Gonorrhea is one of the most common and oldest known sexually transmitted diseases (STDs). This condition is a purulent infection of mucous membrane surfaces caused by Neisseria gonorrhoeae. Gonococcal infection causes urethritis, cervicitis, epididymitis, pharyngitis, proctitis, and pelvic inflammatory disease (PID) and can spread throughout the body to cause both localized and disseminated disease. Complications include ectopic pregnancy and increased susceptibility to human immunodeficiency virus (HIV) infection. Most commonly, the term gonorrhea refers to urethritis and/or cervicitis in a sexually active person.
Gonococcal infections following sexual and perinatal transmission are a major source of morbidity worldwide. In the developed world, where prophylaxis for neonatal eye infection is standard, the vast majority of infections follow genitourinary mucosal exposure.
In the pediatric population, the importance of gonorrhea is 3-fold, as follows:
As a common and preventable STD in the sexually active teenage population
Neisseria gonorrhoeae is a gram-negative, intracellular diplococcus that grows best in the laboratory in an environment rich in carbon dioxide. Organisms are spread by sexual contact and can also be vertically transmitted during childbirth. N gonorrhoeae has a predilection for columnar mucosal cells; virtually any mucous membrane can be infected by this microorganism. The physiologic ectopy of the squamocolumnar junction onto the ectocervix in the adolescent female is one factor that causes particular susceptibility to this infection.
The pathophysiology of N gonorrhoeae and the relative virulence of different subtypes depend on the antigenic characteristics of the respective surface proteins. Certain subtypes are able to evade serum immune responses and are more likely to lead to disseminated (systemic) infection.
Well-characterized plasmids commonly carry antibiotic-resistance genes, most notably penicillinase. Plasmid and nonplasmid genes are transmitted freely between different subtypes. The ensuing exchange of surface protein genes results in high host susceptibility to reinfection. The exchange of antibiotic resistance genes has led to extremely high levels of resistance to beta-lactam antibiotics over the last 2 decades. More recently, fluoroquinolone resistance has also been documented on multiple continents and in widespread populations within the United States.[1]
Infection of the lower genital tract, the most common clinical presentation, primarily manifests as male urethritis and female endocervicitis. Infection of the pharynx, rectum, and female urethra occur frequently but are more likely to be asymptomatic or minimally symptomatic. Retrograde spread of the organisms occurs in as many as 20% of women with cervicitis, often resulting in pelvic inflammatory disease (PID), with salpingitis, endometritis, and/or tubo-ovarian abscess. Retrograde spread can lead to frank abdominal peritonitis and to a perihepatitis known as Fitz-Hugh-Curtis syndrome.
Long-term sequelae of PID, such as tubal factor infertility, ectopic pregnancy, and chronic pain, may occur in up to 25% of affected patients. Epididymitis or epididymo-orchitis may occur in men after gonococcal urethritis. Lower genital infection is a risk factor for the presence of other sexually transmitted diseases (STDs), including human immunodeficiency virus (HIV).
Conjunctivitis can occur in adults as well as in children following direct inoculation of organisms and can lead to blindness.
Disseminated gonococcal infection (DGI) occurs following approximately 1% of genital infections. Patients with disseminated gonococcal infection may present with symptoms of rash, fever, arthralgias, migratory polyarthritis, septic arthritis, tendonitis, tenosynovitis, endocarditis, or meningitis. Three fourths of the cases of disseminated gonococcal infection occur in women; susceptibility is increased if the primary mucosal infection occurs during menstruation or pregnancy. Changes in the vaginal environment at these times may foster changes in the gonococcal surface features and phenotype that render the organisms more resistant to host defenses in the bloodstream and more likely to disseminate.
Gonococcal infection usually follows mucosal inoculation during vaginal, anal, or oral sexual contact. It also may be due to inoculation of mucosa by contaminated fingers or other objects.
Neonatal infection may follow conjunctival inoculation during birth or direct infection through the scalp at the sites of fetal monitoring electrodes. In children, infection may occur from sexual abuse by an infected individual or possibly nonsexual contact in the child's household or in institutional settings.
Risk factors for gonorrhea include the following:
Sexual exposure with an infected partner without barrier protection (eg, failure to use a condom or condom failure)[2]
Multiple sex partners
Low socioeconomic status
Minority status: Blacks, Hispanics, and Native Americans have the highest rates in the United States
History of concurrent or past sexually transmitted diseases (STDs)
Exchange of sex for drugs or money
Use of crack cocaine
Early age of onset of sexual activity
Pelvic inflammatory disease (PID): Use of an intrauterine device (IUD)
Gonorrhea is the second most commonly reported infectious disease in the United States, after chlamydia. The actual incidence is difficult to determine due to high rates of asymptomatic carriage as well as underreporting. In 2008, 336,742 cases were reported in the United States; in 2009, 301,174 cases were reported.[3, 4] The national average in 2009 was 99.1 cases per 100,000 population, a 10.5% decrease from 2008, with considerable state-to-state variation.[3] The rate of gonococcal infection was dropping until 2004, when it was at its lowest level since 1941, but this rate has since stabilized at a plateau. The estimate of total cases is approximately 700,000 cases per year. In children who have been sexually abused, rates of recovery of gonorrhea range from 1% to 30%. In female adolescents who are sexually active, asymptomatic carriage of gonorrhea occurs in 1-5%.
Within the United States, carriage rates highly depend on the geographic area, the racial and ethnic group, and sexual preferences.
The Southeastern states have the highest rates of infection; the rates in the midwest and northeast are much lower. Rates of infection range from about 246.4 cases per 100,000 population in Mississippi to 8 cases per 100,000 population in Vermont. The Centers for Disease Control and Prevention (CDC) set a campaign (Healthy People 2010: http://www.cdc.gov/nchs/healthy_people.htm) that targeted an incidence rate of 19 cases per 100,000 population. Utah, Montana, Idaho, Maine, Vermont, and New Hampshire, are the only states currently exceeding that target, along with Puerto Rico (see the first image below).[3] Healthy People 2020 is in the process of being developed (http://healthypeople.gov/2020/default.aspx).
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Rates of gonococcal infection per 100,000 by state and outlying regions (2009). Data from the Centers for Disease Control and Prevention (CDC):
International statistics
N gonorrhoeae has been the most common sexually transmitted disease (STD) worldwide for at least most of the 20th century, with an estimated 200 million new cases annually. Public health initiatives in the developed world have resulted in declining incidence of the disease since the mid 1970s, but, as noted earlier, gonococcal infection is still the second most common notifiable disease in the United States, and Western European rates approximate those in the United States. Disease rates are unknown for most developing countries.
The incidence of antibiotic-resistant strains has been rising since the late 1940s. Of greatest concern historically was the high percentage of cases due to penicillinase-producing N gonorrhoeae (PPNG). However, fluoroquinolone resistance has increased rapidly over the past decade on most continents and within the United States. The CDC reported fluoroquinolone resistance in 6.8% of 2004 isolates, 9.4% of 2005 isolates, and 13.3% of 2006 isolates.[1]
Racial differences in incidence
Although race has no intrinsic effect on susceptibility, in the United States, the frequency of gonorrhea is increased among urban dwellers, individuals of lower socioeconomic status, and minorities of any population. This may be due to decreased access to diagnosis and treatment, lack of adequate care (ie, education, diagnosis, and treatment) leading to increased transmission rates, and/or reflection bias due to data collection site preference (eg, urban emergency departments [EDs] and STD clinics), as well as true differences in prevalence.
All sexually active populations are at risk and the level of risk rises with the number of sex partners and the presence of other STDs.
Sexual differences in incidence
The male-to-female ratio is approximately 1:1.2; however, females may be asymptomatic, whereas males are rarely asymptomatic. Men who have sex with men (MSM) are much more likely to acquire and carry gonorrhea and have far higher rates of antibiotic-resistant bacteria. Serious sequelae are much more common in women, in whom pelvic inflammatory disease (PID) may lead to ectopic pregnancy or infertility and for whom disseminated gonococcal infection (DGI) is more likely.
Age-related differences in incidence
The highest incidence of gonococcal infection in the United States is among persons aged 15-24 years.[3] This is likely due to the following:
Increased numbers of sexual partners
Decreased access to or use of health care
Physiologic ectopy of the squamocolumnar junction in females
Decreased use of barrier contraceptives
Infection in children is a marker for child sexual abuse and should be reported as such, although a 2007 review provided some support for nonsexual transmission between children and for transmission from adults to children related to poor hand hygiene.[5]
The following image depicts US gonorrhea incidence rates by age and sex.
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Rates per 100,000 of gonorrhea, reported by age and sex (2009). Data from the Centers for Disease Control and Prevention (CDC):
The prognosis for patients with gonorrhea is excellent if the diagnosis is made and treatment is started before progression or complications occur. Most gonococcal infections respond quickly to cephalosporin therapy.
Complications from gonococcal infection may include the following:
Scarring of the upper reproductive tract in women with pelvic inflammatory disease (PID), possibly leading to infertility, chronic pelvic pain, and ectopic pregnancy
Urethral scarring in men, possibly leading to decreased fertility or to bladder-outlet obstruction
Destruction of joint articular surfaces
Possible prematurity, neonatal infection, and miscarriage resulting from gonococcal infections in pregnant women
Possible corneal scarring and permanent vision impairment or blindness resulting from gonococcal ophthalmic infection
Possible sepsis in infants following neonatal exposure to maternal gonorrhea
Possible permanent neurologic sequelae resulting from gonococcal meningitis
Destruction of cardiac valves
Death from congestive heart failure (CHF) or meningitis
Pelvic inflammatory disease
PID is generally the most feared complication of gonococcal infection, because it is one of the leading causes of female infertility and often leads to hospitalization. This can be devastating to any woman, especially an adolescent who potentially has many years of childbearing ahead of her. In a 2011 study, female adolescents with PID were more likely than older women to have a rapid recurrence of PID or to become pregnant despite reporting more consistent condom use.[6]
Tubo-ovarian abscess and, rarely, tubal perforation with peritonitis and death, especially if recurrent. Females with recurrent PID have high rates of ectopic pregnancy and infertility (approximately 8% after 1 episode, 20% after 2 episodes, and 40% after 3 or more episodes).
Epididymitis and orchitis
Epididymitis and orchitis occur infrequently in males who go untreated. These conditions usually respond well to the same antibiotics used for uncomplicated urethritis but are administered for a longer course.
Arthritis
Gonorrhea is the most common cause of arthritis in the adolescent. However, arthritis (septic or reactive) is a rare complication of this disease; but because it mimics septic arthritis, excluding the possibility of gonococcal infection in any adolescent with acute onset of pyogenic arthritis is important. Adequate diagnosis may require culturing extraarticular sites for Neisseria gonorrhoeae.
Other
Perihepatitis secondary to gonorrhea (Fitz-Hugh-Curtis syndrome) presents as right upper quadrant pain and nausea in patients with untreated gonorrhea.
Disseminated gonococcal infection (DGI) is an acute illness that causes fever, asymmetric polyarthralgias, and skin pustules overlying small joints in patients with gonorrhea. Disseminated infection may also lead to meningitis or endocarditis.
In newborns, vertical transmission can cause conjunctivitis, known as ophthalmia neonatorum, and permanent damage and blindness, if untreated.
Oral sex with an infected partner can result in pharyngitis, and, similarly, anal infection can arise from anal sex or local spread from a vaginal source.
Discuss safe sexual practices with all individuals in whom gonorrhea is suspected.
Proper education to prevent gonorrhea may be more effective than simplistic instructions to avoid sex, especially in the teenaged population. Teenagers involved with abstinence-only campaigns have unchanged sexually transmitted disease (STD) rates and disproportionately acquire anal and oral infections, rather than vaginal infections (the perception is that if an activity is not vaginal sex, it is not sex).
Patients should know the method of disease transmission and the adverse impact of recurrent infections on future fertility; they should be counseled about the risks of complications following gonococcal infection and the risk of other STDs; and they should always be instructed to refer any sex partners for prompt evaluation and treatment. In addition, these individuals should be aware they should avoid sexual contact until medication is finished and until their partners are fully evaluated and treated. Thereafter, they should avoid unprotected contact.
The discussion of responsible sexual behavior should not be limited or withheld because of personal religious or moral views because these may not be shared by the patient, and teenagers are notorious for sexual experimentation; evidence suggests that this limited discussion does the teenage population a huge disservice. This advice is especially pertinent in states where sexual education is almost nonexistent in the school system because of abstinence-only teaching, which is misleading and factually inaccurate.
In one study in Peru, a bundle of interventions that included extensive public health efforts, including training of local medical personnel, specific and presumptive treatment, outreach to female sex workers, and supply of barrier contraception, may have been effective at reducing the prevalence of several STDs, although the effect did not reach statistical significance overall. The effects were more greatly pronounced (and significant) among female sex workers and young adult women. The study was hampered by several methodological limitations, such as comparing different cities as controls, which make drawing conclusions from the data difficult.[7]
Abstinence education
Although the most effective STD prevention is abstinence from sex, this is oftentimes an unrealistic expectation, especially in the teenaged population; in fact, 88% of teenagers who pledged abstinence in middle and high school still engaged in premarital sex. Moreover, they tend to have riskier, unprotected sex because of their lack of education; those who pledge before having sex have a 33% higher prevalence rate of STDs than those who had sex and then retrospectively pledged, with nonpledgers falling in between. This is despite a lower number of partners and an older age at first intercourse in pledgers.
Of course, abstinence should be explained to be the best option, but a more practical expectation is abstinence from sex with someone known or suspected of having an STD until treatment is obtained and completed. In light of the difficulty in knowing a potential partner's sexual history (or honesty), strongly recommend the use of condoms as a reasonable alternative to abstinence.[2]
Pledgers are actually less likely to be aware of their STD status and are less likely to seek testing, even if their STD rates are similar overall (again, highlighting a lack of appropriate sexual education). Stress that oral or anal sex can also transmit disease.
Risks of unprotected sex
Patients should also be counseled about the additional risks of unprotected sex, such as the acquisition of more serious or lifelong infections such as herpes, hepatitis B, and human immunodeficiency virus (HIV), and, of course, about the risks of pregnancy. The emotional aspect of sexual relationships may also need to be addressed, especially in teenage girls. Teenagers are vulnerable in that they are sexually mature but not yet emotionally mature.
For patient education information, see Sexual Health Center, Sexually Transmitted Diseases, Gonorrhea, and Chlamydia.
Patient education materials are also available at The Centers for Disease Control and Prevention (CDC) Website (Sexually Transmitted Diseases – Gonorrhea) and from many local public health departments.
The incubation period of gonorrhea is usually 2-7 days after exposure to an infected partner.
In all patients presenting with possible sexually transmitted disease (STD), history taking should include a history of STDs (including human immunodeficiency virus [HIV] infection and viral hepatitis), known symptoms of STDs in current or past partners, type of contraception used, and any history of sexual assault. In women, the history should also include the date of the last menstrual period and the details of parity, including any history of ectopic pregnancies.
A significant percentage of men and women with gonorrhea also have pharyngitis, which is usually asymptomatic but may cause mild-to-severe dysphagia and discomfort.
Secondary gonococcal bacterial conjunctivitis may follow accidental inoculation by fingers in either sex and is usually unilateral.
Males
A male history may include the following:
Urethral discharge (drip)
Dysuria
Condom nonuse or condom failure
Infected contact
Proctitis and/or pharyngitis, depending on types of intercourse and partners
Urethral discomfort, dysuria, and discharge due to uncomplicated urethritis are the most common symptoms in men. Degree of discomfort and discharge are variable, and subjective symptoms may be absent.
The classic presentation of epididymitis is of unilateral pain and swelling localized posteriorly within the scrotum. Neisseria gonorrhoeae and Chlamydia trachomatis account for most cases of epididymitis in men younger than 35 years.
Urethral strictures due to gonococcal infection are now uncommon in the antibiotic era, but they can present with decreased and abnormal urine stream as well as with the secondary complications of prostatitis and cystitis.
Rectal infection may present with pain, pruritus, discharge, or tenesmus.
Females
A female history may include the following:
Vaginal discharge
Dysuria
Slow onset and progression of lower abdominal pain, especially in progression to pelvic inflammatory disease (PID)
Abnormal vaginal bleeding (spotting)
Dyspareunia (painful intercourse)
Condom nonuse or condom failure
Proctitis and/or pharyngitis, depending on type of partners and intercourse
Vaginal discharge from endocervicitis is the most common presenting symptom and is usually described as thin, purulent, and mildly odorous. Many patients have minimal or no symptoms from gonococcal cervicitis. Dysuria or a scant urethral discharge may be due to urethritis accompanying cervicitis.
Pelvic or lower abdominal pain suggests ascending infection of the endometrium, fallopian tubes, ovaries, and peritoneum. Pain may be midline, unilateral, or bilateral. Fever, nausea, and vomiting may be present. The possibility of ectopic pregnancy should always be considered in patients with pelvic or lower abdominal pain.
Right upper quadrant pain from perihepatitis (Fitz-Hugh-Curtis syndrome) may occur following the spread of organisms upward along peritoneal planes.
Rectal infection is often asymptomatic, but rectal pain, pruritus, tenesmus, and rectal discharge may be present if the rectal mucosa is infected. Bloody diarrhea may also occur. Rectal infection may occur from anal intercourse, and, in women, by local spread of the organism.
Infants/neonates: ophthalmologic
Bilateral conjunctivitis (ophthalmia neonatorum) presents with eye pain, redness, and a purulent discharge. The organism is acquired during vaginal birth from the untreated, infected mother. If unrecognized and untreated, the infection can lead to serious destruction of the cornea and blindness.
Blindness from neonatal gonococcal infection is a serious problem in developing countries, but this is uncommon in the United States and other countries where neonatal prophylaxis is routine. Nevertheless, infants of mothers with untreated infections, poor prenatal care, and unmonitored births continue to be at risk.
Infection may also occur at the site of placement of scalp electrodes.
Disseminated gonococcal infection
Disseminated gonococcal infection (DGI) may follow 1-2% of mucosal infections, with symptoms that vary greatly from patient to patient. By the time the symptoms appear, many patients no longer have any localized symptoms of mucosal infection.
Joint or tendon pain is the most common presenting complaint. About 25% of patients with disseminated gonococcal infection complain of pain in a single joint, whereas as many as two thirds describe polyarthralgia, which is often migratory. Severe pain, swelling, and decreased mobility in a single joint suggest a purulent arthritis with effusion. The knee is the most common site of purulent gonococcal arthritis.
Tenosynovitis is also common in this condition, usually affecting the small joints of the hands.
Skin rash is a presenting complaint in approximately 25% of patients, but a careful examination will reveal a rash in most patients with disseminated gonococcal infection. The rash is usually found below the neck and may also involve the palms and soles.
Although fever is common, the temperature is usually less than 39°C. However, headache, neck pain and stiffness, fever, and decreased sensorium may indicate gonococcal meningitis. This disease may be clinically indistinguishable from meningococcal meningitis on presentation, although the course of gonococcal meningitis is usually less rapid.
Subacute onset of fever, chills, sweats, and malaise may indicate the presence of gonococcal endocarditis. Patients with endocarditis may develop atypical chest pain, cough, and dyspnea, as well as the arthralgias and rash typical of disseminated gonococcal infection. Rarely, gonococcal endocarditis can cause severe valvular damage and death if not recognized and treated rapidly. Gonococcal endocarditis is more common in men than in women. Patients with collagen vascular disease (especially those with systemic lupus erythematosus) may also be more prone to this complication.
Disseminated gonococcal infection can occur in infants born to infected mothers.
Neisseria gonorrhoeae infection may be recognized by the typical signs and symptoms of the disease, but it is important to remember that, by the time disseminated or upper reproductive tract disease is present, the primary site of mucosal infection may be normal in appearance, and the patient may have no localized signs or symptoms.
With oropharyngeal infection, pharyngitis may be present, usually mild. With rectal infection, mucopurulent or purulent discharge may be present.
The physical examination should also always include scrutiny for signs of herpes simplex, syphilis, chancroid, lymphogranuloma venereum, and genital warts.
Males
Look for the following in males:
Mucopurulent or purulent urethral discharge, obtained by milking the urethra along the shaft of the penis
Possible epididymitis: Unilateral epididymal tenderness and edema
Females
Look for the following in females:
Mucopurulent or purulent vaginal, urethral, or cervical discharge
Vaginal bleeding; vulvovaginitis in children
Cervical friability (tendency to bleed upon manipulation)
Cervical motion tenderness during bimanual pelvic examination
Fullness and/or tenderness of the adnexa, unilateral or bilateral (eg, ovaries, fallopian tubes)
Lower abdominal pain/tenderness, with or without rebound tenderness
Possible low back pain (more common in progression to pelvic inflammatory disease [PID])
Upper right abdominal tenderness (with perihepatitis)
Neonates
Look for the following in neonates:
Purulent discharge from the eyes (usually bilateral in ophthalmia neonatorum but most often is unilateral when secondary to self-inoculation in older patients) or other infected sites
Temperature instability (fever, hypothermia) in disseminated sepsis
Disseminated gonococcal infection
Disseminated gonococcal infection may present with any of the following findings:
Fever (usually temperature < 39°C)
Skin: Maculopapular, pustular, necrotic, or vesicular rash, typically occurring on the torso, limbs, palms, and soles may be present; the rash usually spares the face, scalp, and mouth; hemorrhagic lesions, erythema nodosum, urticaria, and erythema multiforme occur less frequently; the skin lesions are usually in different stages of development at the time of clinical presentation
Joints: Most patients may have polyarthralgia with joint tenderness, decreased range of motion, and erythema; less often, purulent arthritis may affect a single joint with severe pain, tenderness, edema, erythema, and decreased range of motion
Tenosynovitis presents as erythema and local tenderness along a tendon sheath, with pain on active or passive range of motion; tenosynovitis most often occurs in the hands but may be found in the tendons of the lower extremities as well
Central nervous system: Patients with gonococcal meningitis may present with meningismus or decreased mental status
Cardiac: Patients with gonococcal endocarditis may have a new murmur, tachycardia, and fever; embolic lesions may be present.
Muscle: Disseminated gonococcal infection can cause abscess formation within the soft tissues, presenting as localized tenderness, edema, and pain with motion
In women with symptoms and signs suggestive of pelvic inflammatory disease (PID) who are difficult to diagnose clinically, laparoscopy may be indicated to rule out (and, if need be, treat) appendicitis, ovarian torsion, ectopic pregnancy, or other surgical emergencies.
Imaging studies such as ultrasonography are obviously a less invasive means of obtaining diagnostic information, but potentially emergent cases may require a more definitive examination, which permits rapid intervention if required.
Perform lumbar puncture and joint aspiration, if indicated by clinical findings.
Culdocentesis, although rarely indicated, may demonstrate free purulent exudate and provide material for Gram stain and culture.
Culture is the most common diagnostic test for gonorrhea, followed by the DNA probe, and then polymerase chain reaction (PCR) and ligand chain reaction (LCR). The DNA probe is an antigen detection test that uses a probe to detect gonorrhea DNA in specimens.
Always obtain a pregnancy test for women of childbearing age who present with gonorrhea or any other sexually transmitted diseases (STD).
Culture and nonculture for N gonorrhoeae
Perform a culture or nonculture detection test for N gonorrhoeae on endocervical, urethral, pharyngeal, or rectal discharge. Because organisms are intracellular, attempt to obtain specimens in a manner that will contain mucosal cells and not merely discharge (similar to a Papanicolaou smear).
Nonculture tests are less accurate in the presence of blood or during menses. Use culture instead at these times.
Culture is performed on Thayer-Martin plates that must be stored refrigerated but warmed to room temperature before obtaining sample. The plate is then incubated in a carbon dioxide atmosphere. Poor technique drastically reduces test sensitivity.
Medicolegal cases (eg, child abuse, rape) require culture due to the possibility of false-positive results with nonculture methods. However, performing the more sensitive PCR-based tests to raise the likelihood of detecting an infection, and then following up with culture to produce admissible evidence, is appropriate.
Other STDs
Other tests that might be indicated are those for concurrent STDs. Patients in whom gonococcal disease is suspected should be evaluated for syphilis infection as well as infection with Chlamydia trachomatis (high rate of asymptomatic carriage), human immunodeficiency virus (HIV) (with counseling), hepatitis B virus (HBV), herpes simplex virus (HSV), and any STDs that are suggested by the history and physical examination findings. Administer HBV vaccination to these individuals unless they have received the full vaccine series.
Rapid HIV test technology makes testing in the emergency department (ED) and referral more practical than enzyme-linked immunosorbent assay (ELISA). The need for additional testing depends on the situation; they are often performed as a battery of tests in suspected rape and child abuse cases.
HIV testing in cases of rape or new-onset abuse does not acutely diagnose a new infection but does establish a baseline status of the patient such that subsequent seroconversion might be linked back to the event in question.
Gram stain is a rapid and inexpensive test available in many emergency departments (EDs). The positive predictive value (PPV) is high for urethral infection, but a negative Gram stain does not rule out infection in asymptomatic men.
Collect specimens from the urethra, endocervix, pharynx, rectum, conjunctiva, urine, or blood.
A Gram stain of urethral or cervical discharge may show gram-negative intracellular diplococci (diagnostic in the male) and polymorphonuclear cells. This is very useful if the physician has easy access to a microscope, because the diagnosis may be made without waiting for culture results.
Sensitivity and specificity of the Gram stain are lower for endocervical specimens and rectal specimens. Gram stains from these sites are not recommended for routine use in the ED. In addition, Gram staining is not useful for the diagnosis of pharyngeal infection, because the oropharynx may be colonized by other Neisseria species that can lead to false-positive results.
Culture
Specific culture of a swab from the site of infection is a criterion standard for diagnosis at all potential sites of infection and can potentially guide treatment by determining antibiotic susceptibility.
N gonorrhoeae is a fastidious organism that requires moist carbon dioxide-rich atmosphere and must be grown on enriched media, usually chocolate agar containing lysed blood. Empiric treatment is often necessary because culture results are not available for 24-48 hours.
Cultures are particularly useful when the clinical diagnosis is unclear, when a failure of treatment has occurred, when contact tracing is problematic, and when legal questions arise.
Suspected disseminated gonococcal infection
When disseminated gonococcal infection (DGI) is suspected, blood and joint effusions should be sent for Gram stain and culture, although negative Gram stain results and sterile cultures do not rule out disseminated disease. Cerebrospinal fluid should be stained and cultured if signs or symptoms of meningitis are present.
Gram stains, cultures, and/or nucleic acid amplification tests (NAATs) of genital, rectal, conjunctival, and pharyngeal secretions should also be obtained when disseminated gonococcal infection is suspected, even if the patient has no localized symptoms at any of those sites.
Nucleic acid amplification tests (NAATs) are designed to amplify sequences of DNA unique to a given pathogen, such as Neisseria gonorrhoeae. These tests are more sensitive and specific than nonamplification techniques.
Several US Food and Drug Administration (FDA)–approved NAATs are available for the detection of N gonorrhoeae in urethral swab specimens obtained from males; endocervical swabs; and urine specimens obtained from men and women. These tests are more rapid than culture, more specific than immunoassays, and do not require viable organisms.[8]
NAATs may be of particular use when examination and mucosal swab are difficult (in children or extremely apprehensive patients), and urine specimens are more easily obtained. However, although these tests can be used on eye secretions, their performance is less well validated. In addition, NAATs are not all recommended for rectal and pharyngeal specimens at this time.
Clinicians should be familiar with specimen collection guidelines and performance parameters of the test available at their own hospitals.
Suspected disseminated gonococcal infection
NAATs of genital, rectal, conjunctival, and pharyngeal secretions should also be obtained when disseminated gonococcal infection is suspected, even if the patient has no localized symptoms at any of those sites.
Polymerase chain reaction (PCR) and ligand chain reaction (LCR) are gene amplification techniques that markedly increase the sensitivity of specimen testing. Both techniques amplify the genetic fingerprint of specimens with very few organisms present in order to more easily detect and identify the organisms. Although the sensitivity is significantly increased, these methods of diagnosis are many times more expensive than culture or DNA probe. In many settings, PCR and LCR are not readily available, because they may require a specialized laboratory facility. False positives are generally due to laboratory error (inadvertent contamination).
Ultrasonography may be indicated in women to investigate suspected pelvic inflammatory disease (PID) and to visualize the appendix and ovaries as other possible causes of the symptoms. Pelvic ultrasonography or computed tomography (CT) scanning may demonstrate thick, dilated fallopian tubes or abscess formation.
PID is uncommon in pregnancy when the cervical mucous plug may provide some protection to the upper tract. Ultrasonography should be used to rule out ectopic pregnancy whenever a pregnant patient has signs and symptoms of possible PID.
As discussed in the Workup section, females with diagnosed or suspected sexually transmitted diseases (STDs) should have a concomitant pregnancy test. This guides further care and allows treatment with medications that are not approved for use in pregnancy.
Identification and treatment of the patient's partner and any partners of the partner are important to prevent reinfection and complications.
Prevention of neonatal disease is with the use of silver nitrate 1% eye drops or 1% tetracycline or 0.5% erythromycin ophthalmic ointment within 1 hour of birth.
The main decision once a diagnosis of gonorrhea has been made, either definitively or presumptively, is whether to treat as an outpatient or to hospitalize.
For males, treatment is always outpatient for genital infection; however, admission may be necessary for complications such as disseminated gonococcal infection (DGI) or gonococcal arthritis.
In females, the decision is much more difficult, because the risk of complications is much higher. In light of high rates of noncompliance, reinfection, and poor follow-up, some clinicians advocate admitting the female whenever a question of a complication such as pelvic inflammatory disease (PID) is present, particularly in the adolescent population.
Many institutions have attempted to quantify abnormalities found on pelvic examination (ie, the PID score) in an attempt to admit those patients with a higher likelihood of complications.
In cases in which future fertility is at risk, most physicians are fairly aggressive, especially in situations in which the patient is very young or unfamiliar to them.
Consultations
In cases of suspected rape or child abuse, seeking specialist help (in the form of specialist nurses or physicians) to interview and collect specimens (if necessary) for testing is prudent.
Careful documentation of physical findings, even if apparently normal, is crucial for medicolegal reasons.
Notification of child-protective services is required if abuse is suspected.
In April 2007, the Centers for Disease Control and Prevention (CDC) updated treatment guidelines for gonococcal infection and associated conditions.[1] Fluoroquinolone antibiotics are no longer recommended to treat gonorrhea in the United States and other parts of the world where resistance has become common, but these agents can be considered in areas where quinolone resistance has not yet emerged.
The recommendation was based on analysis of new data from the CDC’s Gonococcal Isolate Surveillance Project (GISP).[9] The data from GISP showed the proportion of gonorrhea cases in heterosexual men that were fluoroquinolone resistant reached 6.7%, an 11-fold increase from 0.6% in 2001. This limits treatment of gonorrhea to drugs in the cephalosporin class (eg, ceftriaxone 250 mg intramuscularly [IM] once as a single dose).
Fluoroquinolones may be an alternative treatment option for disseminated gonococcal infection if antimicrobial susceptibility can be documented. For more information, see the CDC's Websites on antibiotic-resistant gonorrhea and updated recommended gonococcal treatment regimens (April 2007), or Medscape Medical News's article on the CDC's treatment recommendations for gonorrhea.
Clinical Context:
Cefixime is the drug of choice (DOC) for treating gonorrhea because of its oral efficacy, single-dose treatment, and lower cost than parenteral medication. Cefixime inhibits bacterial cell wall synthesis by binding to one or more of the PBPs. After a period of unavailability, oral cefixime is now available again in the United States, in tablet and suspension, for the treatment of uncomplicated urogenital or rectal gonorrhea.[10]
Clinical Context:
Ceftriaxone is the second drug of choice (DOC) for treatment of gonorrhea and for uncomplicated genitourinary infections because of its higher cost, discomfort with administration, and the additional administration expense of injection.
Ceftriaxone is often used as first-line therapy for disseminated gonococcal infection (DGI), outpatient pelvic inflammatory disease (PID), and pharyngeal infection. Ceftriaxone binds to penicillin-binding proteins (PBPs), inhibiting bacterial cell wall growth.
Clinical Context:
Spectinomycin is indicated for patients with beta-lactam intolerance and may be used in instances of allergy to cephalosporins. However, this agent is a second-line choice due to its poor efficacy in pharyngitis. Spectinomycin inhibits protein synthesis in bacterial cells; its site of action is the 30S ribosomal subunit, and it is structurally different from related aminoglycosides.
Clinical Context:
Erythromycin is indicated for infections caused by susceptible strains of microorganisms and for prevention of corneal and conjunctival infections. This agent inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest.
Clinical Context:
Azithromycin is used to treat mild to moderate microbial infections. This agent inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.
Information from the Centers for Disease Control and Prevention (CDC) states that azithromycin 2 g orally (PO) is effective against uncomplicated gonococcal infection, but it is expensive, causes gastrointestinal irritation, and is not recommended for treatment of gonorrhea.
Although azithromycin 1 g theoretically meets alternative regimen criteria, it is not recommended because of concerns regarding the possible rapid emergence of antimicrobial resistance.
Clinical Context:
Doxycycline inhibits protein synthesis and, thus, bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.
Clinical Context:
Silver nitrate inhibits growth of both gram-positive and gram-negative bacteria. The germicidal effects of this agent are attributed to precipitation of bacterial proteins by liberated silver ions.
Medical therapy requires an antibiotic with efficacy against Neisseria gonorrhoeae. Until several years ago, the treatment of choice involved oral medication for as long as 10 days or an injection; however, patients tend to be poorly compliant with medications for various reasons, and the availability of newer medications has allowed in-office, single-dose, oral treatment to ensure compliance.
Many practitioners presumptively treat patients after obtaining specimens for diagnosis, based on history and examination, because of the risk of poor follow-up, complications, and continuing spread to other partners. In addition, because gonorrhea is often simultaneously diagnosed with chlamydia , many practitioners treat patients for both diseases when treating for either one beyond the newborn period. Diagnosis and treatment of the patient's partner and any partners of the partner are important to prevent reinfection and complications.
Disseminated or complicated infections (eg, endocarditis, meningitis) require more prolonged inpatient therapy. For example, ceftriaxone 50 mg/kg intravenously (IV) twice daily (BID) for 7 days plus a macrolide such as azithromycin administered for simple disseminated infection (10-14 d for meningitis or 28 d for endocarditis). Fluoroquinolones are no longer recommended for gonorrhea because of increased resistance.
If cephalosporins are not an option for disseminated gonorrhea or pelvic inflammatory disease (PID), fluoroquinolones may be considered if the local data suggest antimicrobial susceptibility. For these cases, an infectious disease consultation is essential. Children older than 8 years may omit the macrolide in cases of endocarditis.
Information from the Centers for Disease Control and Prevention (CDC) states that 2 g of oral (PO) azithromycin is effective against uncomplicated gonococcal infection, but it is expensive, causes gastrointestinal (GI) irritation, and is not recommended for treatment of gonorrhea. Although 1 g of azithromycin theoretically meets alternative regimen criteria, it is not recommended because of concerns regarding the possible rapid emergence of antimicrobial resistance. N gonorrhoeae in the United States is not adequately susceptible to penicillins, tetracyclines, and macrolides (eg, erythromycin) for these antimicrobials to be recommended.[1]
Nicholas John Bennett, MB, BCh, PhD,, Assistant Professor in Pediatrics, Division of Infectious Diseases, Connecticut Children's Medical Center
Disclosure: Nothing to disclose.
Coauthor(s)
Joseph Domachowske, MD, Professor of Pediatrics, Microbiology and Immunology, Department of Pediatrics, Division of Infectious Diseases, State University of New York Upstate Medical University
Disclosure: Nothing to disclose.
Specialty Editors
Robert W Tolan Jr, MD, Chief, Division of Allergy, Immunology and Infectious Diseases, The Children's Hospital at Saint Peter's University Hospital; Clinical Associate Professor of Pediatrics, Drexel University College of Medicine
Disclosure: Novartis Honoraria Speaking and teaching
Mary L Windle, PharmD, Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Nothing to disclose.
Joseph Domachowske, MD, Professor of Pediatrics, Microbiology and Immunology, Department of Pediatrics, Division of Infectious Diseases, State University of New York Upstate Medical University
Disclosure: Nothing to disclose.
Chief Editor
Russell W Steele, MD, Head, Division of Pediatric Infectious Diseases, Ochsner Children's Health Center; Clinical Professor, Department of Pediatrics, Tulane University School of Medicine
Centers for Disease Control and Prevention. 2009 Sexually transmitted diseases surveillance: gonorrhea. Available at http://www.cdc.gov/STD/stats09/gonorrhea.htm. Accessed 5/27/11.
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