Gonorrhea is caused by the bacteria Neisseria gonorrhoeae. It typically infects epithelia of the urethra, cervix, rectum, pharynx, or eyes, causing irritation or pain and purulent discharge. Dissemination to skin and joints, which is uncommon, causes sores on the skin, fever, and migratory polyarthritis or pauciarticular septic arthritis. Diagnosis is by microscopy, culture, or nucleic acid amplification tests. Several oral or injectable antibiotics can be used, but drug resistance is an increasing problem.
N. gonorrhoeae is a gram-negative diplococcus that occurs only in humans and is almost always transmitted by sexual contact. Urethral and cervical infections are most common, but infection in the pharynx or rectum can occur after oral or anal intercourse, and conjunctivitis may follow contamination of the eye. After an episode of vaginal intercourse, likelihood of transmission from women to men is about 20%, but from men to women, it may be higher. Neonates can acquire conjunctival infection during passage through the birth canal, and children may acquire gonorrhea as a result of sexual abuse.
In 10 to 20% of women, cervical infection ascends via the endometrium to the fallopian tubes (salpingitis) and pelvic peritoneum, causing pelvic inflammatory disease. Chlamydiae or intestinal bacteria may also cause PID. Gonorrheal cervicitis is commonly accompanied by dysuria or inflammation of Skene ducts and Bartholin glands. In a small fraction of men, ascending urethritis progresses to epididymitis. Disseminated gonococcal infection (DGI) due to hematogenous spread occurs in < 1% of cases, predominantly in women. DGI typically affects the skin, tendon sheaths, and joints. Pericarditis, endocarditis, meningitis, and perihepatitis occur rarely.
Coinfection with Chlamydia trachomatis occurs in 15 to 25% of infected heterosexual men and 35 to 50% of women.
Symptoms and Signs
About 10 to 20% of infected women and very few infected men are asymptomatic. About 25% of men have minimal symptoms.
Male urethritis has an incubation period from 2 to 14 days. Onset is usually marked by mild discomfort in the urethra, followed by more severe penile tenderness and pain, dysuria, and a purulent discharge. Urinary frequency and urgency may develop as the infection spreads to the posterior urethra. Examination detects a purulent, yellow-green urethral discharge, and the meatus may be inflamed.
Epididymitis usually causes unilateral scrotal pain, tenderness, and swelling. Rarely, men develop abscesses of Tyson and Littre glands, periurethral abscesses, or infection of Cowper glands, the prostate, or the seminal vesicles.
Cervicitis usually has an incubation period of > 10 days. Symptoms range from mild to severe and include dysuria and vaginal discharge. During pelvic examination, clinicians may note a mucopurulent or purulent cervical discharge, and the cervical os may be red and bleed easily when touched with the speculum. Urethritis may occur concurrently; pus may be expressed from the urethra when the symphysis pubis is pressed or from Skene ducts or Bartholin glands. Rarely, infections in sexually abused prepubertal girls cause dysuria, purulent vaginal discharge, and vulvar irritation, erythema, and edema.
PID occurs in 10 to 20% of infected women. PID may include salpingitis, pelvic peritonitis, and pelvic abscesses and may cause lower abdominal discomfort (typically bilateral), dyspareunia, and marked tenderness on palpation of the abdomen, adnexa, or cervix.
Disseminated gonococcal infection (DGI) , also called the arthritis-dermatitis syndrome, reflects bacteremia and typically manifests with fever, migratory pain or joint swelling (polyarthritis), and pustular skin lesions. In some patients, pain develops and tendons (eg, at the wrist or ankle) redden or swell. Skin lesions occur typically on the arms or legs, have a red base, and are small, slightly painful, and often pustular. Genital gonorrhea, the usual source of disseminated infection, may be asymptomatic. DGI can mimic other disorders that cause fever, skin lesions, and polyarthritis (eg, the prodrome of hepatitis B infection or meningococcemia); some of these other disorders also cause genital symptoms.
Gonococcal septic arthritis is a more localized form of DGI that results in a painful arthritis with effusion, usually of 1 or 2 large joints such as the knees, ankles, wrists, or elbows. Some patients present with or have a history of skin lesions of DGI. Onset is often acute, usually with fever, severe joint pain, and limitation of movement. Infected joints are swollen, and the overlying skin may be warm and red.
• Gram staining and culture
• Nucleic acid–based testing
Gonorrhea is diagnosed when gonococci are detected via microscopic examination using Gram stain, culture, or a nucleic acid–based test of genital fluids, blood, or joint fluids (obtained by needle aspiration).
Gram stain is sensitive and specific for gonorrhea in men with urethral discharge; gram-negative intracellular diplococci typically are seen. Gram stain is much less accurate for infections of the cervix, pharynx, and rectum and is not recommended for diagnosis at these sites.
Culture is sensitive and specific, but because gonococci are fragile and fastidious, samples taken using a swab need to be rapidly plated on an appropriate medium (eg, modified Thayer-Martin) and transported to the laboratory in a CO 2 -containing environment. Blood and joint fluid samples should be sent to the laboratory with notification that gonococcal infection is suspected. Because nucleic acid amplification tests (NAAT) have replaced culture in most laboratories, finding a laboratory that can provide culture and sensitivity testing may be difficult and require consultation with a public health or infectious disease specialist.
Unamplified nucleic acid–based tests may be done on genital, rectal, or oral swabs. Most tests simultaneously detect gonorrhea and chlamydial infection and then differentiate between them in a subsequent specific test. Nucleic acid amplification tests (NAAT) further increase the sensitivity adequately to enable testing of urine samples in both sexes.
In the US, confirmed cases of gonorrhea, chlamydial infection, and syphilis must be reported to the public health system. Serologic tests for syphilis (STS) and HIV and NAAT to screen for chlamydial infection should also be done.
Men with urethritis
Men with obvious discharge may be treated presumptively if likelihood of follow-up is questionable or if clinic-based diagnostic tools are not available. Samples for Gram staining can be obtained by touching a swab or slide to the end of the penis to collect discharge. Gram stain does not identify chlamydiae, so urine or swab samples for NAAT are obtained.
Women with genital symptoms or signs
A cervical swab should be sent for culture or nucleic acid–based testing. If a pelvic examination is not possible, NAAT of a urine sample can detect gonococcal (and chlamydial) infections rapidly and reliably.
Pharyngeal or rectal exposures (either sex)
Swabs of the affected area are sent for culture or nucleic acid–based tests.
Arthritis, DGI, or both
An affected joint should be aspirated, and fluid should be sent for culture and routine analysis. Patients with skin lesions, systemic symptoms, or both should have blood, urethral, cervical, and rectal cultures or NAAT. In about 30 to 40% of patients with DGI, blood cultures are positive during the first week of illness. With gonococcal arthritis, blood cultures are less often positive, but cultures of joint fluids are usually positive. Joint fluid is usually cloudy to purulent because of large numbers of WBCs (typically > 20,000/μL).
• For uncomplicated infection, a single dose of ceftriaxone plus azithromycin or doxycycline
• For DGI with arthritis, a longer course of parenteral antibiotics
• Concomitant treatment for chlamydial infection
• Treatment of sex partners
Uncomplicated gonococcal infection of the urethra, cervix, rectum, and pharynx is treated with a single dose of ceftriaxone 250 mg IM plus azithromycin 1 g po once or doxycycline 100 mg po bid for 7 days. Azithromycin or doxycycline is given to treat coinfection with chlamydiae and possibly to slow development of resistance to ceftriaxone. Monotherapy and previous oral regimens of fluoroquinolones (eg, ciprofloxacin, levofloxacin, ofloxacin) or cefixime are no longer recommended because of increasing drug resistance.
DGI with gonococcal arthritis is initially treated with IM or IV antibiotics (eg, ceftriaxone 1 g IM or IV q 24 h, ceftizoxime 1 g IV q 8 h, cefotaxime 1 g IV q 8 h) continued for 24 to 48 h once symptoms lessen, followed by 4 to 7 days of oral therapy. Antichlamydial therapy is also routinely given.
Gonococcal arthritis does not usually require joint drainage. Initially, the joint is immobilized in a functional position. Passive range-of-motion exercises should be started as soon as patients can tolerate them. Once pain subsides, more active exercises, with stretching and muscle strengthening, should begin. Over 95% of patients treated for gonococcal arthritis recover complete joint function. Because sterile joint fluid accumulations (effusions) may persist for prolonged periods, an anti-inflammatory drug may be beneficial.
All sex partners who have had sexual contact with the patient within 60 days should be tested for gonorrhea and other STDs and treated if results are positive. Sex partners with contact within 2 wk should be treated presumptively for gonorrhea (epidemiologic treatment).
• Gonorrhea typically causes uncomplicated infection of the urethra, cervix, rectum, pharynx, and/or eyes.
• Sometimes gonorrhea spreads to the adnexa, causing salpingitis, or disseminates to skin and/or joints, causing skin sores or septic arthritis.
• Diagnose using NAAT, but culture and sensitivity testing should be done when needed to detect antimicrobial resistance.
• Screen asymptomatic, high-risk patients using NAAT.
• Treat uncomplicated infection with a single dose of ceftriaxone 250 mg IM plus either azithromycin 1 g po once or doxycycline 100 mg po bid for 7 days.
An 18-year-old girl comes to the clinic because of a 3-day history of vaginal discharge. The discharge is malodorous & has a greenish-yellow color. She admits to sexual intercourse with a "random guy at a fraternity party" 5 days earlier. Physical examination shows a malodorous, purulent vaginal discharge. Complete physical & pelvic examinations are unremarkable. A Gram stain of the discharge shows Gram-negative diplococci within polymorphonuclear leukocytes. Culture on a chocolate agar confirms the diagnosis. The most appropriate next step is to
A. admit her to the hospital for intravenous therapy with cefotetan
B. contact the board of health to report a case of gonorrhea
C. contact the "random guy at a fraternity party" and provide treatment and counseling
D. give her a single dose of ceftriaxone, intramuscularly and a single dose of azithromycin, orally
E. prescribe metronidazole for this patient and her sexual partner
The correct answer is D. This patient has a gonococcal infection and should be treated with a single dose of ceftriaxone, intramuscularly and a single dose of azithromycin, orally. The ceftriaxone treats the gonococcal infection and the azithromycin is added for the presumptive treatment of Chlamydia trachomatis. This is because many patients have co-existing infections. After treating the patient, this case should be reported to the board of health because gonorrhea is a notifiable infectious disease. Sexual contacts should be treated and counseled.
It is unnecessary to admit her to the hospital for intravenous therapy with cefotetan (choice A). This is part of the treatment of pelvic inflammatory disease, which is a disease of the upper genital tract. Patients often have cervical motion tenderness, lower abdominal tenderness, and adnexal tenderness, fever, cervical discharge, and laboratory documentation of N. Gonorrhea and/or C. trachomatis. These patients are treated with a cephalosporin for gonorrhea and doxycycline for chlamydia. This patient seems to have an uncomplicated gonococcal infection that can be treated as an outpatient.
Since gonorrhea is a notifiable disease, it is necessary to contact the board of health to report a case of gonorrhea (choice B) after treating the patient with the appropriate antibiotics.
The "random guy at a fraternity party" should be contacted to provide treatment and counseling (choice C) after treating the patient with the appropriate antibiotics.
It is incorrect to prescribe metronidazole for this patient and her sexual partner (choice E) because this is the treatment for Trichomonas vaginalis, not gonorrhea. Trichomonas vaginalis often presents with a frothy vaginal discharge. A wet mount shows motile flagellated organisms. Gram-negative diplococci within polymorphonuclear leukocytes are not found in this infection.
A 25-year-old man presents with complaints of dysuria for the past 6 days. He has had multiple female sexual partners in the past 2 months. Physical examination shows a yellowish penile discharge with inguinal adenopathy but no genital ulcers. Gram’s stain of the discharge shows intracellular gram-negative diplococci in leukocytes. Which one of the follow- ing should be used in the treatment of this patient?
C. Procaine penicillin
D. Ceftriaxone plus doxycycline
The answer is D. This patient has gonococcal urethritis (GCU), which is caused by Neisseria gonorrhoeae. GCU is more common among homosexual men and those of the lower socioeconomic strata. Nongonococcal urethritis (NGU) on the other hand, is more commonly encountered in heterosexual males and those of higher socioeconomic class. NGU is twice as common as gonococcal urethritis in the United States; it is the most common sexually transmitted disease (STD) in men and is usually due to Chlamydia trachomatis. However, Trichomonas vaginalis or herpes simplex virus (HSV) can also cause NGU. At one time, the standard treatment would have been penicillin (choice C). However, because of increasing resistance, penicillin is no longer recommended for gonorrhea. Ceftriaxone (choice A) and cefixime are drugs that inhibit cell wall synthesis and are not susceptible to -lactase hydrolysis; therefore, they are recommended replacements for penicillin in the treatment of gonorrhea. The quinolones, ciprofloxacin (choice B) and ofloxacin, inhibit bacterial DNA gyrase and have a relatively broad spectrum of activity. They too are effective against gonorrhea. However, because chlamydi- al infections so often accompany gonococcal infections, the Centers for Disease Control (CDC) recommends
that all patients with suspected or proved gonococcal urethritis also be treated as if they had chlamydial NGU. Although the quinolones have antichlamydial activity in vitro, they have not been recommended for clinical infections. C. trachomatis is susceptible to tetracyclines such as doxycycline (choice E), but strains of tetracy- cline-resistant N. gonorrhoeae have also become too common to recommend its use. Therefore, combined therapy, such as ceftriaxone and doxycycline (choice D), is required to treat both infections. Alternatively, because both organisms are still susceptible to the relatively new drug azithromycin, it can be used alone.