chlamydia trachomatis, Mycoplasma genitalium, Trichomonas vaginalis, herpes simplex virus, and adenovirus [9–11]. Studies on the role of Ureaplasma have been inconsistent [12, 13], whereas uncultured or fastidious organisms 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 preference and associated sexual practices may have clinical relevance [15, 16]. However, in a significant proportion 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 remain, 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 accompanied 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 organisms (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 bacteriuria. Selection of presumptive therapy is based on risk for chlamydia and gonorrhea and/or enteric organisms.

Chlamydia trachomatis infection is the most frequently reported bacterial STI in the United States [2]. Asymptomatic infection 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 partner, >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 recommend 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 recommended 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 treatment, and current antimicrobial options are severely limited. Dual treatment has been recommended for gonorrhea treatment to improve treatment efficacy and potentially slow the emergence and spread of resistance to cephalosporins. Dual treatment with ceftriaxone 250 mg intramuscularly and azithromycin 1 g orally is recommended for the treatment of uncomplicated 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 azithromycin 2 g orally as a single dose) may be considered as alternative treatment options; however, gastrointestinal adverse events may limit their use [27]. Due the high prevalence of tetracycline resistance in the United States, doxycycline is no longer recommended as a second antimicrobial in either the recommended or alternative dual treatment regimen [2]. Novel antimicrobials or new combinations of antimicrobials 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 significant 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 remaining therapeutic is moxifloxacin, but treatment failures and resistance are emerging [31, 32].

Rates of primary and secondary syphilis have increased significantly in the last several years and represent the highest recorded 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 Treponema pallidum accompanied by laboratory abnormalities is common 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 regardless 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 treatment 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 reduces adverse health events or community burden of infection [8]. Routine screening of asymptomatic women with HIV infection 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 recommended 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 recommended within 3 months following treatment [45]. Persistent infection caused by antimicrobial-resistant T. vaginalis or other causes should be distinguished from the possibility of reinfection 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]. Preexposure vaccination is one of the most effective methods for preventing transmission of HPV. The Advisory Committee on Immunization Practices has specific recommendations for routine HPV vaccination [49]. Appropriate infection control practices, 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 regimen 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 applied to friable tissue [50, 51].

Identification or prevention of STIs is important in the evaluation 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 information 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 treatment regimens, 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 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 content of the manuscript have been disclosed.