Systematic review and survey of Neisseria gonorrhoeae ceftriaxone and azithromycin susceptibility data in the Asia Pacific, 2011 to 2016

Abstract

Background Antimicrobial resistance in Neisseria gonorrhoeae is a global concern, with the ongoing emergence of ceftriaxone and azithromycin resistance threatening current treatment paradigms. To monitor the emergence of antimicrobial resistance in N . gonorrhoeae , the World Health Organization (WHO) Gonococcal Antimicrobial Surveillance Programme (GASP) has operated in the Western Pacific and South East Asian regions since 1992. The true burden of antimicrobial resistance remains unknown. In response, the objective of this study was to survey ceftriaxone and azithromycin susceptibility in N . gonorrhoeae across the western Pacific and south-east Asia, and interlink this data with systematically reviewed reports of ceftriaxone and azithromycin resistance. Methods and findings The WHO Collaborating Centre for Sexually Transmitted Infections and Antimicrobial Resistance, Sydney, coordinated annual surveys of gonococcal susceptibilities with participating laboratories, and additionally undertook a systematic review of reports detailing gonococcal ceftriaxone and azithromycin susceptibility data for locations geographically in the Asia Pacific from 2011 to 2016. It was found that surveillance of gonococcal antimicrobial resistance remains limited in the Asia Pacific, with weaker surveillance of azithromycin versus ceftriaxone. Ninety-three published reports were identified (including national reports) which documented susceptibility data for ceftriaxone and azithromycin. GASP survey data was available for 21 countries, territories or areas, and suggested MICs are increasing for ceftriaxone and azithromycin. Between 2011 and 2016, the percentage of locations reporting >5% of gonococcal isolates with MICs to ceftriaxone meeting WHO’s definition of decreased susceptibility (MIC ≥ 0.125 mg/L) increased from 14.3% to 35.3% and the percentage of locations reporting >5% of gonococcal isolates with azithromycin resistance (MIC ≥ 1 mg/L) increased from 14.3% to 38.9%. Published reports were available for several countries that did not provide GASP surveillance responses for ceftriaxone (n = 5) and azithromycin (n = 3) respectively. Over the study period, there was a 183% increase in the number of countries providing surveillance data for GASP for both ceftriaxone and azithromycin, and a 30.6% increase in ceftriaxone MIC testing across the Asia Pacific facilitated by this project. Conclusion This study provides the first comprehensive illustration of increasing MICs to ceftriaxone in the Asia Pacific. The survey and literature review additionally detail increasing resistance to azithromycin. Further surveillance system strengthening is required to monitor these trends in order to address and curb gonococcal AMR in the region.

Gonococcal resistance can be viewed productively as part of a syndemic of antimicrobial resistance: an ecological analysis of 30 European countries

“…ESCephalosporin AMR emerged rapidly in other organisms in the Asia Pacific region around the same time but, as was the case with N. gonorrhoeae, it did not spread uniformly throughout the region [42][43][44]. In the rural parts of Northern Territory, Australia, for example, there is almost no gonococcal resistance to ESCephalosporins or azithromycin, a finding that is likely attributable to low antimicrobial consumption [43,45]. Likewise, a phylogenetic analysis of 419 isolates from around the world found that modern gonococci were split into two lineages [41].…”

“…At least in part, this was likely due to the extraordinary high ESCephalosporin consumption in Japan at the timeover double the consumption of the country with the next highest consumption [11]. ESCephalosporin AMR emerged rapidly in other organisms in the Asia Pacific region around the same time but, as was the case with N. gonorrhoeae, it did not spread uniformly throughout the region [42][43][44]. In the rural parts of Northern Territory, Australia, for example, there is almost no gonococcal resistance to ESCephalosporins or azithromycin, a finding that is likely attributable to low antimicrobial consumption [43,45].…”

Gonococcal resistance can be viewed productively as part of a syndemic of antimicrobial resistance: an ecological analysis of 30 European countries

“…ESCephalosporin AMR emerged rapidly in other organisms in the Asia Pacific region around the same time but, as was the case with N. gonorrhoeae, it did not spread uniformly throughout the region [36][37][38]. In the Northern Territory, Australia, for example, there is almost no gonococcal resistance to ESCephalosporins or azithromycin, a finding that is likely attributable to low antimicrobial consumption [37,39].…”

Genomic surveillance ofNeisseria gonorrhoeaein the Philippines, 2013–2014

“…1 The WHO Gonococcal Antimicrobial Surveillance Programme (GASP) has operated in the Western Pacific and South East Asian regions since 1992, but surveillance of gonococcal antimicrobial resistance (AMR) remains limited in Asia Pacific. 6 A recent report showed that 18 of 21 countries in the region reported isolates with decreased susceptibility to ceftriaxone and/or isolates resistant to azithromycin between 2011 and 2016. 6 The Philippines Department of Health -Antimicrobial Resistance Surveillance Program (DOH-ARSP) has been contributing AMR surveillance data to the Western Pacific GASP since 1996 and has not confirmed isolates with decreased susceptibility or resistance to these antibiotics during 2011-2016, 6 while high gonococcal resistance rates against other first-line antibiotics has been long reported ( Figure 1).…”

“…6 A recent report showed that 18 of 21 countries in the region reported isolates with decreased susceptibility to ceftriaxone and/or isolates resistant to azithromycin between 2011 and 2016. 6 The Philippines Department of Health -Antimicrobial Resistance Surveillance Program (DOH-ARSP) has been contributing AMR surveillance data to the Western Pacific GASP since 1996 and has not confirmed isolates with decreased susceptibility or resistance to these antibiotics during 2011-2016, 6 while high gonococcal resistance rates against other first-line antibiotics has been long reported ( Figure 1). Ongoing surveillance is thus key to detect potential events of emergence or introduction of resistance to current treatment options.…”