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 Gonorrhea
Treatment and Management
Considerations for the Male Patient
N
eisseria gonorrhoeae is the sec-
ond most common commu-
nicable disease in the United
States, behind Chlamydia trachomatis.1
The CDC estimates that >800,000
new cases of N gonorrhoeae infection
occur every year in the United States.1
From 2010 to 2014, the national rate
of reported N gonorrhoeae infection
increased 10.5%, from 100.2 cases
to 110.7 cases per 100,000 people
(FIGURE 1).2 This increase is primar-
ily due to an upsurge in the number
of males who contracted N gonor-
rhoeae.2
Classification
N gonorrhoeae infections may be clas-
sified as either uncomplicated or
complicated. Uncomplicated infections
are much more common, encompass-
Brian Dalke, Fourth-Year Pharmacy Student
Timothy Ivers, Fourth-Year Pharmacy Student
Karen K. O’Brien, BS Pharm, PharmD, RPh
Assistant Professor of Pharmacy Sciences
Shana Castillo, PharmD, MBA, RPh
Assistant Professor of Pharmacy Practice
Eric Hoie, PharmD, RPh
Associate Professor of Pharmacy Practice
Kimberley Begley, PharmD, RPh
Associate Professor of Pharmacy Practice
Creighton University School of Pharmacy &
Health Professions
Omaha, Nebraska
U.S. Pharmacist • August 2016 • www.uspharmacist.com
© iStock.com / JobsonHealthcare
ABSTRACT: Gonorrhea is the second most common
communicable disease in the United States. From 2010 to
2014, the rate of this sexually transmitted disease increased
by 10.5% in the U.S. Cefixime, which was once the first-line
agent for the treatment of Neisseria gonorrhoeae, is rapidly
waning in efficacy, as are several other cephalosporins.
Similarly, fluoroquinolone-resistant strains of N gonorrhoeae
have been reported. As a result, the use of these agents has
decreased. The CDC currently recommends dual treatment
with ceftriaxone and azithromycin for most gonococcal
infections. Multidrug-resistant gonorrhea is becoming a
serious health threat in the U.S.
ing any urogenital, anogenital, or of N gonorrhoeae infection; and trad-
pharyngeal infection caused by N ing sex for money, drugs, or other
gonorrhoeae that does not result in items.1
bacteremia. An N gonorrhoeae infec- To help prevent the spread of infec-
tion that results in bacteremia and/ tion, the CDC recommends that all
or the spread of bacteria to joints and sexually active women aged <25 years,
tissues is considered a complicated as well as older women with multiple
infection.3,4 risk factors, be screened for N gonor-
rhoeae annually. Men who have had
Risk Factors sexual contact with other males within
Risk factors for N gonorrhoeae include the preceding year should be screened
sexual contact with new or multiple at least annually at the site of possible
partners, sexual contact with an indi- exposure (i.e., urethral, rectal, or pha-
vidual who has concurrent partners, ryngeal). Men aged <35 years and
and sexual contact with a person who women aged <30 years who reside in
is currently infected with N gonor- correctional facilities should be
rhoeae. Other risk factors include screened for N gonorrhoeae at the time
inconsistent condom use while engag- of intake, regardless of risk factors.
ing in sexual contact with nonmo- Pregnant women aged <25 years should
nogamous partners; previous history be screened at the first prenatal visit.1
1
 GONORRHEA TREATMENT AND MANAGEMENT
250
Rate (per 100,000 population)
200
150
100
50
0
1994 1996 1998 2000 2002 2004 2006 2008 2010 2012 2014
Year
Figure 1. Rates of reported cases of gonorrhea in men and women in the United States, 1994–2014.
Source: Reference 2.
Clinical Signs and Symptoms
Many genital gonococcal infections are asymptomatic;
however, these infections are more likely to be symp-
tomatic in men than in women.5 Male urogenital symp-
toms include signs of urethritis or epididymitis, such as
dysuria or unilateral testicular swelling.5 Males with
extragenital infections of the rectum are often asymp-
tomatic, but patients may present with signs of procti-
tis, such as constipation, rectal pain, and rectal bleeding.5
Those with pharyngeal gonococcal infections are usually
asymptomatic, but if symptoms are present, they may
include sore throat and pharyngeal exudates.5
Symptoms of N gonorrhoeae often prompt men to
seek medical attention prior to the development of
complications, but not soon enough to prevent transmis-
sion to other people. Most women remain asymptomatic
until the development of complications such as pelvic
inflammatory disease.1
Several sexually transmitted and non–sexually trans-
mitted pathogens, as well as certain noninfectious
processes, may present with signs and symptoms that
are similar to those occurring in N gonorrhoeae infec-
tion. Therefore, a preliminary diagnosis based on history
and physical examination should be confirmed through
microbiologic testing.5 Nucleic acid amplification test-
ing (NAAT) is typically used for initial microbiologic
confirmation of N gonorrhoeae; in addition, cultures
may be required if antibiotic resistance is a concern.
For males, a urethral swab is sufficient for NAAT, but
females should receive a vaginal or endometrial swab.
Regardless of symptoms, the NAAT method should be
implemented prior to a confirmed diagnosis of N gon-
orrhoeae infection.5 Suspected N gonorrhoeae infections
are often treated empirically before completion of
NAAT.4
U.S. Pharmacist • August 2016 • www.uspharmacist.com
Men
Women
Total
Treatment
N gonorrhoeae is well known for its ability to adapt to
and resist microbial therapies. Updated guidelines were
published in 2015, including new treatment regimens for
multidrug-resistant N gonorrhoeae.1 See TABLE 1 for a
summary of treatment regimens for gonococcal infections.
The new recommendation for the treatment of uncom-
plicated gonococcal infections of the cervix, urethra, and
rectum is for a single dose of ceftriaxone 250 mg given
IM, in addition to a single dose of azithromycin 1 g given
orally. These medications should be administered in the
healthcare provider’s clinic under direct supervision, if
possible, to ensure that the patient completes therapy.1
Azithromycin is preferred over a tetracycline because it
has a lower rate of N gonorrhoeae resistance.
Another key consideration in therapeutic decision
making is patient adherence, which is more likely with
a one-time oral dose of azithromycin than with alterna-
tive multidose therapy. Moreover, azithromycin is an
effective therapeutic option for uncomplicated genital C
trachomatis infections. Therefore, this dual-therapy regi-
men is an appealing option because of the possibility of
gonococcal and chlamydial coinfection.1 Doxycycline
may be used as an alternative if the patient is allergic to
azithromycin. If doxycycline is used, it should be dosed
at 100 mg orally twice daily for 7 days.1 In male patients,
doxycycline may also be used to treat epididymitis or
proctitis caused by gonococcal infections.4
If ceftriaxone is not available at the time of treatment,
cefixime may be used as an alternative. However, N gonor-
rhoeae has developed increased resistance to cefixime. For
this reason, cefixime should be used only when ceftriaxone
is not available.1,2 When used, cefixime should be given
as a single oral dose of 400 mg.1 If the patient has a
cephalosporin allergy, dual treatment with single oral doses
2
 GONORRHEA TREATMENT AND MANAGEMENT

Table 1. Treatment Regimens for Gonococcal Infections

Type of Infection Regimen Duration of Therapy
Uncomplicated Recommended: ceftriaxone 250 mg Recommended: Ceftriaxone and azithromycin are both
gonococcal IM + azithromycin 1 g po single doses
infections of Alternative: cefixime 400 mg po + Alternative: Cefixime and azithromycin are both single
the cervix, azithromycin 1 g po doses
urethra, and Cephalosporin allergy: gemifloxacin Cephalosporin allergy: Gemifloxacin and azithromycin are
rectum 320 mg po + azithromycin 2 g po both single doses
Azithromycin allergy: ceftriaxone 250 mg Azithromycin allergy: Ceftriaxone is a single dose. Continue
IM + doxycycline 100 mg po bid doxycycline for 7 days
Uncomplicated Recommended: ceftriaxone 250 mg Recommended: Ceftriaxone and azithromycin are both
gonococcal IM + azithromycin 1 g po single doses
infections of
the pharynx
Gonococcal Recommended: ceftriaxone 1 g IM or IV Recommended: Continue ceftriaxone for ≥7 days.
arthritis q24h + azithromycin 1 g po Azithromycin is a single dose
Alternative: cefotaxime 1 g IV q8h + Alternative: Continue cefotaxime for ≥7 days. Azithromycin
azithromycin 1 g po is a single dose
Gonococcal Recommended: ceftriaxone 1-2 g IV Recommended: For meningitis, continue ceftriaxone for
meningitis and q12-24h + azithromycin 1 g po 10-14 days. For endocarditis, continue ceftriaxone for 4
endocarditis wk. Azithromycin is a single dose
Source: References 1, 8.

of gemifloxacin 320 mg and azithromycin 2 g is an option.
Alternatively, gentamicin may be given as a single dose of
240 mg IM in place of the gemifloxacin.1
Uncomplicated N gonorrhoeae infections of the phar-
ynx are much more challenging to eradicate than uncom-
plicated urogenital and anorectal infections, and reliable
cure rates of >90% of infections are achieved by very few
antibiotic regimens.1 The CDC currently recommends
that patients with uncomplicated gonococcal infections
of the pharynx be treated with a regimen consisting of
a single dose of ceftriaxone 250 mg IM in addition to a
single oral dose of azithromycin 1 g. Clinical trials showed
that the treatment of pharyngeal infections with ceftri-
axone resulted in a cure rate of 98.9%.1
Patients with uncomplicated gonococcal infections of
the cervix, urethra, and/or rectum do not require a follow-
up test of cure if they are treated with a recommended
first-line or alternative regimen.1 Patients with uncom-
plicated N gonorrhoeae pharyngeal infections do not
require a test of cure if they are treated with ceftriaxone
and azithromycin; however, if an alternative regimen is
used, the patient should return to the physician’s office
14 days after therapy to receive a test of cure.1
Complicated gonococcal infections are much rarer than
uncomplicated infections and may lead to serious condi-
tions, such as septic arthritis, endocarditis, and/or men-
ingitis. Patients with complicated gonococcal infections
resulting in arthritis should receive ceftriaxone 1 g IM or
IV every 24 hours for a minimum of 7 days, in addition
to a single oral azithromycin dose of 1 g. If ceftriaxone is
unavailable, cefotaxime 1 g every 8 hours may be admin-
istered IV for a minimum of 7 days and accompanied by
a single oral azithromycin dose of 1 g.1,6 CDC guidelines
state that patients with arthritis-dermatitis syndrome may
be stepped down to oral therapy guided by antimicrobial
susceptibilities once clinical improvement has been noted
for 24 to 48 hours, for a total therapy duration of at least
7 days. Patients who develop gonorrheal meningitis receive
ceftriaxone 1 to 2 g IV every 12 to 24 hours for 10 to 14
days, plus a single oral dose of azithromycin 1 g. Patients
who develop gonorrheal endocarditis should receive the
same agents, but ceftriaxone should be administered for
at least 4 weeks.1
Antibiotic Resistance
When treating gonococcal infections, providers should
be aware of possible antibiotic resistance. Researchers are
concerned about the emergence of N gonorrhoeae as a
superbug and its potential future resistance to all classes
of antibiotics.7 Penicillin was once widely used to treat
N gonorrhoeae, resulting in a mutation that allowed N
gonorrhoeae to produce beta-lactamase. This enzyme is
responsible for breaking down the beta-lactam ring of
penicillin and rendering the bacteria nonsusceptible to
penicillin’s therapeutic effects.8 Quinolones were also
previously employed as a gonococcal treatment option.
In 2005, quinolone-resistant N gonorrhoeae was reported
at 89% of locations of the Gonococcal Isolate Surveil-

3
U.S. Pharmacist • August 2016 • www.uspharmacist.com
 GONORRHEA TREATMENT AND MANAGEMENT
lance Project (a service that monitors and reports trends
of N gonorrhoeae infections in the U.S.). Because of this
resistance, quinolones are no longer recommended for
the first-line treatment of any type of gonococcal infec-
tion.3 Azithromycin monotherapy given as a single oral
dose of 2 g has demonstrated effectiveness against uncom-
plicated urogenital gonorrhea; however, it is not recom-
mended because N gonorrhoeae has the ability to easily
develop resistance to macrolides and because this regimen
has the potential for increased gastrointestinal side effects.1,3,9
Although cephalosporins remain the drug class most
effective for treating gonococcal infections, some reduc-
tions in susceptibility have been documented.3,9
Since the 1930s, gonorrhea has been treated with, and
developed resistance to, sulfonamides, penicillin, tetracycline,
spectinomycin, quinolones, macrolides, and some cepha-
losporins.7 Antimicrobial stewardship, prescriber awareness,
and appropriate patient education can help prevent N
gonorrhoeae from developing resistance to ceftriaxone.
In 2012, the World Health Organization developed
a global action plan to reduce antibiotic resistance to N
gonorrhoeae.10 The plan includes encouraging early detec-
tion and effective treatment, fostering patient compliance,
educating patients, improving surveillance and laboratory
capacities, increasing advocacy, and ensuring that appro-
priate legislative and regulatory mechanisms are in place.10
Fostering patient compliance is especially important when
multidose treatment regimens are employed.
Prevention and Management
Considerations
Appropriate treatment is of paramount importance for
existing gonococcal infections, but preventive measures
must also be considered and discussed with the patient.
Obtaining an accurate sexual history from the patient is
vital. Although it is sometimes uncomfortable to do so,
the healthcare provider and the patient must have a frank
discussion about the patient’s sexual behavior.11 The CDC
emphasizes the use of a sexually transmitted infection
(STI) and HIV risk assessment in counseling high-risk
patients. This may be accomplished by use of the Five
REFERENCES
1. Workowski KA, Bolan GA; CDC. Sexually transmitted diseases treatment guide-
lines, 2015. MMWR Recomm Rep. 2015;64:1-137.
2. CDC. Sexually Transmitted Disease Surveillance 2014. Atlanta, GA: U.S. Depart-
ment of Health and Human Services; 2015.
3. Newman LM, Moran JS, Workowski KA. Update on the management of gonor-
rhea in adults in the United States. Clin Infect Dis. 2007;44(suppl 3):S84-S101.
4. Swygard H, Seña AC, Cohen MS. Treatment of uncomplicated gonococcal
infections. UpToDate. www.uptodate.com/contents/treatment-of-uncomplicated-
gonococcal-infections. Accessed February 12, 2016.
5. Ghanem KG. Clinical manifestations and diagnosis of Neisseria gonorrhoeae
infection in adults and adolescents. UpToDate. www.uptodate.com/contents/clinical-
manifestations-and-diagnosis-of-neisseria-gonorrhoeae-infection-in-adults-and-
adolescents. Accessed February 12, 2016.
4
U.S. Pharmacist • August 2016 • www.uspharmacist.com
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P’s, which are detailed, open-ended questions designed
to elicit more information about a patient’s sexual part-
ners, sexual practices, pregnancy prevention, STI protec-
tion, and past history of STIs.1 The Five P’s method
fosters an open conversation between the healthcare
provider and patient for a better understanding of the
patient’s risk profile. After risk assessment, individualized
counseling based on responses may be undertaken.
Because males with a gonococcal infection often are
asymptomatic, they may remain undiagnosed for an
extended period of time, which makes prevention a key
priority in high-risk male populations. Consistent use of
male condoms should be recommended to all patients.1
The partner of a patient with a gonococcal infection
should be referred for evaluation and probable treatment
if he or she had sexual contact with the patient within
60 days prior to diagnosis or onset of symptoms, or if
he or she was the patient’s last sexual partner. Unprotected
sexual intercourse should be avoided until 7 days after
treatment of both partners, and for as long as either
partner is symptomatic.1
Conclusion
Most new N gonorrhoeae infections in the U.S. are uncom-
plicated and involve the urogenital, anogenital, or pha-
ryngeal area. Complicated infections resulting in bacte-
remia, septic arthritis, endocarditis, or meningitis are less
common. Individuals who engage in unsafe sexual prac-
tices and those with a history of past gonococcal infections
are at increased risk for contracting N gonorrhoeae. Coin-
fection with C trachomatis must be considered in the
selection of the most appropriate treatment. Ceftriaxone
and azithromycin are the recommended first-line regimen
for most N gonorrhoeae infections. To reduce repeat
infections and the growth of potential resistance to dual
therapy, the prevention measures discussed in this article
must be emphasized in both preexposure and postexpo-
sure patient populations. Early detection, appropriate
antibiotic selection, strict adherence to multidose treat-
ment regimens, and communication with the patient are
crucial to the effective management of gonorrhea.
6. Goldenberg DL, Sexton DJ. Disseminated gonococcal infection. UpToDate.
www.uptodate.com/contents/disseminated-gonococcal-infection. Accessed February
17, 2016.
7. Unemo M, Nicholas RA. Emergence of multidrug-resistant, extensively drug-
resistant and untreatable gonorrhea. Future Microbiol. 2012;7:1401-1422.
8. CDC. CDC Grand Rounds: the growing threat of multidrug-resistant gonor-
rhea. MMWR Morb Mortal Wkly Rep. 2013;62:103-106.
9. Kidd S, Workowski KA. Management of gonorrhea in adolescents and adults in
the United States. Clin Infect Dis. 2015;61(suppl 8):S785-S801.
10. World Health Organization. Global action plan to control the spread and
impact of antimicrobial resistance in Neisseria gonorrhoeae. Geneva, Switzerland:
World Health Organization; 2012.
11. McKie RA. Sexually transmitted diseases. www.ahcmedia.com/articles/78496-
sexually-transmitted-diseases. Accessed May 1, 2016.