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Monitoring on the antimicrobial-resistant Neisseria gonorrhoeae

1) Overview

In the diagnosis of gonococcal infection, the utilization of nucleic acid testing has been promoted. Isolation culture is only implemented for some patients. Because antimicrobial susceptibility tests for Neisseria gonorrhoeae cannot be easily implemented in general laboratories or laboratory companies, it is difficult for JANIS to monitor trends in this bacteria. Therefore, a monitoring on the antimicrobial-resistant Neisseria gonorrhoeae has been undertaken as research activities at AMED since 2015. The collected data are also reported to GLASS, which is operated by WHO.

2) Survey methods

More than 40 cooperating clinics are designated across Japan. Antimicrobial susceptibility tests were performed at five facilities capable of testing across Japan, after collecting specimens from the cooperating clinics, or collecting strains through laboratory companies. Antimicrobial susceptibility tests were performed using an agar plate dilution method, recommended by CLSI or EUCAST, or using Etest. MIC values were measured for ceftriaxone (CTRX) and spectinomycin (SPCM) as recommended agents; for azithromycin (AZM), which was used as part of the two-drug combination therapy overseas; and for penicillin (PCG), cefixime (CFIX), and ciprofloxacin (CPFX), which had been used as recommended agents in the past. The EUCAST standards were used for susceptibility and resistance assessment (Table B). For reference, the proportion of resistant strain based on CLSI Guidelines(M100-S25) (Table C) are indicated in Table D. The figures for AZM in the tables are based on the MIC distribution of strains that have antimicrobial- resistant gene, as indicated by CLSI Guideline (M100-S27).

3) Prospect

Physicians need to empirically choose therapeutic agents for gonococcal infection according to the result of the monitoring given the difficulty in routinely performing antimicrobial susceptibility tests.

For empiric treatment, it is recommended to use an agent with the potential success rate of 95% or higher. At present, ceftriaxone and spectinomycin are the only recommendable agents in Japan. Because Neisseria gonorrhoeae that are present in the pharynx are an important source of infection, Neisseria gonorrhoeae in pharynx should be treated. Due to its in vivo pharmacokinetics, spectinomycin does not have effect on Neisseria gonorrhoeae present in the pharynx. Therefore, ceftriaxone is the only practically recommendable agent.

In sporadic cases, strains are isolated in Japan that indicate the ceftriaxone MIC of 0.5 μg/mL in antimicrobial susceptibility tests. Ceftriaxone is administered by intramuscular injection overseas, and therefore subject to dose limitation. Therefore, if strains that indicate the ceftriaxone MIC of 0.5 μg/mL are transmitted to overseas, it is likely that ceftriaxone loses its effect. Hence, it is required to continue with the careful monitoring of isolated strains in coming years.

Table B. Antimicrobial susceptibility assessment criteria based on EUCAST (μg/mL) for Neisseria gonorrhoeae

Table B. Antimicrobial susceptibility assessment criteria based on EUCAST (μg/mL) for Neisseria gonorrhoeae

Table C. Antimicrobial susceptibility assessment criteria based on CLSI (μg/mL) for Neisseria gonorrhoeae

Table C. Antimicrobial susceptibility assessment criteria based on CLSI (μg/mL) for Neisseria gonorrhoeae

* Epidemiological cutoff value indicated in CLSI Standards (M100-S27): wild type (WT) ≤ 1; non-WT ≥ 2

Table D. The proportion (%) of antimicrobial-resistant Neisseria gonorrhoeae based on the CLSI (M100-S25)

Table D. The proportion (%) of antimicrobial-resistant Neisseria gonorrhoeae based on the CLSI (M100-S25)

* The figures are based on the epidemiological cutoff value (non-WT ≥ 2 μg/mL) indicated in CLSI Standards (M100-S27), and differ from resistance proportion.
† * Figures in parentheses indicate the sum of resistance and intermediate resistance.