Introduction
Background
Gonococcal arthritis is caused by infection with the gram-negative diplococcus Neisseria gonorrhoeae. In the United States, gonococcal arthritis is the most common form of septic arthritis.1 This is in contrast to Western Europe, where gonococcal arthritis is uncommon,2 likely owing to a 70% decline in gonococcal infections over the last 2 decades.1
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; 60% of cases) or as a localized septic arthritis (remaining 40%). Arthritis-dermatitis syndrome includes the classic triad of dermatitis, tenosynovitis, and migratory polyarthritis.
Patients with gonococcal arthritis usually require initial hospitalization for intravenous antibiotic therapy; upon improvement, they can be transitioned to oral antibiotics. Unlike in Staphylococcus aureus septic arthritis, joint destruction is rare in gonococcal arthritis.
Pathophysiology
N gonorrhoeae is a highly infectious organism capable of colonizing diverse mucosal surfaces. The risk of infection from a single contact with the organism is estimated at 60%-90% among women and 20%-50% among men.1 Common sites of infection include the urethra, cervix, pharynx, and rectum; however, infection may be asymptomatic in some patients. Hematogenous spread of the mucosal infection occurs in 0.5%-3% of cases,3 and disseminated infection is thought to play a major role in the pathogenesis of gonococcal arthritis. 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.
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:2
* Female sex
* Pregnancy
* Menses
* Systemic lupus erythematosus
* Complement deficiency
* Low socioeconomic or educational status
* Intravenous drug use
* HIV infection
* Multiple sexual partners
Characteristics of the gonococcus associated with DGI include the following:1,2,3
* Antigenic variation of pili
* Protein IA on the outer membrane (inhibits host factor H and C4-binding protein, making host complement cascade less effective)
* Lack of protein II
* AHU strains with nutritional requirements for arginine, hypoxanthine, and uracil (often associated with protein IA)
Frequency
United States
In 2005, 339,593 cases of gonococcal infection were reported in the United States, making it the second most commonly reported communicable disease.4 Although rates of gonococcal infection declined from 1975-1997, the national rate of gonococcal infection increased in 2005 to 115 cases per 100,000 persons.4 However, rates vary by region and demographics, as described below.
International
* According to the World Health Organization, gonococcal infection is among the curable sexually transmitted infections, of which 340 million cases occur annually.5
* The incidence of gonococcal infection is lower in Europe than in North America. For example, the incidence of gonococcal infection in Sweden in 1992 was less than 5 per 100,000 population, while the incidence in the United States in 1995 was 150 per 100,000.2
* Gonococcal infection is high in developing countries, 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. Complications of DGI including pericarditis, endocarditis, meningitis, perihepatitis, pyomyositis, osteomyelitis, and glomerulonephritis are now rare and occur in only 1%-3% of cases.1
Race
In the United States, gonococcal infection is most common in African Americans.4 The prevalences in with, Hispanic, Native American, and Asian populations are similar and dramatically lower than in African Americans.4
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.2
Age
The highest rates of infection in the United States are among persons aged 15-29 years; however, older adults may be affected.4
Clinical
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.1
* Bacteremic form (arthritis-dermatitis syndrome)6
o Symptoms are typically present 3-5 days before diagnosis.
o 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.
o 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. Diffuse involvement of fingers can result in dactylitis.1
o 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.
o Nonspecific constitutional symptoms may include myalgias, fever, and malaise.
* Septic arthritis form6
o Joint symptoms begin within days to weeks of gonococcal infection.
o Patients may experience pain, redness, and swelling in usually one or sometimes multiple joints, most commonly the knees, wrists, ankles, and elbows.1
Physical
* Bacteremic form (classic triad of migratory polyarthritis, tenosynovitis, and dermatitis)6
o 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.
o Tenosynovitis is asymmetric, usually affecting the dorsum of wrists, hands, and ankles. Tenosynovitis of the fingers may result in dactylitis.
o 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.
o Fever rarely involves a temperature of greater than 39°C.
o Other presentations of DGI include the following, which now occur in only 1%-3% of cases:1
+ Fitz-Hugh-Curtis syndrome (gonococcal perihepatitis)
+ Sepsis with Waterhouse-Friderichsen syndrome
+ Gonococcal endocarditis (rare in the antibiotic era)
+ Gonococcal meningitis (very rare in the antibiotic era)
* Septic arthritis form6
o Septic arthritis is characterized by acute arthritis with signs of joint effusion, warmth, tenderness, decreased range of motion, and marked erythema.
o Septic arthritis most commonly involves the wrists, hands, knees, and elbows. 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 Pathophysiology.Differential Diagnoses
Hepatitis B
Reactive Arthritis
Hepatitis C
Rheumatic Fever
Lyme Disease
Septic Arthritis
Meningococcemia
Syphilis
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
Noninfectious causes of fever and purpuric skin lesions include the following:
* Systemic lupus erythematosus with small-vessel vasculitis
* Rheumatoid arthritis with small-vessel vasculitis
* Polyarteritis nodosa
* Hypersensitivity vasculitis
* Henoch-Schönlein purpura
Workup
Laboratory Studies
* Cultures of likely sites of gonococcal infection are the most important tests to perform for the diagnosis of disseminated gonococcal infection (DGI). Synovial fluid cultures are positive for N gonorrhoeae in no more than 50% of cases1 and alone are insufficient to make a diagnosis of DGI. In addition to synovial fluid culture, cultures of blood, cervix, rectum, urethra, and pharynx should be taken.7 Positive culture results help confirm the diagnosis of DGI and provide antibiotic sensitivities for the particular infecting strain of the organism.
* Other laboratory tests that are useful in DGI or gonococcal arthritis include the following:
o Complete blood cell count: Most cases involve mild leukocytosis.
o Erythrocyte sedimentation rate (ESR): This is elevated in most cases.
o 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).
o Culture of mucosal surfaces: Yield is highest if the culture is obtained from the primary infection site. Findings are positive in more than 80% of cases. 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.1 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.
o 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.
o 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).
o Blood cultures: Bottled blood culture media containing sodium polyethylene sulfate (SPS) inhibits growth.
o 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.
Other Tests
* Nucleic acid amplification tests (NAATs): NAATs may be used as an adjunct to culture and can be performed on samples from the cervix, urethra, rectum, urine, pharynx, synovial fluid,8 and skin9 . These tests can help to confirm a diagnosis of DGI when cultures are negative.8,9,10 However, an important limitation of polymerase chain reaction (PCR) or other NAATs is they do not provide antibiotic sensitivities to guide choice of antibiotic for treatment.
Procedures
* Arthrocentesis is mandatory in cases of suspected septic arthritis.
* Laboratory tests typically performed on synovial fluid include cell count, crystal analysis, Gram stain, and culture (see Lab Studies).
* Repeat arthrocentesis should be performed when inflammatory synovial effusions recur in order to remove inflammatory mediators, debris, and purulence.
* Surgical drainage may be needed in joints refractory to drainage via arthrocentesis; however, this is rarely necessary in gonococcal arthritis.
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
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. S 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 United States, particularly on the West Coast.4 For this reason, the Centers for Disease Control (CDC) no longer recommends quinolones for the treatment of gonococcal infections.11
* According to 2006 CDC guidelines, the initial treatment of choice for gonococcal arthritis or disseminated gonococcal infection (DGI) in adults is ceftriaxone 1 g IM or IV every 24 hours.12 Alternatives include ceftizoxime 1 g IV q8h or cefotaxime 1 g IV q8h.12 In patients intolerant of cephalosporins, spectinomycin 2 g IM every 12 hours is another option12 ; however, this antibiotic may not be readily available.13
* The April 2007 update of CDC guidelines states that fluoroquinolones are no longer recommended in the treatment of gonococcal infections in the United States.11 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% in the first half of 2006, an 11-fold increase from 0.6% in 2001.11 This effectively limits treatment of gonorrhea to drugs in the cephalosporin class (see above).
* 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) or levofloxacin (250 mg/d IV; 500 mg/d PO).
* Oral regimens that can be started 24-48 hours after initial improvement include the following:
o Cefixime 400 mg PO bid14 (once again available in the United States via Lupin Pharmaceuticals, Inc., of Baltimore, MD)
o Cefixime suspension 500 mg PO bid
o Cefpodoxime 400 mg PO bid13 (clinical study ongoing)
* 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.12 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. These patients require ceftriaxone 1-2 g IV every 12 hours.12 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).12 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:12
o Children who weigh less than 45 kg - Erythromycin base or ethylsuccinate 50 mg/kg PO divided qid for 14 days
o Children who weigh more than 45 kg but who are younger than 8 years - Azithromycin 1 g PO as a single dose
o 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 assistance in the evaluation and management of septic joints.
* 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
The goals of pharmacotherapy are to eradicate the infection, to reduce morbidity, and to prevent complications.
See Medical Care.
Antibiotics
These agents are indicated to treat gonococcal infection. Agents effective against chlamydial infection are included because of the significant co-infection rate.
Ceftriaxone (Rocephin)
Ceftriaxone is the DOC for disseminated gonococcal infection (DGI) or gonococcal arthritis, according to CDC guidelines. Bactericidal action is through inhibition of cell wall synthesis. No activity against Chlamydia.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
DGI or gonococcal arthritis: 1g IM or IV q24h
Pediatric
50 mg/kg IV q24h
* Dosing
* Interactions
* Contraindications
* Precautions
Probenecid and loop diuretics may increase cephalosporin levels; coadministration with aminoglycosides may increase nephrotoxicity
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity
* Dosing
* Interactions
* Contraindications
* Precautions
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)
Cefotaxime (Claforan)
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.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
DGI or gonococcal arthritis: 1 g IV q8h
Pediatric
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
* Dosing
* Interactions
* Contraindications
* Precautions
Probenecid and loop diuretics may increase cephalosporin levels; coadministration with aminoglycosides may increase nephrotoxicity
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity
* Dosing
* Interactions
* Contraindications
* Precautions
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)
Ceftizoxime (Cefizox)
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.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
1-2 g IV q8-12h
Pediatric
<6 months: Not established
>6 months: 50 mg/kg PO q6-8h
* Dosing
* Interactions
* Contraindications
* Precautions
Coadministration of aminoglycosides increases nephrotoxicity; probenecid may increase effects
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity
* Dosing
* Interactions
* Contraindications
* Precautions
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
Cefixime (Suprax)
By binding to one or more of the penicillin-binding proteins, it arrests bacterial cell wall synthesis and inhibits bacterial growth. In 2008, Morbidity and Mortality Weekly Report reported that manufacture of this medication resumed in the United States.14 It is the only oral cephalosporin that the CDC recommends for use in patients with DGI or gonococcal arthritis.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
400 mg PO qd
Pediatric
<6 years: Not established
>6 years: 8 mg/kg/d of susp PO
* Dosing
* Interactions
* Contraindications
* Precautions
Coadministration of aminoglycosides increases nephrotoxicity; probenecid may increase effects of cefixime
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity
* Dosing
* Interactions
* Contraindications
* Precautions
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
Doxycycline (Vibramycin)
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.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
100 mg PO bid for 7 d
Pediatric
<8 years: Not recommended
>8 years: 100 mg PO bid for 7d
* Dosing
* Interactions
* Contraindications
* Precautions
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
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; severe hepatic dysfunction
* Dosing
* Interactions
* Contraindications
* Precautions
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
Azithromycin (Zithromax)
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.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
1 g PO once
Pediatric
<45 kg: Not recommended
>45 kg but <8 years: 1 g PO once
>8 years: 1 g PO once
* Dosing
* Interactions
* Contraindications
* Precautions
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
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; hepatic impairment; administration with pimozide
* Dosing
* Interactions
* Contraindications
* Precautions
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
Erythromycin (E-mycin)
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.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
500 mg PO qid for 7 days
Pediatric
50 mg/kg/d PO divided q6h for 14 days
* Dosing
* Interactions
* Contraindications
* Precautions
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
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity; hepatic impairment
* Dosing
* Interactions
* Contraindications
* Precautions
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)
Amoxicillin (Amoxil, Biomox, Trimox)
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.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
500 mg PO tid for 7 d
Pediatric
Not established
* Dosing
* Interactions
* Contraindications
* Precautions
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
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity
* Dosing
* Interactions
* Contraindications
* Precautions
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
Spectinomycin (Trobicin)
Inhibits protein synthesis in bacterial cells. Site of action is 30S ribosomal subunit and is structurally different from related aminoglycosides. Recommended by the CDC as an option in patients intolerant of cephalosporin antibiotics12 ; however, this medication is not currently manufactured in the United States and may not be available.15
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
2 g IM q12h
Pediatric
Not established
* Dosing
* Interactions
* Contraindications
* Precautions
None reported
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity
* Dosing
* Interactions
* Contraindications
* Precautions
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
Levofloxacin (Levaquin)
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 if culture shows sensitivity to fluoroquinolones.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
Complicated skin infection: 750 mg/d PO/IV for 7-14 d
Uncomplicated skin infection: 500 mg/d PO for 7-14 d
Pediatric
<18 years: Not recommended
>18 years: Administer as in adults
* Dosing
* Interactions
* Contraindications
* Precautions
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)
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity
* Dosing
* Interactions
* Contraindications
* Precautions
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
Ciprofloxacin (Cipro)
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 if culture shows sensitivity to fluoroquinolones.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
DGI or gonococcal arthritis: 400 mg q12h IV or 500 mg q12h PO
Pediatric
<18 years: Not recommended
>18 years: Administer as in adults
* Dosing
* Interactions
* Contraindications
* Precautions
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)
* Dosing
* Interactions
* Contraindications
* Precautions
Documented hypersensitivity
* Dosing
* Interactions
* Contraindications
* Precautions
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
Ofloxacin (Floxin)
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 if culture shows sensitivity to fluoroquinolones.
* Dosing
* Interactions
* Contraindications
* Precautions
Adult
DGI or gonococcal arthritis: 400 mg IV or PO q12h
Pediatric
<18 years: Not recommended
>18 years: Administer as in adultsFollow-up
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.
Inpatient & Outpatient Medications
* 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:
o Permanent joint damage
o Meningitis
o Endocarditis
o 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
Medicolegal 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.
