New treatment options for infections caused by increasingly antimicrobial-resistant Neisseria gonorrhoeae

ABSTRACT

The emergence of high-level resistance to ceftriaxone is giving rise to serious concern about absence of effective treatment options to cure gonococcal infections. Increasing the dosage regimen can be applied to ceftriaxone and azithromycin, but the emergence of high-level resistance has already been reported. Spectinomycin is another active drug but has low efficacy in the treatment of pharyngeal gonorrhoea. Conventional antibiotics could be introduced for gonococcal treatment, but they have some limitations, such as the absence of clinical trials and breakpoint. Combining antibiotics is another promising method to cure patients and to prevent the emergence of resistance. The most important strategy to maintain the efficacy of antibiotics is rapid detection and dissemination control of novel resistant isolate.

KEYWORDS:

• Neisseria gonorrhoeae
• New treatment options
• Combination therapy
• Dual therapy
• Ceftriaxone
• Azithromycin
• Spectinomycin
• Solithromycin
• ETX0914

Financial & competing interests disclosure

The manuscript was supported by grants from the National Institute of Health, Korea Centers for Disease Control and Prevention, Ministry of Health and Welfare, Republic of Korea. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• The emergence and dissemination of antimicrobial resistance in Neisseria gonorrhoeae are great concern and require new options for treatment.

• Ceftriaxone is the most potent antibiotic and is used as monotherapy or combination therapy with azithromycin. However, high-level resistance has been reported in a few countries and more than 500 mg may be recommended in countries in which N. gonorrhoeae with a minimum inhibitory concentration (MIC) of 0.25 µg/mL is present.

• Azithromycin can be used by oral administration and has additional activity for frequently coinfecting Chlamydia trachomatis and Mycoplasma genitalium. Because of side effects of high-dose treatment and high-level resistance in many countries, azithromycin may be used in combination.

• Spectinomycin has remained effective in spite of nationwide use for 10 years in Korea, but it is unavailable in many other countries and showed low efficacy in pharyngeal gonorrhea. Azithromycin combination may extend the efficacy for the treatment of pharyngeal infection.

• Alternative drugs have some limitations; gentamicin has no evidence for treating pharyngeal or rectal gonorrhea; fosfomycin resistance can be acquired easily by long-term use; ertapenem showed elevated MIC in cephalosporin-resistant isolates; tigecycline has insufficient PK data for gonococcal treatment; and sitafloxacin has too old and region-specific data.

• Most antimicrobial combinations show additive/indifferent effects; antagonism is fortunately rare. Clinical correlations between in vivo and in vitro results need to be investigated, and standardization of synergy testing method is also required.

• Solithromycin showed high efficacy in clinical trial, but elevated MIC values that may be associated with treatment failure have already been reported. ETX0914 has low potential for the emergence of resistance, but clinical trials are required.

• A vaccine could be the most active measure to prevent gonococcal infection in a population, but development remains in an early stage, and many obstacles must be overcome before it can be introduced into the market.