Gonococcal urethritis
Authors
In-Chang Cho (Department of Urology, National Police Hospital, Seoul, South Korea)
Executive summary
Epidemiology and pathogenesis
1. The World Health Organization (WHO) estimated the 87 million of new cases of the gonococcal infections in 2016 in adults between the ages of 15 and 49 worldwide.
Diagnosis
1. Diagnostic methods for Neisseria Gonorrhoea: gram staining, culture, and NAAT
Treatment
1. Dual therapy with a intravenous or intramuscular ceftriaxone (500 mg–1 g) in combination with a single oral dose of 1 g of azithromycin. If there is an allergy to ceftriaxone or ceftriaxone is not available in the country, intramuscular spectinomycin 2 g in combination with azithromycin 1 g orally once a day is recommended. However, spectinomycin is not recommended for confirmed pharyngeal gonococcal infection.
Introduction
A variety of antimicrobial agents have been used for the treatment of gonorrhea. The introduction of new drugs to treat gonorrhoea has repeatedly brought about the emergence and spread of Neisseria gonorrhoeae with resistance to these drugs. After clinical strains of N. gonorrhoeae became resistant to penicillin or tetracycline, ceftriaxone was recommended as the primary regimen for thetreatment of gonorrhea with ciprofloxacin as an alternative treatment option in 1989[1]. In addition to ceftriaxone, single doses of fluoroquinolones and a thirdgeneration cephalosporin were recommended as primary treatment regimens in 1993[2]. However now oral regimens of fluoroquinolones or third-generation cephalosporins are no longer recommended because of the continuous increase in clinical strains of N. gonorrhoeae with decreased susceptibilities to these agents[3][4]. Since the early 1990s, however, clinical strains with decreased susceptibility to azithromycin have emerged in several countries worldwide[5][6].
Furthermore, high resistance to azithromycin was reported from Argentina[7]. Furthermore, the high-level ceftriaxone-resistant strain H041 was isolated from the pharynx of a female commercial sex worker in Japan in 2009[8]. The first “super-resistant” strains were recently reported in the United Kingdom and Australia, showing resistance against the current first line treatment, dual therapy with azithromycin and ceftriaxone[9]. The emergence and spread of N. gonorrhoeae with resistance or decreased susceptibility to these agents have led to difficulty in treating gonorrhea.Thus, other drugs for gonococcal infections are required.
Epidemiology
The World Health Organization (WHO) estimated the 87 million of new cases of the gonococcal infections in 2016 in adults between the ages of 15 and 49 worldwide[10]. The 2016 estimate of the number of new cases for the gonococcal infections is 11.5% higher than the estimate for 2012.
Clinical features
The signs and symptoms of male gonococcal urethritis include micturition pain, burning sensation of urethra,or a white or yellow purulent urethral discharge that usually appears 1 to 10 days after infection. Rectal infection may be asymptomatic. When present, symptoms of rectal infection may include discharge, anal itching, soreness, bleeding, or painful bowel movements.
Pharyngitis caused by N. gonorrhoeae is rare and many cases are pharyngeal infection.
Pharyngeal infection may cause a sore throat, but usually is asymptomatic.
Diagnosis
See chapter “Diagnostic Strategy for Sexually Transmitted Infections”
Treatment
Oral regimens of penicillin, tetracycline, fluoroquinolones or thirdgenerationcephalosporins are no longer recommended to treat gonorrhea because of the continuous increase in clinical strains of N. gonorrhoeae with decreased susceptibilities to these agents[3][4]. Single-dose intramuscular gentamicin for the treatment of uncomplicated gonococcal urethritis in men were reported cure rates of 62% to 98%[11].
Spectinomycin is good for gonococcal urethritis,[11] but clinical efficacy is low for pharyngeal infection of N. gonorrhoeae by less tissue penetration.[13],[14] Even in heterosexual men with gonococcal urethritis, 20% have been reported to be positive for N. gonorrhoeae in the pharynx[15]. Treatment of pharyngeal gonorrhea with antibiotics is more difficult than that of urethritis. Most cases of pharyngeal infection are asymptomatic, and no point-of-care tests for identifying N. gonorrhoeae from pharyngeal specimens are available in practice. The antibiotic regimens that treat not only urogenital but also pharyngeal gonorrhea should be adopted in all patients with gonorrhea. Therefore spectinomycin is not recommended to treat gonococcal urethritis.
Ceftriaxone is good for gonococcal infections including urethritis, pharyngeal infection[16]. The high-level ceftriaxone-resistant strain H041 was isolated from the pharynx of a female commercial sex worker in Japan, in 2009. Fortunately, such isolates to resistant for ceftriaxone were reported only several cases in the world afterwards. Selection of ceftriaxone resistance could occur more frequently in the pharynx than at the urogenital and anorectal sites. However, it is necessary to use high dose of ceftriaxone as much as possible to prevent antimicrobial resistance.
Combination therapy using two antimicrobials with different mechanisms of action (e.g., a cephalosporin plus azithromycin) may improve treatment efficacy and potentially slow the emergence and spread of resistance to cephalosporins[17][18]. Use of azithromycin as the second antimicrobial is preferred to doxycycline because of the convenience and compliance advantages of single-dose therapy and the substantially higher prevalence of gonococcal resistance to tetracycline than to azithromycin among Gonococcal Isolate Surveillance Project (GISP) isolates, particularly in strains with elevated cefixime minimum inhibitory concentration (MIC)s[18][19]. In addition, clinical trials have demonstrated the efficacy of azithromycin 1 g for the treatment of uncomplicated urogenital gonococcal infection[20]. However, these treatment options will not be useful in the near future, as they have already been reported as ineffective in treating some patients. With this in mind, it is evident that, in the absence of a vaccine, the future control of this disease relies completely on the development of new antibiotics and alternative treatments.
Recommended treatment regimen
Dual therapy with a intravenous or intramuscular maximum dose for gonorrhea in each country of ceftriaxone (500 mg–1 g) in combination with a single oral dose of 1g of azithromycin. If there is an allergy to ceftriaxone or ceftriaxone is not available in the country, intramuscular spectinomycin 2g in combination with azithromycin 1 g orally once a day is recommended. However, spectinomycin is not recommended for confirmed pharyngeal gonococcal infection.
Abbreviation
N. gonorrhoeae: Neisseria gonorrhoeae
References
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