Lessons learnt from ceftriaxone-resistant gonorrhoea in the UK and Australia.

Neisseria gonorrhoeae, the causative pathogen of gonorrhoea, has shown impressive agility in developing resistance to successive classes of antimicrobials used for therapy, leading to a progressive reduction in available treatment options. Ceftriaxone is the last-line treatment option for gonorrhoea, and many countries recommend dual therapy with ceftriaxone (250–1000 mg) in combination with azithromycin (1–2 g). However, since the introduction of dual therapy, the global prevalence of azithromycin resistance has increased. Additionally, the extensively drug-resistant N gonorrhoeae FC428 clone, which is associated with ceftriaxone resistance and intermediate resistance to azithromycin, has been reported to have spread internationally, with epidemiological links to the Asia-Pacific region

Genetic relatedness of ceftriaxone-resistant and high-level azithromycin resistant Neisseria gonorrhoeae cases, United Kingdom and Australia, February to April 2018.

Between February and April 2018, three ceftriaxone-resistant and high-level azithromycin-resistant Neisseria gonorrhoeae cases were identified; one in the United Kingdom and two in Australia. Whole genome sequencing was used to show that the isolates from these cases belong to a single gonococcal clone, which we name the A2543 clone

Defining the phylogenetics and resistome of the major clostridioides difficile ribotypes circulating in Australia

Clostridioides difficile infection (CDI) remains a significant public health threat globally. New interventions to treat CDI rely on an understanding of the evolution and epidemiology of circulating strains. Here we provide longitudinal genomic data on strain diversity, transmission dynamics and antimicrobial resistance (AMR) of C. difficile ribotypes (RTs) 014/020 (n=169), 002 (n=77) and 056 (n=36), the three most prominent C. difficile strains causing CDI in Australia. Genome scrutiny showed that AMR was uncommon in these lineages, with resistance-conferring alleles present in only 15/169 RT014/020 strains (8.9 %), 1/36 RT056 strains (2.78 %) and none of 77 RT002 strains. Notably, ~90 % of strains were resistant to MLSB agents in vitro, but only ~5.9 % harboured known resistance alleles, highlighting an incongruence between AMR genotype and phenotype. Core genome analyses revealed all three RTs contained genetically heterogeneous strain populations with limited evidence of clonal transmission between CDI cases. The average number of pairwise core genome SNP (cgSNP) differences within each RT group ranged from 23.3 (RT056, ST34, n=36) to 115.6 (RT002, ST8, n=77) and 315.9 (RT014/020, STs 2, 13, 14, 49, n=169). Just 19 clonal groups (encompassing 40 isolates), defined as isolates differing by ≤2 cgSNPs, were identified across all three RTs (RT014/020, n=14; RT002, n=3; RT056, n=2). Of these clonal groups, 63 % (12/19) comprised isolates from the same Australian State and 37 % (7/19) comprised isolates from different States. The low number of plausible transmission events found for these major RTs (and previously documented populations in animal and environmental sources/reservoirs) points to widespread and persistent community sources of diverse C. difficile strains as opposed to ongoing nationwide healthcare outbreaks dominated by a single clone. Together, these data provide new insights into the evolution of major lineages causing CDI in Australia and highlight the urgent need for enhanced surveillance, and for public health interventions to move beyond the healthcare setting and into a One Health paradigm to effectively combat this complex pathogen

Molecular Antimicrobial Resistance Surveillance for Neisseria gonorrhoeae, Northern Territory, Australia

Emerging Infectious Disease's an open access journal in the public domain. All content is freely available without charge to the user or his/her institution.Neisseria gonorrhoeae antimicrobial resistance (AMR) is a globally recognized health threat; new strategies are needed to enhance AMR surveillance. The Northern Territory of Australia is unique in that 2 different first-line therapies, based primarily on geographic location, are used for gonorrhea treatment. We tested 1,629 N. gonorrhoeae nucleic acid amplification test-positive clinical samples, collected from regions where ceftriaxone plus azithromycin or amoxicillin plus azithromycin are recommended first-line treatments, by using 8 N. gonorrhoeae AMR PCR assays. We compared results with those from routine culture-based surveillance data. PCR data confirmed an absence of ceftriaxone resistance and a low level of azithromycin resistance (0.2%), and that penicillin resistance was <5% in amoxicillin plus azithromycin regions. Rates of ciprofloxacin resistance and penicillinase-producing N. gonorrhoeae were lower when molecular methods were used. Molecular methods to detect N. gonorrhoeae AMR can increase the evidence base for treatment guidelines, particularly in settings where culture-based surveillance is limited

WHO global research priorities for antimicrobial resistance in human health

The WHO research agenda for antimicrobial resistance (AMR) in human health has identified 40 research priorities to be addressed by the year 2030. These priorities focus on bacterial and fungal pathogens of crucial importance in addressing AMR, including drug-resistant pathogens causing tuberculosis. These research priorities encompass the entire people-centred journey, covering prevention, diagnosis, and treatment of antimicrobial-resistant infections, in addition to addressing the overarching knowledge gaps in AMR epidemiology, burden and drivers, policies and regulations, and awareness and education. The research priorities were identified through a multistage process, starting with a comprehensive scoping review of knowledge gaps, with expert inputs gathered through a survey and open call. The priority setting involved a rigorous modified Child Health and Nutrition Research Initiative approach, ensuring global representation and applicability of the findings. The ultimate goal of this research agenda is to encourage research and investment in the generation of evidence to better understand AMR dynamics and facilitate policy translation for reducing the burden and consequences of AMR

Gonococcal antimicrobial resistance in the Western Pacific Region

Objective To outline the current situation of gonococcal antimicrobial resistance (AMR) in the Western Pacific region and factors that impact on this. Background The Western Pacific region is densely populated with many living in poverty. There are high rates of infectious diseases, and a disproportionate burden of gonococcal disease. In many countries there is uncontrolled antimicrobial use: these are ideal conditions for the emergence of AMR. Methods Gonococcal AMR in this region has been monitored for more than 20 years. Clinical isolates, predominantly from unselected patients attending sexually transmitted diseases clinics, are tested against a panel of antibiotics. Quality assurance and control strategies are in place. Results There is widespread, high level resistance to penicillin and ciprofloxacin. Decreased susceptibility to ceftriaxone (MIC=0.06 mg/L) is reported in high levels from some countries in the region. Low numbers of isolates tested in some countries reflect capacity for testing, and are suboptimal for surveillance. Conclusion The raised MIC values to ceftriaxone, and the emergence and spread of ceftriaxone resistant strains regionally is alarming. Sustaining and enhancing surveillance is critical; however obtaining an adequate sample size is a long-standing issue. The implementation of molecular surveillance strategies could provide broader information on the spread and threat of AMR