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There is an unmet need for developing drugs for the treatment of gonorrhea, due to rapidly evolving resistance of Neisseria gonorrhoeae against antimicrobial drugs used for empiric therapy, an increase in globally reported multidrug resistant cases, and the limited available therapeutic options. Furthermore, few drugs are under development. Development of antimicrobials is hampered by challenges in clinical trial design, limitations of available diagnostics, changes in and varying standards of care, lack of robust animal models, and clinically relevant pharmacodynamic targets. On April 23, 2021, the U.S. Food and Drug Administration; Centers for Disease Control and Prevention; and National Institute of Allergy and Infectious Diseases, National Institutes of Health co-sponsored a workshop with stakeholders from academia, industry, and regulatory agencies to discuss the challenges and strategies, including potential collaborations and incentives, to facilitate the development of drugs for the treatment of gonorrhea. This article provides a summary of the workshop., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Pressing challenges in the treatment of invasive fungal infections (IFIs) include emerging and rare pathogens, resistant/refractory infections, and antifungal armamentarium limited by toxicity, drug-drug interactions, and lack of oral formulations. Development of new antifungal drugs is hampered by the limitations of the available diagnostics, clinical trial endpoints, prolonged trial duration, difficulties in patient recruitment, including subpopulations (eg, pediatrics), and heterogeneity of the IFIs. On 4 August 2020, the US Food and Drug Administration convened a workshop that included IFI experts from academia, industry, and other government agencies to discuss the IFI landscape, unmet need, and potential strategies to facilitate the development of antifungal drugs for treatment and prophylaxis. This article summarizes the key topics presented and discussed during the workshop, such as incentives and research support for drug developers, nonclinical development, clinical trial design challenges, lessons learned from industry, and potential collaborations to facilitate antifungal drug development., Competing Interests: Potential conflicts of interest. P. C. was employed at the Food and Drug Administration until 31 December 2020. S. N.'s contributions occurred entirely while she worked at the Food and Drug Administration. She is currently employed by Johnson & Johnson, and as an employee her travel to conferences/meetings is covered; she also owns Johnson & Johnson stock or stock options. D. A. is an employee and own shares of Scynexis. A. D. of DaneStat Consulting is a statistical consultant for the Pharmaceutical and Biotechnology Industry; he has acted as a consultant for Adaigo, AN2, Achaogen, Allecra, Amicrobe, Amplyx, Artizan, Bioscript, Bugworks, CARBX, Cidara, Closed Loop Medicine, Correvio, ContraFect, DaVolterra, Destiny, F2G, Entasis, Gates, Geom, GSK, Gyroscope, Humanigen, Kymab, Liverpool University, Melinta, Mironid, Modis, Nabriva, Orca, Pfizer, Phico, Pled, Quince, Roche, SFunga, Scynexis, Spero, Sinovent, SNIPR Biome, TenNor, Transcrip, VenatoRx, and Zavante (payments to DaneStat Consulting). He also reports as the independent statistician on data safety monitoring boards for a number of companies, including Aridis, ContraFect Midatech, Pfizer, Pled, Rare Thyroid, Sanofi, and Transcrip. M. R. H. reports support as a full-time employee of Amplyx Pharmaceuticals, a biotech company that was developing fosmanogepix, and received stock potions and a salary. T. S. is a full-time employee of and owns stock or stock options in Cidara Therapeutics. W. H. reports grants or contracts from F2G and Pfizer; personal consulting fees from F2G, Amplyx, Pfizer, Mundipharma, and Gilead (payments to DaneStat Consulting); participation on F2G's advisory board; a role as National Institutes of Health Research Specialty Co-lead for Infection; and a data sharing agreement with Astellas without any financial commitment. T. J. W. has received grants for experimental and clinical antimicrobial pharmacology and therapeutics to his institution from Allergan, Amplyx, Astellas, Lediant, Medicines Company, Merck, Scynexis, and Tetraphase; has served as consultant to Amplyx, Astellas, Allergan, ContraFect, Gilead, Leadiant, Medicines Company, Merck, Methylgene, Pfizer, and Scynexis; reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Astellas, Leadiant, Scynexis, Shinogi, Statera, and T2 Biosystems; and reports a leadership or fiduciary role in the Medical Mycological Society of the Americas. P. P. reports grants from Merck, Astellas, Scynexis, Cidara, and F2G and consulting fees from F2G and Cidara. L. K. reports support as a full-time employee of Astellas Pharma Global Development. J. H. R. is chief medical officer and director of F2G, operating partner and consultant for Advent Life Sciences, and expert in residence for Wellcome Trust. He sits on the scientific advisory boards of Bugworks Research, Basilea Pharmaceutica, Forge Therapeutics, Novo Holdings, and Roche Pharma Research & Early Development and is a shareholder in AstraZeneca Pharmaceuticals, F2G, Advent Life Sciences, Macrolide Pharmaceuticals, and Bugworks Research. He has also received consulting fees from Phico Therapeutics, ABAC Therapeutics, Polyphor, Heptares Therapeutics, Gangagen, Meiji Seika Pharma, Basilea Pharmaceutica International, Allecra Therapeutics, Forge Therapeutics, SinSa Labs, AtoxBio, Peptilogics, F. Hoffmann-LaRoche, Novo Holdings, Innocoll, Vedanta, Progenity, Nosopharm, Roivant Sciences, and Shionogi. K. A. M. is founder and chief executive officer of MycoMed Technologies and a consultant and advisory board member for Cidara Therapeutics and Sfunga Therapeutics. She has consulted for Amplyx Pharmaceuticals, Astellas Pharma, Advaxis, Chimerix, F2G, Genentech, Incyte, Merck & Co, OncoSec, RTI Surgical, Scynexis. and Vical. She receives authorship and editorial royalties from UpToDate and a grant from Merck, owns shares in Pearl Diagnostics and Sfunga Therapeutics, and is an employee of Sfunga Therapeutics. L. O. Z. has received research funding and/or personal honoraria for consulting or speaking from Pulmocide, Pfizer, Merck, Astellas, Cidara, Scynexis, F2G, Amplyx, Gilead, Therapeutics, Viracor, Octapharma, Biotoscana, Stendhal, Mayne, Takeda, RealTime Labs, and Viracor. L. O. Z. also reports honoraria from F2G, Pfizer, and Gilead; participation on a data safety monitoring board or advisory board for Octapharma, Cidara, F2G, and Pfizer; and leadership roles as president for the Mycoses Study Group and Education Consortium, president-elect for the Immunocompromised Host Society, senior editor for Journal of Antimicrobial Chemotherapy, and an associate editor for Clinical Infectious Diseases. J. F. reports being a US government employee. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

Coccidioidomycosis is a fungal disease endemic to the southwestern United States, Mexico, and Central and South America. Prevalence rates are increasing steadily, and new endemic areas of Coccidioides are emerging. Standard treatment is often administered for months to decades, and intolerance to medications and treatment failures are common. No new treatments for coccidioidomycosis have been approved in the United States in nearly 40 years. On 5 August 2020, the US Food and Drug Administration convened experts in coccidioidomycosis from academia, industry, patient groups, and other government agencies to discuss the disease landscape and strategies to facilitate product development for treatment of coccidioidomycosis. This article summarizes the key topics concerning drug development for coccidioidomycosis presented by speakers and panelists during the workshop, such as unmet need, trial designs, endpoints, incentives, research and development support, and collaborations to facilitate antifungal drug development., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Pathogenesis of neonatal candidiasis (NC) is distinct from systemic candidiasis in adults and older pediatric patients due to the significant incidence of central nervous system involvement in neonates. Thus, although adequate and well-controlled trials in NC are often unfeasible due to difficulty enrolling patients, extrapolation of efficacy from antifungal drug trials in adults is generally not appropriate. However, treatment of NC is an area of great unmet need. We describe a regulatory review approach that combined the assessment of limited clinical efficacy, pharmacokinetics, and safety data from neonates and young infants along with microbiology outcomes and pharmacokinetic data from relevant nonclinical models of candidemia/invasive candidiasis to inform the use of micafungin in pediatric patients younger than 4 months, while communicating areas of remaining uncertainty in labeling., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

For treatment of severe malaria, the World Health Organization recommends 3 mg/kg intravenous artesunate in pediatric patients weighing less than 20 kg. Here we describe the Food and Drug Administration's rationale for selecting 2.4 mg/kg in pediatric patients weighing less than 20 kg based on literature review and independent analyses., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Unique challenges remain in the development of new drugs for the treatment of TB. While existing multidrug treatment regimens are prolonged and difficult for patients to adhere to, they are highly efficacious, setting a high bar for the performance of new agents. Complicating matters more, regulatory standards have changed since the first drugs for TB were introduced, with a rigorous characterization of the effect of a new drug within a combination regimen expected. If these demands are to be satisfied, innovative models will be needed to demonstrate drug efficacy. In the past, mycobacterial cultures performed on solid media at the end of treatment have been used as critical biomarkers of drug efficacy, but their inability to predict long-term outcomes with precision has limited their utility. This article reviews a range of nonclinical and clinical models to characterize the bactericidal and/or sterilizing activity of new compounds. Novel approaches, using in vitro and animal models, sensitive biomarkers, as well as creative new clinical trial designs, are discussed. These promise a timely expansion of our TB treatment armamentarium to include potent new drugs and shorter, simpler treatment regimens.

Antimicrobial resistance is increasing among bacterial pathogens. In particular, organisms producing extended spectrum beta-lactamase enzymes (ESBLs) and AmpC chromosomal beta-lactamase enzymes are resistant to third generation cephalosporins and pose a formidable challenge in the management of seriously ill patients. Carbapenems are a class of broad-spectrum antibiotics with stability against ESBL and AmpC chromosomal beta-lactamases. They are well tolerated by patients. This review will examine the pharmacokinetic and pharmacodynamic properties of two carbapenems imipenem and meropenem and discuss their clinical use in children. References are limited to the English language and extend back to 1980. Sources include computerized databases such as MEDLINE searched using PubMed, and bibliographies of recent articles and books. Approximately 50% of the articles initially reviewed are included in the bibliography. Carbapenems are efficacious in the treatment of a variety of bacterial infections including meningitis, pneumonia, intraabdominal infections, bone, joint and urinary tract infections. The broad spectrum activity and comparatively low toxicity of carbapenems make them valuable therapeutic agents in the treatment of seriously ill patients with bacterial infections. These agents should be used judiciously in order to minimize the risk for development of carbapenem-resistant pathogens.