Sexually Transmitted Bacterial Infections

Key Words

sexually transmitted bacterial infection, gonorrhea, chlamydia, PID, genital warts, genital herpes, urethritis, gonococcal, syphilis, cervicitis, lymphogranuloma venereum

Sexually Transmitted Disease Presentations

Sexually transmitted diseases (STDs) can present as follows:

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Genital ulcers or sores
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Urethral discharge
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Vaginal discharge
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Cervical infection
•

Lower abdominal pain
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Inguinal bubo
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Scrotal swelling
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Rectal or pharyngeal inflammation
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Papules

The Centers for Disease Control and Prevention criteria for the treatment of all STDs is presented in Table 10.1 . An overview of these diseases and their World Health Organization (WHO) syndromic diagnosis and management criteria is presented on pp. 384–385 . An overview of these diseases and their syndromic diagnosis and management is presented in Figs. 10.1 to 10.5

TABLE 10.1

Bacterial Infection Protocol According to 2015 CDC

From Centers for Disease Control and Prevention (CDC) ( www.cdc.gov ).

Coverage	Recommended Regimens	Alternative Regimens	Special Considerations
Mycobacterium genitalium	Azithromycin 1-g single oral dose OR Azithromycin 500-mg dose followed by 250 mg daily for 4 days	Moxifloxacin 400 mg daily for 4, 7, or 10 days	If PID is suspected, moxifloxacin 400 mg/day for 14 days is recommended
Chancroid	Azithromycin 1 g orally in a single dose OR Ceftriaxone 250 mg IM in a single dose OR Ciprofloxacin 500 mg orally twice a day for 3 days OR Erythromycin base 500 mg orally 3 times a day for 7 days		If patient is pregnant, consider: Azithromycin 1 g orally as a single dose OR Ceftriaxone 250 mg as a single IM injection
Granuloma inguinale (donovanosis)	Azithromycin 1 g orally once per week or 500 mg daily for at least 3 weeks and all lesions are completely healed	Doxycycline 100 mg orally twice a day for at least 3 weeks and until all lesions have completely healed OR Ciprofloxacin 750 mg orally twice a day for at least 3 weeks and until all lesions have completely healed OR Erythromycin base 500 mg orally 4 times a day for at least 3 weeks and until all lesions have completely healed OR Trimethoprim–sulfamethoxazole one double-strength (160 mg/800 mg) tablet orally twice a day for at least 3 weeks and until all lesions have completely healed	If no improvement is noted within the first few days of therapy, gentamycin 1 mg/kg IV every 8 hours Pregnant and lactating women should be treated with erythromycin or azithromycin
Lymphogranuloma venereum	Doxycycline 100 mg orally twice a day for 21 days	Erythromycin base 500 mg orally 4 times a day for 21 days	Pregnant and lactating women should be treated with erythromycin
Syphilis	Adults: Benzathine penicillin G 2.4 million units IM in a single dose Infants and children: Benzathine penicillin G 50,000 units/kg IM up to the adult dose of 2.4 million units in a single dose	Ceftriaxone (1–2 g daily either IM or IV for 10–14 days) OR Doxycycline 100 mg orally twice daily for 14 days OR Tetracycline 500 mg 4 times daily for 14 days	For infants and children without clinical symptoms: Procaine penicillin G, 50,000 U/kg/dose IM a day in a single dose for 10 days OR Benzathine penicillin G, 50,000 U/kg IM as a single dose Infants, children, and pregnant women allergic to penicillin should be desensitized and treated with penicillin Azithromycin 2 g single dose can be considered when penicillin or doxycycline is not an option
Nongonococcal urethritis (NGU)	Azithromycin 1 g orally in a single dose OR Doxycycline 100 mg orally twice a day for 7 days	Erythromycin base 500 mg orally 4 times a day for 7 days OR Erythromycin ethylsuccinate 800 mg orally 4 times a day for 7 days OR Levofloxacin 500 mg orally once daily for 7 days OR Ofloxacin 300 mg orally twice a day for 7 days	Treat with moxifloxacin 400 mg orally once daily for 7 days for recurrent NGU
Cervicitis	Azithromycin 1 g orally in a single dose OR Doxycycline 100 mg orally twice a day for 7 days
Chlamydia	Azithromycin 1 g orally in a single dose OR Doxycycline 100 mg orally twice a day for 7 days	Erythromycin base 500 mg orally 4 times a day for 7 days OR Erythromycin ethylsuccinate 800 mg orally 4 times a day for 7 days OR Levofloxacin 500 mg orally once daily for 7 days OR Ofloxacin 300 mg orally twice a day for 7 days OR Doxycycline delayed-release 200 mg daily for 7 days	Recommended regimen for pregnant women: Azithromycin 1 g orally in a single dose Alternative regimens for pregnant women: Amoxicillin 500 mg orally 3 times a day for 7 days OR Erythromycin base 500 mg orally 4 times a day for 7 days OR Erythromycin base 250 mg orally 4 times a day for 14 days OR Erythromycin ethylsuccinate 800 mg orally 4 times a day for 7 days OR Erythromycin ethylsuccinate 400 mg orally 4 times a day for 14 days
Chlamydia in infants	Recommended regimen for infants and children who weigh <45 kg: Erythromycin base or ethylsuccinate 50 mg/kg/day orally divided into 4 doses daily for 14 days Recommended regimen for children who weigh ≥45 kg but who are aged <8 years: Azithromycin 1 g orally in a single dose Recommended regimens for children aged ≥8 years: Azithromycin 1 g orally in a single dose OR Doxycycline 100 mg orally twice a day for 7 days
Ophthalmia neonatorum	Erythromycin base or ethylsuccinate 50 mg/kg/day orally divided into 4 doses daily for 14 days	Azithromycin suspension, 20 mg/kg/day orally, 1 dose daily for 3 days*	*An association between oral erythromycin and azithromycin and infantile hypertrophic pyloric stenosis (IHPS) has been reported in infants aged <6 weeks. Infants treated with either of these antimicrobials should be followed for signs and symptoms of IHPS
Infant pneumonia caused by C. trachomatis	Erythromycin base or ethylsuccinate 50 mg/kg/day orally divided into 4 doses daily for 14 days	Azithromycin 20 mg/kg/day orally, 1 dose daily for 3 days
Gonococcal infections	For uncomplicated infections of the cervix, urethra, rectum, and pharynx: Ceftriaxone 250 mg IM in a single dose PLUS Azithromycin 1 g orally in a single dose	If ceftriaxone is not available: Cefixime 400 mg orally in a single dose PLUS Azithromycin 1 g orally in a single dose
Gonococcal conjunctivitis	Ceftriaxone 1 g IM in a single dose PLUS Azithromycin 1 g orally in a single dose		Consider one-time lavage of the infected eye with saline solution
Arthritis and arthritis–dermatitis syndrome	Ceftriaxone 1 g IM or IV every 24 hours PLUS Azithromycin 1 g orally in a single dose	Cefotaxime 1 g IV every 8 hours OR Ceftizoxime 1 g IV every 8 hours PLUS Azithromycin 1 g orally in a single dose
Gonococcal meningitis and endocarditis	Ceftriaxone 1–2 g IV every 12–14 hours PLUS Azithromycin 1 g orally in a single dose
Ophthalmia neonatorum prophylaxis	Erythromycin (0.5%) ophthalmic ointment in each eye in a single application at birth
Infant gonococcal ophthalmia	Ceftriaxone 25–50 mg/g IV or IM in a single dose, not to exceed 125 mg
Disseminated gonococcal infection (DGI) and gonococcal scalp abscesses in neonates	Ceftriaxone 25–50 mg/kg/day IV or IM in a single daily dose for 7 days, with a duration of 10–14 days if meningitis is documented OR Cefotaxime 25 mg/kg IV or IM every 12 hours for 7 days, with a duration of 10–14 days if meningitis is documented
Infant gonococcal prophylaxis	In the absence of signs of gonococcal infection: Ceftriaxone 25–50 mg/g IV or IM in a single dose, not to exceed 125 mg
Infants and children with uncomplicated gonococcal vulvovaginitis, cervicitis, urethritis, pharyngitis, or proctitis	Weigh ≤45 kg: Ceftriaxone 25–50 mg/kg IV or IM in a single dose, not to exceed 125 mg IM Weigh >45 kg: Treat with one of the regimens recommended for adults
Gonococcal infections in children with bacteremia or arthritis	Weigh ≤45 kg: Ceftriaxone 50 mg/kg (maximum dose: 1 g) IM or IV in a single dose daily for 7 days Weigh >45 kg: Ceftriaxone 1 g IM or IV in a single dose daily every 24 hours for 7 days
Bacterial vaginosis	Metronidazole 500 mg orally twice a day for 7 days OR Metronidazole gel 0.75%, one full applicator (5 g) intravaginally, once a day for 5 days OR Clindamycin cream 2%, one full applicator (5 g) intravaginally at bedtime for 7 days	Tinidazole 2 g orally once daily for 2 days OR Tinidazole 1 g orally once daily for 5 days OR Clindamycin 300 mg orally twice daily for 7 days OR Clindamycin ovules 100 mg intravaginally once at bedtime for 3 days	Clindamycin ovules use an oleaginous base that might weaken latex or rubber products (e.g., condoms and vaginal contraceptive diaphragms). Use of such products within 72 hours following treatment with clindamycin ovules is not recommended
Vulvovaginal candidiasis (VVC)	Over-the-counter intravaginal agents: Clotrimazole 1% cream 5 g intravaginally daily for 7–14 days OR Clotrimazole 2% cream 5 g intravaginally daily for 3 days OR Miconazole 2% cream 5 g intravaginally daily for 7 days OR Miconazole 4% cream 5 g intravaginally daily for 3 days OR Miconazole 100-mg vaginal suppository, one suppository daily for 7 days OR Miconazole 200-mg vaginal suppository, one suppository for 3 days OR Miconazole 1200-mg vaginal suppository, one suppository for 1 day OR Tioconazole 6.5% ointment 5 g intravaginally in a single application Prescription intravaginal agents: Butoconazole 2% cream (single dose bioadhesive product), 5 g intravaginally in a single application OR Terconazole 0.4% cream 5 g intravaginally daily for 7 days OR Terconazole 0.8% cream 5 g intravaginally daily for 3 days OR Terconazole 80 mg vaginal suppository, one suppository daily for 3 days Oral agent: Fluconazole 150 mg orally in a single dose		Options for nonalbicans VVC includes a longer duration of therapy (7–14 days) with a nonfluconazole azole. If there is recurrence, 600 mg of boric acid in a gelatin capsule administered vaginally once daily for 2 weeks is recommended
Severe vulvovaginitis	Topical azole for 7–14 days OR Fluconazole 150 mg in two sequential oral doses (second dose 72 hours after initial dose)
Pelvic inflammatory disease (PID)	Parenteral: Cefotetan 2 g IV every 12 hours PLUS Doxycycline 100 mg orally or IV every 12 hours OR Cefoxitin 2 g IV every 6 hours PLUS Doxycycline 100 mg orally or IV every 12 hours OR Clindamycin 900 mg IV every 8 hours PLUS Gentamicin loading dose IV or IM (2 mg/kg), followed by a maintenance dose (1.5 mg/kg) every 8 hours. Single daily dosing (3–5 mg/kg) can be substituted Intramuscular/oral: Ceftriaxone 250 mg IM in a single dose PLUS Doxycycline 100 mg orally twice a day for 14 days WITH ^†or WITHOUT Metronidazole 500 mg orally twice a day for 14 days OR Cefoxitin 2 g IM in a single dose and Probenecid 1 g orally administered concurrently in a single dose PLUS Doxycycline 100 mg orally twice a day for 14 days WITH or WITHOUT Metronidazole 500 mg orally twice a day for 14 days OR Other parenteral third generation cephalosporin (e.g., ceftizoxime or cefotaxime) PLUS Doxycycline 100 mg orally twice a day for 14 days WITH ^†or WITHOUT Metronidazole 500 mg orally twice a day for 14 days	Parenteral: Ampicillin/Sulbactam 3 g IV every 6 hours PLUS Doxycycline 100 mg orally or IV every 12 hours In case of allergy, diagnostic tests for gonorrhea must be obtained before beginning therapy ^‡: Levofloxacin 500 mg orally once daily OR Ofloxacin 400 mg twice daily OR Moxifloxacin 400 mg orally once daily WITH metronidazole for 14 days (500 mg orally twice daily)	^†The recommended third-generation cephalosporins are limited in the coverage of anaerobes. Therefore, until it is known that extended anaerobic coverage is not important for treatment of acute PID, the addition of metronidazole to treatment regimens with third-generation cephalosporins should be considered ^‡If the culture for gonorrhea is positive, treatment should be based on results of antimicrobial susceptibility testing. If the isolate is determined to be quinolone-resistant N. gonorrhoeae (QRNG) or if antimicrobial susceptibility cannot be assessed (e.g., if only NAAT testing is available), consultation with an infectious-disease specialist is recommended.
Epididymitis	For acute epididymitis most likely caused by sexually transmitted chlamydia and gonorrhea: Ceftriaxone 250 mg IM in a single dose PLUS Doxycycline 100 mg orally twice a day for 10 days For acute epididymitis most likely caused by sexually transmitted chlamydia and gonorrhea and enteric organisms (men who practice insertive anal sex): Ceftriaxone 250 mg IM in a single dose PLUS Levofloxacin 500 mg orally once a day for 10 days OR Ofloxacin 300 mg orally twice a day for 10 days For acute epididymitis most likely caused by enteric organisms: Levofloxacin 500 mg orally once daily for 10 days OR Ofloxacin 300 mg orally twice a day for 10 days
Acute proctitis	Ceftriaxone 250 mg IM in a single dose PLUS Doxycycline 100 mg orally twice a day for 7 days		Bloody discharge, perianal ulcers, or mucosal ulcers among MSM with acute proctitis and either a positive rectal chlamydia NAAT or HIV infection should be offered presumptive treatment for LGV with doxycycline 100 mg twice daily orally for a total of 3 weeks

CDC, Centers for Disease Control and Prevention; IM, intramuscular; IV intravenously; MSM, men who have sex with men; NAAT, nucleic acid amiplification test.

Genital Ulcers

Developed Countries

In developed countries, most patients who have genital ulcers have herpes simplex virus (HSV), syphilis, or chancroid. The differential diagnosis of genital ulcers is presented in Table 10.2 . The frequency of each disease differs by geographic area and patient population. Herpes is the most prevalent. A patient may have more than one of these diseases. Not all genital ulcers are caused by sexually transmitted infections STIs. Each disease is associated with an increased risk for human immunodeficiency virus (HIV) infection. A diagnosis-based history and physical examination is often inaccurate. All patients who have genital ulcers should have a serologic test for syphilis and diagnostic tests for herpes. Tests to consider include the following:

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Rapid plasma reagin (RPR) or Venereal Disease Research Laboratories (VDRL)
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Syphilis immunoglobulin G (IgG), and if positive order RPR
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Dark-field examination for Treponema pallidum
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Culture, polymerase chain reaction (PCR), and/or antigen test for HSV
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Culture for Haemophilus ducreyi (special media)
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Biopsy if treatment fails
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HIV testing if ulcers are caused by T. pallidum or H. ducreyi
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Consider HIV testing for patients with HSV

HIV testing should be performed in patients who have genital ulcers caused by T. pallidum or H. ducreyi and considered for those who have ulcers caused by HSV.

TABLE 10.2

Differential Diagnosis of Genital Ulcerations

	Chancroid	Granuloma Inguinale	Lymphogranuloma Venereum (LVG)	Primary Syphilis	Herpes Simplex
Etiology	Haemophilus ducreyi	Klebsiella granulomatis (Donovanosis)	Chlamydia trachomatis (L1, L2, L3 serovars)	Treponema pallidum	HSV-1 and HSV-2
Incubation period	4–10 days	Avg 50 days	3–12 days for primary infection	3–90 days (avg 21)	2–12 days (avg 4)
Initial lesion	Starts as a pustule that degrades to a painful ulcer with erythematous base. Size between 1 and 2 cm	Present as painless, “red-beefy” nodular lesions that enlarge and ulcerate, resulting in rolled edges	Round or oval papule, vesicle, or ulcer. Can be elevated (usually resolved by time patient seeks care)	Painless eroded, nonexudative papule with raised indurated border, size between 1–2 cm	Vesicles that rupture into painful ulcers. Can present as fissures or irritation of the vulva in females
Number of lesions	Multiple, may combine	Usually one, but “kissing lesions” possible with adjacent skin	Variable	Usually one	Multiple, may combine
Duration	Uncertain (months)	Uncertain (years)	Several weeks	3–6 weeks	Primary: 2–4 weeks Recurrent: avg 10 days
Site	Genital or perianal	Genital, perianal, or inguinal	Genital, perianal, or rectal	Pharynx, genital, perianal, or rectal	Oral, genital, or perianal
Regional adenopathy	Tender inguinal lymphadenopathy. Commonly unilateral. May result in fluctuant buboes that may become purulent	Lymphadenopathy uncommon. Nodular lesions may present as pseudobuboes	“Groove” sign from swelling of superficial and deep inguinal and/or femoral nodes. May develop into painful buboes, can rupture	Nontender, rubbery bilateral lymphadenopathy	Tender, local bilateral inguinal lymphadenopathy with primary infection
Diagnostic tests	Culture, Gram stain, PCR (not FDA cleared), dark-field microscopy to rule out T. pallidum	Biopsy of an ulcer or tissue crush prep. Wright’s stain reveals dark purple Donovan bodies	Culture, serologic testing, NAAT	Dark-field microscopy for T. pallidum FTA-ABS, VDRL, RPR	Direct fluorescent antibody test on ulcer scraping, PCR, NAAT, culture (preferably with vesicular fluid), serologic testing

FDA, U.S. Food and Drug Administration; FTA-ABS, fluorescent treponemal antibody absorption; NAAT, nucleic acid amplification test; PCR, polymerase chain reaction; RPR, rapid plasma reagin test; TPHA, T. pallidum hemagglutination assay; VDRL, Venereal Disease Research Laboratory test.

Treatment of genital ulcers is often desirable before test results are available. Treat for the most likely diagnosis. If the diagnosis is unclear, treat for syphilis or for both syphilis and chancroid if the patient lives in an area where H. ducreyi is a significant cause of genital ulcers. Even after complete diagnostic evaluation, at least 25% of patients who have genital ulcers have no laboratory-confirmed diagnosis ( Tables 10.2 and 10.3 ).

TABLE 10.3

Signs, Symptoms, and Causes for Sexually Transmitted Infection Syndromes (World Health Organization Terms and Definitions)

Syndrome	Symptoms	Signs	Most Common Causes
Genital ulcer	Genital sore	Genital ulcer	Syphilis Chancroid Genital herpes
Urethral discharge	Urethral discharge Dysuria Frequent urination	Urethral discharge (if necessary, ask patient to milk urethra)	Gonorrhea Chlamydia
Vaginal discharge Cervical infection	Unusual vaginal discharge Vaginal itching Dysuria (pain on urination) Dyspareunia (pain during sexual intercourse)	Abnormal vaginal discharge	Vaginitis: • Trichomoniasis • Candidiasis Cervicitis: • Gonorrhea • Chlamydia
Lower abdominal pain	Lower abdominal pain Dyspareunia	Vaginal discharge Lower abdominal tenderness on palpation Temperature >38° C	Gonorrhea Chlamydia
Inguinal bubo	Painful enlarged inguinal lymph nodes	Enlarged inguinal lymph nodes Fluctuation Abscesses or fistulas	Lymphogranuloma venereum Chancroid

Syndromic Management of Sexually Transmitted Diseases

World Health Organization (WHO).

Many health care facilities in developing countries lack the equipment and trained personnel required for etiologic diagnosis of STDs. To overcome this problem, a syndrome-based approach rather than a conventional approach based on laboratory tests has been developed in a large number of countries. The syndromic management approach is based on the identification of consistent groups of symptoms and easily recognized signs (syndromes), and the provision of treatment that will handle the majority of, or the most serious, organisms responsible for producing a syndrome.

A more definite or etiologic diagnosis may be possible with sophisticated laboratory facilities, but this is often not possible. Laboratory tests require resources, add cost, may require extra visits, and may delay treatment. For these reasons, syndromic management guidelines are widely used for syndromes even in developed countries with advanced laboratory facilities.

WHO has developed a flow chart to guide health workers in the implementation of syndromic management of STDs. These charts appear in a modified form on the following pages.

The syndromes that cause STIs are presented in Tables 10.3 to 10.11 .

TABLE 10.9

Recommended Treatment for Cervical Infection (Therapy for Uncomplicated Gonorrhea Plus Therapy for Chlamydia)

From WHO. Sexually transmitted and other reproductive tract infections: a guide to essential practice. Geneva, Switzerland: World Health Organization; 2005.

Coverage	First Choice: Choose 1 From Each Box (Total of 2 Drugs)	Effective Substitutes	If Patient Is Pregnant, Breast-Feeding, or <16 Years Old: Choose 1 From Each Box
Gonorrhea	Cefixime 400 mg orally as a single dose, or Ceftriaxone 125 mg by intramuscular injection	Ciprofloxacin * ^,^†500 mg orally as a single dose, or Spectinomycin 2 g by intramuscular injection	Cefixime 400 mg orally as a single dose, or Ceftriaxone 125 mg by intramuscular injection
Chlamydia	Azithromycin 1 g orally as a single dose, or Doxycycline * 100 mg orally twice a day for 7 days	Ofloxacin * ^,^†^,^‡300 mg orally twice a day for 7 days, or Tetracycline * 500 mg orally 4 times a day for 7 days, or Erythromycin 500 mg orally 4 times a day for 7 days	Erythromycin ^§500 mg orally 4 times a day for 7 days, or Azithromycin 1 g orally as a single dose, or Amoxicillin 500 mg orally 3 times a day for 7 days

* Doxycycline, tetracycline, ciprofloxacin, norfloxacin, and ofloxacin should be avoided in pregnancy and when breast-feeding.

† The use of quinolones should take into consideration the patterns of Neisseria gonorrhoeae resistance, such as in the WHO Southeast Asia and Western Pacific regions.

‡ Ofloxacin, when used as indicated for chlamydial infection, also provides coverage for gonorrhea.

§ Erythromycin estolate is contraindicated in pregnancy because of drug-related hepatotoxicity; only erythromycin base or erythromycin ethylsuccinate should be used.

TABLE 10.4

Recommended Treatment for Genital Ulcers *

Adapted from WHO. Sexually transmitted and other reproductive tract infections: a guide to essential practice. Geneva, Switzerland: World Health Organization; 2005.

Coverage	First Choice: Choose 1 From Each Box (Total of 2 Drugs)	Effective Substitutes	If Patient Is Pregnant, Breast-Feeding, or <16 Years Old: Choose 1 From Each Box (Total of 2 Drugs)
Syphilis	Benzathine penicillin 2.4 million units by single intramuscular injection Note: For patients with a positive syphilis test and no ulcer, administer same dose at weekly intervals for total of 3 doses	Doxycycline ^†100 mg twice a day for 13 days, or Tetracycline ^†500 mg orally 4 times a day for 14 days	Benzathine penicillin 2.4 million units by single intramuscular injection, or Erythromycin ^‡500 mg orally 4 times a day for 15 days
Chancroid	Ciprofloxacin ^§500 mg orally twice a day for 3 days, or Azithromycin 1 g orally as a single dose, or Erythromycin ^‡500 mg orally 4 times a day for 7 days	Ceftriaxone 250 mg as a single intramuscular injection	Erythromycin ^‡500 mg orally 4 times a day for 7 days, or Azithromycin 1 g orally as a single dose, or Ceftriaxone 250 mg as a single intramuscular injection
ADDITIONAL THERAPY FOR HSV-2 WHERE HSV-2 IS COMMON
Genital herpes	Primary infection Acyclovir ^†200 mg orally 5 times a day for 7 days, or Acyclovir ^†400 mg orally 3 times a day for 7 days	Primary infection Famciclovir ^†250 mg orally 3 times a day for 7 days, or Valacyclovir ^†1 g twice a day for 7 days	Use acyclovir only when benefit outweighs risk
	Recurrent infection Acyclovir ^†200 mg orally 5 times a day for 5 days, or Acyclovir ^†400 mg orally 3 times a day for 5 days	Recurrent infection Famciclovir ^†125 mg orally 3 times a day for 5 days, or Valacyclovir ^†500 mg orally twice a day for 5 days	Dosage is the same as for primary infection

* Recommended treatment for genital ulcers: (1) single-dose therapy for syphilis plus (2) single-dose or multidose therapy for chancroid. See Table 10.5 for additional genitourinary disease treatment that may be needed for some regions.

† These drugs are contraindicated for pregnant or breast-feeding women.

‡ Erythromycin estolate is contraindicated in pregnancy because of drug-related hepatotoxicity; only erythromycin base or erythromycin ethylsuccinate should be used.

§ The use of quinolones should take into consideration the patterns of Neisseria gonorrhoeae resistance, such as in the WHO Southeast Asia and Western Pacific regions.

TABLE 10.5

Recommended Additional Treatment for Genital Ulcers (in Areas Where Granuloma Inguinale and Lymphogranuloma Venereum Are Important Causes of Genital Ulcers)

From WHO. Sexually transmitted and other reproductive tract infections: a guide to essential practice. Geneva, Switzerland: World Health Organization; 2005.

Coverage	First Choice	Effective Substitutes	If Patient Is Pregnant, Breast-Feeding, or <16 Years Old
Granuloma inguinale (donovanosis): Treatment should be continued until all lesions have completely epithelialized	Azithromycin 1 g orally as a single dose followed by 500 mg once a day, or Doxycycline * 100 mg orally twice a day	Erythromycin ^†500 mg orally 4 times a day, or Tetracycline ^†500 mg orally 4 times a day, or Trimethoprim (80 mg)/sulfamethoxazole (400 mg), 2 tablets orally twice a day	Azithromycin 1 g orally as a single dose, or Erythromycin ^†500 mg orally 4 times a day
Lymphogranuloma venereum	Doxycycline * 100 mg orally twice a day for 14 days, or Erythromycin ^†500 mg orally 4 times a day for 14 days	Tetracycline ^†500 mg orally 4 times a day for 14 days	Erythromycin ^†500 mg orally 4 times a day for 14 days

* These drugs are contraindicated for pregnant or breast-feeding women.

† Erythromycin estolate is contraindicated in pregnancy because of drug-related hepatotoxicity; only erythromycin base or erythromycin ethylsuccinate should be used.

TABLE 10.6

Recommended Treatment for Urethral Discharge (Males Only) (Therapy for Uncomplicated Gonorrhea Plus Therapy for Chlamydia)

From WHO. Sexually transmitted and other reproductive tract infections: a guide to essential practice. Geneva, Switzerland: World Health Organization; 2005.

Coverage	First Choice: Choose 1 From Each Box (Total of 2 Drugs)	Effective Substitutes
Gonorrhea	Cefixime 400 mg orally as a single dose, or Ceftriaxone 125 mg by intramuscular injection	Ciprofloxacin * 500 mg orally as a single dose, or Spectinomycin 2 g by intramuscular injection
Chlamydia	Azithromycin 1 g orally as single dose, or Doxycycline 100 mg orally twice a day for 7 days	Ofloxacin * ^,^†300 mg orally twice a day for 7 days, or Tetracycline 500 mg orally 4 times a day for 7 days, or Erythromycin 500 mg orally 4 times a day for 7 days

* The use of quinolones should take into consideration the patterns of Neisseria gonorrhoeae resistance, such as in the WHO Southeast Asia and Western Pacific regions.

† Ofloxacin, when used as indicated for chlamydial infection, also provides coverage for gonorrhea.

TABLE 10.7

Recommended Treatment for Vaginal Infection *

From WHO. Sexually transmitted and other reproductive tract infections: a guide to essential practice. Geneva, Switzerland: World Health Organization; 2005.

Coverage	First Choice: Choose 1 From BV/TV Box, or 1 From Each Box if Yeast Infection Is Suspected	Effective Substitutes	If Patient Is Pregnant, Breast-Feeding: Choose 1 From BV/TV Box, or 1 From Each Box if Yeast Infection Is Suspected
Bacterial vaginosis (BV)	Metronidazole ^†2 g orally in a single dose, or Metronidazole ^†400 or 500 mg orally twice a day for 7 days	Clindamycin cream 2%, one full applicator (5 g) intravaginally at bedtime for 7 days, or Clindamycin 300 mg orally twice a day for 7 days	Preferably after first trimester Metronidazole ^†200 or 250 mg orally 3 times a day for 7 days, or Metronidazole ^†gel 0.75%, one full applicator (5 g) intravaginally twice a day for 5 days, or Clindamycin 300 mg orally twice a day for 7 days
Trichomoniasis vaginalis (TV)		Tinidazole ^†2 g orally in a single dose, or Tinidazole ^†500 mg orally twice a day for 5 days
Candida albicans (CA) (yeast)	Miconazole 200-mg vaginal suppository, one a day for 3 days, or Clotrimazole ^‡100-mg vaginal tablet, 2 tablets a day for 3 days, or Fluconazole 150-mg oral tablet, in a single dose	Nystatin 100,000-unit vaginal tablet, one a day for 14 days	Miconazole 200-mg vaginal suppository, once a day for 3 days, or Clotrimazole ^‡100-mg vaginal tablet, 2 tablets a day for 3 days, or Nystatin 100,000-unit vaginal tablet, one a day for 14 days

* Therapy for bacterial vaginosis and trichomoniasis plus therapy for yeast infection if curd-like white discharge, vulvovaginal redness, and itching are present.

† Patients taking metronidazole or tinidazole should be cautioned to avoid alcohol. Use of metronidazole is not recommended in the first trimester of pregnancy.

‡ Single-dose clotrimazole (500 mg) available in some places is also effective for yeast infection (CA).

TABLE 10.8

Recommended Outpatient Treatment for Pelvic Inflammatory Disease (PID) * (Single-Dose Therapy for Gonorrhea Plus Single-Dose or Multidose Therapy for Chlamydia Plus Therapy for Anaerobic Infections)

From WHO. Sexually transmitted and other reproductive tract infections: a guide to essential practice. Geneva, Switzerland: World Health Organization; 2005.

Coverage	Choose 1 From Each Box (Total of 3 Drugs)
Gonorrhea	Ceftriaxone 250 mg by intramuscular injection, or Cefixime 400 mg orally as a single dose, or Ciprofloxacin ^†500 mg orally as a single dose, or Spectinomycin 2 g by intramuscular injection
Chlamydia	Doxycycline ^‡100 mg orally twice a day for 14 days, or Tetracycline ^‡500 mg orally 4 times a day for 14 days
Anaerobes	Metronidazole ^§400–500 mg orally, twice a day for 14 days

* Note: Hospitalization of patients with acute PID should be seriously considered when (a) a surgical emergency, such as appendicitis or ectopic pregnancy, cannot be excluded; (b) a pelvic abscess is suspected; (c) severe illness precludes management on an outpatient basis; (d) the patient is pregnant; (e) the patient is an adolescent; (f) the patient is unable to follow or tolerate an outpatient regimen; or (g) the patient has failed to respond to outpatient therapy (see Table 10.10 ).

† The use of quinolones should take into consideration the patterns of Neisseria gonorrhoeae resistance, such as in the WHO Southeast Asia and Western Pacific regions.

‡ These drugs are contraindicated for pregnant or breast-feeding women. PID is uncommon in pregnancy.

§ Patients taking metronidazole should be cautioned to avoid alcohol. Metronidazole should also be avoided during the first trimester of pregnancy.

TABLE 10.10

Recommended Inpatient Treatment for Pelvic Inflammatory Disease (PID) (Therapy for Gonorrhea Plus Therapy for Chlamydia Plus Therapy for Anaerobic Infections) *

From WHO. Sexually transmitted and other reproductive tract infections: a guide to essential practice. Geneva, Switzerland: World Health Organization; 2005.

Coverage	Option 1: Choose 1 From Each Box (Total of 3 Drugs), and Follow With Oral Outpatient Therapy	Option 2: Give Both Drugs and Follow With Oral Outpatient Therapy	Option 3: Commonly Available; Give All 3 Drugs Plus Oral Outpatient Therapy
Gonorrhea	Ceftriaxone 250 mg by intramuscular injection, once a day, or Ciprofloxacin ^†500 mg orally as a single dose, or Spectinomycin 2 g by intramuscular injection	Gentamicin 1.5 mg/kg of body weight by intravenous injection every 8 h plus Clindamycin 900 mg by intravenous injection every 8 h	Ampicillin 2 g by intravenous or intramuscular injection, then 1 g every 6 h, plus Gentamicin 80 mg by intramuscular injection every 8 h, plus Metronidazole 500 mg or 100 mL by intravenous infusion every 8 h
Chlamydia	Doxycycline ^‡^,^§100 mg orally or by intravenous injection, twice a day, or Tetracycline ^§500 mg orally 4 times a day
Anaerobes	Metronidazole 400–500 mg orally or by intravenous injection, twice a day, or Chloramphenicol ^§500 mg orally or by intravenous injection, 4 times a day

* For all three options, therapy should be continued until at least 2 days after the patient has improved and should then be followed by one of the following oral treatments for a total of 14 days: doxycycline ^§100 mg orally twice a day, or tetracycline ^§500 mg orally 4 times a day.

† The use of quinolones should take into consideration the patterns of Neisseria gonorrhoeae resistance, such as in the WHO Southeast Asia and Western Pacific regions.

‡ Intravenous doxycycline is painful and has no advantage over the oral route if the patient is able to take medicine by mouth.

§ Contraindicated for pregnant or breast-feeding women. PID is uncommon in pregnancy.

TABLE 10.11

Recommended Treatment for Inguinal Bubo (Single-Dose or Multidose Therapies for Chancroid Plus Multidose Therapies for Lymphogranuloma Venereum [LGV]) *

From WHO. Sexually transmitted and other reproductive tract infections: a guide to essential practice. Geneva, Switzerland: World Health Organization; 2005.

Coverage	First Choice: Choose 1 From Each Box (Total of 2 Drugs)	Effective Substitutes	If Patient Is Pregnant, Breast-Feeding, or <16 Years Old
Chancroid	Ciprofloxacin * ^,^†500 mg orally twice a day for 3 days, or Erythromycin ^‡500 mg orally 4 times a day for 7 days	Azithromycin 1 g orally as a single dose, or Ceftriaxone 250 mg as a single intramuscular injection	Erythromycin ^‡500 mg orally 4 times a day for 14 days ^§(covers both chancroid and LGV)
LGV	Doxycycline * 100 mg orally twice a day for 14 days	Tetracycline ^†500 mg orally 4 times a day for 14 days

* These drugs are contraindicated for pregnant or breast-feeding women.

† The use of quinolones should take into consideration the patterns of Neisseria gonorrhoeae resistance, such as in the WHO Southeast Asia and Western Pacific regions.

‡ Erythromycin estolate is contraindicated in pregnancy because of drug-related hepatotoxicity; only erythromycin base or erythromycin ethylsuccinate should be used.

§ N ote : Some cases may require longer treatment than the 14 days recommended. Fluctuant lymph nodes should be aspirated through healthy skin. Incision and drainage or excision of nodes may delay healing and should not be attempted.

Syphilis

Syphilis is a human infectious disease caused by the bacterium Treponema pallidum . The disease is transmitted by direct contact with a lesion during the primary or secondary stage, in utero by the transplacental route, or during delivery as the baby passes through an infected canal. Like the gonococcus, this bacterium is fragile and dies when removed from the human environment. Unlike the gonococcus, T. pallidum may infect any organ, causing an infinite number of clinical presentations; thus the old adage, “he who knows syphilis knows medicine.”

Incidence

In the United States, the CDC reports that there were 88,042 newly diagnosed (all stages) cases of syphilis in 2016, compared with 39,513 diagnoses of HIV in 2015 ( Fig. 10.6 ). Of the syphilis cases 27,814 were primary and secondary syphilis and the majority occurred among gay, bisexual, and men who have sex with men. This is an increase of 17.6% from 2015. The rates of syphilis have been increasing in heterosexual men and women as well. In 2016, 628 cases of congenital syphilis were reported—the highest since 1998. Congenital syphilis is more likely to occur in infants born to black and Hispanic mothers. In developing countries, several hundred thousand stillbirths and neonatal deaths occur yearly and after malaria, syphilis is the second leading cause of preventable neonatal deaths. Syphilis is becoming a global public health problem (5.6 million new cases per year) with the highest prevalence in Africa and more than 60% of new cases occurring in low-income and middle-income countries. Urban settings in high- and middle-income countries are seeing a resurgence of syphilis in men who have sex with men, as well as an increase in neurosyphilis and ocular syphilis.

Stages

Untreated syphilis may pass through three stages. Syphilis begins with the infectious cutaneous primary and secondary stages that may terminate without further sequelae or may evolve into a latent stage that lasts for months or years before the now-rare tertiary stage, marked by the appearance of cardiovascular, neurologic, and deep cutaneous complications ( Fig. 10.7 ).

The CDC defines the stages of syphilis as follows:

1.

Infectious syphilis includes the stages of primary, secondary, and early latent syphilis of less than 1 year’s duration.
2.

Latent infections (i.e., those lacking clinical manifestations) are detected by serologic testing. Latent syphilis is divided into early latent disease of less than 1 year’s duration and early latent disease of greater than 1 year’s duration.

Late latent disease has a duration of 4 years or longer ( Table 10.12 ).

TABLE 10.12

Staging in Persons With a Diagnosis of Syphilis (i.e., Confirmed Reactive Serology)

From New York City Department of Health and Mental Hygiene and the New York City STD Prevention Training Center. The Diagnosis and Management of Syphilis: An Update and Review. March 2019. Reprinted by permission. The table is based on Nandwani R, Evans D. Are you sure it’s syphilis? a review of false positive serology. Int J STD AIDS 1995;6(4):241–8 and Hook III EW, Marra CM. Acquired syphilis in adults. N Engl J Med 1992;326(16):1060–69.

Stage	Diagnostic Criteria	Probable Exposure Date
Primary	Consistent Exam Findings Usually a single, painless, rubbery ulcer (genital or nongenital) that is found to be positive by dark-field/DFA/PCR or that is highly suspicious for a syphilitic chancre on clinical grounds	Within the past 3 months
Secondary	Consistent Exam Findings (± dark-field positive lesion) • Cutaneous eruption (generalized or localized) without explanation • Palmar or plantar rash • Mucous patches (membranous lesions of tongue, buccal mucosa, lips) • Condylomata lata (moist, flat, whitish-gray plaques) • Patchy alopecia	Within the past 6 months
Early latent	Negative exam (i.e., no findings consistent with primary or secondary syphilis) plus Any of the following within the past 12 months: 1. History of unequivocal symptoms of primary or secondary syphilis or 2. Serologic conversion or 3. A 2 dilution (4-fold) rise in nontreponemal titer in a person who has previously received adequate treatment for a syphilis infection or 4. Exposure to an infectious case of syphilis * or 5. Only possible exposure has been within the past 12 months	Within the past year
Late latent	Negative exam (i.e., no findings consistent with primary or secondary syphilis) plus Any of the following more than 12 months ago: 1. History of unequivocal symptoms of primary or secondary syphilis or 2. Serologic conversion or 3. A 2 dilution (4-fold) rise in nontreponemal titer in a person who has previously received adequate treatment for a syphilis infection or 4. Exposure to an infectious case of syphilis * or 5. No possible exposure within the past 12 months	Longer than 1 year ago
Latent syphilis of unknown duration	No signs or symptoms of primary or secondary syphilis and insufficient information to determine the duration of infection or the most likely time of exposure	Uncertain If the nontreponemal titer is ≥1:32, there is a greater likelihood of recent infection (i.e., within the previous 12 months)