Emergency Department Diagnosis and Treatment of Sexually Transmitted Diseases

Table of Contents

 

Sexually transmitted disease can cause severe outcomes for patients, their partners, and their unborn babies, and swift and accurate diagnosis and treatment is essential to reduce morbidity and minimize the potential public health risks.

How can you be sure you’re asking the right questions when taking a history in a patient with suspected STDs?

Syphilis can present in primary, secondary, and tertiary stages. What are the presenting signs for each, and how will diagnosis and treatment differ?

Do you need to do a pelvic exam when STD is suspected?

Which STDs increase the chances of pelvic inflammatory disease, HIV, and cancer?

Should you order clean-catch urine samples, urethral or vaginal swabs, or blood sample?

Which STDs have FDA approval for NAAT testing? Should wet mounts be used for trichomoniasis?

What are the particular risks of STDs in pregnant women, and what are optimal treatments?

When can expedited partner therapy be used?

1. Abstract
2. Case Presentations
3. Introduction
4. Critical Appraisal of the Literature
5. Etiology and Pathophysiology
   1. Chlamydia trachomatis Infection
   2. Gonorrhea
   3. Syphilis
   4. Bacterial Vaginosis
   5. Granuloma Inguinale
   6. Lymphogranuloma Venereum
   7. Mycoplasma genitalium
   8. Genital Herpes
   9. Human Papillomavirus
   10. Trichomoniasis
6. Differential Diagnosis
7. Prehospital Care
8. Emergency Department Evaluation
   1. History
   2. Physical Examination
      1. Physical Examination Findings in Chlamydia
      2. Physical Examination Findings in Gonorrhea
      3. Physical Examination Findings in Syphilis
      4. Physical Examination Findings in Bacterial Vaginosis
      5. Physical Examination Findings in Granuloma Inguinale
      6. Physical Examination Findings in Lymphogranuloma Venereum
      7. Physical Examination Findings in Genital Herpes
      8. Physical Examination Findings in Human Papillomavirus
      9. Physical Examination Findings in Trichomoniasis
9. Diagnostic Studies
   1. Chlamydia Testing
   2. Gonorrhea Testing
   3. Syphilis Testing
   4. Bacterial Vaginosis Testing
   5. Granuloma Inguinale Testing
   6. Lymphogranuloma Venereum Testing
   7. Mycoplasma genitalium Testing
   8. Genital Herpes Testing
   9. Human Papillomavirus Testing
   10. Trichomoniasis Testing
10. Treatment
    1. Chlamydia Treatment
    2. Gonorrhea Treatment
    3. Syphilis Treatment
    4. Bacterial Vaginosis Treatment
    5. Granuloma Inguinale Treatment
    6. Lymphogranuloma Venereum Treatment
    7. Mycoplasma genitalium Treatment
    8. Genital Herpes Treatment
    9. Human Papillomavirus Treatment
    10. Trichomoniasis Treatment
11. Special Populations
    1. Pregnant Women
       1. Chlamydia
       2. Gonorrhea
       3. Syphilis
       4. Bacterial Vaginosis
       5. Genital Herpes
       6. Human Papillomavirus
       7. Trichomoniasis
    2. Persons in Correctional Facilities
12. Controversies and Cutting Edge
    1. Ceftriaxone Administration Route for Treatment of Gonorrhea
    2. Strategies for Partner Therapies
       1. Chlamydia
       2. Gonorrhea
       3. Syphilis
       4. Bacterial Vaginosis
       5. Genital Herpes
       6. Human Papillomavirus
       7. Trichomoniasis
13. Disposition
14. Summary
15. Risk Management Pitfalls in Management of Sexually Transmitted Diseases in the Emergency Department
16. Time- and Cost-Effective Strategies
17. Case Conclusions
18. Clinical Pathway for Management of Sexually Transmitted Diseases in the Emergency Department
19. Tables, Figures and Appendixes
    1. Table 1. Sexually Transmitted Diseases Differential
    2. Table 2. Diagnostic Sample Options
    3. Table 3. Recommended Treatments for Sexually Transmitted Diseases
    4. Figure 1. Chlamydial Cervicitis
    5. Figure 2. Chlamydial Conjunctivitis
    6. Figure 3. Gonorrhea Penile Discharge
    7. Figure 4. Disseminated Gonorrhea
    8. Figure 5. Primary Syphilis: Chancres
    9. Figure 6. Secondary Syphilis: Rash
    10. Figure 7. Secondary Syphilis: Condylomata lata
    11. Figure 8. Tertiary Syphilis: Gummatous Lesion
    12. Figure 9. Bacterial Vaginosis Discharge
    13. Figure 10. Granuloma Inguinale Lesion
    14. Figure 11. Lymphogranuloma Venereum
    15. Figure 12. Female Herpes Lesions
    16. Figure 13. Male Herpes Lesions
    17. Figure 14. Traditional Syphilis Serologic Screening Algorithm
    18. Figure 15. Reverse Sequence Syphilis Screening
    19. Appendix 1. Physical Examination Findings for Sexually Transmitted Diseases: Eyes, Ears, Mouth/Throat/Nose, Skin, and Lymph
    20. Appendix 2. Physical Examination Findings for Sexually Transmitted Diseases: Cardiac, Pulmonary, Abdominal, Musculoskeletal, Neurological, and Psychiatric
    21. Appendix 3. Physical Examination Findings for Sexually Transmitted Diseases: Pelvic, Genital, Anal/Rectal
20. References

Abstract

Sexually transmitted diseases are a growing threat to public health, but are often underrecognized, due to the often nonspecific (or absent) signs and symptoms, the myriad diseases, and the possibility of co-infection. Emergency clinicians play a critical role in improving healthcare outcomes for both patients and their partners. Optimizing the history and physical examination, ordering appropriate testing, and prescribing antimicrobial therapies, when required, will improve outcomes for men, women, and pregnant women and their babies. This issue reviews the latest evidence in the diagnosis and treatment of sexually transmitted diseases, focusing on efficient and safe strategies to optimize outcomes.

Case Presentations

You are getting close to the end of your busy shift, but you have time to pick up 1 more low-acuity patient triaged with the chief complaint of urinary tract infection. On review of her chart, you note reassuring vital signs, with a blood pressure of 120/63 mm Hg; heart rate of 71 beats/min; respiratory rate of 18 breaths/min; oxygen saturation of 100% on room air; and temperature of 37°C (98.6°F). Nurse triage note states: “Patient presents today with 3 weeks of dysuria, urinary frequency, and lower abdominal pain despite a full course of nitrofurantoin prescribed by a local urgent care clinic, followed by a full course of ciprofloxacin prescribed by her primary care provider.” When you examine the patient, she claims mild improvement in her symptoms 2 days prior, but now has persistent dysuria again. Initial physical exam is positive only for mild suprapubic discomfort with palpation. Urinalysis is notable for negative pregnancy test, small leukocyte esterase, and negative nitrite. You wonder whether to prescribe a third antibiotic and send a urine culture, or if there is something else you should be considering . . .

Just as you are walking out of the first patient’s room, you are called urgently to the room of a 50-year-old man who is agitated, aggressive, and profoundly tachycardic. The patient had been brought in by family for a “psychiatric eval.” His family reports a history of worsening bizarre behaviors, staying up all night, and hallucinations. These symptoms have been worsening over several weeks, but they brought him to the ED tonight after his brother realized that he had not slept in 3 days. The family is unaware of any recent fevers or infectious symptoms. They are also unaware of any recent alcohol or drug use, but his brother notes that he had a “wild” youth. The family is unaware of any history of psychiatric illness. On exam, the patient appears disheveled and is fidgeting frequently. He appears to be responding to internal stimuli. He is oriented to person only and states that he is not sure why his family brought him to the ED. He is able to recall 0 of 3 objects at 5 minutes. He denies recent drug or alcohol use, and there are no track marks visible on his arms. He has an ataxic gait and diminished reflexes in his lower extremities. You decide to pursue further medical evaluation before calling psychiatry. Basic metabolic panel and CBC are unremarkable. A CT scan shows mild atrophy, but no acute findings. You decide to perform a lumbar puncture for evaluation and wonder if there are any specialized tests you should consider…

The charge nurse approaches you and asks if you are willing to stay past your shift to assist with management of a local college student who has just presented stating that she was sexually assaulted at a party 3 nights ago. On arrival, the 19-year-old otherwise healthy woman is hysterical, stating that she does not know what happened. She believes she was “drugged” by someone at the fraternity party and only remembers waking up with no clothing. She is refusing a sexual assault exam and evidence collection kit, but is asking for STD treatment. You wonder about the current recommendations for treatment and the drugs of choice . . .

Introduction

Sexually transmitted diseases (STDs), sometimes referred to as sexually transmitted infections (STIs), are common diseases involving the transmission of an organism between sex partners through vaginal intercourse, anal sex, or oral sex. STDs continue to be underrecognized by the public and by healthcare professionals and continue to lead to devastating health consequences including infertility and facilitation of HIV transmission.¹ In addition to the tremendous health impacts, the high prevalence and rising rates of STDs in the United States continue to be a significant economic burden on the healthcare system. Data suggest that there are an estimated 20 million new STD diagnoses in the United States each year, leading to a direct cost of treating STDs of $16 billion annually.²

The prevalence of STDs continues to be very high, due partly to the fact that many infected patients have minimal or no symptoms and can unwittingly pass these diseases to their partners. Emergency clinicians and primary care providers are positioned to identify these patients, to treat and counsel infected persons, and to potentially treat sex partners who are infected. Diagnosis and treatment can help prevent serious, life-threatening complications of STDs including infertility, ectopic pregnancy, spontaneous abortion, chronic pelvic pain, and chronic infections. At the same time, emergency clinicians must be aware of growing antibiotic resistance, especially in the treatment of gonorrhea. This issue of Emergency Medicine Practice presents a comprehensive review of the current evidence and best-practice guidelines of the evaluation and treatment of STDs and complements the February 2016 issue, “The HIV-Infected Adult Patient in the Emergency Department: The Changing Landscape of Disease.”

Critical Appraisal of the Literature

A literature search was performed using PubMed and the Cochrane Database of Systematic Reviews, with the search terms, sexually transmitted disease, sexually transmitted infection, bacterial vaginosis, chlamydia, genital herpes, gonorrhea, human papillomavirus, syphilis, trichomoniasis, and expedited partner therapy. The search was focused on articles published in the English language that are relevant to the emergency clinician, those published after 1990, and on articles that discussed current STD first-line treatment, management, and diagnostic evaluation. Priority was given to clinical trials, evidence-based guidelines, and high-quality reviews, which resulted in the 107 references cited. The National Guideline Clearinghouse was also accessed and identified guidelines that provide recommendations general to all STDs, including the key resource published by the United States Centers for Disease Control and Prevention (CDC), Sexually Transmitted Diseases Treatment Guidelines 2015.³ When available, recommendations in this article are evidence-based; however, most of the studies are retrospective, with the prospective studies focused primarily on treatment.

Risk Management Pitfalls in Management of Sexually Transmitted Diseases in the Emergency Department

4. “I’m unsure about giving high-dose penicillin to my patient with primary syphilis because I have heard about the signs and symptoms associated with the Jarisch-Herxheimer reaction.” Although these symptoms are unpleasant, they are self-limited, and concern about the development of the Jarisch-Herxheimer reaction should not delay treatment. Penicillin G benzathine remains the most effective treatment for syphilis and should be given to all patients without confirmed allergy. In patients with a penicillin allergy, desensitization should be considered.

8. “Why does this patient keep coming back with a UTI?”

Avoid the misdiagnosis of a UTI and perform a pelvic examination or genital examination in patients with overlapping symptoms and inconclusive urine studies. The pelvic examination and associated diagnostic studies can lead to the accurate STD diagnosis and prevent potential complications and repeat visits to the ED. A urine culture should be sent if there is any continued concern for recurrent UTI.

9. “The patient says that she does not want to take acyclovir for the new HSV-2 diagnosis because she is nursing her baby.”

The use of acyclovir is safe in lactating mothers. There is no evidence that acyclovir causes any adverse effects in breast-fed infants. The United States National Library of Medicine at the National Institutes of Health maintains the LactMed database to assist providers with information regarding medications to treat STDs during breastfeeding.

References

Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study, such as the type of study and the number of patients in the study is included in bold type following the references, where available. In addition, the most informative references cited in this paper, as determined by the author, are highlighted.

1. Satterwhite CL, Torrone E, Meites E, et al. Sexually transmitted infections among US women and men: prevalence and incidence estimates, 2008. Sex Transm Dis. 2013;40(3):187-193. (Review)
2. Owusu-Edusei K, Jr., Chesson HW, Gift TL, et al. The estimated direct medical cost of selected sexually transmitted infections in the United States, 2008. Sex Transm Dis. 2013;40(3):197-201. (Review)
3. Workowski KA, Bolan GA. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64(Rr-03):1-137. (Expert guidelines/systematic review)
4. Centers for Disease Control and Prevention. Sexually transmitted disease surveillance 2017. 2017 STD Surveillance Report 2017. Accessed March 10, 2019. (CDC report)
5. Torrone E, Papp J, Weinstock H. Prevalence of Chlamydia trachomatis genital infection among persons aged 14-39 years--United States, 2007-2012. MMWR Morb Mortal Wkly Rep. 2014;63(38):834-838. (Expert guideline/systematic review)
6. Newman L, Rowley J, Vander Hoorn S, et al. Global estimates of the prevalence and incidence of four curable sexually transmitted infections in 2012 based on systematic review and global reporting. PLoS One. 2015;10(12):e0143304. (Review)
7. Fethers KA, Fairley CK, Morton A, et al. Early sexual experiences and risk factors for bacterial vaginosis. J Infect Dis. 2009;200(11):1662-1670. (Cross-sectional study; 540 patients)
8. Centers for Disease Control and Prevention. Sexually transmitted disease surveillance 2017: syphilis. 2019. Accessed March 10, 2019. (CDC guidelines)
9. Peeling RW, Hook EW 3rd. The pathogenesis of syphilis: the Great Mimicker, revisited. J Pathol. 2006;208(2):224-232. (Review)
10. Liu LL, Zheng WH, Tong ML, et al. Ischemic stroke as a primary symptom of neurosyphilis among HIV-negative emergency patients. J Neurol Sci. 2012;317(1-2):35-39. (Retrospective review; 149 patients with neurosyphilis)
11. Esber A, Vicetti Miguel RD, Cherpes TL, et al. Risk of bacterial vaginosis among women with herpes simplex virus type 2 infection: a systematic review and meta-analysis. J Infect Dis. 2015;212(1):8-17. (Meta-analysis/systematic review; 17 studies)
12. Myer L, Denny L, Telerant R, et al. Bacterial vaginosis and susceptibility to HIV infection in South African women: a nested case-control study. J Infect Dis. 2005;192(8):1372-1380. (Case control study; 5110 patients)
13. Balkus JE, Richardson BA, Rabe LK, et al. Bacterial vaginosis and the risk of Trichomonas vaginalis acquisition among HIV-1-negative women. Sex Transm Dis. 2014;41(2):123-128. (Randomized controlled trial; 2920 patients)
14. O’Farrell N. Donovanosis. Sex Transm Infect. 2002;78(6):452-457. (Review)
15. Mabey D, Peeling RW. Lymphogranuloma venereum. Sex Transm Infect. 2002;78(2):90-92. (Review)
16. Ceovic R, Gulin SJ. Lymphogranuloma venereum: diagnostic and treatment challenges. Infect Drug Resist. 2015;8:39-47. (Review)
17. Sethi S, Singh G, Samanta P, et al. Mycoplasma genitalium: an emerging sexually transmitted pathogen. Indian J Med Res. 2012;136(6):942-955. (Review)
18. Alfarraj DA, Somily AM. Isolation of Mycoplasma genitalium from endocervical swabs of infertile women. Saudi Med J. 2017;38(5):549-552. (Prospective case control study; 200 patients)
19. Bradley H, Markowitz LE, Gibson T, et al. Seroprevalence of herpes simplex virus types 1 and 2--United States, 1999-2010. J Infect Dis. 2014;209(3):325-333. (Review)
20. Bernstein DI, Bellamy AR, Hook EW 3rd, et al. Epidemiology, clinical presentation, and antibody response to primary infection with herpes simplex virus type 1 and type 2 in young women. Clin Infect Dis. 2013;56(3):344-351. (Prospective cohort study;3438 patients)
21. Centers for Disease Control and Prevention. What is HPV?  Accessed March 10, 2019. (CDC website)
22. Rathod SD, Krupp K, Klausner JD, et al. Bacterial vaginosis and risk for Trichomonas vaginalis infection: a longitudinal analysis. Sex Transm Dis. 2011;38(9):882-886. (Prospective cohort study; 853 patients)
23. Centers for Disease Control and Prevention. A guide to taking a sexual history. 2005. Accessed March 10, 2019. (CDC information sheet)
24. Choudhry S, Ramachandran VG, Das S, et al. Characterization of patients with multiple sexually transmitted infections: a hospital-based survey. Indian J Sex Transm Dis AIDS. 2010;31(2):87-91. (Retrospective; 102 patients)
25. Ward H, Rönn M. The contribution of STIs to the sexual transmission of HIV. Curr Opin HIV AIDS. 2010; 5(4):305-310. (Review)
26. Brown J, Fleming R, Aristzabel J, et al. Does pelvic exam in the emergency department add useful information? West J Emerg Med. 2011;12(2):208-212. (Prospective study; 183 patients)
27. Tomas ME, Getman D, Donskey C J, Hecker MT. Overdiagnosis of urinary tract infection and underdiagnosis of sexually transmitted infection in adult women presenting to an emergency department. J Clin Microbiol. 2015;53(8):2686-2692. (Cohort study; 264 women)
28. Geisler WM, Chow JM, Schachter J, et al. Pelvic examination findings and Chlamydia trachomatis infection in asymptomatic young women screened with a nucleic acid amplification test. Sex Transm Dis. 2007;34(6):335-338. (Retrospective study;577 patients)
29. Sherrard J, Barlow D. Gonorrhoea in men: clinical and diagnostic aspects. Genitourin Med. 1996;72(6):422-426. (Retrospective study; 1382 patients)
30. Koumans EH, Sternberg M, Bruce C, et al. The prevalence of bacterial vaginosis in the United States, 2001-2004; associations with symptoms, sexual behaviors, and reproductive health. Sex Transm Dis. 2007;34(11):864-869. (Prospective study; 3739 patients)
31. Richens J. Donovanosis (granuloma inguinale). Sex Transm Infect. 2006;82 Suppl 4:iv21-iv22. (Review)
32. Roest RW, van der Meijden WI. European guideline for the management of tropical genito-ulcerative diseases. Int J STD AIDS. 2001;12 Suppl 3:78-83. (Practice guidelines)
33. White JA. Manifestations and management of lymphogranuloma venereum. Curr Opin Infect Dis. 2009;22(1):57-66. (Review)
34. Xu F, Sternberg MR, Kottiri BJ, et al. Trends in herpes simplex virus type 1 and type 2 seroprevalence in the United States. JAMA. 2006;296(8):964-973. (Cross-sectional review)
35. Mertz GJ. Asymptomatic shedding of herpes simplex virus 1 and 2: implications for prevention of transmission. J Infect Dis. 2008;198(8):1098-1100. (Review)
36. Merin A, Pachankis JE. The psychological impact of genital herpes stigma. J Health Psychol. 2011;16(1):80-90. (Review)
37. Ault KA. Epidemiology and natural history of human papillomavirus infections in the female genital tract. Infect Dis Obstet Gynecol. 2006;2006 Suppl:40470. (Review)
38. Schwebke JR, Burgess D. Trichomoniasis. Clin Microbiol Rev. 2004;17(4):794-803. (Review)
39. Landers DV, Wiesenfeld HC, Heine RP, et al. Predictive value of the clinical diagnosis of lower genital tract infection in women. Am J Obstet Gynecol. 2004;190(4):1004-1010. (Prospective study; 598 patients)
40. Centers for Disease Control and Prevention. Recommendations for the laboratory-based detection of Chlamydia trachomatis and Neisseria gonorrhoeae--2014. MMWR Recomm Rep. 2014;63(Rr-02):1-19. (Expert guidelines/systematic review)
41. Skidmore S, Horner P, Herring A, et al. Vulvovaginal-swab or first-catch urine specimen to detect Chlamydia trachomatis in women in a community setting? J Clin Microbiol. 2006;44(12):4389-4394. (Retrospective study; 2745 specimens)
42. Hobbs MM, van der Pol B, Totten P, et al. From the NIH: proceedings of a workshop on the importance of self-obtained vaginal specimens for detection of sexually transmitted infections. Sex Transm Dis. 2008;35(1):8-13. (Expert guidelines/workshop review)
43. Cook RL, Hutchison SL, Ostergaard L, et al. Systematic review: noninvasive testing for Chlamydia trachomatis and Neisseria gonorrhoeae. Ann Intern Med. 2005;142(11):914-925. (Systematic review; 29 studies)
44. Kowalski RP, Karenchak LM, Raju LV, et al. The verification of nucleic acid amplification testing (Gen-Probe Aptima Assay) for Chlamydia trachomatis from ocular samples. Ophthalmology. 2015;122(2):244-247. (Retrospective laboratory verification study; 25 specimens)
45. Renault CA, Hall C, Kent CK, et al. Use of NAATs for STD diagnosis of GC and CT in non-FDA-cleared anatomic specimens. MLO Med Lab Obs. 2006;38(7):10. (Guidelines and review)
46. Stewart CMW, Schoeman SA, Booth RA, et al. Assessment of self taken swabs versus clinician taken swab cultures for diagnosing gonorrhoea in women: single centre, diagnostic accuracy study. BMJ. 2012;345(dec12 1):e8107-e8107. (Prospective study; 3850patients)
47. Association of Public Health Laboratories, Centers for Disease Control and Prevention. Laboratory diagnostic testing for Treponema pallidum: expert consultation meeting summary report. Accessed March 10, 2019. (Expert guidelines)
48. Soreng K, Levy R, Fakile Y. Serologic testing for syphilis: benefits and challenges of a reverse algorithm. Clin Microbiol Newsl. 2014;36(24):195-202. (Review)
49. Centers for Disease Control and Prevention. Discordant results from reverse sequence syphilis screening--five laboratories, United States, 2006-2010. MMWR Morb Mortal Wkly Rep. 2011;60(5):133-137. (Data analysis; 5 laboratories)
50. Noy M, Rayment M, Sullivan A, et al. The utility of cerebrospinal fluid analysis in the investigation and treatment of neurosyphilis. Sex Transm Infect. 2014;90(6):451. (Expert guidelines)
51. Wolner-Hanssen P, Krieger JN, Stevens CE, et al. Clinical manifestations of vaginal trichomoniasis. JAMA. 1989;261(4):571-576. (Prospective study; 779 patients)
52. Eschenbach DA, Hillier S, Critchlow C, et al. Diagnosis and clinical manifestations of bacterial vaginosis. Am J Obstet Gynecol. 1988;158(4):819-828. (Prospective study; 640 patients)
53. Amsel R, Totten PA, Spiegel CA, et al. Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations. Am J Med. 1983;74(1):14-22. (Prospective study; 397 patients)
54. Van der Bij AK, Spaargaren J, Morre SA, et al. Diagnostic and clinical implications of anorectal lymphogranuloma venereum in men who have sex with men: a retrospective case-control study. Clin Infect Dis. 2006;42(2):186-194. (Retrospective; 87 patients)
55. Corey L, Huang ML, Selke S, et al. Differentiation of herpes simplex virus types 1 and 2 in clinical samples by a real-time taqman PCR assay. J Med Virol. 2005;76(3):350-355. (Prospective; 3131 specimens)
56. Roth AM, Williams JA, Ly R, et al. Changing sexually transmitted infection screening protocol will result in improved case finding for Trichomonas vaginalis among high-risk female populations. Sex Transm Dis. 2011;38(5):398-400. (Prospective studies; 222 patients and 471 patients)
57. Schwebke JR, Hobbs MM, Taylor SN, et al. Molecular testing for Trichomonas vaginalis in women: results from a prospective U.S. clinical trial. J Clin Microbiol. 2011;49(12):4106-4111. (Prospective multicenter study; 1025 patients)
58. Cristillo AD, Bristow CC, Peeling R, et al. Point-of-care sexually transmitted infection diagnostics: proceedings of the STAR Sexually Transmitted Infection-Clinical Trial Group programmatic meeting. Sex Transm Dis. 2017;44(4):211-218. (Review)
59. Lau CY, Qureshi AK. Azithromycin versus doxycycline for genital chlamydial infections: a meta-analysis of randomized clinical trials. Sex Transm Dis. 2002;29(9):497-502. (Meta-analysis; 12 clinical trials)
60. Workowski KA, Berman SM, Douglas JM Jr. Emerging antimicrobial resistance in Neisseria gonorrhoeae: urgent need to strengthen prevention strategies. Ann Intern Med. 2008;148(8):606-613. (Review)
61. Yokoi S, Deguchi T, Ozawa T, et al. Threat to cefixime treatment for gonorrhea. Emerg Infect Dis. 2007;13(8):1275-1277. (Prospective study; 4 patients)
62. Kirkcaldy RD, Weinstock HS, Moore PC, et al. The efficacy and safety of gentamicin plus azithromycin and gemifloxacin plus azithromycin as treatment of uncomplicated gonorrhea. Clin Infect Dis. 2014;59(8):1083-1091. (Randomized controlled trial; 401patients)
63. Centers for Disease Control and Prevention. Update to CDC’s sexually transmitted diseases treatment guidelines, 2010: oral cephalosporins no longer a recommended treatment for gonococcal infections. MMWR Morb Mortal Wkly Rep. 2012;61(31):590-594. (CDC guidelines)
64. United States Food and Drug Administration. FDA Drug Shortages. Accessed March 10, 2019. (FDA drug shortage report)
65. Centers for Disease Control and Prevention. 2015 sexually transmitted diseases treatment guidelines. Accessed March 10, 2019. (CDC guidelines)
66. Clement ME, Okeke NL, Hicks CB. Treatment of syphilis: a systematic review. JAMA. 2014;312(18):1905-1917. (Review)
67. Hook EW 3rd, Martin DH, Stephens J, et al. A randomized, comparative pilot study of azithromycin versus benzathine penicillin G for treatment of early syphilis. Sex Transm Dis. 2002;29(8):486-490. (Randomized comparative pilot study; 60 patients)
68. Riedner G, Rusizoka M, Todd J, et al. Single-dose azithromycin versus penicillin G benzathine for the treatment of early syphilis. N Engl J Med. 2005;353(12):1236-1244. (Randomized controlled study; 328 patients)
69. Belum GR, Belum VR, Chaitanya Arudra SK, et al. The Jarisch-Herxheimer reaction: revisited. Travel Med Infect Dis. 2013;11(4):231-237. (Review)
70. Caro-Paton T, Carvajal A, Martin de Diego I, et al. Is metronidazole teratogenic? A meta-analysis. Br J Clin Pharmacol. 1997;44(2):179-182. (Meta-analysis of 1 case-control and 4 cohort studies)
71. Hanson JM, McGregor JA, Hillier SL, et al. Metronidazole for bacterial vaginosis. A comparison of vaginal gel vs. oral therapy. J Reprod Med. 2000;45(11):889-896. (Randomized controlled trial, comparative study; 112 patients)
72. Mehta SD. Systematic review of randomized trials of treatment of male sexual partners for improved bacteria vaginosis outcomes in women. Sex Transm Dis. 2012;39(10):822-830. (Systematic review of 8 randomized controlled trials)
73. Homayouni A, Bastani P, Ziyadi S, et al. Effects of probiotics on the recurrence of bacterial vaginosis: a review. J Low Genit Tract Dis. 2014;18(1):79-86. (Systematic review)
74. Mena LA, Mroczkowski TF, Nsuami M, et al. A randomized comparison of azithromycin and doxycycline for the treatment of Mycoplasma genitalium-positive urethritis in men. Clin Infect Dis. 2009;48(12):1649-1654. (Randomized controlled trial; 398 patients)
75. Bjornelius E, Anagrius C, Bojs G, et al. Antibiotic treatment of symptomatic Mycoplasma genitalium infection in Scandinavia: a controlled clinical trial. Sex Transm Infect. 2008;84(1):72-76. (Randomized controlled trial; 212 patients))
76. Jernberg E, Moghaddam A, Moi H. Azithromycin and moxifloxacin for microbiological cure of Mycoplasma genitalium infection: an open study. Int J STD AIDS. 2008;19(10):676-679. (Retrospective study; 452 patients)
77. Johnston C, Saracino M, Kuntz S, et al. Standard-dose and high-dose daily antiviral therapy for short episodes of genital HSV-2 reactivation: three randomised, open-label, cross-over trials. Lancet. 2012;379(9816):641-647. (Three complementary crossover studies; 113 patients)
78. Cernik C, Gallina K, Brodell RT. The treatment of herpes simplex infections: an evidence-based review. Arch Intern Med. 2008;168(11):1137-1144. (Review)
79. Chosidow O, Drouault Y, Leconte-Veyriac F, et al. Famciclovir vs. aciclovir in immunocompetent patients with recurrent genital herpes infections: a parallel-groups, randomized, double-blind clinical trial. Br J Dermatol. 2001;144(4):818-824. (Randomized controlled study; 204 patients)
80. Lipke MM. An armamentarium of wart treatments. Clin Med Res. 2006;4(4):273-293. (Review)
81. Meites E, Kempe A, Markowitz LE. Use of a 2-dose schedule for human papillomavirus vaccination - updated recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 2016;65(49):1405-1408. (Guidelines/systematic review)
82. Forna F, Gulmezoglu AM. Interventions for treating trichomoniasis in women. Cochrane Database Syst Rev. 2003(2):CD000218. (Cochrane review; 54 trials)
83. Kang-Birken SL, Castel U, Prichard JG. Oral doxycycline for treatment of neurosyphilis in two patients infected with human immunodeficiency virus. Pharmacotherapy. 2010;30(4):119e-122e. (Case series; 2 patients)
84. Mechai F, de Barbeyrac B, Aoun O, et al. Doxycycline failure in lymphogranuloma venereum. Sex Transm Infect. 2010;86(4):278-279. (Case report)
85. Wyrick PB. Chlamydia trachomatis persistence in vitro: an overview. J Infect Dis. 2010;201 Suppl 2:S88-S95. (Review)
86. Liu B, Roberts CL, Clarke M, et al. Chlamydia and gonorrhoea infections and the risk of adverse obstetric outcomes: a retrospective cohort study. Sex Transm Infect. 2013;89(8):672-678. (Retrospective cohort study; 354,217 patients)
87. Newman L, Kamb M, Hawkes S, et al. Global estimates of syphilis in pregnancy and associated adverse outcomes: analysis of multinational antenatal surveillance data. PLoS Med. 2013;10(2):e1001396. (Review)
88. Centers for Disease Control and Prevention. Syphilis - CDC fact sheet (detailed). Accessed March 10, 2019. (CDC fact sheet)
89. Walker GJ. Antibiotics for syphilis diagnosed during pregnancy. Cochrane Database Syst Rev. 2001(3):CD001143. (Cochrane review; 0 studies meeting criteria)
90. McGregor JA, French JI. Bacterial vaginosis in pregnancy. Obstet Gynecol Surv. 2000;55(5 Suppl 1):S1-S19. (Review)
91. ACOG Committee on Practice Bulletins. ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists. No. 82 June 2007. Management of herpes in pregnancy. Obstet Gynecol. 2007;109(6):1489-1498. (Practice guidelines)
92. Watts DH, Brown ZA, Money D, et al. A double-blind, randomized, placebo-controlled trial of acyclovir in late pregnancy for the reduction of herpes simplex virus shedding and cesarean delivery. Am J Obstet Gynecol. 2003;188(3):836-843. (Randomized controlled trial; 162 patients)
93. Castellsague X, Drudis T, Canadas MP, et al. Human papillomavirus (HPV) infection in pregnant women and mother-to-child transmission of genital HPV genotypes: a prospective study in Spain. BMC Infect Dis. 2009;9:74. (Prospective cohort study; 143 patients)
94. Cotch MF, Pastorek JG 2nd, Nugent RP, et al. Trichomonas vaginalis associated with low birth weight and preterm delivery. The Vaginal Infections and Prematurity Study Group. Sex Transm Dis. 1997;24(6):353-360. (Prospective cohort study; 3816 patients)
95. Gulmezoglu AM. Interventions for trichomoniasis in pregnancy. Cochrane Database Syst Rev. 2002(3):CD000220. (Cochrane review; 2 trials, 842 women)
96. Joesoef MR, Weinstock HS, Kent CK, et al. Sex and age correlates of chlamydia prevalence in adolescents and adults entering correctional facilities, 2005: implications for screening policy. Sex Transm Dis. 2009;36(2 Suppl):S67-S71. (Cross-sectionalanalysis; 150,166 patients)
97. Roche. Product Information: ROCEPHIN® (ceftriaxone sodium) for injection. Accessed March 10, 2019. (Drug company package insert)
98. Schillinger JA, Gorwitz R, Rietmeijer C, et al. The expedited partner therapy continuum: a conceptual framework to guide programmatic efforts to increase partner treatment. Sex Transm Dis. 2016;43(2 Suppl 1):S63-S75. (Systematic review; 42 articles)
99. Shiely F, Hayes K, Thomas KK, et al. Expedited partner therapy: a robust intervention. Sex Transm Dis. 2010;37(10):602-607. (Randomized controlled trial; 1860 patients)
100. Centers for Disease Control and Prevention. Expedited partner therapy. Sexually Transmitted Diseases (STDs). Accessed March 10, 2019. (CDC website)
101. Hogben M. Partner notification for sexually transmitted diseases. Clin Infect Dis. 2007;44 Suppl 3:S160-S174. (Review)
102. Kissinger P, Schmidt N, Mohammed H, et al. Patient-delivered partner treatment for Trichomonas vaginalis infection: a randomized controlled trial. Sex Transm Dis. 2006;33(7):445-450. (Randomized controlled trial; 463 patients)
103. Centers for Disease Control and Prevention. 2018 National Notifiable Conditions (Historical). National Notifiable Diseases Surveillance System (NNDSS). Accessed March 10, 2019. (CDC website)
104. Hosenfeld CB, Workowski KA, Berman S, et al. Repeat infection with chlamydia and gonorrhea among females: a systematic review of the literature. Sex Transm Dis. 2009;36(8):478-489. (Systematic review; 47 studies)
105. Carter MW, Wu H, Cohen S, et al. Linkage and referral to HIV and other medical and social services: a focused literature review for sexually transmitted disease prevention and control programs. Sex Transm Dis. 2016;43(2 Suppl 1):S76-S82. (Systematic review; 33 studies)
106. Menchine M, Zhou M, Lotfipour S, et al. Moving beyond screening: how emergency departments can help extinguish the HIV/AIDS epidemic. West J Emerg Med. 2016;17(2):135-138. (Review)
107. Hess KL, Javanbakht M, Brown JM, et al. Intimate partner violence and sexually transmitted infections among young adult women. Sex Transm Dis. 2012;39(5):366-371. (Retrospective study; 3548 patients)