Clinical Reference / Therapeutic Strategies / Gonorrhea / Gonococcemia

Gonorrhea / Gonococcemia


Key points

  • Gonorrhea is a common sexually transmitted infection (STI) that can cause genital and extragenital manifestations.
  • Many patients may be co-infected with other STIs, and Neisseria gonorrhoeae antimicrobial resistance is common, both of which can complicate the evaluation and treatment of patients with gonorrhea.
  • Patients should receive counseling regarding safe sex practices and their partners should be evaluated and treated if appropriate.

Introduction

Worldwide, gonorrhea is a common sexually transmitted infection (STI) that can cause a range of effects both locally at the site of infection and through secondary effects and dissemination. Gonorrhea is caused by Neisseria gonorrhoeae, a gram-negative bacteria, and at this point is the second most common STI in the U.S., with over 330,000 cases diagnosed annually—the Centers for Disease Control and Prevention (CDC) estimates that more than double that number of new cases are going undiagnosed. The highest incidence is in persons aged 15-24. Higher prevalence of gonorrhea may be seen in patients with HIV infection, illicit drug users, sex workers, and potentially men who have sex with men (MSM), with rectal gonorrhea commonly occurring in MSM. Patients with gonorrhea often have other concurrent STIs and require thorough evaluation and broad testing and treatment for additional infections. Management of gonorrhea is becoming more complicated with the development of widespread gonococcal resistance to multiple antimicrobial agents, making this infection a public health threat requiring accurate and timely diagnosis, thorough evaluation, and appropriate treatment. Gonococcal infection can occur in multiple sites; this article will focus primarily on disseminated infection and the cutaneous manifestations that occur in that setting.

Gonorrhea primarily causes urethritis in men, and cervicitis in women. In men the urethritis can range from asymptomatic or mild disease to pain, dysuria, and/or a purulent discharge, which tends to be abundant (thus the historic slang term for gonorrhea, “drip” or “clap”). Epididymitis may occur as well. In women, many patients may have asymptomatic infection. A subset of women will progress to develop pelvic inflammatory disease, which may be the first symptom of gonorrhea in women. Women can also develop involvement of the liver or Bartholin’s glands. Pregnant women with gonococcal infections can develop complications and can transmit the bacteria to the infant, which can manifest as a gonococcal conjunctivitis.

Extragenital gonococcal infection can occur in the pharynx, as a result of oral sex, and is more common in women than in men. Most cases are asymptomatic, though exudates can occur and patients may develop a sore throat or lymphadenopathy. Proctitis can occur, particularly in MSM, and may be spread through receptive anal intercourse.

Disseminated gonococcal infection is a rare complication of gonorrhea. Patients with inherited complement deficiencies, immunosuppression, or other factors may be at increased risk. Certain strains of N. gonorrhoeae may be more virulent and confer increased risk for dissemination. Dissemination of N. gonorrhoeae can lead to endocarditis, meningitis, and osteomyelitis. Disseminated gonococcemia can also lead to fever, arthralgia and/or arthritis (mono- or oligo-, particularly of the knees), and cutaneous lesions. The characteristic triad is tenosynovitis, dermatitis, and polyarthralgias. Patients have fever, chills, and malaise and then develop multiple inflamed tendons and subsequent cutaneous manifestations. The skin lesions classically start as flat erythematous macules, which rapidly develop into hemorrhagic vesiculopustules. These tend to occur distally, particularly on the palms and soles, and furthermore tend to localize over joints. There are usually only a handful of lesions, generally two to ten. These lesions are often painful and tender. The eruption can look similar to skin findings seen in bacterial endocarditis and septic embolic phenomena.

Diagnosis of N. gonorrhoeae infection generally involves recognition of the clinical syndrome and physical exam findings. Confirmatory testing of a suspected infection is usually via nucleic acid amplification testing. Culture may be indicated if antimicrobial resistance is suspected. This is generally through first-catch urine for men or vaginal swab for women. Generally, when testing for N. gonorrhoeae, physicians should consider evaluation for co-infections, particularly Chlamydia trachomatis, and also HIV testing, with additional testing depending on the clinical presentation and risk factors. All patients should be counseled regarding the nature of STIs and methods of prevention. Patients with recent exposure to known gonorrhea should be treated empirically but should still undergo comprehensive STI testing. Infection in children should prompt evaluation for sexual abuse. Gonococcal infection is a reportable disease.

Treatment has evolved over time and recommendations are rapidly changing; physicians should ensure they are utilizing the most up-to-date treatment recommendations, which may vary regionally and be based on drug availability, local resistance patterns, and patient-specific factors. Generally treatment had been with ceftriaxone (IM administration), however, increasing resistance has led to new recommendations.   Given the rising rates of antibiotic resistance, current recommendations suggest higher doses and combination regimens. The preferred regimen currently is ceftriaxone 250 mg IM plus azithromycin 1g orally. Doxycycline is an alternative to azithromycin. Disseminated gonococcemia is usually treated with ceftriaxone 1 g every 24 hours plus azithromycin 1 g as a single dose, with decreased dose ceftriaxone continued after clinical improvement is observed.

N. gonorrhoeae has shown a concerning ability to acquire and develop antimicrobial resistance, with emerging multidrug resistant strains representing a public health crisis, particularly with the development of ceftriaxone resistance. This threat continues to grow with multidrug-resistant N. gonorrhoeae, including strains developing azithromycin resistance. Antimicrobial resistant strains may be more common in certain populations, particularly MSM, and certain geographic regions. Patients undergoing treatment for N. gonorrhoeae should also be treated for co-infection, which is generally with C. trachomatis.

Patients should be counseled to avoid sexual activity for seven days and until symptoms resolve. Gonococcal infection is a reportable disease. All sexual contacts within the previous two months and the most recent sexual partner should be informed, evaluated, and treated.

Treatment failures should prompt evaluation for both patient compliance/non-adherence, and for antimicrobial resistance. Repeat infection, or concurrent co-infection, is possible, and patients with persistent symptoms warrant a thorough re-evaluation. Patients should be asked to inform their partners of the need for evaluation; this may be particularly important for female partners as the disease may be asymptomatic without obvious physical exam signs.

Primary care providers should be aware of recommendations for screening in asymptomatic patients. The US Preventive Services Task Force (USPSTF) produced updated screening recommendations for both chlamydia and gonorrhea in 2014, wherein they recommended that all sexually active females younger than 24 and older women at risk for infection undergo screening for chlamydia and gonorrhea. There was insufficient evidence to recommend screening in men. The CDC also recommends screening in sexually active females under 25, but further recommends genital and extragenital screening in sexually active MSM.

Initial Evaluation

Differential diagnosis

Meningococcemia

Hand, foot, and mouth disease

Herpes simplex virus

Herpetic whitlow

Small vessel vasculitis / leukocytoclastic vasculitis

Treatment

First-line therapy: Treatment has evolved over time and recommendations are rapidly changing; physicians should ensure they are utilizing the most up-to-date treatment recommendations, which may vary regionally and be based on drug availability, local resistance patterns, and patient-specific factors.

Genital/localized infection: The preferred regimen currently is ceftriaxone 250 mg IM plus azithromycin 1 g oral dose. Doxycycline is an alternative to azithromycin.

Disseminated gonococcal infection: Usually treated with ceftriaxone 1 g every 24 hours plus azithromycin 1 g as a single dose, with decreased dose ceftriaxone continued after clinical improvement is observed.

Patients should be counseled to avoid sexual activity for seven days and until symptoms resolve. Gonococcal infection is a reportable disease. All sexual contacts within the previous two months and the most recent sexual partner should be informed, evaluated, and treated.

Additional treatment information

Antimicrobial resistance in N. gonorrhoeae is common. Treatment failures should prompt evaluation for both patient compliance and for antimicrobial resistance. Cultures for sensitivities may be necessary, and treatment failures may warrant repeat thorough evaluation for comorbid conditions, co-infection, and antimicrobial resistance.

Pitfalls

  • Co-infection is common; patients should often receive empiric dual therapy for C. trachomatis at least, with additional treatments depending on individual clinical signs, symptoms, history, and risk factors.
  • Antimicrobial resistance is a common and growing threat. Treatment failures should prompt cultures for sensitivity testing
  • The patient’s sexual partners are at risk and the patient should be counseled to inform them of the need to seek treatment and get evaluated, tested, and treated.

Clinical Case

Case 1

  • 21-year-old healthy man
  • No significant past medical history
  • Review of systems is noncontributory
  • Social history is notable for five sexual partners in the last 12 months, including two in the last 60 days, with occasional use of barrier methods of contraception
  • Presents to the emergency department complaining of a fever, chills, malaise, and joint swelling of his ankles and wrists, and a rash on his fingers

Initial evaluation

  • Uncomfortable man with temperature 39.2°C
  • Overlying two MCP joints, two DIP joints, and one PIP joint there are vesiculopustules with a purpuric base, one of which appears to be a hemorrhagic pustule
  • The wrists and ankles are painful bilaterally with flexor tenosynovitis
  • The patient is admitted to the hospital where blood cultures are taken and an echocardiogram is performed to exclude endocarditis. He is tested for syphilis, HIV, gonorrhea, and chlamydia. Rheumatology is consulted and concludes there is no fluid within the joints and no inflammation amenable to arthrocentesis

Follow-up evaluation

  • The patient is diagnosed with gonorrhoeae by nucleic acid amplification testing and is started on ceftriaxone with a dose of azithromycin
  • He demonstrated gradual improvement over 3-5 days and was discharged one week after admission
  • His infection was reported and the patient was advised to have his partners screened
  • He received safe sex counseling regarding STIs and barrier methods of contraception

References

de Vries HJC. Skin as an indicator for sexually transmitted infections. (2014). Clin Dermatol, 32:196-208.

Lancaster JW, Mahoney MV, Mandal S, Lawrence KR. (2015). Update on treatment options for gonococcal infections. Pharmacotherapy, 35:856-868.

Skerlev M, Culav-Koscak I. (2014). Gonorrhea: new challenges. Clin Dermatol, 32:275-281.

Sharon VR, Armstrong AW. (2015). Screening recommendations for chlamydia and gonorrhea. JAMA Dermatol, 9:1014-1016.

Suzuki A, Hayashi K, Kosuge K, Soma M, Hayakawa S. (2011). Dissemianted gonococcal infection in Japan: a case report and literature review. Intern Med, 50:2039-2043.

Unemo M. (2015). Current and future antimicrobial treatment of gonorrhea—the rapidly evolving Neisseria gonorrhoeae continues to challenge. BMC Infectious Disease, 15:364.