Authors

Sarah M. McLeod, Samir H. Moussa, Meredith Hackel, Carmen Au, Pierre Daram

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Antimicrobial resistance (AMR) is a major and growing threat to global health, development, and security, with the greatest burden borne by low-income and middle-income countries (LMICs). Without urgent intervention, cumulative deaths between 2020 and 2050, attributable to AMR, are projected to be 39·1 million globally. Effective diagnostics are important to bacterial pathogen detection and antimicrobial susceptibility testing, and such diagnostics support antibiotic stewardship by reducing adverse drug events (eg, toxicity or allergy) and restricting the emergence and spread of AMR. Yet, access to appropriate diagnostics in LMICs remains constrained.

Authors

Valeria Gigante PhD, Maurine Murtagh JD, Prof Till T Bachmann PhD, Tamarie Rocke MD, Betsy W Trainor BSc, Susan M Poutanen MD MPH, Teri Roberts PhD, Prof Jordi Vila MD PhD, Alexandra Cameron PhD

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Zoliflodacin is a first-in-class oral spiropyrimidinetrione antibiotic being developed for patients with uncomplicated gonorrhea, including those infected with multidrug-resistant strains. Because zoliflodacin is metabolized by cytochrome P450 3A4 (CYP3A4), concomitant administration with a CYP3A inhibitor has the potential to increase zoliflodacin plasma exposure. The aim of this phase 1 drug–drug interaction (DDI) study was to assess the effect of the strong CYP3A4 inhibitor itraconazole on the pharmacokinetics (PK) and safety of a 3 g single oral dose of zoliflodacin.

Authors

Alison Luckey, Kajal B. Larson, Noha Rayad, Markus Heep, Sophie Delhomme, Gabrielle Kornmann, John P. Mueller, John P. O’Donnell, Seamus O’Brien, Rainard Fuhr, Jean-Yves Gillon

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Sexually-transmitted pathogens Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) cause curable but often asymptomatic bacterial infections. Missed diagnoses and treatment, leading to chronic infections, can cause clinical complications and increase transmission. Accurate prevalence estimates are essential for the effective public health control of these sexually transmitted infections, especially in Africa, where data are scarce.

Authors

Catherine Ngugi,Borna A. Nyaoke,Leonard Kingwara,Pacific Akinyi,Mildred Mmbone,Thaddaeus W. Egondi,George M. Nyangweso,Helen Broadhurst,Gabrielle Kornmann,Rashmi Mathur ,Esther Bettiol

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In 2020, WHO estimated that Neisseria gonorrhoeae caused 82·4 million new cases of gonorrhoea among those aged 15–49 years worldwide. Without effective treatment, the morbidity associated with gonorrhoea complications can be considerable. Additionally, N gonorrhoeae infection enhances the risk of acquiring or transmitting HIV.

N gonorrhoeae has developed resistance to all current and previously used classes of antibiotics used to treat gonorrhoea, with ceftriaxone the sole remaining empirical treatment option for first-line gonorrhoea monotherapy. In 2017–18, the WHO Gonococcal Antimicrobial Surveillance Programme (GASP) reported high global rates of fluoroquinolone resistance, increasing azithromycin resistance, and, worryingly, progressively increasing multidrug resistance, including to extended-spectrum cephalosporins, such as ceftriaxone. Resistance patterns vary considerably by region; the WHO Enhanced GASP has highlighted situations of particular concern in Cambodia and Viet Nam. In 2022, nearly a third of isolates (32%) in Cambodia showed resistance to either broad-spectrum cephalosporins or azithromycin (with 7% showing resistance to both), and in Viet Nam, 27% of isolates were resistant to ceftriaxone in 2023. The WHO global action plan highlighted the development of new antibiotics for gonorrhoea as a high priority, and in 2019 the US Centers for Disease Control and Prevention declared antimicrobial-resistant N gonorrhoeae an urgent public health threat.

Authors

Alison Luckey, Manica Balasegaram, Lindley A Barbee, Teresa A Batteiger, Helen Broadhurst, Stephanie E Cohen, Sinead Delany-Moretlwe, Henry J C de Vries, Jodie A Dionne, Katherine Gill, Chris Kenyon, Rossaphorn Kittiyaowamarn, Drew Lewis, John P Mueller, Vimla Naicker, Seamus O’Brien, John P O’Donnell, Nittaya Phanuphak, Elizabeth Spooner, Subasree Srinivasan, Stephanie N Taylor, Magnus Unemo, Zinhle Zwane, Edward W Hook 3rd, for the Zoliflodacin Phase 3 Study Group*

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Over the past quarter century, antimicrobial resistance (AMR) has emerged as a major global health threat. It is estimated that almost 1·1 million deaths annually are a direct result of AMR—more than the combined deaths from HIV/AIDS and malaria in 2022.1–3 Overwhelmingly, low-income and middle-income countries (LMICs) bear this burden—nearly 90% of AMR-related deaths each year are estimated to occur in LMICs. Today, a child born in Africa is 58 times more likely to die from a drug-resistant infection in the first 5 years of life than one born in a high-income country. With bacterial drug resistance rates continuing to increase, and without concerted action, almost 40 million cumulative deaths are projected by 2050.

Authors: 

Anant Mishra, Rahul Dwivedi, Kim Faure, Prof Daniel J Morgan, Jennifer Cohn

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The lack of access to safe and effective antibiotics is a threat to global health security and contributes to the emergence and spread of antimicrobial resistance (AMR) [1–3]. Increasingly common, shortages of antibiotics are an additional threat, hindering effective antimicrobial stewardship programmes (AMS) [4]. In a recent review of existing National Action Plans for AMR, we described the lack of clear objectives for responding to the need to ensure robust, stable, and quality assured antibiotics [5]. The threat of antibiotic drug shortages impacts low-income and middle-income countries (LMICs) and high-income countries (HICs) [6–8]. The COVID-19 pandemic has highlighted the fragility of existing supply chain systems and the risk of antibiotic agents being struck off the manufacturing priorities of pharmaceutical companies [9,10].

Authors

Avaneesh Kumar Pandey, Jennifer Cohn, Vrinda Nampoothiri, Uttara Gadde, Amrita Ghataure, Ashish Kumar Kakkar, Yogendra, Kumar Gupta, Samir Malhotra, Oluchi Mbamalu, Marc Mendelson, Anne-Grete Märtson, Sanjeev Singh, Thomas Tängdén, Nusrat Shafiq, Esmita Charani

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Authors

Prof Ramanan Laxminarayan, PhD, Isabella Impalli, BSE, Radha Rangarajan, PhD, Jennifer Cohn, MD, Kavi Ramjeet, PhD, Betsy Wonderly Trainor, BSc, Prof Steffanie Strathdee, PhD, Nithima Sumpradit, PhD, Daniel Berman, MIA, Prof Heiman Wertheim, PhD, Prof Kevin Outterson, JD, Padmini Srikantiah, MD, Ursula Theuretzbacher, PhD

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Authors 

Biljana Kakaraskoska Boceska, Tuba Vilken, Basil Britto Xavier, Tomislav Kostyanev, Qiang Lin, Christine Lammens, Sally Ellis, Seamus O’Brien, Renata Maria Augusto da Costa, Aislinn Cook, Neal Russell, Julia Bielicki, Amy Riddell, Wolfgang Stohr, Ann Sarah Walker, Eitan Naaman Berezin, Emmanuel Roilides, Maia De Luca, Lorenza Romani, Daynia Ballot, Angela Dramowski, Jeannette Wadula, Sorasak Lochindarat, Suppawat Boonkasidecha, Flavia Namiiro, Hoang Thi Bich Ngoc, Minh Dien Tran, Tim R. Cressey, Kanchana Preedisripipat, James A. Berkley, Robert Musyimi, Charalampos Zarras, Trusha Nana, Andrew Whitelaw, Cely Barreto da Silva, Prenika Jaglal, Willy Ssengooba, Samir K. Saha, Mohammad Shahidul Islam, Marisa Marcia Mussi-Pinhata, Cristina Gardonyi Carvalheiro, Laura J. V. Piddock, Paul T. Heath, Surbhi Malhotra-Kumar, Michael Sharland, Youri Glupczynski & Herman Goossens

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Although numerous efflux inhibitors have been identified to date, none have progressed into clinical use because of formulation, toxicity, and pharmacokinetic issues or a narrow spectrum of inhibition. For these reasons, the development of efflux inhibitors has been considered a difficult and complex area of research, and few active preclinical studies on efflux inhibitors are in progress. However, recently developed tools, including but not limited to computational tools including molecular docking models, offer hope that further research on efflux inhibitors can be a platform for research and development of new bacterial efflux inhibitors.

Authors

Maëlle Duffey, Ravindra P. Jumde, Renata M.A. da Costa, Henni-Karoliina Ropponen, Benjamin Blasco, and Laura J.V. Piddock

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