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Gonococcus
Article Last Updated: Nov 2, 2007
AUTHOR AND EDITOR INFORMATION
Section 1 of 10  
Author: Mounir Bashour, MD, CM, FRCS(C), PhD, FACS, Assistant Professor of Ophthalmology, McGill University; Clinical Assistant Professor of Ophthalmology, Sherbrooke University; Medical Director, Cornea Laser and Lasik MD
Mounir Bashour is a member of the following medical societies: American Academy of Ophthalmology, American Association for Pediatric Ophthalmology and Strabismus, American College of International Physicians, American College of Surgeons, American Medical Association, American Society of Cataract and Refractive Surgery, American Society of Mechanical Engineers, American Society of Ophthalmic Plastic and Reconstructive Surgery, Biomedical Engineering Society, Canadian Medical Association, Canadian Ophthalmological Society, Contact Lens Association of Ophthalmologists, International College of Surgeons US Section, Ontario Medical Association, Quebec Medical Association, and Royal College of Physicians and Surgeons of Canada
Editors: Fernando H Murillo-Lopez, MD, Senior Surgeon, Unidad Privada de Oftalmologia CEMES; Simon K Law, MD, PharmD, Assistant Professor of Ophthalmology, Jules Stein Eye Institute; Chief of Section of Ophthalmology Surgical Services, Department of Veterans Affairs Healthcare Center, West Los Angeles; Christopher J Rapuano, MD, Professor, Department of Ophthalmology, Jefferson Medical College; Co-Chairman of the Cornea Service, Co-Chairman of Refractive Surgery Department, Wills Eye Hospital; Lance L Brown, OD, MD, Ophthalmologist, Affiliated With Freeman Hospital and St John's Hospital, Regional Eye Center, Joplin, Missouri; Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences
Author and Editor Disclosure
Synonyms and related keywords:
gonorrhea, Neisseria gonorrhoeae, N gonorrhoeae, hyperacute conjunctivitis, sexually transmitted disease, STD
Background
Historically, gonorrhea is one of the first described infectious diseases. It is caused by the gram-negative diplococcus, Neisseria gonorrhoeae. Ocularly, it affects 2 populations, the sexually active adult population and the neonate. Ophthalmia neonatorum (neonatal conjunctivitis) is described in the article Conjunctivitis, Neonatal. This article discusses the adult disease.
Pathophysiology
Conjunctivitis can occur in adults, as well as children, following direct inoculation of organisms (usually as a result of hand-eye inoculation in adults) and can lead to blindness.
Frequency
United States
In the United States, gonorrhea is the second most commonly reported notifiable disease, with 339,593 cases documented in 2005.1 More cases may be unrecognized or unreported. Incidence, once believed to be on the decline because of public health initiatives, has been rising since 1984; however, rates in some demographic segments (eg, homosexuals) have decreased.
Incidence of antibiotic-resistant strains has been rising since the late 1940s. Of greatest concern is the rise in the percentage of cases due to penicillinase-producing N gonorrhoeae (PPNG).
International
Similar to the United States, in most countries, it is a ubiquitous infectious disease. Approximately 200 million new cases of gonorrhea occur worldwide each year.
Mortality/Morbidity
Gonorrhea is a major cause of morbidity throughout the world.
- The most common long-term sequelae of gonorrhea are chronic pelvic pain in women after pelvic inflammatory disease (PID), septic abortion, chorioamnionitis in pregnancy, blindness after either neonatal conjunctivitis or adult conjunctivitis, and infertility of either sex.
- Ectopic pregnancy is a life-threatening complication that may follow scarring of the female upper reproductive tract.
- Disseminated infection may lead to meningitis or endocarditis.
Race
No racial predilection exists, but the disease is most common among urban poor and minority groups.
Sex
Gonococcal infections are 1.5 times more common in men than in women.
- All sexually active populations are at risk, and the level of risk rises with the number of sex partners and the presence of other sexually transmitted diseases (STDs).
- Serious sequelae are more common in women than in men. PID may lead to ectopic pregnancy or infertility, and disseminated gonorrheal infection (DGI) is more likely in women than in men.
Age
- Gonococcal infection is more common in the sexually active age group (ie, 15-35 y).
- Infection in children is a marker for child sexual abuse.
History
In all patients presenting with possible STDs, history should include past history of STDs (including HIV), known symptoms of STDs in current or past partners, type of contraception, and any history of sexual assault.
In women, history also should include the date of the last menstrual period and the details of parity, including any history of ectopic pregnancies.
Physical
- Ocular or periocular manifestations
- Anterior chamber - Cellular reaction, hypopyon, endophthalmitis
- Conjunctiva - Chemosis, acute purulent exudate, hemorrhages
- Cornea - Punctate epithelial keratitis; marginal, sterile stromal infiltrates; epithelial defects; infectious stromal infiltrates; stromal ulcerations; descemetocele; perforation; opacification
- Lids - Erythema, edema
- Genitourinary tract, male
- Mucopurulent or purulent urethral discharge
- Unilateral epididymal tenderness and edema
- Lower genitourinary tract, female
- Mucopurulent or purulent cervical discharge
- Vaginal discharge or bleeding; vulvovaginitis in children
- Upper genitourinary tract, female
- PID
- Lower abdominal tenderness with or without rebound tenderness
- Cervical motion tenderness
- Adnexal tenderness
- Fever
- Upper right abdominal tenderness (with perihepatitis)
- Rectal - Mucopurulent or purulent discharge
- DGI may present with any of the following findings:
- Fever - Usually below 39°C
- Skin changes - Maculopapular, pustular, necrotic, or vesicular rash typically occurs on the torso, limbs, palms, and soles. The rash usually spares the face, scalp, and mouth. Hemorrhagic lesions, erythema nodosum, urticaria, and erythema multiforme occur less frequently. Skin lesions are usually in different stages of development at the time of clinical presentation.
- Joints - Most patients may have polyarthralgia with pain, 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 it may be found in the tendons of the lower extremities.
- 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 - DGI can cause abscess formation within the soft tissues, presenting as localized tenderness, edema, and pain with motion.
Causes
Gonococcal infection usually follows mucosal inoculation during vaginal, anal, or oral sexual contact. It also may be caused by 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.
- Risk factors
- Sexual exposure to an infected individual without barrier protection
- Multiple sexual partners
- Infants - Passage through the infected birth canal of the mother
- Children - Sexual abuse by an infected individual
- For PID, use of an intrauterine device (IUD)
Conjunctivitis, Allergic
Conjunctivitis, Bacterial
Conjunctivitis, Neonatal
Conjunctivitis, Viral
Contact Lens Complications
Dacryocystitis
Endophthalmitis, Bacterial
Keratitis, Bacterial
Trachoma
Lab Studies
- Diagnosis is based on clinical appearance and laboratory tests.
- Cultures of conjunctiva: Chocolate agar in carbon dioxide–enriched environment is the best medium. Blood agar, MacConkey medium, and phenylethyl alcohol with 5% sheep blood also are good media.
- Gram stain reveals gram-negative intracellular diplococci.
- Testing for concurrent chlamydia should be completed. For further information, see Chlamydia.
Other Tests
- Complete a STD workup of patient and partners.
Histologic Findings
Gram-negative intracellular diplococci are seen microscopically.
Medical Care
- It is important to treat all sexual partners simultaneously to prevent reinfection.
- It is prudent to examine all sexual partners for other venereal diseases (eg, gonorrhea, syphilis).
- Treatment consists of systemic antibiotics; topical antibiotics are relatively ineffective in the treatment of eye disease.
- Since 1993, fluoroquinolones (ie, ciprofloxacin, ofloxacin, levofloxacin) have been used frequently in the treatment of gonorrhea because of their high efficacy, ready availability, and convenience as a single-dose, oral therapy. However, the prevalence of fluoroquinolone resistance in N gonorrhoeae has been increasing and is becoming widespread in the United States, thereby necessitating changes in treatment regimens.
- Beginning in 2000, fluoroquinolones were no longer recommended for the treatment of persons with gonorrhea who acquired their infections in Asia or the Pacific Islands (including Hawaii); in 2002, this recommendation was extended to California.
- In 2004, the Centers for Disease Control and Prevention (CDC) recommended that fluoroquinolones not be used in the United States to treat gonorrhea in men who have sex with men (MSM). This report, based on data from the Gonococcal Isolate Surveillance Project (GISP), summarizes data on fluoroquinolone-resistant N gonorrhoeae (QRNG) in heterosexual males and in MSM throughout the United States. This report also updates the CDC's Sexually Transmitted Diseases Treatment Guidelines (2006) regarding the treatment of infections caused by N gonorrhoeae. On the basis of the most recent evidence, the CDC no longer recommends the use of fluoroquinolones for the treatment of gonococcal infections and associated conditions (eg, PID).
- Consequently, only one class of drugs, cephalosporins, is still recommended and available for the treatment of gonorrhea.1
- Current recommended treatment is ceftriaxone 125 mg intramuscularly in a single dose or cefixime 400 mg orally in a single dose or 400 mg by suspension (200 mg/5 mL). Spectinomycin (2 g IM) can be given to patients who are allergic to penicillin; however, it is not currently available in the United States.2
- Concurrent treatment of chlamydia should be given for 3-6 weeks, to include oral tetracycline 500 mg 4 times a day, oral doxycycline 100 mg twice a day, or oral erythromycin stearate 500 mg 4 times a day. Azithromycin can be given as a single 1-g dose.
- If the eye is involved beyond the conjunctiva (ie, cornea, vitreous), then dosages are similar to those of disseminated infection, and topical antibiotics are added. See Endophthalmitis, Bacterial.
- If the cornea is involved or if corneal involvement cannot be excluded due to lid swelling or chemosis, some physicians treat with a 3-day course of intravenous antibiotics (eg, ceftriaxone 1 g IV q12-24h).
Treatment of N gonorrhoeae and Chlamydia trachomatis is generally indicated for lower genitourinary infections, PID, epididymitis, proctitis, pharyngitis, conjunctivitis, and DGI. Antibiotics for coverage of gonococcal infection are listed below. Additional regimens are available but show no clear advantage over the antibiotics. Chlamydial infection or suspected infection is covered by azithromycin or doxycycline. Erythromycin and amoxicillin are less effective but should be substituted in pregnant women and children. Treatment of PID may require coverage for additional organisms, including enteric anaerobes.
Drug Category: Antibiotics
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.
| Drug Name | Ceftriaxone (Rocephin) |
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| Description | Bactericidal activity results from inhibition of cell wall synthesis. Has high degree of stability in presence of beta-lactamases, both penicillinases and cephalosporinases, of gram-negative and gram-positive bacteria. |
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| Adult Dose | Urethral, endocervical, rectal, pharyngeal, or conjunctivitis: 125 mg IM once
Deep ophthalmic or disseminated (arthritis, meningitis): 2 g/d IV/IM |
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| Pediatric Dose | Urethral, endocervical, rectal, pharyngeal, or conjunctivitis: Administer as in adults
Deep ophthalmic or disseminated (arthritis, meningitis): 50-100 mg/kg/d IV/IM |
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| Contraindications | Documented hypersensitivity |
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| Interactions | Probenecid may increase ceftriaxone levels; coadministration with ethacrynic acid, furosemide, and aminoglycosides may increase nephrotoxicity |
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| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
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| Precautions | Although transient elevations of BUN and serum creatinine have been observed, at recommended dosages, nephrotoxic potential is similar to that of other cephalosporins; in hepatic dysfunction and significant renal disease, dosage should not exceed 2 g qd if not monitoring closely; alterations in prothrombin times may occur; in impaired vitamin K synthesis or low vitamin K stores (eg, chronic hepatic disease, malnutrition) monitoring of prothrombin time may be required; vitamin K administration (10 mg weekly) may be necessary if prothrombin time is prolonged before or during therapy
Prolonged use may result in overgrowth of nonsusceptible organisms; caution in individuals with history of gastrointestinal disease, especially colitis; sonographic abnormalities in gallbladder of patients treated with Rocephin may occur; chemical nature of sonographically detected material has been determined to be predominantly a ceftriaxone-calcium salt (condition appears to be transient and reversible upon discontinuation of medication and institution of conservative management)
Discontinue treatment if symptoms suggestive of gallbladder disease and/or the sonographic findings described above develop |
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| Drug Name | Azithromycin (Zithromax) |
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| Description | Treats mild-to-moderate microbial infections. |
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| Adult Dose | Day 1: 500 mg PO
Days 2-5: 250 mg PO qd |
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| Pediatric Dose | Day 1: 10 mg/kg PO once; not to exceed 500 mg/d
Days 2-5: 5 mg/kg PO qd; not to exceed 250 mg/d |
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| Contraindications | Documented hypersensitivity; hepatic impairment; do not administer with pimozide |
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| Interactions | May increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids; nephrotoxicity and neurotoxicity may occur when coadministered with cyclosporine |
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| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
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| Precautions | Site reactions can occur with IV route; bacterial or fungal overgrowth may result with prolonged antibiotic use; may increase hepatic enzymes and cholestatic jaundice; caution in patients with impaired hepatic function, prolonged QT intervals, or pneumonia; caution in hospitalized, geriatric, or debilitated patients |
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| Drug Name | Doxycycline (Bio-Tab, Doryx, Vibramycin) |
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| Description | Inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. |
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| Adult Dose | 100-200 mg/d PO qd or divided bid for 10-14 d |
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| Pediatric Dose | <8 years: Not recommended
>8 years: 2-5 mg/kg/d qd or divided bid; not to exceed 200 mg/d |
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| Contraindications | Documented hypersensitivity; severe hepatic dysfunction |
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| Interactions | Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy |
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| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
|
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| Precautions | Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last one half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines |
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| Drug Name | Erythromycin (EES, E-Mycin, Ery-Tab) |
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| Description | Inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes causing RNA-dependent protein synthesis to arrest. For treatment of staphylococcal and streptococcal infections.
In children, age, weight, and severity of infection determine proper dosage. When bid dosing is desired, half-total daily dose may be taken q12h. For more severe infections, double the dose. |
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| Adult Dose | 250 mg erythromycin stearate/base (or 400 mg ethylsuccinate) PO q6h, or 500 mg q12h (1 h ac or 2 pc)
Alternatively, 333 mg PO q8h; increase to 4 g/d depending on severity of infection |
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| Pediatric Dose | 30-50 mg/kg/d (15-25 mg/lb/d) PO divided q6-8h; double dose for severe infection |
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| Contraindications | Documented hypersensitivity; hepatic impairment |
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| Interactions | Coadministration may increase toxicity of theophylline, digoxin, carbamazepine, and cyclosporine; may potentiate anticoagulant effects of warfarin; coadministration with lovastatin and simvastatin, increases risk of rhabdomyolysis |
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| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
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| Precautions | Caution in liver disease; estolate formulation may cause cholestatic jaundice; GI adverse effects are common (give doses pc); discontinue use if nausea, vomiting, malaise, abdominal colic, or fever occur |
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| Drug Name | Amoxicillin (Amoxil, Polymox, Trimox) |
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| Description | Interferes with synthesis of cell wall mucopeptides during active multiplication resulting in bactericidal activity against susceptible bacteria. |
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| Adult Dose | 250-500 mg PO q8h; not to exceed 3 g/d |
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| Pediatric Dose | 20-50 mg/kg/d PO divided q8h |
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| Contraindications | Documented hypersensitivity |
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| Interactions | Reduces the efficacy of oral contraceptives |
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| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
|
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| Precautions | Adjust dose in renal impairment |
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| Drug Name | Spectinomycin (Trobicin) |
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| Description | Used to treat most types of gonorrhea. Given by injection into a muscle. Sometimes given with other medicines for gonorrhea and related infections.
May be used in patients who are allergic to penicillins, cephalosporins, or probenecid (eg, Benemid). This medicine also is used to treat recent sexual partners of patients who have gonorrhea.
Second-line treatment of gonorrhea and gonococcal urethritis, cervicitis, or proctitis in patients who are infected with penicillin-resistant strains of N gonorrhoeae. Treatment of gonorrhea and gonococcal urethritis, cervicitis, or proctitis in patients allergic to beta-lactam anti-infectives (including ceftriaxone).
Inhibits bacterial protein synthesis at the level of the 30S ribosome. Bactericidal action against susceptible organisms. Most notable for activity against N gonorrhoeae, including penicillinase-producing strains (PPNG). Not active against Treponema pallidum or C trachomatis. |
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| Adult Dose | Adults and children 45 kg (99 lb) and over: 2 g IM single dose |
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| Pediatric Dose | Infants: Not recommended
Children up to 45 kg (99 lb): 40 mg/kg of body weight IM single dose |
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| Contraindications | Documented hypersensitivity; neonates (diluent contains benzyl alcohol) |
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| Interactions | None reported |
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| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
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| Precautions | Concurrent infection with other STD (additional anti-infectives may be required); pregnancy, breastfeeding, or children (safety not established; has been used) |
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| Drug Name | Tetracycline (Sumycin) |
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| Description | Treats gram-positive and gram-negative organisms, as well as mycoplasmal, chlamydial, and rickettsial infections. Inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunit(s). |
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| Adult Dose | 500 mg PO qid |
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| Pediatric Dose | <8 years: Not recommended
>8 years: 25-50 mg/kg/d (10-20 mg/lb) PO qid |
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| Contraindications | Documented hypersensitivity; severe hepatic dysfunction |
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| Interactions | Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy; tetracyclines can increase hypoprothrombinemic effects of anticoagulants |
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| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
|
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| Precautions | Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last one half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines |
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| Drug Name | Cefixime (Suprax) |
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| Description | Third-generation oral cephalosporin with broad activity against gram-negative bacteria. By binding to one or more of the penicillin-binding proteins, it arrests bacterial cell wall synthesis and inhibits bacterial growth.
Note: After a period of inavailability, oral cefixime is again FDA-approved in tablet and suspension forms. However, at the time of writing, tablets remain unavailable in the United States. Wyeth Pharmaceuticals (Collegeville, Pa) discontinued manufacturing cefixime (Suprax) in the United States. In October 2002, the company ceased marketing cefixime tablets (200 mg and 400 mg) because of depletion of company inventory; the company's patent for cefixime expired on November 10, 2002.
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| Adult Dose | 400 mg/d PO (recommended for gonococcal infections) or 200 mg PO q12h |
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| Pediatric Dose | <12 years: 8 mg/kg/d suspension PO or 4 mg/kg bid
>50 kg or >12 years: Administer as in adults
|
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| Contraindications | Documented hypersensitivity |
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| Interactions | Coadministration of aminoglycosides increase nephrotoxicity; probenecid may increase effects of cefixime |
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| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
|
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| Precautions | Adjust dose in severe renal insufficiency (high doses may cause CNS toxicity); superinfections and promotion of nonsusceptible organisms may occur with prolonged use or repeated therapy |
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Further Inpatient Care
- Many physicians admit patients who have corneal involvement for intravenous antibiotics. They can be discharged once the infection is under control and the corneal infection is improving.
Further Outpatient Care
- Patients require close follow-up care to ensure that the infection is improving and the cornea is not becoming involved.
Deterrence/Prevention
- Safe sexual practices, including condom use
Complications
- Disseminated systemic infection, meningitis, corneal ulceration, corneal perforation, and endophthalmitis
Prognosis
- Prognosis is excellent if treated quickly; prognosis is poor if untreated or treated late.
Patient Education
Medical/Legal Pitfalls
- Failure to check sexual partners and evaluate them for other STDs
Special Concerns
- Check patient and sexual partners to make ensure that no other STDs are present.
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- Centers for Disease Control and Prevention (CDC). Updated recommended treatment regimens for gonococcal infections and associated conditions - United States, April 2007. CDC. Available at http://www.cdc.gov/std/treatment/2006/updated-regimens.htm. Accessed July 17, 2007.
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- Ullman S, Roussel TJ, Culbertson WW, Forster RK, Alfonso E, Mendelsohn AD, et al. Neisseria gonorrhoeae keratoconjunctivitis. Ophthalmology. May 1987;94(5):525-31. [Medline].
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Gonococcus excerpt Article Last Updated: Nov 2, 2007
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