Vol.68 No.2 March 2020
Update on the treatment of sexually transmitted infections diseases -Significance of a single 1 g dose of ceftriaxone and single 2 g dose of azithromycin for urethritis in Japan and comparison with guidelines from Western countries-
1)Center for Nutrition Support and Infection Control, Gifu University Hospital, 1-1 Yanagido, Gifu, Gifu, Japan
2)Gifu University Center for Conservation of Microbial Genetic Resource (GCMR), Organization for Research and Community Development
3)Department of Urology, Kobe University School of Medicine
4)Health Science, Kobe University School of Medicine
5)Kobe University Hospital Infection Control Team
5)i Clinic
Abstract
Antimicrobial resistance has become a serious problem in the treatment of sexually transmitted infections. It is of particular concern in regard to the causative pathogens of urethritis. We investigated the position of ceftriaxone (CTRX) and azithromycin (AZM) for the treatment of urethritis, and compared the Japanese guidelines with the European Association of Urology (EAU) guideline and Centers for Diseases Control and Prevention (CDC) guideline.
In Japan, isolates of Neisseria gonorrhoeae with decreased susceptibilities to CTRX have nearly not been isolated. Even using "Therapeutic time", one of the methods for predicting clinical efficacy, single-dose administration of CTRX 1 g is considered to be effective for the treatment of gonococcal urethritis, and has also been reported to be effective in clinical practice. Although there have been no reports of strain like a CTRX-resistant N. gonorrhoeae isolated, a few strains with an MIC of CTRX of 0.5 mg/L have been isolated.
On the other hand, the isolation rates of AZM-resistant N. gonorrhoeae have been increasing, and the efficacy rates of AZM against gonococcal urethritis are actually decreasing. Moreover, isolation of AZM-highly resistant isolates has also been reported from around the world, and single-dose AZM-ER is not recommended as the initial therapy for gonococcal urethritis. However, there have been no reports of isolation of AZM-resistant strains of Chlamydia trachomatis which is one of causative pathogen for non-gonococcal. Therefore, AZM is recommended as the regimen of choice for the treatment of chlamydial urethritis. However, the efficacy rates of AZM therapy against Mycoplasma genitalium-urethritis are actually decreasing. It has also been reported that 70% of M. genitalium strains have a mutation in the 23S rRNA gene associated with macrolide resistance in Japan, and the position of a macrolide as first-line therapy for non-gonococcal non-chlamydial urethritis remains questionable.
Comparison of Japanese and Western guidelines revealed almost no difference in the recommended treatment of non-gonococcal urethritis. However, for the case of gonococcal urethritis, a single administration of a high dose of CTRX is recommended in Japan, whereas in the US and Europe, dual therapy with low doses of CTRX+AZM is recommended. Low doses of CTRX may be less pharmacologically effective and may promote the development of resistance. In addition, no synergistic effect of dual therapy has been observed with the CTRX+AZM regimen, and it is essential for each of the drugs to be individually is effective; however, the frequency of AZM-resistant N. gonorrhoeae is increasing. Therefore, single administration of CTRX at a high dose may be desirable, as recommended in Japan. From this point of view, in the case of gonococcal urethritis, the dose of CTRX in Japan is the light in the sense that it is the highest dose in the world, but rather it may be said that Western guidelines are a lower dose and a shadow.
Key word
urethritis, ceftriaxone, azithromycin, antimicrobial resistance, guideline
Received
July 23, 2019
Accepted
August 30, 2019
Jpn. J. Chemother. 68 (2): 186-197, 2020
