Azithromycin-resistant Neisseria gonorrhoeae spreading amongst men who have sex with men (MSM) and heterosexuals in New South Wales, Australia, 2017.

Objectives: To identify the genetic basis of resistance as well as to better understand the epidemiology of a recent surge in azithromycin-resistant Neisseria gonorrhoeae in New South Wales, Australia. Methods: Azithromycin-resistant N. gonorrhoeae isolates (n = 118) collected from 107 males, 10 females and 1 transsexual between January and July 2017 were genotyped using a previously described iPLEX method. The results were compared with phenotypic resistance profiles and available patient data. Results: The iPLEX results revealed 10 different N. gonorrhoeae genotypes (designated AZI-G1 to AZI-G10) of which three were responsible for the majority of infections; AZI-G10 (74.6%, 88 isolates; 87 males and 1 transsexual), AZI-G4 (11.0%, 13 isolates; 7 males and 6 females) and AZI-G7 (6.8%, 8 isolates; 7 males and 1 female). The observed resistance was attributable to one of two different azithromycin resistance mechanisms; the 23S rRNA C2611T mutation was identified in 24% of isolates, whereas the majority of resistance (76%) was associated with a meningococcal-type mtrR variant. Additionally, one isolate was found to harbour both the 23S rRNA C2611T mutation and a type XXXIV mosaic penA sequence associated with cephalosporin resistance. Conclusions: These data indicate outbreaks of azithromycin-resistant gonococci amongst networks of MSM and heterosexuals in New South Wales. The results also provide further evidence that azithromycin may soon be an ineffective treatment option for gonococcal infection and highlight the urgent need to explore alternative therapies.

Australian Meningococcal Surveillance Programme annual report, 2016.

In 2016, there were 243 laboratory-confirmed cases of invasive meningococcal disease analysed by the Australian National Neisseria Network. This number was the highest number of laboratory confirmed cases since 2008. Probable and laboratory confirmed invasive meningococcal disease (IMD) are notifiable in Australia, and there were 252 IMD cases notified to the National Notifiable Diseases Surveillance System in 2016, the highest number reported since 2010. Meningococcal serogrouping was able to be determined for 98% (237/243) of laboratory confirmed IMD cases. Serogroup B infections accounted for 87 cases (37%), the lowest number and proportion reported since inception of the Australian Meningococcal Surveillance Programme (AMSP) in 1997. In contrast, the number and proportion of serogroup W infections (44%, 107 cases) in 2016 was the highest since the AMSP began. In addition, the number and proportion of serogroup Y infections (16%, 40 cases) was also the highest recorded by the AMSP. Molecular typing results were available for 225 of the 243 IMD cases. Of the serogroup W IMD strains that were able to be genotyped, 92% (97/105) have the PorA antigen encoding gene type P1.5,2 and of these, 72% (70/97) 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, and in adolescents aged 15-19 years. Serogroup B infections predominated in the age groups less than 1 year and 20-24 years, whereas serogroup W infections predominated in those aged 45 years or more. For all other age groups, distribution of serogroup B and W infections was roughly equal. Of the IMD isolates tested for antimicrobial susceptibility, 6% (11/189) were resistant to penicillin, and decreased susceptibility to penicillin was observed in a further 90% (170/189) of isolates. One Men W isolate demonstrated an elevated minimum inhibitory concentration (MIC) to ceftriaxone (0.125mg/L), the highest reported in Australia. All isolates tested were susceptible to rifampicin and ciprofloxacin.

Australian Meningococcal Surveillance Programme, 1 April to 30 June 2017.

The reference laboratories of the Australian Meningococcal Surveillance Programme (AMSP) report data on the number of cases of invasive meningococcal disease (IMD) confirmed by laboratory testing using culture and by non-culture based techniques. Data contained in quar-terly reports are restricted to a description of the number of cases of IMD by jurisdiction and serogroup, where known. A full analysis of laboratory confirmed cases of IMD in each calen-dar year is contained in the AMSP annual reports.

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.

Australian Meningococcal Surveillance Programme annual report, 2015.

In 2015, there were 174 laboratory-confirmed cases of invasive meningococcal disease analysed by the Australian National Neisseria Network. This number was higher than that reported in 2013 and 2014, which were the lowest and second-lowest totals reported, respectively, since inception of the Australian Meningococcal Surveillance Programme in 1994. Probable and laboratory confirmed invasive meningococcal disease (IMD) is notifiable in Australia. There were 182 IMD cases notified to the National Notifiable Diseases Surveillance System in 2015, again, higher than in 2013 and 2014, which were the lowest and second-lowest totals of IMD cases recorded, respectively, by this system. Meningococcal serogrouping was able to be determined for 168/174 (97%) laboratory confirmed IMD cases. Of these, 64.2% (108 cases) were serogroup B infections, the lowest reported since 2003. Further, the number and proportion of cases of serogroup C IMD, (1.2%, 2 cases), was the lowest yet reported. By contrast, in 2015 in Australia, there was a marked increase in the number and proportion of serogroup W IMD (21.4%, 36 cases), and an increase in serogroup Y IMD (13.1%, 22 cases). The number and proportion of IMD cases caused by serogroups W and Y was the highest reported since the inception of the Australian Meningococcal Surveillance Programme in 1994. Molecular typing results were available for 140 of the 174 IMD cases. Of the 31 serogroup W IMD strains that were able to be genotyped, 25/31 (81%) were sequence type (ST)-11, and have the porA antigen encoding gene type P1.5,2, the same genotype as the hypervirulent serogroup W strain of that has been circulating in the United Kingdom and South America since 2009. In 2015, the most common serogroup B porA genotype circulating in Australia was P1.7-2,4. The primary IMD age peak was observed in adults aged 45 years or more, which was the first time that this was noted by the AMSP, whilst secondary disease peaks were observed in those aged 4 years or less, and in adolescents (15-19 years). Serogroup B cases predominated in all jurisdictions and age groups, except for those aged 45 years or over where serogroups W and Y predominated. All IMD isolates tested were susceptible to ceftriaxone and ciprofloxacin. One isolate was resistant to rifampicin. Four isolates were resistant to penicillin. Decreased susceptibility to penicillin was observed in 86% of isolates.

Australian Meningococcal Surveillance Programme annual report, 2013.

In 2013, there were 143 laboratory-confirmed cases of invasive meningococcal disease (IMD) analysed by the Australian National Neisseria Network (NNN). This was the lowest number of laboratory confirmed IMD cases referred to the NNN since the inception of the Australian Meningococcal Surveillance Programme in 1994. Probable and laboratory confirmed IMD is notifiable in Australia. There were 149 IMD cases notified to the National Notifiable Diseases Surveillance System in 2013. Meningococcal serogrouping was determined for 139/143 laboratory confirmed IMD cases; 74.8% (104 cases) were serogroup B infections; 5.8% (8 cases) were serogroup C infections; 8.6% (12 cases) were serogroup W135; and 10.8% (15 cases) were serogroup Y. Primary and secondary disease peaks were observed, respectively, in those aged 4 years or less, and in adolescents (15-19 years). Serogroup B cases predominated in all jurisdictions and age groups, except for those aged 65 years or over where serogroup Y predominated. The overall proportion and number of IMD caused by serogroup B decreased from previous years. The number of cases of IMD caused by serogroup C was low, and has been proportionally stable over recent years. The number of IMD cases caused by W135 and Y serogroups was similar to previous years but the proportion has increased with the overall reduction in numbers of IMD cases. Molecular typing was performed on 92 of the 93 IMD isolates, and 23 of the 50 cases confirmed by nucleic acid amplification testing. In 2013, the most common porA genotype circulating in Australia was P1.7-2,4. All IMD isolates tested were susceptible to ceftriaxone; ciprofloxacin and rifampicin. Decreased susceptibility to penicillin was observed in 78.5% of isolates.

Australian Meningococcal Surveillance Programme annual report, 2012.

In 2012, there were 208 laboratory-confirmed cases of invasive meningococcal disease (IMD) analysed by the National Neisseria Network, and 222 cases notified to the National Notifiable Diseases Surveillance System, thus laboratory data were available for 93.7% of cases of IMD in Australia in 2012. Isolates of Neisseria meningitidis from 116 invasive cases of meningococcal disease were available for testing, and the phenotype (serogroup, serotype and serosubtype) and/or genotype, and antibiotic susceptibility were determined. Molecular typing was performed for the 92 cases confirmed by nucleic acid amplification testing (NAAT). Typing information was available for 194 of the 208 laboratory confirmed cases and 83% (161 cases) were serogroup B infections, 5.7% (11 cases) were serogroup C infections, 3.6% (11 cases) were serogroup W135, and 7.7% (15 cases) were serogroup Y meningococci. The number of laboratory confirmed IMD cases in 2012 was the lowest since laboratory surveillance data have been reported. Primary and secondary disease peaks were observed in those aged 4 years or less and in adolescents (15-19 years) and young adults (20-24 years), respectively. Serogroup B cases predominated in all age groups and jurisdictions. In 2012, the most common porA genotype circulating in Australia was P1.7-2,4. Serogroup C, W135 and Y cases were numerically low, similar to previous years. Decreased susceptibility to the penicillin group of antibiotics was observed in 81.9% of isolates, and 1 isolate exhibited resistance to penicillin. All isolates remained susceptible to ceftriaxone, ciprofloxacin and rifampicin.

Annual report of the Australian Meningococcal Surveillance Programme, 2011.

In 2011, there were 241 laboratory-confirmed cases of invasive meningococcal disease (IMD) analysed by the National Neisseria Network, which represented 100% of cases notified to the National Notifiable Diseases Surveillance System. One hundred and twenty-five isolates of Neisseria meningitidis from invasive cases of meningococcal disease were available for which the phenotypes (serogroup, serotype and serosubtype) and/or genotype and antibiotic susceptibility were determined. An additional 116 cases were confirmed by non-culture based methods (95 by nucleic acid amplification testing (NAAT) and 21 by serology), and where possible, serotyping was determined. Nationally, 179 (83.6%) laboratory-confirmed cases, where a serogroup was determined, were infected with serogroup B; 9 (4.2%) with serogroup C; 11 (5.2%) with serogroup W135 and 15 (7%) with serogroup Y meningococci. In 2011 there was a modest increase in the number of cases of IMD notified from that reported in 2010 (214). However, with the exception of 2010, this was the lowest number of laboratory confirmed IMD cases since surveillance data were recorded. Primary and secondary disease peaks were observed in those aged 4 years or less and in adolescents (15-19 years) and young adults respectively (20-24 years). There was also a disease peak observed in those aged 45-64 years. Serogroup B cases predominated in all age groups and jurisdictions. In 2011, the most common phenotype circulating in Australia was B:4:P1.7, corresponding to the porA genotype P1.7,2-4. Serogroup C cases were again numerically low, as were serogroups W135 and Y, however there was an increase in incidence of serogroup Y cases (7 in 2010, 15 in 2011). The proportion of isolates with decreased susceptibility to the penicillin group of antibiotics minimal inhibitory concentration (MIC) (0.06 to 0.5 mg/L) was 84.6% and 1 isolate exhibited relative resistance to penicillin (MIC = 1.0 mg/L). All isolates remained susceptible to ceftriaxone and ciprofloxacin. One isolate had reduced susceptibility to rifampicin (MIC = 0.5 mg/L).

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.