regimen should be treated based on antimicrobial susceptibility
TABLE 1 Centers for Disease Control and Prevention 2015 testing results in consultation with an infectious diseases
Treatment Recommendations for Complicated
and Uncomplicated Gonorrhea
DISEASE TREATMENT
Uncomplicated infections Ceftriaxone (Rocephin) 250 mg IM
1
of the cervix, urethra,
plus
and rectum*
Azithromycin (Zithromax) 1 g PO
1
Infections of the pharynx As above
Epididymitis Ceftriaxone (Rocephin) 250 mg IM
1
plus
Azithromycin (Zithromax) 1 g PO
bid
10 d
Gonococcal Ceftriaxone (Rocephin) 1 g IM
1
conjunctivitis plus
Azithromycin (Zithromax) 1 g PO
1
Disseminated gonococcal Ceftriaxone (Rocephin) 1 g IM or IV q24h
infections plus
Azithromycin (Zithromax) 1 g PO
1
*Alternative regimen: Cefixime 400 mg PO plus azithromycin (Zithromax) 1 g PO.
13 The Sexually Transmitted Diseases
(Bactrim),1 and fluoroquinolones has made the treatment of gon-
orrhea more challenging.
Fluoroquinolone-resistant N. gonorrhoeae (FQRNG) strains
emerged in the 1990s. In April 2007, the CDC recommended that
fluoroquinolones not be used to treat gonococcal infections in the
United States.
Table 1 summarizes the 2015 CDC recommendations for treating
gonococcal infections. There have been no reports of ceftriaxone-
resistant strains in the United States, although strains resistant to
oral cephalosporins have been reported. Increasing MICs to cepha-
losporins prompted the CDC to recommend dual therapy for gon-
orrhea using cephalosporins and either azithromycin (Zithromax)
or doxycycline (Vibramycin)—even if concomitant infection with
Chlamydia trachomatis is excluded. Ceftriaxone (Rocephin), the
preferred cephalosporin, is given intramuscularly and is effective
914
for infections at all sites. Cefixime (Suprax) is effective for anogenital
infections, but it may have lower efficacy than ceftriaxone for pha-
ryngeal infections. Cephalosporins and macrolides are safe to use in
pregnancy. All sexual contacts in the preceding 60 days of index
patients should also be treated.
For penicillin-allergic patients, treatment of gonorrhea has
become more challenging. Initially, spectinomycin was recom-
mended as a second-line agent. Spectinomycin has only 80% effi-
cacy in treating pharyngeal gonococcal infections, but
spectinomycin is no longer available in the United States.
Alternative regimens include a single dose of azithromycin
(Zithromax) 2 g PO. This regimen has excellent activity against
anogenital and pharyngeal infections. Azithromycin has been used
in pregnant women without evidence of teratogenicity. Cases of
high-level resistance to azithromycin have been described recently
in the United States. Another approved alternative regimen is cefix-
ime 400 mg PO plus either 1 g of azithromycin or 1 week of oral
doxycycline.
If any alternative regimen is used, a test of cure within 2 weeks
following therapy is currently recommended by the CDC. Sus-
pected treatment failures should prompt clinicians to obtain cul-
tures and antimicrobial susceptibility testing. Treatment failures
following therapy with an alternative regimen must be treated
with ceftriaxone 250 mg IM plus azithromycin 2 g PO. Con-
firmed treatment failures using the preferred ceftriaxone-based
1 rescreened 3 to 6 months after treatment.
Not FDA approved for this indication.
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specialist.
To prevent gonococcal ophthalmia neonatorum, 1% silver
nitrate aqueous solution, 0.5% erythromycin ophthalmic ointment
(Ilotycin), or 1% tetracycline ophthalmic ointment1 should be
instilled into the eyes of all newborns. Treatment of gonococcal
ophthalmia requires hospitalization, evaluation for evidence of dis-
seminated infection, and ceftriaxone (Rocephin) 25 to 50 mg/kg
IM or IV
1 dose.
Prevention and Screening
Abstinence from sexual intercourse is the single most reliable
method of preventing infection. Male condoms, when used cor-
rectly and consistently, are highly effective in preventing infection.
Diaphragms may help prevent gonococcal infections in women.
There have not been any successful vaccine candidates.
The CDC does not recommend universal screening for N. gonor-
rhoeae. All sexually active men who have sex with men should be
screened annually at all sites of exposure. High-risk women (e.g.,
multiple sexual partners, illicit drug use, history of gonorrhea or
other sexually transmitted infection, commercial sex worker,
inconsistent condom use) should be screened. Up to 20% persons
diagnosed with gonorrhea become reinfected in the next few
months. Rescreening 3 months after infection is treated is recom-
mended in both men and women. High-risk pregnant women
should be screened during the first prenatal visit. Repeat testing
during the third trimester for those at continued risk is
recommended.
References
Centers for Disease Control and Prevention: Update to CDC’s sexually trans-
mitted diseases treatment guidelines, 2010: oral cephalosporins no longer a
recommended treatment for gonococcal infections, MMWR 61:590–594,
2012.
Deguchi T, et al: Management of pharyngeal gonorrhea is crucial to prevent the emer-
gence and spread of antibiotic-resistant Neisseria gonorrhoeae, Antimicrob Agents
Chemother 56:4039–4040, 2012.
Katz KA, Pierce EF, Aiem H, et al: Neisseria gonorrhoeae with reduced suscep-
tibility to azithromycin—San Diego County, CA, 2009, MMWR 60:579–581,
2011.
Kircaldy RD, et al: Cephalosporin-resistant gonorrhea in North America, JAMA
309:185–187, 2013.
Workowski KA: Chlamydia and gonorrhea, Ann Int Med 158:ITC2–1, 2013.
Workowski KA, Berman SM: For the Centers for Disease Control and Prevention.
Sexually transmitted diseases treatment guidelines, 2010, MMWR Morb Mortal
Wkly Rep 59(RR-2):1–114, 2010.
NONGONOCOCCAL URETHRITIS
Method of
Robert S. Freelove, MD
CURRENT DIAGNOSIS
• Urethritis is diagnosed by the presence of mucopurulent/puru-
lent urethral discharge, >5 WBC/hpf on Gram stain of urethral
secretions, a positive leukocyte esterase test or 10 WBC/hpf on
microscopic examination of first-void urine.
• Testing first-void urine/urethral discharge using NAAT has
replaced culture as the “gold standard” in diagnosis of
chlamydial NGU.
• Test for cure is indicated in pregnant women and should wait at
least 3 to 4 weeks after treatment.
• Patients with confirmed Chlamydia infection should be
 CURRENT THERAPY
• Treatment of choice is azithromycin (Zithromax) 1 g orally in a
single dose.
• Other first-line treatment is doxycycline (Vibramycin) 100 mg
orally twice a day for 7 days.
• If test results are not immediately available, patients should
receive concurrent treatment for gonorrhea with ceftriaxone
(Rocephin) 250 mg IM.
• Expedited partner therapy should be offered where allowed.
• Persistent symptoms in compliant patients who have not been
reexposed can be treated with metronidazole (Flagyl) 2 g orally
in a single dose.
Epidemiology
Chlamydia trachomatis is the most common pathogen identified in
nongonococcal urethritis (NGU) in men. Other potential causes
include Mycoplasma genitalium, Trichomonas vaginalis, herpes
simplex virus, adenovirus, and urethral trauma. Chlamydia is
the most commonly reported sexually transmitted infection (STI)
in the United States. Determining the exact prevalence of C. tracho-
matis infection is difficult, because most infected individuals are
asymptomatic. Additionally, although screening commonly occurs
in women, empiric treatment without confirmatory testing is rou-
tinely extended to sexual partners of those who test positive. While
1,307,893 cases were reported to the CDC in 2010, the estimated
prevalence is 2.8 million.
Risk Factors
C. trachomatis infection is associated with young age (less than
25 years), multiple sex partners, history of prior STI, low condom
use, cervical ectopy, lower socioeconomic status, and low/interme-
diate education. Insertive oral sex among men who have sex with
men is associated with urethritis caused by HSV or adenovirus. Post-
traumatic urethritis is 10 times more likely in patients using latex
catheters than silicone catheters for intermittent catheterization.
Pathophysiology
Urethritis is inflammation of the urethra caused by infection or trau-
matic injury. The term nongonococcal urethritis is typically reserved
to describe an STI of the male urethra with a negative Gram stain of
urethral discharge, most commonly due to Chlamydia. In women,
urethral infection often accompanies chlamydial cervicitis.
C. trachomatis is an obligate intracellular parasite with a two-
phase life cycle: an extracellular, nonreplicating, infectious elemen-
tary body; and an intracellular, replicating, noninfectious reticulate
body. A cycle can take 3 to 5 days, requiring prolonged courses of
treatment. Immunity to infection is relatively short-lived, contrib-
uting to reinfection or persistent infection.
Prevention
Primary prevention of NGU relies on education regarding chla-
mydial infection targeted at adolescents and young adults. Educa-
tion should include promotion of behavioral changes aimed at
reducing the risk of acquiring and transmitting STIs such as absti-
nence from sexual activity, delaying coitarche, reducing the num-
ber of sexual partners, and consistent and correct condom use.
Because most infections in males and females are asymptomatic,
screening at-risk individuals is a cornerstone of secondary preven-
tion. As most reproductive complications of Chlamydia infection
occur in women, the CDC recommends annual screening of all
sexually active, nonpregnant women 25 years old or younger and
sexually active older women with a new partner or multiple part-
ners. Because of the potential for maternal complications and trans-
mission to the neonate, the CDC also recommends screening all
pregnant women regardless of age. The CDC reserves screening
of males for those at highest risk, including men attending STI
clinics, under age 30 in the military, in correctional facilities, whose
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Figure 1. Mucopurulent urethral discharge in patient with NGU.
partners test positive, and who have sex with men. The United States
Preventive Services Task Force recommends screening all sexually
Nongonococcal Urethritis
active and pregnant women age 24 or younger; recommends screen-
ing women age 25 or older only if they are at increased risk, whether
or not they are pregnant; and concludes that there is insufficient evi-
dence to assess benefits and harms of screening in men.
Clinical Manifestations
Many patients with NGU are asymptomatic, including up to 42%
of men and 75% of women. The most common complaints are of
urethral discharge and/or dysuria, usually appearing 1 to 3 weeks
after exposure. The discharge can be watery, mucoid, or muco-
purulent (Figure 1). The dysuria is commonly described as a burn-
ing sensation. Men may also have some itching and/or redness at
the urethral meatus. Symptoms appear 1 to 3 weeks after exposure. 915
Physical examination should include inspection for inguinal
lymphadenopathy, ulcers, and/or urethral discharge.
Diagnosis
Urethritis is diagnosed clinically based on the presence of muco-
purulent or purulent urethral discharge, greater than 5 WBC/hpf
on Gram stain of urethral secretions, a positive leukocyte esterase
test on first-void urine or 10 WBC/hpf or greater on microscopic
examination of first-void urine sediment. All patients who have
confirmed or suspected urethritis should be tested for both gonor-
rhea and chlamydia, and consideration should be given to check for
other STIs. C. trachomatis cannot be cultured on artificial media
and instead requires a tissue culture. However, nucleic acid ampli-
fication techniques (NAAT) are both sensitive and specific and
have replaced culture as the “gold standard” in diagnosis of chla-
mydial NGU. Testing can be performed on urethral specimens or
on urine. Performing the testing on urine avoids invasive sampling
of the urethra and may improve patient acceptance. Testing first-
morning void improves detection rate.
Differential Diagnosis
The differential diagnoses include gonococcal urethritis, urinary
tract infection (UTI), and urethritis caused by M. genitalium,
HSV, and T. vaginalis. The incubation period for gonococcal ure-
thritis is typically shorter and the discharge is more copious and
purulent. UTIs usually cause more dysuria as well as other urinary
symptoms, and bacteria can often be identified on Gram stain dur-
ing urinalysis.

13 The Sexually Transmitted Diseases
916
Therapy (or Treatment)
Treatment for chlamydial urethritis should be initiated immediately
after diagnosis, ideally observed and in the health-care provider’s
office to ensure compliance. Recommended first-line agents are azi-
thromycin (Zithromax) 1 g orally in a single dose or doxycycline
(Vibramycin) 100 mg orally twice a day for 7 days. Alternative reg-
imens include erythromycin base (Ery-Tab) 500 mg orally four
times a day for 7 days; or erythromycin ethylsuccinate (E.E.S.)
800 mg orally four times a day for 7 days; or ofloxacin (Floxin)
300 mg orally twice a day for 7 days; or levofloxacin (Levaquin)
500 mg orally once daily for 7 days. Patients with confirmed urethri-
tis in whom test results are not already known or immediately avail-
able should also be treated empirically for gonorrhea with
ceftriaxone (Rocephin) 250 mg intramuscularly in a single dose.
All sexual partners should be referred for evaluation and treatment.
Alternatively, expedited partner therapy (EPT), providing prescrip-
tions or medications to the patient to take to his/her partner, should
be offered where allowed; EPT has been shown to increase partner
treatment and reduce reinfection. Patients with symptoms of persis-
tent or recurrent infection can be re-treated with the initial regimen if
they were not compliant with treatment or have been reexposed to
an untreated partner. If the patient was compliant and was not reex-
posed, he or she should be treated with metronidazole (Flagyl) 2 g
orally in a single dose; or tinidazole (Tindamax) 2 g orally in a single
dose plus azithromycin (Zithromax) 1 g orally in a single dose.
Monitoring
Testing for cure is not recommended except in pregnant women or
those in whom therapeutic compliance is in question, and must
wait for at least 3 to 4 weeks after treatment, because NAAT
may be positive in the presence of dead organisms. All patients with
Chlamydia infection should be screened again 3 to 6 months after
treatment.
Complications
In men, untreated chlamydial NGU can lead to epididymitis and/or
prostatitis. Reactive arthritis is an uncommon complication in men,
as is Reiter syndrome (arthritis, conjunctivitis/uveitis, urethritis,
mucocutaneous lesions). In women, concurrent cervicitis can lead
to PID. Transmission to newborns can result in conjunctivitis or
pneumonia.
References
Workowski KA, Berman S: Centers for Disease Control and Prevention. Sexually
transmitted diseases treatment guidelines, 2010, MMWR 59(RR-12):1–110, 2010.
Centers for Disease Control and Prevention. STD trends in the United States: 2010
national data for gonorrhea, chlamydia, and syphilis. Table. http://www.cdc.
gov/std/stats10/tables/trends-table.htm; [accessed 05.08.13].
Centers for Disease Control and Prevention: Expedited partner therapy in the man-
agement of sexually transmitted diseases, Atlanta, GA, 2006, US Department of
Health and Human Services.
U.S. Preventive Services Task Force: Screening for chlamydial infection: U.S. Preven-
tive Services Task Force Recommendation Statement, Ann Intern Med
147:128–133, 2007.
SYPHILIS
Method of
Jennifer Frank, MD
CURRENT DIAGNOSIS
• Serologic testing includes both nontreponemal-specific testing
(VDRL and RPR) and treponemal-specific testing (FTA-Abs [fluo-
rescent treponemal antibody absorption] and TP-PA [Trepo-
nema pallidum particle agglutination]).
• Cerebrospinal fluid testing (VDRL [Venereal Disease Research
Laboratory], protein, cell count) is performed to diagnose
neurosyphilis.
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CURRENT THERAPY
• Penicillin is first-line therapy for all types and stages of syphilis.
• Penicillin is the only recommended treatment for pregnant
women and for congenital syphilis. Penicillin-allergic patients
should undergo desensitization.
Epidemiology
The rate of primary and secondary syphilis reached a low point
(2.1 per 100,000) in 2000 and has increased since that time, reach-
ing a rate of 7.5 per 100,000 in 2015. The recent increase in rates
has occurred in both men and women, in all regions, in all age
groups between 15 and 44 years of age, and in all ethnicities except
for Native Hawaiians/Other Pacific Islanders. Men who have sex
with men (MSM) have the highest rates of primary and secondary
syphilis. Increased rates were also seen in men ages 20-29, in the
West and South, and in black men. Congenital syphilis is also
increasing with a rate of 12.4 cases per 100,000 live births in 2015.
Risk Factors
MSM and HIV-positive persons are at highest risk for primary and
secondary syphilis. Other risk factors include living in the southern
part of the United States or an urban area, young age (20 to
29 years), and being born to a mother infected with syphilis.
Pathophysiology
Syphilis is caused by infection with the spirochete Treponema pal-
lidum subspecies pallidum (Figure 1). Primary infection manifests
with signs and symptoms at the site of infection; secondary and ter-
tiary syphilis manifest with systemic signs and symptoms. Syphilis
is primarily sexually transmitted but may be transmitted perina-
tally or through nonsexual cutaneous transmission.
Prevention
Prevention includes both avoiding initial infection and preventing
disease progression through early detection and treatment. Trans-
mission of syphilis can be reduced (although not eliminated) by
using condoms. Screening for syphilis in pregnancy combined with
treatment of infected women reduces perinatal transmission.
Clinical Manifestations
Primary syphilis manifests as a chancre at the site of inoculation.
The chancre, a painless ulcer with sharp borders, is usually solitary
and associated with regional lymphadenopathy. Atypical presenta-
tions include extragenital location (most commonly oral or anal)
and the presence of pain or multiple lesions. Secondary syphilis
characteristically manifests with a generalized rash with variable
features (Figure 2). The palms and soles are affected in the majority
of patients. Typically, the rash is maculopapular or papulosqua-
mous and nonpruritic. Other clinical manifestations include highly
Figure 1. Treponema pallidum on darkfield microscopy.