A single 2 g oral dose of extended-release azithromycin for treatment of gonococcal urethritis

Abstract

Objectives: We treated gonococcal urethritis in men with a single 2 g dose of azithromycin extended-release formulation (azithromycin-SR) to determine its microbiological outcomes and tolerability. Patients and methods:We enrolled 189 Japanese men with gonococcal urethritis between April 2009 and December 2013. The patients were given a single 2 g dose of azithromycin-SR. Microbiological efficacy was evaluated by the results of the post-treatment molecular testing of Neisseria gonorrhoeae. MIC testing was performed only for pretreatment isolates of N. gonorrhoeae collected from the patients. Results:We evaluated 130 patients for microbiological outcomes. Of these patients, 122 (93.8%) were judged to be microbiologically cured on the basis of negative test results. All isolates for which the azithromycin MICs were ≤0.25 mg/L were eradicated, whereas 5 of 12 isolates for which the MICs were 1 mg/L persisted after the treatment. Forty-six adverse events occurred in 41 patients. However, all adverse events were classified as mild. Conclusions:The eradication rate of N. gonorrhoeae was 93.8% in men with gonococcal urethritis treated with a single 2 g dose of azithromycin-SR. The breakpoint MIC of a 2 g dose of azithromycin-SR for gonococcal urethritis associated with clinical treatment failures appeared to be 1 mg/L. With regard to side effects of higher doses of azithromycin, the 2 g dose of azithromycin-SR appeared to improve tolerability. However, the widespread use of a high-dose regimen of azithromycin might lead to the development of further resistance to azithromycin.

High Prevalence of Azithromycin-Resistant Neisseria gonorrhoeae Isolates With a Multidrug Resistance Phenotype in Fukuoka, Japan

“…A study recently conducted in Japan revealed that the eradication rate of N.gonorrhoeae isolates with azithromycin MICs of 0.5 mg/L or less was 98.9% (88/89) and that of the isolates with MICs of 1 to 4 mg/L was only 50.0% (7/14) in men with gonococcal urethritis treated with a single 2-g dose of azithromycin. 16 In the present study, a high proportion of azithromycin-resistant gonococci (22.6%; MIC > 0.5 mg/L) was observed in 2013.…”

Evaluation of the Microbiological Efficacy of a Single 2-Gram Dose of Extended-Release Azithromycin by Population Pharmacokinetics and Simulation in Japanese Patients with Gonococcal Urethritis

“…Although descriptions of the effectiveness of AZM for the treatment of gonococcal urethritis have been added to the guidelines revised in 2016 (4), the decreasing susceptibility of N. gonorrhoeae to AZM has been reported in Japan (22,24). In our current study, the microbiological efficacy of a single 2-g dose of AZM-SR was 83.3%, which was lower than that previously reported (93.8%) (14). Additionally, gonococcal strains exhibiting high levels of AZM resistance (MICs Ն 256 mg/liter) have been reported in an increasing number of countries (10,11,(25)(26)(27).…”

“…Although a single 2-g dose of an immediate-release formulation of AZM (conventional AZM) remains effective against uncomplicated gonorrhea (12), this monotherapy could cause an unacceptable rate of adverse events, particularly gastrointestinal upset. Recently, a single 2-g dose of a microsphere-based extended-release formulation of AZM (AZM-SR) was developed and was found to be effective against N. gonorrhoeae (13)(14)(15), and the frequency of adverse events also decreased compared with that achieved with a single 2-g dose of conventional AZM (12,(15)(16)(17)(18). Therefore, a single 2-g dose of AZM-SR is considered useful for the treatment of gonorrhea.…”

Azithromycin Resistance and Its Mechanism in Neisseria gonorrhoeae Strains in Hyogo, Japan

“…Oral antibiotics for outpatient treatment would be highly desirable for this kind of infection. Azithromycin (AZM) is an oral antibiotic with medical insurance approval for use against chlamydia infections (14), and there are many reports of good activity against N. gonorrhoeae infection (15). Other reports suggest that N. gonorrhoeae infection is less susceptible to AZM and that AZM-resistant strains have emerged (5).…”