in uncomplicated urinary tract infections. Int J Antimicrob Agents. 2009;34:407–413.
residents. Infect Control Hosp Epidemiol. 2009;30:1116–1119.
Antimicrob Agents. 2010;35:62–67.
community. J Antimicrob Chemother. 2005;56:52–59.
impact. Curr Opin Infect Dis. 2010;23:3206–3213.
urinary tract infections managed in general practice. Int J Antimicrob Agents. 2009;33:255–257.
Database Syst Rev. 2010;(10):CD007182.
Masters PA et al. Trimethoprim-sulfamethoxazole revisited. Arch Intern Med. 2003;163:402–410.
Zinner SH, Mayer KH. Sulfonamides and trimethoprim. In: Bennett JE et al, eds. Mandell, Douglas, and
Raz R et al. Empiric use of trimethoprim-sulfamethoxazole (TMP-SMX) in the treatment of women with
uropathogens. Clin Infect Dis. 2002;34:1165–1169.
Database Syst Rev. 2005;(2):CD004682.
Intern Med. 2007;167:2207–2212.
Phenazopyridine hydrochloride. In: McEvoy GK, ed. AHFS Drug Information®. Bethesda, MD: American
Society of Health-System Pharmacists; 2015. ISBN 978–1-58528–418-4. ISSN 8756–6028. STAT!Ref Online
Electronic Medical Library. http://online.statref.com/Document.aspx?
tract infection in primary care. J Antimicrob Chemother. 2006;58:1000–1008.
Gupta K, Stamm WE. Outcomes associated with trimethoprim/sulfamethoxazole (TMP/SMX) therapy in
TMP/SMX resistant community-acquired UTI. Int J Antimicrob Agents. 2002;19:554–556.
Escherichia coli isolates in Michigan. Clin Infect Dis. 2002;34:1061–1066.
Practice of Infectious Diseases. 8th ed. New York, NY: Churchill Livingstone; 2015:419–439.
Resistance Study. Antimicrob Agents Chemother. 2006;50:2251–2254.
Lin DC, Bhally H. Nitrofurantoin-induced interstitial lung disease. N Z Med J. 2007;120:U2753.
Sabharwal V, Marchant CD. Fluoroquinolone use in children. Pediatr Infect Dis J. 2006;25:257–258.
Scholes D et al. Risk factors associated with acute pyelonephritis in healthy women. Ann Intern Med.
Clin Microbiol Infect. 2014;20:O476.
pharmacokinetic/pharmacodynamic considerations. J Hosp Infect. 2005;60:191–200.
with acute pyelonephritis: a systematic review of randomized controlled trials. Curr Med Res Opin.
treatment of re-infection. Br J Gen Pract. 2010;60:511–513.
Database Syst Rev. 2004;(3):CD001209.
antimicrobials. JAMA. 2007;298:179–186.
2009;361:1748–1759. [published correction appears in N EnglJ Med. 2010;362:1250]
review and meta-analysis. Arch Dis Child. 2010;95:499–508.
populations. Arch intern Med. 2012;172:988–996.
Staphylococcus saprophyticus. Arch Intern Med. 1998;158:281–287.
Enzler MJ et al. Antimicrobial prophylaxis in adults. Mayo Clin Proc. 2011;86:686–701.
nationwide population-based study. Acta Obstet Gynecol. 2010;89:882–888.
randomized controlled trial. Obstet Gynecol. 2009;113:339–345.
Database Syst Rev. 2010;(9):CD007855.
Hamilton-Miller JM. The urethral syndrome and its management. J Antimicrob Chemother. 1994;33(Suppl
Potts JM, Payne CK. Urologic chronic pelvic pain. Pain. 2012;153:755–758.
urinary tract infections. Exp Opin Pharmacother. 2013;14:587–596.
Med. 2005;118(Suppl 7A):14S–20S.
Urethral gonorrhea is initially characterized in males by a purulent
discharge associated with dysuria. Discharge may become more
profuse and blood tinged as the infection progresses. Some strains of
gonorrhea have a propensity to cause asymptomatic or minimally
In females, the most common symptom of urethral gonorrhea is vaginal
discharge. Many women infected with gonorrhea have abnormalities of
the cervix, including purulent or mucopurulent endocervical discharge,
erythema, friability, and edema of the zone of ectopy. Pelvic
inflammatory disease (PID) is a serious complication and can lead to
infertility and chronic pelvic pain.
The standard of treatment for gonorrhea is third-generation
cephalosporins, such as ceftriaxone. Fluoroquinolones should not be
used owing to high levels of resistance.
Depending on the site of exposure, gonococcal infections may also cause
anorectal and pharyngeal infections. Anorectal infections may cause
proctitis with anorectal pain, mucopurulent anorectal discharge,
constipation, tenesmus, and anorectal bleeding. Pharyngeal infections
may be characterized by sore throat, pharyngeal exudates, or cervical
lymphadenitis. The treatment for anorectal or pharyngeal gonorrhea is
Disseminated gonococcal infection (DGI) can lead to complicated
gonorrhea infections that cause pustular acralskin lesions, tenosynovitis,
polyarthralgia, or arthritis. DGI may also lead to rare cases of
perihepatitis, endocarditis, or meningitis. Treatment for DGIs requires
antibiotics; however, clinical efficacy and overall outcomes are equal
between parental and oral therapy.
Nongonococcal urethritis (NGU) is a common sexually transmitted
disease (STD) in males and is frequently caused by Chlamydia
NGU typically produces less severe and less frequent dysuria and less
penile discharge as compared with gonococcal urethritis. NGU and
gonococcal urethritis cannot be reliably differentiated on the basis of
NGU may be treated with either azithromycin or doxycycline; however,
azithromycin is superior in its coverage of both Mycoplasma genitalium
Lymphogranuloma venereum (LGV) is characterized by three stages of
infection and may be treated with either doxycycline, erythromycin
Syphilis is characterized by four stages of infection: primary, secondary,
latent, and tertiary. Penicillin G is the drug of choice for allstages of
The Jarisch–Herxheimer reaction is a benign, self-limited complication of
antibiotic therapy that may develop after treatment of primary and
Uncircumcised males have an increased risk of infection and may not
respond to therapy as well as circumcised males. Current treatment
options include azithromycin, ceftriaxone, ciprofloxacin, and
Common causes of vaginitis include bacterial vaginosis, trichomoniasis,
and vulvovaginal candidiasis. Generalsymptoms may include itching,
burning, irritation, and abnormal discharge and can be differentiated
based on signs, symptoms, and laboratory testing.
Vulvovaginal candidiasis may be effectively treated with nonprescription
medications; however, patients must be assessed fully before selftreatment is initiated.
Genital herpes, transmitted either from symptomatic or asymptomatic
individuals, often presents with painful vesicles in those with HSV-2
primary infection, and recurrent infections are common, although the
frequency decreases with time.
Genital herpes is best treated with oral antivirals, such as acyclovir or
valacyclovir, and prevented with either suppressive or standby antivirals.
Genital HPV warts are highly contagious and may now be prevented by
vaccination, in addition to condoms.
Genital warts often recur even with treatment, which is primarily local,
including antimitotics, immune modulators, chemical and surgical
Sexually transmitted diseases (STDs) are discussed in the earliest written records.
However, only in the last several decades have the common STDs been
differentiated from each other; unique STD syndromes continue to be described
today. For example, of the common STDs, bacterial vaginosis (BV) was not
described clearly as a syndrome (initially called Haemophilus vaginalis vaginitis)
until the 1950s; herpes simplex virus (HSV) type 2 (the cause of genital herpes) was
not differentiated from HSV type 1 until the 1960s; the spectrum of genital chlamydial
infections was not defined until the 1970s; and the human immunodeficiency virus
(HIV) as an STD was not recognized until the 1980s. Since 1980, eight additional
sexually transmitted pathogens have been identified. They include the human
papillomaviruses (HPV), human T-lymphotropic virus (HTLV-I and II), Mycoplasma
genitalium, Mobiluncus species, HIV-1 and -2, and the human herpes virus type 8
(associated with Kaposi sarcoma).
1 More recently, the Centers for Disease Control
and Prevention (CDC) report while hepatitis C virus (HCV) infection is not
efficiently transmitted through sexual contact, men who have sex with men (MSM)
coinfected with HIV are more likely to transmit to HCV than through heterosexual
2 See http://www.cdc.gov/std/training/othertraining.htm for general
resources from the Centers for Disease Control and Prevention for various sexually
Gonorrhea (see http://www.cdc.gov/std/training/clinicalslides/slides-dl.htm for
symptoms of this STD) is caused by Neisseria gonorrhoeae, a gram-negative
diplococcus. Depending on the site of exposure, this disease can cause
uncomplicated cervical, urethral, rectal, and oropharyngeal infections in both males
and females. N. gonorrhoeae infection in women is also a major cause of pelvic
inflammatory disease (PID). Disseminated gonococcal infection (DGI), the bactermic
spread of N. gonorrhoeae to joints and other tissues, can lead to complicated
gonorrhea infections that cause pustular acral skin lesions, tenosynovitis,
polyarthralgia, or arthritis. DGI may lead to rare cases of perihepatitis, endocarditis,
or meningitis. In the 1930s, sulfonamides became the first form of effective
antimicrobial therapy for gonorrhea until penicillins and tetracyclines became the
mainstays of therapy; however, the high levels of resistance to these two
antimicrobial agents have eliminated their use in the treatment of this disease state.
Atlanta, GA: US Dept of Health and Human Services; 2014.
In the United States, the incidence of gonorrhea fell 74.3% between 1975 and 1997
after the establishment of national gonorrhea control programs. From 1996 to 2006,
the rate fluctuated at around 115 cases per 100,000 individuals, and from 2006 to
2009, the rates declined to a historic low of 98.1 cases per 100,000 individuals in
4 After slight rate increases each year from 2009, the national gonorrhea rate
of 106.1 cases per 100,000 individuals in 2013 (representing a total of 333,004
cases) was a decrease from 107.5 in 2012.
4 The current Healthy People 2020 goals
for gonorrhea are 257 cases per 100,000 women aged 15 to 44 and 198 cases per
100,000 men aged 15 to 44 (Fig. 72-1).
5 Although there was a decrease of 9.1% in
gonorrhea rates among African Americans from 2009 to 2013, rates of gonorrhea
remain the highest among African Americans compared to other race and ethnic
groups. During this same time period, all other race and ethnic groups saw an
The highest incidence of gonorrhea is in men aged 20 to 24 years and in women
aged 15 to 24 years of age. Additional risk factors for women acquiring gonorrhea
include a previous gonococcal or other STD infection, new or multiple sex partners,
inconsistent condom use, or engaging in commercial sex work or drug use.
the risk of gonorrhea was greater in homosexual men than in heterosexual men in the
past, the incidence dropped in homosexual men during the 1980s AIDS epidemic,
because of a reduction in sexual risk behaviors. Currently, the incidence of gonorrhea
in MSM continues to rise, from 21.5% in 2006 to 35.1% in 2013.
gonorrhea, what is the likelihood that D.S. and C.S. have been infected?
After one or two episodes of unprotected vaginal intercourse with an
asymptomatic infected prostitute, a man has approximately 50% risk of acquiring a
urethral infection; the risk increases with repeated exposures and high prevalence
7 The prevalence of infection in women who are
secondary sex contacts of infected men is as high as 80% to 90%.
likelihood that D.S. and C.S. are infected is high. Because D.S. had sex with a
prostitute, both D.S. and C.S. should also be tested for HIV infection.
CASE 72-1, QUESTION 2: What signs and symptoms in D.S. are consistent with the diagnosis of
gonorrhea? Describe D.S.’s anticipated clinical course if he remains untreated.
In men, gonorrhea usually becomes clinically apparent 1 to 7 days after contact
with an infected source. A purulent discharge associated with dysuria is the first sign
of infection; D.S. exhibits both. The discharge, which is presumably caused by
chemotactic factors such as C5a released when antigonococcal antibody binds
complement, may become more profuse and blood tinged as the infection progresses.
Some strains of gonorrhea have a propensity to cause asymptomatic or minimally
symptomatic infection with negative Gram stain.
Patients with asymptomatic or minimally symptomatic disease may serve as
reservoirs for the infection, evading treatment for prolonged periods.
only women were thought to have asymptomatic gonorrhea, but now it is known that
men may be asymptomatic carriers as well.
In the area before antimicrobials, gonococci occasionally spread to the
epididymis, causing unilateral epididymitis; the prevalence was 5% or more in
patients in some studies. Now epididymitis occurs in less than 1% of men with
gonorrhea. Urethral stricture after repeated attacks and sterility after epididymitis are
rare complications of gonococcal infection owing to the effectiveness of antibiotics.
CDC Recommendations for Treatment of Uncomplicated Gonorrhea
Cured) Dosage Alternative Regimens
Ceftriaxone (99.2) 250 mg IM once Cephalosporin single dose
a Ceftriaxone (98.9) 250 mg IM once
(administered with probenecid 1 g PO), and cefotaxime 500 mg IM.
Adapted from Workowski KA, Bolan GA; Centers for Disease Control and Prevention (CDC). Sexually
transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64(RR-03):1–137.
CASE 72-1, QUESTION 3: Intracellular gram-negative diplococci were seen on the Gram stain of D.S.’s
urethral exudate. Is any further diagnostic testing required?
Demonstration of intracellular gram-negative diplococci in the gram-stained
exudate confirms the diagnosis in symptomatic men. Until recently, some experts
recommended that cultures be reserved for individuals with negative Gram stain of
urethral exudate. However, today cultures are recommended for all patients to permit
isolation and testing of the bacteria for antibiotic susceptibility. Cultures usually are
performed on Thayer–Martin medium, an enriched chocolate agar to which
vancomycin, colistimethate, and nystatin have been added. Cultures from the throat
should be obtained if D.S. were exposed by cunnilingus to the prostitute. In D.S.’s
case, a urethral culture is indicated.
CASE 72-1, QUESTION 4: C.S., D.S.’s wife, is asymptomatic. What symptoms would be consistent with
Urogenital gonococcal infections in women are commonly asymptomatic. Because
the endocervical canal is the primary site of urogenital gonococcal infection in
women, the most common symptom is vaginal discharge. Many women infected with
gonorrhea have abnormalities of the cervix, including purulent or mucopurulent
endocervical discharge, erythema, friability, and edema of the zone of ectopy.
incubation period for urogenital gonorrhea in women is variable.
complication in 10% to 20% of women with acute gonococcal infection and can lead
to infertility and chronic pelvic pain.
12 The assessment of signs and symptoms in
women with gonorrhea often is confounded by nonspecific signs and symptoms and a
high prevalence of coexisting infection, especially with Chlamydia trachomatis or
Although lower genital tract symptoms in women may disappear, they remain
carriers of N. gonorrhoeae and should be treated. Complications of urogenital
gonorrhea in pregnancy include spontaneous abortion, premature rupture of the fetal
membranes, premature delivery, and acute chorioamnionitis.
include gonococcal arthritis (see Case 72-4, Question 1) conjunctivitis, and
ophthalmia neonatorum in the newborn.
15 For these reasons, it is critical that C.S. be
worked up thoroughly for gonorrhea.
CASE 72-1, QUESTION 5: How should gonorrhea be ruled out in C.S.?
Nucleic acid amplification tests (NAATs), such as polymerase chain reaction, are
recommended for the detection of N. gonorrhoeae at urogenital sites in men and
women regardless if symptoms are present.
approved for the detection of N. gonorrhoeae at non-urogenital sites, laboratories
should meet CLIA requirements and performance specifications for use with rectal
and oropharyngeal specimens; NAATs are the recommended detection method for
rectal and orophyaryngeal specimens. Although culture for N. gonorrhoeae is not
ideal for routine diagnosis, cultures should be performed for isolation and
identification, antibiotic susceptibility, and resistance surveillance. Cultures should
also be performed in cases of suspected treatment failures, defined as those that have
received CDC-recommended treatment and subsequently has a positive N.
gonorrhoeae test result 7 days after treatment and did not engage in sexual activity
In C.S., a NAAT from anal specimen also could be performed
because the rectum can serve as a reservoir for gonococci.
CASE 72-1, QUESTION 6: Compare the various drug regimens used for uncomplicated gonorrhea.
The CDC recommendations are summarized in Table 72-1. Many strains of N.
gonorrhoeae exhibit plasmid-mediated resistance to penicillin and tetracycline
(penicillinase-producing N. gonorrhoeae [PPNG] and/or tetracycline-resistant N.
gonorrhoeae [TRNG], respectively (Fig. 72-2). In addition, significant levels of
chromosomally mediated resistance to penicillin, tetracycline, and cefoxitin have
In 2013, all isolates in the Gonococcal Isolate Surveillance Project
(GISP) were susceptible to ceftriaxone; therefore, a single dose of intramuscular
(IM) ceftriaxone 250 mg is preferred for the treatment of gonorrhea.
400 mg orally (PO) as a single dose is no longer recommended as a first-line
treatment by the CDC but as an alternative option when ceftriaxone cannot be used.
Because of the emergence of high levels of quinolone-resistant N. gonorrhoeae
(QRNG), the CDC no longer recommends the use of fluroquinolones, such as
ciprofloxacin and ofloxacin, for the treatment of gonorrhea.
percentage of patients with gonorrhea are also coinfected with C. trachomatis, a
single dose of azithromycin is recommended to be taken concurrently for a presumed
infection (see Case 72-1, Question 7).
Intramuscular spectinomycin, which traditionally had been used in individuals who
could not tolerate fluoroquinolones or cephalosporins, is still unavailable from the
21 Although limited data exists for treatment of gonorrhea in patients
with cephalosporin or IgE-mediated penicillin allergy, potential alternative
treatments are a single dose of gemifloxacin 320 mg PO plus azithromycin 2 g PO, or
a single dose of gentamicin 240 mg intramuscularly plus azithromycin 2 g PO.
Individuals who have either penicillin or cephalosporin allergies should be
desensitized to cephalosporins before treatment begins.
tetracycline-resistant N. gonorrhoeae; and QRNG, quinolone-resistant N. gonorrhoeae.
Ceftriaxone and Other Cephalosporins
Ceftriaxone, a third-generation cephalosporin, is given as a single, small-volume IM
injection that eradicates gonorrhea at all anatomic sites and is also safe in pregnancy
(U.S. Food and Drug Administration [FDA] pregnancy category B). Ceftriaxone is
ineffective against C. trachomatis and in the prevention of postgonococcal urethritis,
whereas ofloxacin and levofloxacin for 7 days have similar efficacy to doxycycline.
Other injectable cephalosporins (notably ceftizoxime, cefoxitin, and cefotaxime)
have been found to be safe and highly effective, but they do not offer any advantage
over ceftriaxone for urogenital infections, and their efficacy in pharyngeal infections
is not as well-established. A single oral dose of cefixime 400 mg is also effective in
curing 92.3% of uncomplicated urogenital and anorectal gonorrhea infections.
