Australian Gonococcal Surveillance Programme Annual Report, 2018.

The Australian Gonococcal Surveillance Programme (AGSP) has continuously monitored antimicrobial resistance in clinical isolates of Neisseria gonorrhoeae from all states and territories since 1981. In 2018, there were 9,006 clinical isolates of gonococci from public and private sector sources tested for in vitro antimicrobial susceptibility by standardised methods. This was the highest annual total of isolates tested since the inception of the AGSP. The current treatment recommendation for gonorrhoea, for the majority of Australia, remains dual therapy with ceftriaxone and azithromycin. Decreased susceptibility to ceftriaxone (minimum inhibitory concentration (MIC) value ≥0.06 mg/L) was found nationally in 1.73% of isolates. The highest proportions were reported from Tasmania and non-remote Western Australia (7.3% and 2.1% respectively). In 2018 two extensively drug-resistant isolates were reported from Queensland patients. These two isolates, with ceftriaxone MIC values of 0.50 mg/L, high-level resistance to azithromycin (MIC ≥ 256 mg/L), and resistance to penicillin and ciprofloxacin were identified and reported to the World Health Organization as isolates of international significance. Resistance to azithromycin (MIC value ≥1.0 mg/L) was found nationally in 6.2% of isolates, lower than the 9.3% reported in 2017, but more than double the proportion reported in 2015 (2.6%). The highest proportions were reported from the Australian Capital Territory (8.7%), Victoria (8.3%), and New South Wales (6.5%). High-level resistance to azithromycin (MIC value ≥256 mg/L) was reported in nine isolates nationally in 2018: four from New South Wales, three from Victoria, and two from Queensland. The proportion of isolates resistant to penicillin in non-remote Australia ranged from 8.8% in non-remote Northern Territory to 44.1% in South Australia. In remote Northern Territory penicillin resistance rates remain low (1.9%), and higher in remote Western Australia (6.5%). The proportion of isolates resistant to ciprofloxacin in non-remote Australia ranged from 10.3% in non-remote Northern Territory to 48.3% in South Australia. Ciprofloxacin resistance rates remain comparatively low in remote Northern Territory (1.9%) and remote Western Australia (4.6%).

Australian Meningococcal Surveillance Programme annual report, 2018.

Invasive meningococcal disease (IMD) is a notifiable disease in Australia, and both probable and laboratory-confirmed cases of IMD are reported to the National Notifiable Diseases Surveillance System (NNDSS). In 2018, there were 281 IMD cases notified to the NNDSS. Of these, 278 were laboratory-confirmed cases analysed by the reference laboratories of the Australian National Neisseria Network (NNN). On investigation, the serogroup was able to be determined for 98.6% (274/278) of laboratory-confirmed cases. Serogroup B infections accounted for 44.2% of cases (123 cases); serogroup W for 36.3% of cases (101 cases); serogroup Y infections for 15.8% (44 cases) and serogroup C 1.4% (4 cases); and there were two unrelated cases (0.7%) of IMD attributable to serogroup E. Using molecular methods, 181/278 IMD cases were able to be typed. Of note was that 89% of typed serogroup W IMD cases (66/74) were porA antigen type P1.5,2; of this number, 44% (29/66) were sequence type 11, the hypervirulent strain reported in recent outbreaks in Australia and overseas. The primary age peak of IMD in Australia in 2018 was again observed in adults aged 45 years or more; a secondary disease peak was observed in children and infants aged less than 5 years. Serogroup B infections predominated in those aged less than 5 years, whereas serogroup W and serogroup Y infections predominated in those aged 45 years or more. Of the IMD isolates tested for antimicrobial susceptibility, 1.4% (3/210) were resistant to penicillin with an MIC ≥ 1 mg/L, and decreased susceptibility to penicillin was observed in a further 93.8% (197/210) of isolates. All isolates were susceptible to ceftriaxone and rifampicin; there was one isolate less susceptible to ciprofloxacin.

Australian Meningococcal Surveillance Programme annual report, 2017.

In 2017, there were 374 laboratory-confirmed cases of invasive meningococcal disease (IMD) analysed by the Australian National Neisseria Network. This was the highest number of laboratory-confirmed cases since 2003. Probable and confirmed cases of IMD are notifiable in Australia; there were 379 IMD cases notified to the National Notifiable Diseases Surveillance System in 2017, the highest number reported since 2005. Meningococcal sero-grouping was determined for 98% (367/374) of laboratory-confirmed IMD cases. Serogroup B infections accounted for 137 cases (37%). The number of serogroup W infections (141 cases, 38%) in 2017 was the highest since the Australian Meningococcal Surveillance Programme (AMSP) began. In addition, the number and proportion of serogroup Y infections (75 cases, 20%) was also the highest recorded by the AMSP. Molecular typing results were available for 315 of the 374 IMD cases (83%). Of the serogroup W IMD strains that were able to be genotyped, 97% (125/129) had the PorA antigen encoding gene type P1.5,2 and of these, 59% (74/125) were sequence type 11, the same type as the hypervirulent serogroup W strain that has been circulating in the UK and South America since 2009. The primary IMD age peak was observed in adults aged 45 years or more, whilst secondary disease peaks were observed in those aged less than 5 years. Serogroup B infections predominated in the age group 15-19 years. Serogroup W infections predominated in those aged 65 years or more. Serogroup Y infections were predominately seen in adults aged 45 years or more. Of the IMD isolates tested for antimicrobial susceptibility, 5.1% (14/276) were resistant to penicillin; decreased susceptibility to penicillin was observed in a further 89% (247/276) of isolates. All isolates tested were susceptible to ceftriaxone; two isolates were less susceptible to ciprofloxacin; and one isolate was resistant to rifampicin.

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

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.

Australian Gonococcal Surveillance Programme annual report, 2015.

The Australian Gonococcal Surveillance Programme (AGSP) has continuously monitored antimicrobial resistance in clinical isolates of Neisseria gonorrhoeae from all Australian states and territories since 1981. In 2015, there were 5,411 clinical isolates of gonococci from public and private sector sources tested for in vitro antimicrobial susceptibility by standardised methods. Current treatment recommendations for the majority of Australian states and territories is a dual therapeutic strategy of ceftriaxone and azithromycin. Decreased susceptibility to ceftriaxone (minimum inhibitory concentration or MIC value 0.06-0.125 mg/L) was found nationally in 1.8% of isolates, which was lower than that reported in the AGSP annual report 2014 (5.4%). The highest proportions were reported from South Australia and New South Wales (3.6% and 2.7% respectively). High level resistance to azithromycin (MIC value ≥ 256 mg/L) was again reported in 2015, with 1 strain in each of New South Wales and urban Western Australia. There was no reported Azithromycin resistance in the Australian Capital Territory, the Northern Territory, or remote Western Australia. The proportion of strains resistant to penicillin in urban and rural Australia ranged from 8.7% in Tasmania to 33% in the Australian Capital Territory. In rural and remote Northern Territory, penicillin resistance rates remain low (2.2%). In remote Western Australia relatively low numbers of strains are available for testing, however there is now widespread molecular testing for penicillin resistance in Western Australia to monitor resistance and inform guidelines and these data are included in the AGSP annual report. Quinolone resistance ranged from 11% in the urban and rural areas of the Northern Territory, to 41% in South Australia. Quinolone resistance rates remain comparatively low in remote areas of the Northern Territory (3.3%) and remote areas of Western Australia (3.4%). There was no reported quinolone resistance in Tasmania, but the number of isolates tested was relatively low. Azithromycin resistance ranged from 1.8% in Victoria to 5.8% in Queensland.

Australian Meningococcal Surveillance Programme annual report, 2014.

In 2014 there were 165 laboratory-confirmed cases of invasive meningococcal disease analysed by the Australian National Neisseria Network. This number was higher than the number reported in 2013, but was the second lowest reported since inception of the Australian Meningococcal Surveillance Programme in 1994. Probable and laboratory confirmed invasive meningococcal disease (IMD) are notifiable in Australia, and there were 170 IMD cases notified to the National Notifiable Diseases Surveillance System (NNDSS) in 2014. This was also higher than in 2013, but was the second lowest number of IMD cases reported to the NNDSS. The meningococcal serogroup was determined for 161/165 (98%) of laboratory confirmed IMD cases. Of these, 80.1% (129 cases) were serogroup B infections; 1.9% (3 cases) were serogroup C infections; 9.9% (16 cases) were serogroup W135; and 8.1% (13 cases) were serogroup Y. Primary and secondary disease peaks were observed in those aged 4 years or less, and in adolescents (15-19 years) respectively. Serogroup B cases predominated in all jurisdictions and age groups, except for those aged 65 years or over, where serogroups Y and W135 combined predominated. The overall proportion and number of IMD caused by serogroup B was higher than in 2013, but has decreased from previous years. The number of cases of IMD caused by serogroup C was the lowest reported to date. The number of IMD cases caused by serogroup Y was similar to previous years, but the number of IMD cases caused serogroup W135 was higher than in 2013. The proportion of IMD cases caused by serogroups Y and W135 has increased in recent years, whilst the overall number of cases of IMD has decreased. Molecular typing was able to be performed on 106 of the 165 IMD cases. In 2014, the most common porA genotypes circulating in Australia were P1.7-2,4 and P1.22,14. All IMD isolates tested were susceptible to ceftriaxone and ciprofloxacin. There were 2 isolates that were resistant to rifampicin. Decreased susceptibility to penicillin was observed in 88% of isolates.

A comparison of agar dilution with the Calibrated Dichotomous Sensitivity (CDS) and Etest methods for determining the minimum inhibitory concentration of ceftriaxone against Neisseria gonorrhoeae.

OBJECTIVES: The objective of this study was to compare the Calibrated Dichotomous Sensitivity (CDS) based agar dilution (CDS AD) method with the Etest (bioMérieux SA) methods using 2 method protocols for determining the minimum inhibitory concentration (MIC) of ceftriaxone against Neisseria gonorrhoeae. The two method protocols were the manufacturer's protocol for which the Clinical and Laboratory Standards Institute (CLSI) interpretative criteria for Neisseria gonorrhoeae could be applied, and the CDS-adapted protocol. Comparability of MIC data is critical for situation analysis and monitoring trends in global antimicrobial analysis. METHODS: Two hundred and forty eight clinical isolates of N. gonorrhoeae and the World Health Organisation (WHO) N. gonorrhoeae reference strains were tested using the three methods. RESULTS: When compared, CDS AD and CDS Etest gave a regression R(2) value of 94%, the Pearson's correlation coefficient was 97% and a paired comparison within one log2 dilution was 98%. The CDS AD and the Etest (CLSI) comparison gave a regression R(2) value of 90%, a Pearson's correlation coefficient of 95% and a paired comparison within one log2 dilution was 98%. The comparison of the CDS Etest and CLSI Etest gave a regression R(2) value of 91%, a Pearson's correlation coefficient of 95% and a paired comparison within one log2 dilution of 99%. Importantly, there was robust agreement between all three methods for the categorization of susceptibility of Neisseria gonorrhoeae isolates using the WHO nominated breakpoint for decreased susceptibility to ceftriaxone (≥0.125 µg/mL). CONCLUSIONS: The CDS Etest method is comparable to agar dilution and the Etest methods for determining the MIC of ceftriaxone against N. gonorrhoeae.