Global Antibiotic Research & Development Partnership

Background. The United Nations General Assembly High-level Meeting on Antimicrobial Resistance (UNGA HLM-AMR) committed to a target that 70% of global human antibiotic use (ABU) should be from the Access group of the WHO AWaRe system. Methods. We used 2019 IQVIA MIDAS global ABU Quarterly value sales, volumes (kg/SU) and average ex-manufacturer prices to evaluate price per daily defined dose (DDD) by AWaRe group across countries. IQVIA MIDAS volumes/value data reflect public, private, or mixed sectors. We estimated potential national pharmaceutical expenditure savings if i) the UNGA 70% Access target was met, and ii) national ABU aligned with the WHO Model List of Essential Medicines (EML). We evaluated 7-day treatment prices for common oral and parenteral antibiotics across AWaRe groups. We measured affordability in middle-income countries (MICs) by income group, as the percentage of the population at risk of falling below national poverty lines if paying out-of-pocket, using income distributions and generalised beta distributions of the second kind. Prices were reported in 2019 international dollars (I$). Results. Volume-weighted ex-manufacturer prices per DDD were lower for Access (I$1.2, IQR I$0.7) than Watch (I$2.6, IQR I$2.1) and highest (I$83.8, IQR I$80.9) for Reserve antibiotics. Lower prices were seen in high-income countries for Access antibiotics. Meeting the 70% Access target could save countries I$0.1 million-I$4.9 billion annually. Global savings could reach I$10.4 billion if only WHO EML-listed antibiotics were used. Seven-day parenteral meropenem could put 7% (IQR 9%) of the population in MICs at risk of impoverishment. Conclusion. Antibiotic policies focused on achieving the UNGA-AMR 70% Access target could generate significant potential national and global expenditure savings.

BackgroundZoliflodacin is an oral, single-dose, first-in-class spiropyrimidinetrione bacterial topoisomerase inhibitor with activity against multidrug-resistant strains of Neisseria gonorrhoeae. Efficacy and safety of zoliflodacin for the treatment of uncomplicated gonorrhea was studied in a global Phase 3 trial that demonstrated non-inferiority to ceftriaxone plus azithromycin. In this study, the antibiotic susceptibility of baseline N. gonorrhoeae isolates from US participants in the Phase 3 trial was characterized.MethodsOverall, 163 N. gonorrhoeae baseline isolates (139 urogenital, 13 pharyngeal, 11 rectal) were cultured from participants enrolled at 5 US clinical sites. Isolates were speciated using MALDI-TOF. MICs were performed using agar dilution according to CLSI guidelines. CLSI interpretive criteria were applied where available.ResultsThe zoliflodacin MIC50/90 was 0.06/0.12 µg/mL (MIC range ≤0.008 – 0.25 µg/mL) against 139 baseline urogenital N. gonorrhoeae isolates, which is consistent with that seen among pharyngeal and rectal US isolates and the global set of baseline isolates from the Phase 3 trial (Table 1). Azithromycin susceptibility rates were lower for the US isolates (69-91% depending on the body site of infection) compared to the global isolates (89-95%); however, susceptibility to ciprofloxacin was higher (62-73% vs 17-28%). For all isolates, susceptibility to tetracycline was low (0-12%) while ceftriaxone susceptibility was high ( >99%). There was 1 ceftriaxone resistant isolate from a US patient (MIC >0.5 µg/mL). This was a pharyngeal isolate also resistant to ciprofloxacin and tetracycline, but susceptible to azithromycin. Zoliflodacin demonstrated an MIC of 0.12 µg/mL against this isolate.ConclusionAgainst N. gonorrhoeae baseline isolates from US participants from a Phase 3 trial for uncomplicated gonorrhea, the in vitro potency of zoliflodacin was consistent with that observed against the global set of baseline isolates and US surveillance studies. Zoliflodacin maintained activity against multidrug-resistant isolates. These data complement the recent Phase 3 results and support the continued development of zoliflodacin for patients with uncomplicated gonorrhea.DisclosuresSarah McLeod, PhD, Innoviva Specialty Therapeutics: Employee|Innoviva Specialty Therapeutics: Stocks/Bonds (Public Company) Alison Luckey, MD, GARDP: Employee of GARDP, a non-profit Swiss-based foundation, which receives government and private-funded institutional grants/research support

The Bellagio Group for Accelerating AMR Action met in April 2024 to develop the ambitious but achievable 1–10-100 unifying goals to galvanize global policy change and investments for antimicrobial resistance mitigation: 1 Health; 10 million lives saved; and 100% sustainable access to effective antimicrobials. High profile political goals such as the Paris Agreement’s objective to keep global warming well below 2° Celsius compared to pre-industrial levels, UNAIDS’ 90–90-90 goal, and the Sustainable Development Goals challenge global norms, direct attention towards relevant activities, and serve an energizing function to motivate action over an extended period of time. The 1–10-100 unifying goals propose to unite the world through a One Health approach to safeguard human health, animal welfare, agrifood systems, and the environment from the emergence and spread of drug-resistant microbes and infections; save over 10 million lives by 2040 through concerted efforts to prevent and appropriately treat infections while preserving the vital systems and services that depend on sustained antimicrobial effectiveness; and commit to ensuring that antimicrobials are available and affordable for all, used prudently, and secured for the future through innovation. Compared to existing technical targets, these unifying goals offer advantages of focusing on prevention, encouraging multisectoral action and collaboration, promoting health equity, recognizing the need for innovation, and integrating with Sustainable Development Goals. By committing to 1 Health, 10 million lives saved, and 100% sustainable access to effective antimicrobials, we can protect lives and livelihoods today and safeguard options for tomorrow.

Background: The UNHLM pledged to enroll 30 million in TB preventive treatment (TPT) by 2022, necessitating TPT expansion to all at TB risk. We assessed uptake and completion of a 12-dose, weekly isoniazid-rifapentine (3HP) TPT regimen. Methods: Between February 2018 - March 2019 in Dhaka, community-based TPT using 3HP targeted household contacts of 883 confirmed drug-sensitive pulmonary TB patients. Adhering to WHO guidelines, contacts underwent active TB screening before TPT initiation. Results: Of 3,193 contacts who advised health facility visits for screening, 67% (n=2,149) complied. Among these, 1,804 (84%) received chest X-rays. Active TB was diagnosed in 39 (2%) contacts; they commenced TB treatment. Over 97% of 1,216 contacts began 3HP TPT, with completion rates higher among females, those with more education and income, non-slum residents, and those without 3HP-related adverse events. Adverse events, mainly mild, occurred in 5% of participants. Conclusions: The 3HP weekly regimen, with its short duration, self-administered option, and minimal side effects, achieved satisfactory completion rates. A community-focused 3HP TPT approach is feasible, scalable nationally, and aligns with UNHLM targets.

Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a substantial global public health problem. Gonococcal infections acquired in or from Asia represent most verified ceftriaxone treatment failures, and several ceftriaxone-resistant strains have emerged in Asia and subsequently spread globally. Additionally, in Thailand the gonorrhoea incidence remains high. Herein, we investigate the genomic diversity, AMR and AMR determinants in gonococcal isolates cultured in 2018 in Bangkok, Thailand. Gonococcal isolates from males (n = 37) and females (n = 62) were examined by Etest and WGS. AMR determinants and molecular epidemiological STs were characterized. For phylogenomic comparison, raw sequence data were included from China (432 isolates), Japan (n = 270), Vietnam (n = 229), Thailand (n = 3), a global dataset (n = 12 440) and the 2016 WHO reference strains plus WHO Q (n = 15). In total, 88, 66 and 41 different NG-MAST, NG-STAR and MLST STs, respectively, and 31 different NG-STAR clonal complexes were found. A remarkably high frequency (88%) of β-lactamase TEM genes was detected and two novel TEM alleles were found. The phylogenomic analysis divided the isolates into the previously described lineages A and B, with a large proportion of Thai isolates belonging to the novel sublineage A3. We describe the first molecular epidemiological study using WGS on gonococcal isolates from Thailand. The high prevalence of AMR and AMR determinants for ciprofloxacin, tetracycline and benzylpenicillin, and some strains belonging to clones/clades especially in sublineage A2 that are prone to develop resistance to extended-spectrum cephalosporins (ESCs) and azithromycin, should prompt continued and strengthened AMR surveillance, including WGS, of N. gonorrhoeae in Thailand.