Running head: ANTIBIOTIC RESISTANT GONORRHEA

Gonorrheas Emerging Resistance to Antibiotic Therapy

Melissa B. Scholtens
Ferris State University

ANTIBIOTIC RESISTANT GONORRHEA

Abstract

Gonorrhea is a sexually transmitted infection that affects males and females in all regions of the
globe. Gonorrhea presents differently between men and women thus making diagnosis and
treatment difficult. Gonorrhea has been dated as far back as the second century with therapies
from the obscure to the generally accepted. Antibiotics were introduced in the 1930s and have
been the gold standard of treatment for a N. gonorrhoeae infection. In the last 50 years
gonorrhea has mutated and altered its DNA structure to evolve into a bacterium that is resistant
to most antimicrobial therapies; thus emerging into an infectious disease posing a threat of
epidemic proportions. The Centers for Disease Control and Prevention (CDC) and the World
Health Organization (WHO) have surveillance systems in place to track and monitor gonorrhea
as well as various strains antimicrobial resistance. With utilization of the surveillance
information in addition to the recommendations of the CDC there is hope for avoidance of a
worldwide epidemic.
Keywords: gonorrhea, antibiotic-resistant gonorrhea, infectious disease

ANTIBIOTIC RESISTANT GONORRHEA

Gonorrheas Emerging Resistance to Antibiotic Therapy

Gonorrhea or Neisseria gonorrhea is the second most prevalent bacterial sexually
transmitted infection in the world (Unemo & Shafer, 2011). Gonorrhea can be contracted by
men or women and is prevalent among people ages 15-24. Gonorrhea can cause infections in the
throat, genitals and rectum (CDC, 2014). Antibiotics were discovered have been and utilized
since in the early 20th century with the introduction of penicillin by A. Fleming; since the
introduction of antibiotics microbes have been altering and evolving thus creating antibiotic
resistance. Neisseria gonorrhea is the organism that is responsible for gonorrhea infections and
this organism has the propensity to rapidly mutate; thus far making it impossible to create a
vaccine to prevent this infection (Rise of antibiotic-resistant gonorrhea needs urgent action,
2011). Gonorrhea is an infection that affects men and women, individuals young and old,
gonorrhea knows no racial or ethnic boundaries and can be found in all parts of the world. With
continued mutation and resistance to traditional antibiotics, the Centers for Disease Control and
Prevention recognize gonorrhea with an urgent threat level indicating that the bacteria is an
immediate public health threat that requires urgent and aggressive action (2013).
Gonorrhea as an emerging infectious disease
In 2012 the World Health Organization and The Centers for Disease Control and
Prevention (CDC) issued to the public an alert and warning that there is an increasing incidence
of strains of antibiotic-resistant gonorrhea (Antibiotic-resistant gonorrhea spurs international
concerns, 2012). An article by Kidd, Kirkcaldy, Weinstick & Bolan reveals that gonorrhea
presents a worldwide public health challenge as more than 88 million new cases of this
infectious disease occurring each year. Initially gonorrhea was easily treated with antibiotic

ANTIBIOTIC RESISTANT GONORRHEA

therapy utilizing a sulfanilamide; however N.gonorrhoeae has systematically gained resistance to

all of the treatment agents that have been recommended for treatment over the last seven
decades. Gonorrhea has now developed resistance to not only sulfonamides, but penicillins,
tetracyclines and most recently fluoroqunolones leaving only cephalosporins of the third
generation as effective treatment last line against this sexually transmitted infection. New
reports suggest that there are now gonorrhea strains developing resistance to 3rd generation
cephalosporins as well. Not only in the United States, but in many countries the first treatment
for gonorrhea is a cephalosporin and if this treatment regimen also becomes useless due to drug
resistance the public health threat becomes uncontrollable (Kidd, Kirkcaldy, Weinstick & Bolan,
2012).
Transmission & Isolation, Clinical Presentation, Diagnosis & Therapy
Analysis of the information provided to the public by The Centers for Disease Control
and Prevention indicated that gonorrhea can be transmitted by having sex either vaginally,
rectally or orally with an individual who is infected with the disease. Although gonorrhea is
proving to be difficult to treat due to mutations and antibiotic-resistance, the organism itself it
fairly fragile and does not live on surfaces outside of the mucosa thus making it impossible to
contract the infection through toilet seats or hard surfaces. In addition to sexual activity, a
woman and pass the gonococcal infection to her child via childbirth. Considering this infection
is not passed from one person to another via casual contact or droplet via a cough or sneeze,
there are not currently any isolation recommendation for this infection. Avoidance or abstinence
from sexual contact with an individual who is affected with this infection will completely
eliminate your risk for disease contraction.

ANTIBIOTIC RESISTANT GONORRHEA

The clinical presentation, or lack of presentation of gonorrhea is one of the reasons that
this infection is difficult to treat and spreads so easily. In men, there are occasions where there
are absolutely no symptoms at all of this infection, however when there are symptoms present
they can include one or more of the following: painful burning urination, a white or yellow or
green discharge from the penis, and painful or swollen testicles. In women clinical
manifestations of gonorrhea become even more unclear as the majority of women exhibit no
symptoms of this infection. If a woman does experience symptoms they are often mistaken for a
bladder or vaginal infection. Symptoms in women can include painful urination, increased
vaginal discharge and vaginal bleeding between periods. Serious complications from gonorrhea
are likely in women even if they do not experience any symptoms and fail to get proper
treatment. These complications include the following: pelvic inflammatory disease, scar tissue
formation of the fallopian tubes, ectopic pregnancy, infertility and long term pelvic/abdominal
pain. If the infection was contracted rectally, the symptoms can include the following: anal
itching, discharge, soreness, bleeding, and painful bowel movements (Centers for Disease
Control and Prevention, 2014).
According to the National Institute of Allergy and Infectious Disease diagnosis of a
gonorrhea infection can be made using one of three laboratory tests. The three laboratory tests
are: staining samples of bacteria, detection of DNA or bacterial genes within the urine and
through the growth of bacteria in laboratory cultures. Frequently healthcare providers utilize
more than one method of detection in an effort to accurately diagnose the infection. Swabs from
the throat, rectum or cervix can be used for detecting the genes; this is a more accurate test than
those just testing for the presence of the bacteria. Cultures of the bacteria allow for the

ANTIBIOTIC RESISTANT GONORRHEA

determination of sensitivity to the treatment regimen (2011). In addition to the clinical tests,
another important aspect of diagnosis is completion of a thorough medical and sexual history.
The best treatment of gonorrhea is prevention. Individuals participating in a
monogamous relationship where neither partner are infected with the infection or the practice of
abstinence is the ideal way to treat gonorrhea by preventing it in the first place. If prevention is
unavoidable, the current treatment as recommended by the Centers for Disease Control and
Prevention is an injection of ceftriaxone coupled with either oral azithromycin or oral
doxycycline. This new recommendation is related to the rising resistance of gonorrhea to
cefixime, not currently within the United States, but abroad as noted by the CDCs Gonococcal
Isolate Surveillance Project (2013). In addition to the treatment of gonorrhea with this therapy it
is recommended that women participating in high-risk sexual activity as well as gay and bisexual
men get tested for gonorrhea annually in an effort to diagnosis this infection sooner so as to
avoid a delay in treatment and potentially numerous other becoming infected (CDC, 2013).
Analysis of the Evidence
Gonorrhea is an infection that has impacted people for centuries although gonorrhea itself
is not an emerging infectious disease; antibiotic resistant gonorrhea is raging and demanding
awareness and recognition as a force to be reckoned with. A thorough review of a JAMA article
in 2013 entitled CDC Grand Rounds: The Growing Threat of Multidrug-Resistant Gonorrhea
highlights the history and treatment of gonorrhea as well as why the current therapy is in
jeopardy of failing. Sulfonamides were introduced in the 1930s as an effective treatment for
gonorrhea and resistance was achieved by the 1940s. In the 1940s penicillin was the gold
standard of treatment, but by the 1970s due to mutations in the bacteria, again resistance to the
treatment occurred. The next recommended therapy was tetracyclines, and by the late 1980s

ANTIBIOTIC RESISTANT GONORRHEA

there was widespread resistance to this gonorrhea treatment within the U.S. During the 1990s
and 2000s the treatment of choice mainly due to safety and effectiveness was fluoroquinolones.
Unfortunately once again due to mutations within the DNA of the bacteria, resistance that began
overseas in Asia made way to the United States and this treatment is now futile due to resistance.
With the failure of all of the above listed classes of antibiotic therapy, the remaining hold out is
an injectable cephalosporin, specifically ceftriaxone in conjunction with oral antibiotics
(azithromycin or doxycycline). There is a definite need for acquisition of new antimicrobial
therapies as well as the development of a vaccination again gonorrhea. If there were to be an
epidemic of cephalosporin resistant gonorrhea, treatment would be complicated as all classes of
antibiotics would now fail to treat the infection. While many other resistant bacteria may later
down the road be effectively treated with an antimicrobial that has been abandoned for year, N.
gonorrhoeae strains may actually have improved resistance in the absence of previously used
antimicrobials (CDC Grand Rounds, 2013).
Factors that Promote this Emerging Infectious Disease
Gonorrhea is a sexually transmitted infection that affects men and women, young and old,
all races and ethnicities across all socioeconomic backgrounds. In an article review by
Groopman, evidence suggests that gonorrhea has been traced back as far as the second century
and has been treated with everything from bloodletting and painful procedures to a variety of
antibiotics. Intimate relations in addition to or in place of sexual intercourse have the potential to
transmit gonorrhea. Oral, vaginal or rectal intercourse has the propensity to cause a gonoccocal
infection even with the utilization of a barrier method. Antibiotic therapy is an effective
treatment if the current recommended therapy is prescribed and assuming the strain of gonorrhea
is not resistant. The emergence of antibiotic-resistant gonorrhea occurs most often with men

ANTIBIOTIC RESISTANT GONORRHEA

having sex with other men and those who work within the sex trade; this is likely due to the
repeated exposure to the bacterial infection. Therefore, those men who have sex with other men
and members of the commercial sex trade are at a disproportionally higher risk of contracting
this infectious disease than those who do not participate in these activities. Overall, in the United
States, gonorrhea is more prevalent among non-Hispanic blacks than among whites and among
people between the ages of 15-24. The adaptive nature of the gonococcus, coupled with the
prevalence of unprotected oral sex, all but insures that the drug-resistant gonorrhea will
eventually take root in the general heterosexual population and if this occurs it can quickly
spread (Groopman, 2012).
A study completed by Moonesinghe, Fleming, Truman and Dean in 2012 evaluated linear
and non-linear associations of a diagnosis of gonorrhea with various social determinants of
health and came to several conclusions. These conclusions include that the most significant
proportions of the population that were diagnosed with gonorrhea were unmarried, black and or a
minority race/ethnicity. Non-Hispanic black persons have had the highest diagnosis rate of
gonorrhea for the past 10 year and in 2010 the diagnosis rate among non-Hispanic blacks was
more than 18 times greater than the rate of whites (Moonesinghe, Fleming, Truman & Dean,
2012).
According to the Centers for Disease Control and Prevention within the United States
there is a surveillance system in place called The Gonococcal Isolate Surveillance Project
(GISP). The purpose of the system is to track and monitor the susceptibility of gonorrhea to
antimicrobial therapy in approximately 30 regions of the U.S, this acts as a representation of the
country as a whole. This data tracks men only and then further subdivided these men into two
categories, men who only have sex with other men and men who only have sex with women.

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Currently ciprofloxacin is the only effective therapy to treat a gonococcal infection and the rising
resistance rates of this bacteria to the last line therapy represents gonorrhea as an emerging
infectious disease. Rates of ciprofloxacin resistant gonorrhea are approximately twice as great
for men who only have sex with men; however, the rates are climbing among the group of men
who only have sex with women. In 2012, the percentages of resistant gonorrhea among the two
groups are 27% resistance among the men-men sex and 8% among the men-women sex
representing a steady increase in the latter group since the inception of this research in 1995
(CDC, 2014).
In 2012 the World Health Organization or WHO, initiated the global action plan to
control the spread and impact of antimicrobial resistance in Neisseria gonorrhoeae with the
primary vision of controlling the spread and decreasing the impact of resistance to the last line
therapy of cephalosporins. With spreading resistance limiting treatment options gonorrhea has
the potential to be untreatable. Within the healthcare community there needs to be an increased
awareness of not only proper diagnosis but the correct prescription of antimicrobial therapies.
Within the communities there is a need for an increased push for education and awareness
especially in the populations that are at an increased risk. Those with greater risk include
adolescents, sex trade workers and men who have sex with men. Reports of clinical treatment
failures with cefixime have been verified and reported from countries as diverse as Japan,
Norway and the United Kingdom of Great Britain and Northern Ireland (WHO, 2012).
Since the era and introduction of antibiotics, gonorrhea has been evolving and evading
treatment therapies. N. gonorrhoeae is a crafty bacterium that genetically alters its DNA and has
created a plethora of antimicrobial resistant strains. Education pertaining to the infection is
important for prevention, and if prevention is unavoidable due to the lack of a vaccine or sexual

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10

abstinence, prompt and proper treatment is crucial. Antibiotic recommendations are given
through the CDC and should be closely followed in an effort to reduce or eliminate resistant
infections. The CDC actively partners with the World Health Organization to monitor and report
all gonococcal infections and that specific infections susceptibility to various treatment
modalities. The bottom line is that without close monitoring and accurate treatment, gonorrhea
has the potential to adapt and maintain resistance to any and all of the available antimicrobial
therapies thus creating the opportunity for an epidemic of global proportions with morbidity and
mortality similar to an era pre-antibiotic discovery.

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