AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Gonococcal arthritis is the most common acute septic arthritis in young adults. It is caused by the gram-negative diplococcus Neisseria gonorrhoeae. Although the pathogenesis of articular involvement is controversial, it is ultimately a consequence of disseminated gonococcal infection (DGI). Gonococcal arthritis manifests as either a bacteremic infection (arthritis-dermatitis syndrome) in 60% of cases or as a localized septic arthritis in the other 40%. Arthritis-dermatitis syndrome includes the classic triad of dermatitis, tenosynovitis, and migratory polyarthritis. Patients with gonococcal arthritis who develop joint destruction (rare) usually require hospitalization for antibiotic therapy to avoid other potentially serious complications of DGI.

Pathophysiology

N gonorrhoeae is a highly infectious organism capable of colonizing diverse mucosal surfaces. The risk of infection from a single contact is estimated at 60-90% among women and 20-50% among men. Infection may not cause symptoms and often affects genitourinary, rectal, or pharyngeal mucosal surfaces. Hematogenous spread of the mucosal infection (0.5-3% of cases) is caused by a delay in antibiotic treatment, physiologic changes in the host, host immune system failures, and particularly virulent strains of N gonorrhoeae and can occur even in the absence of symptoms. Patients with DGI may present with dermatitis-arthritis syndrome or with a localized septic arthritis. These presentations may represent different phases of a disease continuum.

Frequency

United States

Although decreasing or stable in the 1990s, the national incidence of gonococcal infection increased in 2005 to 115 cases per 100,000 persons. However, rates vary by region. In the western United States, rates increased from 57 cases per 100,000 persons in 2000 to 81.5 cases per 100,000 persons in 2005to. Incidence rates declined in the northeast, south, and Midwest regions over the same period. Demographic risk factors include nonwhite ancestry, lower socioeconomic or educational status, urban residency, promiscuity or sexual activity at a young age, single marital status, homosexuality, previous history of gonorrhea infection, and intravenous drug abuse.

International

Two hundred million cases of N gonorrhoeae infection occur worldwide each year. The incidence appears to be lower in Europe than in North America. Developing countries, however, continue to have a high incidence of disease, partly because of limited public health infrastructure and limited access to health care.

Mortality/Morbidity

Morbidity associated with DGI has decreased dramatically in the postantibiotic era. Pericarditis, endocarditis, meningitis, perihepatitis, pyomyositis, osteomyelitis, and glomerulonephritis have been reported but are now rare. Arthritis in more unusual joints (eg, sternoclavicular, hip) in patients with HIV may be more aggressive than typical cases in the general population. Factors that correlate with increased risk of a disseminated infection have been identified for both the host and the organism.

Host factors for disseminated infection include the following:

• General
• • Extragenital infection
  • Promiscuity
  • Systemic lupus erythematosus
  • Low socioeconomic or educational status
  • Intravenous drug abuse
  • HIV infection
• Women
• • Menses
  • Pregnancy 
  • Puerperium
  • Chronic asymptomatic endocervical infection  
• Men: Homosexuality
• Inherited: Patients with an inherited terminal complement deficiency (C5-C9) are susceptible to recurrent gonococcal infections, especially DGI with meningitis.

Characteristics of the gonococcus associated with increased virulence and, hence, bacteremia and DGI include the following:

• The presence of pili
• Protein IA on the outer membrane (inhibits neutrophil exocytosis and promotes organism endocytosis by epithelial cells)
• Lack of protein II (transparent colonies [associated with DGI]) and protein III (blocking antibodies that reduce serum bactericidal activity)
• Lipo-oligosaccharide ([LOS] endotoxic activity and possible reduced serum bactericidal activity)
• Immunoglobulin A (IgA) proteases (protection from mucosal surface defenses)
• Nutritional requirements such as arginine, hypoxanthine, and uracil (associated with lack of protein II)

Race

In the United States, the disease is more prevalent among African American, Hispanic, and Native American populations.

Sex

The disease is 3-4 times more common in females than in males, possibly because of the increased risk of asymptomatic infection in females.

Age

Persons younger than 30 years are at the greatest risk; however, older adults may be affected.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

The clinical presentation of disseminated gonococcal infection (DGI) is typically divided into a bacteremic form and a septic arthritis form. Approximately 60% of patients present with symptoms consistent with the bacteremic form, and the remaining 40% present with symptoms of more localized infection. Although each form presents with its own symptom complex, the overlap can be considerable. The time from initial infection to initial manifestations of DGI ranges from 1 day to 3 months.

• Bacteremic form (arthritis-dermatitis syndrome)
• • Symptoms are present 3-5 days before diagnosis.
  • Migratory arthralgias are the most common presenting symptom in persons with DGI and are usually polyarticular. The arthralgias are typically asymmetric and tend to involve the upper extremities more than the lower extremities. The wrist, elbows, ankles, and knees are most commonly affected. Symptoms resolve spontaneously in 30-40% of cases or evolve into a septic arthritis in one or several joints.
  • Pain may also be due to tenosynovitis. The tenosynovitis of DGI is asymmetric and most commonly occurs over the dorsum of the wrist and hand, as well as over the metacarpophalangeal joints, ankles, and knees.
  • The rash associated with the bacteremic form of DGI may be overlooked by patients because it is painless and nonpruritic and consists of small papular, pustular, or vesicular lesions.
  • Nonspecific constitutional symptoms may include myalgias, fever, and malaise.
• Septic arthritis form
• • Joint symptoms begin within days to weeks of gonococcal infection.
  • Patients may experience pain, redness, and swelling in usually one or sometimes multiple joints.

Physical

• Bacteremic form (classic triad of migratory polyarthritis, tenosynovitis, and dermatitis)
• • Migratory arthritis has an asymmetric distribution, most commonly affecting wrists, ankles, and elbows. Seventy percent of patients have 1-3 joints with clear inflammatory signs after just a few days. Symmetric polyarthritis is less common but may occur in approximately 10% of patients.
  • Tenosynovitis is asymmetric, usually affecting the dorsum of wrists, hands, and ankles. Tenosynovitis of the fingers may result in dactylitis.
  • Dermatitis occurs in 40-70% of patients and typically involves the extremities. Lesions are usually tiny maculopapular, pustular, or vesicular lesions on an erythematous base. The center of the lesion may become necrotic or hemorrhagic. Despite their appearance, they are painless and nonpruritic. The lesions tend to disappear within a few days after treatment is initiated. Usually, 4-50 lesions are reported. Rarely, the lesions may resemble erythema nodosum or erythema multiforme.
  • Fever rarely involves a temperature of greater than 39°C.
  • Other presentations of DGI include the following:
  • • Fitz-Hugh and Curtis syndrome (gonococcal perihepatitis)
    • Sepsis with Waterhouse-Friderichsen syndrome (rare)
    • Gonococcal endocarditis (rare in the antibiotic era)
    • Gonococcal meningitis (very rare in the antibiotic era)
• Septic arthritis form
• • Septic arthritis is characterized by acute arthritis with signs of joint effusion, warmth, tenderness, decreased range of motion, and marked erythema.
  • Septic arthritis most commonly involves the wrists, hands, knees, elbows, and shoulders. Chronic arthritis with joint destruction is rare with appropriate antibiotic therapy.

Causes

Gonococcal arthritis is caused by infection with the gram-negative diplococcus N gonorrhoeae. The risk of dissemination following mucosal infection depends on both the ability of the patient's immune system to control the infection and the virulence of the organism. See Mortality/Morbidity.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Nongonococcal septic arthritis
Bacterial endocarditis
Parvovirus infection
Gout (may mimic septic arthritis and rarely occurs with gonococcal arthritis)

Infectious causes of fever and purpuric skin lesions include the following:

• Rickettsial infections
• Rocky Mountain spotted fever
• Staphylococcal bacteremia
• Enterovirus infection
• Coxsackievirus infection
• Echovirus infection

• Systemic lupus erythematosus with small-vessel vasculitis
• Rheumatoid arthritis with small-vessel vasculitis
• Polyarteritis nodosa
• Hypersensitivity vasculitis
• Henoch-Schönlein purpura

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Culture of the organism, is the most important test that can be performed with this disease process, although the results are not always positive. It the confirmatory test for diagnosis and is used to establish antibiotic sensitivities for the particular infecting strain of the organism. A positive finding on culture from the synovial fluid, although absent in many suspected cases, is the criterion standard for the diagnosis of gonococcal arthritis. Suspected disseminated gonococcal infection (DGI) may be classified according to specific culture results.
• • Proven DGI - Positive finding on blood culture, skin lesion, or other site source
  • Probable DGI - Positive result for primary mucosal infection but sterile site cultures
  • Possible DGI - Typical clinical syndrome and treatment response but findings on all cultures are negative
• Other laboratory tests that are of some use in DGI or gonococcal arthritis include the following:
• • Complete blood cell count: Most cases involve mild leukocytosis.
  • Erythrocyte sedimentation rate (ESR): This is elevated in most cases.
  • Synovial fluid analysis
  • • Cell count: The cell count is usually greater than 50,000 WBC/µL (typically >90% polymorphonuclear cells). Synovial fluid with this much inflammation may appear purulent.
    • Analysis for crystals
    • Gram stain: Gram-negative intracellular organisms may be demonstrated, although in less than 25% of synovial fluid aspirates.
    • Culture: Note that synovial fluid should be cultured on prewarmed chocolate agar for highest yield (positive findings in only 50% of patients with gonococcal arthritis and 25-30% of patients with DGI).
  • Evaluation of all mucosal surfaces
  • • Culture: Yield is highest if the culture is obtained from the primary site of infection. Findings are positive in more than 80% of cases. Less than 5% are positive in patients with DGI because the primary infection may have occurred weeks prior. When obtained from the primary site of infection, 90% of results are positive in cervical samples, 50-75% in male urethral samples, 20% in pharyngeal samples, and 15% in rectal samples. The pharynx is an important site of infection in pregnant women and in men who have sex with men (MSM). Mucosal surface cultures should be placed on prewarmed selective plates (ie, Thayer-Martin, modified New York media) and blood agar for identification of other possible organisms.
    • Nucleic acid amplification tests (NAATs): NAATs may be used as an adjunct to culture and can be performed on cervical samples, vaginal samples, urethral samples, and urine. However, polymerase chain reaction (PCR) or other NAATs do not provide antibiotic sensitivities. These tests are more appropriately used in the screening of asymptomatic patients. 
  • Urine culture: Culture is noted to produce a higher yield if the sample is the first-void urine (FVU) from the first 20 mL of the void.
  • Rectal culture: The swab is inserted approximately 2.5 cm into the canal (ie, to crypts of Morgagni, which is a frequent focus of infection).
  • Blood cultures: Bottled blood culture media containing sodium polyethylene sulfate (SPS) inhibits growth.
  • Other sexually transmitted infections: Patients should also be tested for other sexually transmitted infections, including HIV, hepatitis B, chlamydia, and syphilis.

Imaging Studies

• Plain radiography findings of the affected joint are usually normal. However, they may be indicated to exclude articular damage and to rule out other processes, such as fracture.

Procedures

• Arthrocentesis should be performed in cases of suspected septic arthritis. Synovial fluid from locations where bacterial infection is suspected should undergo appropriate stains and cultures. This is essential in the case of monoarthritis.
• Laboratory tests typically performed on synovial fluid include cell count, crystal analysis, Gram stain, and culture (see Lab Studies).
• In addition, the inflammatory synovial effusions associated with gonococcal arthritis should be aspirated repeatedly to remove inflammatory mediators, debris, and purulence.
• More aggressive draining procedures may be needed in joints refractory to this therapy; however, surgical drainage or arthroscopy is rarely necessary.

Histologic Findings

Biopsy of skin lesions shows dermal vasculitis with perivascular neutrophils. Neutrophilic infiltration of the epidermis may also be seen in pustular lesions.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

The management of acute septic arthritis is discussed in the eMedicine article Septic Arthritis. When septic arthritis is suspected, empiric antibiotics directed against likely pathogens should be used until confirmatory laboratory data are available. Antibiotic coverage in healthy hosts should initially include gram-positive organisms, which account for approximately 80% of nongonococcal monoarthritis cases. Staphylococcus aureus accounts for 60%, non–group A Streptococcus species cause 15%, and Streptococcus pneumoniae cause 3%. Gram-negative organisms, accounting for another 18% should be covered in patients who are immunocompromised, elderly, or otherwise at risk.

Additional management considerations for gonococcal arthritis include the following:

• Most patients with suspected acute infectious arthritis, including gonococcal arthritis, should be hospitalized to establish a diagnosis and to monitor for improvement or complications. Daily synovial fluid drainage is recommended for purulent effusions associated with gonococcal arthritis. Surgical drainage is needed when arthrocentesis is ineffective. The transition to oral antibiotics can usually be made 24-48 hours after clinical improvement.
• A thorough travel history for the patient and any sexual partners is important in selecting initial therapy for gonococcal infections. Quinolone-resistant N gonorrhoeae (QRNG) is common in the Pacific and parts of Asia and is increasing in the western United States. For this reason, the Centers for Disease Control (CDC) no longer recommends quinolones for the treatment of gonococcal infections (see below).
• According to 2006 CDC guidelines and recent updates (April 2007), the initial treatment of choice for gonococcal arthritis or disseminated gonococcal infection (DGI) in adults is a third-generation cephalosporin: ceftriaxone 1 g IM/IV q24 h (q12h when meningitis or endocarditis is suspected), ceftizoxime 1 g IV q8h, or cefotaxime 1 g IV q8h.  
• The April 2007 update of CDC guidelines states that fluoroquinolone antibiotics are no longer recommended to treat gonorrhea in the United States. The recommendation was based on analysis of new data from the CDC's Gonococcal Isolate Surveillance Project (GISP), which showed the proportion of fluoroquinolone-resistant (QRNG) gonorrhea cases in heterosexual men  reached 6.7%, an 11-fold increase from 0.6% in 2001.¹ This limits treatment of gonorrhea to drugs in the cephalosporin class (eg, ceftriaxone 125 mg IM once as a single dose). Fluoroquinolones may be an alternative treatment option for DGI if antimicrobial susceptibility can be documented. For more information, see the CDC's Antibiotic-Resistant Gonorrhea Web site; CDC's Updated gonococcal treatment recommendations (April 2007); or Medscape Medical News on CDC Issues - New Treatment Recommendations for Gonorrhea.
• Fluoroquinolones may be considered as alternative agents for DGI in patients unable to take cephalosporins if antimicrobial susceptibility can be documented with culture results. Fluoroquinolone regimens include ciprofloxacin (400 mg IV q12h; 400 mg PO bid), ofloxacin (400 mg IV/PO q12h), levofloxacin (250 mg/d IV; 500 mg/d PO), or spectinomycin (2 g IM q12h).
• Oral regimens that can be started 24-48 hours after initial improvement include the following:
• • Cefixime 400 mg PO bid (not available in the United States)
  • Cefixime suspension 500 mg PO bid
  • Cefpodoxime 400 mg PO bid
• Patients should continue oral antibiotics for at least 1 week.
• Special situations include pregnant and pediatric patients (<8 y). These patients should not be treated with quinolones or tetracyclines. Pregnant patients with gonococcal infections should be treated with a recommended cephalosporin. Spectinomycin is indicated for patients who cannot tolerate a cephalosporin. Pediatric patients can be treated with ceftriaxone 50 mg/kg/d IV or IM for 7 days. Data are insufficient to support the use of oral cephalosporins for DGI or arthritis in children.
• Examine patients with DGI for clinical evidence of endocarditis and meningitis. Patients with endocarditis require much longer courses of antibiotics (4-6 wk) and may require surgical intervention.
• Patients with confirmed diagnosis of a localized gonococcal infection can probably be discharged with outpatient medications if they are considered reliable for follow-up care. Synovial effusions may require a longer duration of antibiotics, but open drainage is rarely required. Intra-articular antibiotics have no known benefit.
• Because 30-50% of patients are co-infected with Chlamydia, test all patients and treat with azithromycin (1 g PO as a single dose) or doxycycline (100 mg PO bid for 7 d). Alternatives for pregnant patients include erythromycin (500 mg PO qid for 7 d) or amoxicillin (500 mg tid for 7 d). Regimens for the treatment of chlamydial infection in children include the following:
• • Children who weigh less than 45 kg - Erythromycin base or ethylsuccinate 50 mg/kg PO divided qid for 14 days
  • Children who weigh more than 45 kg but who are younger than 8 years - Azithromycin 1 g PO as a single dose
  • Children older than 8 years - Azithromycin 1 g PO in a single dose or doxycycline 100 mg PO bid for 7 days
• Patients should be advised to refer their sexual partners for evaluation and treatment.

Surgical Care

Open drainage or arthroscopy of infected joints is needed when arthrocentesis is insufficient. However, joint effusions in gonococcal arthritis rarely result in permanent damage.

Consultations

• Consider consulting a rheumatologist for management of septic joints and for follow-up outpatient appointments.
• Consider consulting an infectious disease specialist for management of DGI cases and determination of optimal antibiotic therapy later in the course of the disease.
• Consider consulting a cardiologist if acute endocarditis is suspected.
• Consulting an orthopedist may be required for arthroscopic or surgical drainage of an inaccessible joint (eg, hip) or for failure of nonsurgical management (daily aspiration).

Activity

Bedrest during inpatient status and brief immobilization of the septic joint aid in decreasing pain, especially when nonsteroidal anti-inflammatory drugs (NSAIDs) are not used.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

The goals of pharmacotherapy are to eradicate the infection, to reduce morbidity, and to prevent complications.

See Medical Care.

Drug Category: Antibiotics

These agents are indicated to treat gonococcal infection. Agents effective against chlamydial infection are included because of the significant co-infection rate.

Drug Name	Cefotaxime (Claforan)
Description	An alternative third-generation cephalosporin to ceftriaxone for DGI or gonococcal arthritis. Bactericidal action is through inhibition of cell wall synthesis. No activity against Chlamydia.
Adult Dose	DGI or gonococcal arthritis: 1 g IV q8h
Pediatric Dose	Not specified in CDC guidelines <50 kg: 50-180 mg/kg IV/IM divided q4-6h >50 kg: Administer as in adults; not to exceed 12 g; dose increased in patients with meningitis
Contraindications	Documented hypersensitivity
Interactions	Probenecid and loop diuretics may increase cephalosporin levels; coadministration with aminoglycosides may increase nephrotoxicity
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Adjust dose in renal impairment; caution in breastfeeding patients; cross-allergenicity with penicillins possible (caution in patients with known penicillin allergy)

Drug Name	Ceftizoxime (Cefizox)
Description	Third-generation cephalosporin with broad-spectrum, gram-negative activity. May be used as an alternative to ceftriaxone for gonococcal arthritis or DGI. Lower efficacy against gram-positive organisms. Higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin-binding proteins.
Adult Dose	1-2 g IV q8-12h
Pediatric Dose	<6 months: Not established >6 months: 50 mg/kg PO q6-8h
Contraindications	Documented hypersensitivity
Interactions	Coadministration of aminoglycosides increases nephrotoxicity; probenecid may increase effects
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Adjust dose in renal impairment; transaminitis, anemia, leukopenia, thrombocytopenia, transient elevations in BUN/creatinine levels, or GI adverse effects may occur

Drug Name	Cefixime (Suprax)
Description	By binding to one or more of the penicillin-binding proteins, it arrests bacterial cell wall synthesis and inhibits bacterial growth. Morbidity and Mortality Weekly Report reported in 2002 that manufacture of this medication was discontinued in the United States. It was the only oral cephalosporin that the CDC recommended for use in patients with DGI or gonococcal arthritis.
Adult Dose	400 mg PO qd
Pediatric Dose	<6 years: Not established >6 years: 8 mg/kg/d of susp PO
Contraindications	Documented hypersensitivity
Interactions	Coadministration of aminoglycosides increases nephrotoxicity; probenecid may increase effects of cefixime
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Adjust dose in renal impairment; GI adverse effects, hepatotoxicity, headaches, dizziness, thrombocytopenia, and leukopenia may occur

Drug Name	Doxycycline (Vibramycin)
Description	Commonly used as a cotreatment for suspected Chlamydia infection. May be used in complicated cases of gonococcal urethritis but not recommended for septic arthritis from gonococcus or a disseminated infection. Bacteriostatic by inhibiting bacterial protein synthesis.
Adult Dose	100 mg PO bid for 7 d
Pediatric Dose	<8 years: Not recommended >8 years: 100 mg PO bid for 7d
Contraindications	Documented hypersensitivity; severe hepatic dysfunction
Interactions	Bioavailability decreases with antacids that contain aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of PO contraceptives, causing breakthrough bleeding and increased risk of pregnancy
Pregnancy	D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
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 (<8 y) can cause permanent discoloration of teeth; Fanconi-like syndrome may occur with outdated tetracyclines; drink fluids to reduce risk of esophageal irritation

Drug Name	Azithromycin (Zithromax)
Description	Alternative to doxycycline as cotreatment aimed at Chlamydia infection. Ideal for the noncompliant patient because may be given as a one-time dose. Not a cited DOC for gonococcal arthritis or DGI.
Adult Dose	1 g PO once
Pediatric Dose	<45 kg: Not recommended >45 kg but <8 years: 1 g PO once >8 years: 1 g PO once
Contraindications	Documented hypersensitivity; hepatic impairment; administration with pimozide
Interactions	May increase toxicity of theophylline, warfarin, and digoxin; effects are reduced with coadministration of aluminum and/or magnesium antacids; increases cyclosporine levels, increasing risk of toxicity; increases effect of warfarin and triazolam, carbamazepine, hexobarbital, and phenytoin
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
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 patients who are hospitalized, geriatric, or debilitated; although rare, reports of allergic reactions (including anaphylaxis), Stevens-Johnson syndrome, and toxic epidermal necrolysis complicating therapy exist; adverse effects include nausea, vomiting, diarrhea, and abdominal pain

Drug Name	Erythromycin (E-mycin)
Description	Alternative to doxycycline for Chlamydia infection. Medication used to cotreat Chlamydia infection in pregnancy. Not a cited DOC for treatment of gonococcal arthritis or DGI. Acts through inhibition of bacterial protein synthesis.
Adult Dose	500 mg PO qid for 7 days
Pediatric Dose	50 mg/kg/d PO divided q6h for 14 days
Contraindications	Documented hypersensitivity; hepatic impairment
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; reported antagonism between clindamycin and erythromycin; may result in ergot toxicity when used concomitantly with ergotamines; may increase the effect of various benzodiazepines through decreased clearance
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Reports of severe allergic reactions include SJS and toxic epidermal necrolysis; reports of hepatic dysfunction, including increased liver enzymes and hepatocellular and/or cholestatic hepatitis; monitor creatine kinase and serum transaminase levels in patients receiving concomitant lovastatin and erythromycin; may exacerbate symptoms of weakness in myasthenia gravis; adverse effects include nausea, vomiting, diarrhea, abdominal pain, and loss of appetite; reports of transient reversible hearing loss (in patients with renal dysfunction)

Drug Name	Amoxicillin (Amoxil, Biomox, Trimox)
Description	According to CDC guidelines, amoxicillin may be used for the treatment of chlamydia in pregnant women. Not a cited DOC for DGI or gonococcal arthritis.
Adult Dose	500 mg PO tid for 7 d
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	Coadministration with warfarin or heparin increases risk of bleeding; probenecid decreases renal tubular secretion of amoxicillin; may reduce efficacy of PO contraceptives; may increase incidence of rashes in patients on allopurinol
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Caution in patients with history of multiple medication allergies, hepatic dysfunction, and breastfeeding women (excreted in breast milk); pseudomembranous colitis, bone marrow suppression, or CNS effects may occur

Drug Name	Spectinomycin (Trobicin)
Description	Inhibits protein synthesis in bacterial cells. Site of action is 30S ribosomal subunit and is structurally different from related aminoglycosides.
Adult Dose	2 g IM once
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions	Benzyl alcohol used as a diluent is associated with fatal gasping syndrome in infants; antibiotics may mask or delay symptoms of incubating syphilis; perform a serologic test for syphilis in all patients with gonorrhea at time of diagnosis followed by additional test after 3 mo; monitor clinical effectiveness to detect resistance by N gonorrhoeae; fever, nausea, and urticaria following injection, anaphylaxis, anemia, or transiently reduced CrCl may occur

Drug Name	Levofloxacin (Levaquin)
Description	Used to treat complicated and uncomplicated skin and skin structure infections. Fluoroquinolones should be used empirically in patients likely to develop exacerbation due to organisms resistant to other antibiotics. This is the L stereoisomer of the D/L parent compound ofloxacin, the D form being inactive. Good monotherapy with extended coverage against Pseudomonas species, as well as excellent activity against pneumococcus. Agent acts by inhibition of DNA gyrase activity. Oral form has a reported bioavailability of 99%. New CDC guidelines no longer recommend fluoroquinolones because of resistance. May be used as alternative for DGI in patients unable to take cephalosporins.
Adult Dose	Complicated skin infection: 750 mg/d PO/IV for 7-14 d Uncomplicated skin infection: 500 mg/d PO for 7-14 d
Pediatric Dose	<18 years: Not recommended >18 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Concomitant use of theophylline may be associated with cardiac arrest, seizure, status epilepticus, and respiratory failure; antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; ciprofloxacin reduces therapeutic effects of phenytoin; probenecid may increase ciprofloxacin serum concentrations; may increase toxicity of caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)
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
Precautions	In prolonged therapy, periodically evaluate organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in patients with renal impairment; superinfections may occur with prolonged or repeated antibiotic therapy; associated with various CNS effects, including dizziness, psychosis, depression, increased intracranial pressure, convulsions, and suicidal ideation; caution in patients with known CNS disease, illness, or medications that may predispose to seizures; phototoxicity has been reported (avoid excessive sunlight), arthralgias and tendinopathies may occur, including tendon rupture; levofloxacin is also excreted in breast mild and should not be used in nursing mothers

Drug Name	Ciprofloxacin (Cipro)
Description	Useful for initial therapy when given intravenously and for oral therapy after initial response to intravenous therapy. Also effective against Chlamydia. Can be used to treat patients who are penicillin allergic. Do not use in pregnant or pediatric persons. New CDC guidelines no longer recommend fluoroquinolones because of resistance. May be used as alternative for DGI in patients unable to take cephalosporins.
Adult Dose	DGI or gonococcal arthritis: 400 mg q12h IV or 500 mg q12h PO
Pediatric Dose	<18 years: Not recommended >18 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Concomitant use of theophylline may be associated with cardiac arrest, seizure, status epilepticus, and respiratory failure; antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; ciprofloxacin reduces therapeutic effects of phenytoin; probenecid may increase ciprofloxacin serum concentrations; may increase toxicity of caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)
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
Precautions	In prolonged therapy, periodically evaluate organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal impairment; superinfections may occur with prolonged or repeated antibiotic therapy; associated with various CNS effects, including dizziness, psychosis, depression, increased intracranial pressure, convulsions, and suicidal ideation; caution in patients with known CNS disease, illness, or medications that may predispose to seizures; phototoxicity has been reported (avoid excessive sunlight), arthralgias and tendinopathies may occur, including tendon rupture; not for use in breastfeeding mothers

Drug Name	Ofloxacin (Floxin)
Description	Useful medication for initial therapy when given IV and for oral therapy after an initial response to IV therapy. Also effective against Chlamydia and can be used to treat patients who are penicillin allergic. Do not use in pregnant or pediatric population. New CDC guidelines no longer recommend fluoroquinolones because of resistance. May be used as alternative for DGI in patients unable to take cephalosporins.
Adult Dose	DGI or gonococcal arthritis: 400 mg IV or PO q12h
Pediatric Dose	<18 years: Not recommended >18 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Concomitant use of theophylline may be associated with cardiac arrest, seizure, status epilepticus, and respiratory failure; antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; ciprofloxacin reduces therapeutic effects of phenytoin; probenecid may increase ciprofloxacin serum concentrations; may increase toxicity of caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)
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
Precautions	In prolonged therapy, periodically evaluate organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in patients with renal impairment; superinfections may occur with prolonged or repeated antibiotic therapy; associated with various CNS effects, including dizziness, psychosis, depression, increased intracranial pressure, convulsions, and suicidal ideation; caution in patients with known CNS disease, illness, or medications that may predispose to seizures; phototoxicity has been reported (avoid excessive sunlight), arthralgias and tendinopathies may occur, including tendon rupture; ofloxacin is also excreted in breast milk and should not be used in nursing mothers

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• See Medical Care.
• Daily aspiration with synovial fluid drainage has also been recommended for purulent effusions associated with gonococcal arthritis.
• Examine patients with disseminated gonococcal infection (DGI) for clinical evidence of endocarditis and meningitis, although both of these complications are rare.

Further Outpatient Care

• Re-evaluate patients to ensure resolution of illness.
• Reculture all known infected sites at least 5-7 days after the last dose of antibiotic therapy.
• Patients screened for syphilis must be screened again in 4-6 weeks, and HIV screening must be repeated again in 6 months.
• Contact, examine, and possibly treat the patient's sexual partners.

In/Out Patient Meds

• Continue parenteral antibiotic therapy for at least 24-48 hours to allow for improvement, at which time an oral antibiotic regimen may be instituted.
• Oral antibiotic duration may vary depending on the presence of any complications of DGI (endocarditis), but all patients should continue for at least 7 more days. See Medical Care.

Transfer

• Although patients with persistent joint effusion despite early antibiotic therapy may require frequent joint aspiration, arthroscopic evaluation or surgical drainage that requires an orthopedic surgeon is rarely needed.
• Patients with acute endocarditis secondary to gonococcus may require cardiothoracic surgery.

Deterrence/Prevention

• Patient education
• Identification of high-risk sexual practices
• Promoting use of protective barrier contraceptives (ie, condom)
• Contacting the patient's sexual partners for education, examination, and possible treatment

Complications

• All complications are rare but include the following:
• • Permanent joint damage
  • Meningitis
  • Endocarditis
  • Osteomyelitis

Prognosis

• With the proper antibiotic treatment and joint drainage, full recovery is expected in patients determined to have septic arthritis from gonococcus infection.
• The prognosis in patients with more severe manifestations of DGI varies depending on the complication or comorbidities. Patients with acute endocarditis, for example, may require valve surgery and can expect at least 4-6 weeks of antibiotics.

Patient Education

• Patient education is an integral part of proper therapy. Patients should learn about the sexual transmission of the disease and barrier methods of prevention (condoms). In addition, education regarding specific risk factors or high-risk behaviors may be a deterrent for further infections from gonococcus or more severe sexually transmitted diseases such as HIV. Also important is the identification, examination, and treatment of patients' sexual partners.
• For excellent patient education resources, visit eMedicine's Sexually Transmitted Diseases Center and Arthritis Center. Also, see eMedicine's patient education articles Gonorrhea, Knee Pain, Birth Control Overview, and Birth Control FAQs.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to consider the diagnosis in a patient who presents with acute septic arthritis
• Failure to treat for adequate duration with effective antibiotics
• Failure to recognize endocarditis, meningitis, or osteomyelitis as complications of disseminated gonococcal infection (DGI)
• Failure to treat for concomitant infection with Chlamydia or to properly screen for other sexually transmitted diseases (eg, HIV, syphilis)
• Failure to recognize that recurrent DGI may represent a complement deficiency
• Failure to treat sexual partners for the same disease
• Failure to provide adequate follow-up care

Special Concerns

• In the pediatric population, the diagnosis must be considered if the patient is sexually active or abused.
• In the geriatric population, gonococcal arthritis is uncommon but should be considered based on the patient's sexual history.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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19. Siva C, Velazquez C, Mody A, Brasington R. Diagnosing acute monoarthritis in adults: a practical approach for the family physician. Am Fam Physician. Jul 1 2003;68(1):83-90. [Medline]. [Full Text].
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Article Last Updated: Aug 17, 2007