Neisseria gonorrhoeae
Mary Allen Staat
A commonly reported infectious disease in the United States, gonorrhea is sexually transmitted and principally affects adolescents and young adults. Infants can be infected by passage through an infected birth canal. Children can acquire the disease through sexual play, molestation, and sexual abuse. The principal manifestation of the uncomplicated infection is a urethral or vaginal discharge; however, localized infections of the fallopian tubes, joints, conjunctiva, and anus, as well as disseminated infection, can occur.
The gonococcus is a gram-negative kidney bean–shaped diplococcus, nonmotile and non-encapsulated, fastidious in its nutritional requirements. It grows best aerobically in CO2 with increased humidity on a medium of chocolate agar with antibiotics (Thayer-Martin medium) that suppress the growth of other microorganisms.1,2
Neisseria gonorrhoeae infects nonciliated columnar and transitional epithelial cells.2 Attachment to the cells is mediated by pili and the outer-membrane opacity proteins. Within 24 to 48 hours after attachment, the organism synthesizes enzymes to facilitate penetration to submucosal tissues. The host produces a neutrophil response, which results in sloughing of the epithelium, submucosal abscesses, and a purulent exudate. N gonorrhoeae is capable of invading the bloodstream and disseminating to other sites, such as the joints and meninges. Bacteremic spread is also more likely to occur in conjunction with menstruation, which facilitates spread to the upper genital tract (salpingitis). Deficiency of one of the terminal components of the complement system (especially factors 5, 6, 7, or 8) places the patient at increased risk of disseminated, chronic, or recurrent gonococcal disease.3
EPIDEMIOLOGY
Gonococcal infections are limited to humans, and transmission is almost always sexual (genital, anal, or oral). Over the past two decades, there was a steady decline in reported gonorrhea cases; however, in 2005 and 2006 rates of gonorrhea in the United States increased.4 Rates varied by age: In those younger than 1 year old, rates were 5/100,000, and in children 1 to 4 years of age rates were 0.82/100,000. In children 5 to 14 years of age, rates were 11/100,000. Rates were highest in adolescents and young adults ages 15 to 24 years at 490/100,000.4 Sexual transmission and risk factors for goncoccal infection are further discussed in Chapter 233.
CLINICAL FEATURES
The incubation period of gonorrheal infection is 2 to 7 days.6 Infection may occur in the newborn period, in prepubertal children, and in sexually active adolescents and adults. The majority of infected males present with urethritis, which has been described at all ages, even in the newborn. Most gonococcal infections in the mature female are asymptomatic, but there may be thick purulent cervical or urethral discharge and pain upon manipulation of the cervix. The following types of gonococcal infections are of particular relevance to the pediatrician.
Localized Infections
Pharyngeal Infections
Pharyngeal infection is increasingly common in adults and adolescents as a result of orogenital sexual practices,7,8 and has been reported in children. The clinical findings, when present, are cryptic tonsillitis, pharyngitis and erythema, and swelling of the soft palate. Infection is diagnosed by culture of the organism.
Vulvovaginitis
N gonorrhoeae is one of the etiologic agents to consider in preadolescent girls with vulvovaginitis.6 Before puberty, the vaginal mucosa is more susceptible to infection than it is in the mature female. The majority of gonococcal infections in girls younger than 9 years of age result from sexual abuse. Typically, girls with vulvovaginitis present with a voluminous thick green or creamy vaginal discharge. Asymptomatic infections with labial erythema and scanty secretions have been described. Because the endocervical glands in the prepubertal female are not developed, infection rarely spreads to the fallopian tubes and upper genital tract, although tubal infection or peritonitis can rarely occur.9 Septic complications, such as arthritis, have also been reported.
Cervicitis
In postpubertal females, the endocervix is the primary site of infection. A mucopurulent discharge from the cervical os is frequently accompanied by severe pelvic pain upon manipulation of the cervix. The infection may ascend from the vagina or cervix to the upper genital tract to cause inflammation of the endometrium (endometritis), fallopian tubes (salpingitis), ovaries (oophoritis), or the pelvic peritoneal cavity (pelvic peritonitis).
Urethritis
Infection in young men usually presents with a purulent urethral discharge; it is commonly associated with dysuria, frequency of urination, and meatal erythema. Gonococcal urethritis occurs in preadolescent boys, in whom it is usually the result of sexual experimentation or molestation. Urethritis can also occur women.
Anorectal Infections
Anorectal gonorrhea occurs in children who have been molested, in sexually active young men and women, and in the neonate. Symptoms include rectal pain, tenesmus, mucopurulent rectal discharge, and rectal bleeding.
Pelvic Inflammatory Disease (Salpingitis)
Infection rarely spreads to the upper genital tract in prepubertal girls. However, with the onset of menarche and sexual intercourse, some 10% to 20% of young women with gonorrhea will develop tubal infections. Infection can spread along the paracolic gutters to the liver, causing Fitz-Hugh Curtis syndrome (see Chapter 233).
Gonococcal Ophthalmia
Unilateral or bilateral gonococcal ophthalmia can occur at any age, but it notoriously afflicts the newborn infant, who is infected by contact with gonococci from the birth canal.6 Instillation of 1% silver nitrate solution into the eyes of all newborns shortly after birth has greatly reduced but not completely eliminated gonococcal ophthalmia neonatorum.
The appearance of a purulent or serosanguineous discharge 2 to 7 days after delivery should prompt a Gram-stained smear and culture for N gonorrhoeae. Purulent discharge occurring within 48 hours of birth is most often the result of chemical conjunctivitis; during the second week of life the likely diagnosis is C trachomatis. Edema, congestion of lids and conjunctiva, periorbital swelling, and adherence of eyelashes (“matting”) due to purulent exudate are typical of gonococcal ophthalmia. Spontaneous recovery may occur, but permanent damage, such as iridocyclitis and corneal ulceration, occurs in about one third of untreated individuals. In view of the serious consequences of gonococcal ophthalmitis, treatment should be commenced as early as feasible, based on a Gram-stained smear, without awaiting cultural confirmation. Infants with suspected gonococcal ophthalmia should have a blood culture and lumbar puncture and should be treated with systemic antibiotics until results of the cultures are known.
Prophylaxis of ophthalmia neonatorum continues to be important because of the high prevalence of N gonorrhoeae among pregnant women.10,11 The classic method described by Credé involves the instillation of 1% silver nitrate into the conjunctival sac shortly after birth. However, erythromycin (0.5%) or tetracycline (1%) ophthalmic ointment from a single-use tube or ampule appears to be equally effective and has the virtue of not producing chemical conjunctivitis.
Disseminated Infections
Disseminated disease constitutes less than 1% of gonococcal infections. Hematogenous spread of gonococci can originate from local infections and can occur at any age; there is a predisposition to dissemination during the neonatal period, during pregnancy, and at the time of menses, as well as in drug users and in patients with accompanying liver disease. Disseminated infection is frequent among asymptomatic female carriers. Disseminated gonococcemia in the neonatal period may be associated with scalp abscesses secondary to fetal monitoring through scalp electrodes, arthritis, and meningitis.12,13
Arthritis and tenosynovitis are the most common manifestations in adolescents and adults. During the phase of bacteremia, a migratory polyarthritis is typical. All joints may be affected, but knees, ankles, and wrists are most frequently affected. Accompanying skin lesions are common and consist of clusters of erythematous or hemorrhagic lesions about 2 mm in diameter, whose centers are gray or black because of necrosis, or hemorrhage, or both.
More than 30 instances of gonococcal meningitis have been reported among newborn infants and adults. Infection may present as a typical pyogenic meningitis, but frequently the simultaneous presence of urethritis, arthritis, or cutaneous lesions affords clues to its cause.
DIAGNOSTIC EVALUATION
In gonococcal ophthalmia, vulvovaginitis, and urethritis, examination of a stained smear of the purulent discharge will usually reveal intracellular gram-negative diplococci.1,2 Although this finding is virtually diagnostic, confirmatory cultures are important for precise bacteriologic identification, especially for medicolegal purposes.6,10,14 In females, symptoms are usually insufficient evidence for presumptive diagnosis, and Gram-stained smears of secretions from the vagina or endocervix are frequently negative. The diagnosis of gonorrhea in females is best accomplished by culture of both the endocervical canal and the rectum.
Disseminated disease is difficult to diagnose because cultures of blood, joint fluid, or skin lesions show growth of gonococci in less than one third of patients; even under optimal circumstances in which all 3 tissues are cultured, fewer than 50% of suspected cases are confirmed bacteriologically.
Specimens should be collected using swabs made of a synthetic fiber (eg, calcium alginate) and transported in a medium that will keep the organisms alive (eg, Transgrow agar, a modification of Thayer-Martin medium). Rapid diagnosis using DNA probes, enzyme immunoassays, and DNA amplification techniques in urine and secretions from the vagina or endocervix provide increased sensitivity. However, these tests are not useful if there are medicolegal concerns such as sexual abuse.6,10,14
TREATMENT
The Centers for Disease Control and Prevention provides guidelines for treatment of sexually transmitted infections including gonococcal infections.10 Increases in quinolone-resistant N gonorrhoeae in 2006 now limit the recommended treatment of gonorrhea to a single class of drugs, the cephalosporins.15
Uncomplicated Gonococci Infections in Adolescents (Vaginal, Cervical, Urethral, Rectal Infections)
The treatment regimens for uncomplicated infections in adolescents is 400 mg cefixime orally or ceftriaxone 125 mg intramuscularly in a single dose.10
Uncomplicated Gonococcal Infections in the Pharynx
Pharyngeal infections are more difficult to eradicate than genital infections. The recommended regimen for treatment of gonococcal pharyngitis is 125 mg ceftriaxone intramuscularly in a single dose.10
Gonococcal Conjunctivitis in Adolescents
The recommended treatment is a single 1-g dose of ceftriaxone and one-time lavage of the infected eye with saline solution.10
Disseminated Gonococcal Infection in Adolescents
The treatment of disseminated gonococcal infection is 1 g ceftriaxone intramuscularly or intravenously every 24 hours.10 Alternative treatments include 1 g cefotaxime or ceftizoxime intravenously every 8 hours. Spectinomycin, 2 g every 12 hours, can be used for those who are allergic to β-lactam drugs.
These regimens should be continued for 24 to 48 hours after improvement is seen and then followed by 400 mg cefixime orally twice daily for a total of 7 days of therapy. The recommended therapy for meningitis and endocarditis is 1 to 2 g ceftriaxone intravenously every 12 hours for a duration of 10 to 14 days for meningitis and at least 4 weeks for endocarditis. Treatment of complicated disseminated gonococcal infection should be undertaken in consultation with a specialists.
Ophthalmia Neonatorum
The key to treatment is parenteral administration of an effective antimicrobial agent. Because of the high prevalence of penicillin resistance, 25 to 50 mg/kg ceftriaxone intravenously or intramuscularly should be administered in a single dose.10 Although 1 dose of ceftriaxone is sufficient therapy for neonatal conjunctivitis, most infants receive antibiotics for 48 to 72 hours until blood and cerebrospinal fluid cultures are found to be negative.
Local treatment includes lavage of the eye with 0.9% NaCl solution and instillation of topical antimicrobial drops (chloramphenicol or tetracycline drops can be used). When iritis is present, a mydriatic drug (1% atropine) should also be used. Topical therapy alone is not sufficient for cure.
Disseminated Gonococcal Infection and Scalp Abscesses in Infants
Treatment consists of 25 to 50 mg/kg ceftriaxone per day intravenously or intramuscularly in a single daily dose for 7 days (10–14 days if meningitis is documented).10 Cefotaxime, 25 mg/kg intravenously or intramuscularly every 12 hours, may be used instead of ceftriaxone. Cefixime has not yet been approved for the treatment of this disease in children or infants.
Treatment for Children Allergic to or Intolerant of Penicillin and Cephalosporins
Treatment with spectinomycin in a single dose of 40 mg/kg (maximum of 2 g) is recommended.10
PREVENTION
Part of management of gonorrhea is to identify and treat the sexual contacts of the patient; therefore, patients should be instructed to refer sexual partners for evaluation and treatment (see Chapter 233).6,10
REFERENCES
See references on DVD.
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