The antimicrobial resistance (AMR) crisis necessitates strategies to revitalize existing antibiotics against multidrug-resistant pathogens. While cationic antimicrobial polymers can disrupt bacterial membranes, their clinical translation is hindered by host toxicity. Here we report a hierarchical, stimuli-responsive nanomedicine designed on principles of safety, specificity, switchability, and synergy. We synthesized phenylboronic ester-caged biodegradable polymers shielded by functional polysaccharide shells. These nanoparticles remain inert during circulation but selectively activate within infection microenvironments. Upon activation, the exposed cationic polymer physically compromises bacterial membranes, enabling the entry of co-delivered antibiotics such as rifampicin into Gram-positive, Gram-negative, mycobacterial, and biofilm-embedded pathogens. Our research led to the discovery of glycans that significantly improve therapeutic outcomes. We found that different glycans exhibited distinct effects in various tissues and conditions: chondroitin sulfate effectively targeted CD44-abundant infectious niches, enabling precise localization and enhanced therapeutic efficacy, whereas levan uniquely stimulated macrophage oxidative bursts, promoting intracellular pathogen clearance. By leveraging these distinct biological interactions, our platform overcomes the physical and biological barriers of AMR, offering a universal strategy to treat diverse, multidrug-resistant infections.

Use of mouse infection models for antimicrobial pharmacokinetic/pharmacodynamic (PK/PD) analysis can assist in dosing regimen design and susceptibility breakpoint development. A major hurdle for clinical translation of in vivo study output is defining the model endpoint linked to clinical success. Validation of the in vivo endpoint requires a clinical data set composed of success or failure linked to minimum inhibitory concentration (MIC), dosing regimen, and if possible human pharmacokinetic measures. The present studies utilized a clinical library of eight Aspergillus fumigatus strains in a mouse pneumonia model to define the endpoint associated with humanized treatment regimens of the triazole, posaconazole. This includes wild-type strains associated with successful treatment and strains with resistance mutations leading to elevated MICs and associated with treatment failure. We found humanized posaconazole exposures resulted in a net stasis or net decrease in organism burden in the animal model compared to the start of therapy for all wild-type strains. However, a net increase in organism burden despite treatment with the humanized regimen was noted for strains with higher MIC values and defined Cyp51 mutations. The ratio of posaconazole free-drug area under the concentration-time curve to the MIC (AUC/MIC) associated with a stasis endpoint in the mouse model was then utilized with in vitro surveillance data and a human posaconazole population pharmacokinetic model to perform simulations and PK/PD target attainment analyses. The results of these analyses demonstrated >90% probability of PK/PD target attainment for A. fumigatus strains with MICs of ≤0.5 mg/L, thus supporting this susceptible breakpoint threshold.

Despite transformative advances in antiretroviral therapy, human immunodeficiency virus (HIV) remains a lifelong condition driven by durable viral reservoirs, chronic immune dysfunction, and complex interactions with host biology, coinfections, and aging. While implementation science is essential to ensure that effective interventions reach populations most affected by HIV, implementation cannot succeed in isolation from continued discovery or from the political and social contexts in which care is delivered. This editorial highlights critical gaps in our understanding of sex-based immunologic differences, tissue-specific viral persistence, resistance evolution, and the long-term inflammatory and metabolic consequences of treated HIV-gaps that directly constrain the durability, equity, and scalability of prevention, treatment, and cure strategies. We further emphasize that successful translation depends on stable policy environments, sustained public investment, and trust-based partnerships with affected communities, without which even highly effective biomedical advances fail to achieve impact. Sustained investment across the full translational spectrum-from basic and mechanistic science through clinical, behavioral, and implementation research-is therefore essential. HIV research has repeatedly served as a model system driving advances across immunology, vaccinology, oncology, aging, and pandemic preparedness, underscoring its broader relevance to human infectious diseases.

Background:16S bacterial identification is a molecular diagnostic test that can aid in the diagnosis and management of orthopedic infections. The study aims to describe the diagnostic value of 16S for orthopedic infections and whether results of 16S impact antibiotic de-escalation. Methods:This retrospective cohort study included all patient encounters with 16S performed for evaluation of orthopedic infections at 1 Midwest academic center over a 5-year prepandemic period. Qualitative descriptions of the clinical cases, antibiotics, and 16S results were evaluated. Results:Four hundred fifty-two episodes were included for analysis. Overall, 9.5% of 16S tests detected bacteria. The most common indication for testing was for evaluation of septic arthritis. For diagnosing infectious episodes, 16S had a sensitivity of 15.5%, a specificity of 98%, a positive predictive value of 90.7%, and a negative predictive value of 47.9%. Analysis of all episodes demonstrated antibiotic de-escalation from pre-16S to post-16S time points. However, antibiotics were continued for a large number of episodes with negative 16S when judged as infectious by the treating clinician. Conclusions:16S bacterial identification aided in the diagnosis and treatment of only a minority of orthopedic infections and results did not serve as a useful tool for antimicrobial de-escalation.

The study describes the in vivo isolation, characterization, and relevance of fungal biofilm extracellular vesicles.

Candida biofilms produce an extracellular matrix that sequesters antifungals, allowing cells to proliferate despite otherwise therapeutic concentrations. A prior study found turbinmicin to inhibit the release of the extracellular vesicles (EVs) required for matrix delivery and drug resistance. Here, we show that turbinmicin also alters the cargo loaded into EVs, decreasing the relative abundance of proteins that drive production of the drug-sequestering matrix. Turbinmicin displays a new dual antifungal action, disrupting both EV quantity and cargo.

The commensal yeast Candida albicans is a major inducer of human mucosal Th17 cells. How C. albicans drives Th17 cell responses at homeostasis, and whether such responses contribute to inflammatory diseases, remains poorly understood. Here, we showed that C. albicans-reactive Th17 cells targeted a limited set of proteins enriched in fungal extracellular vesicles. At homeostasis, these cells predominantly resided in the oral mucosa. However, T cell receptor profiling revealed shared clonotypes across oral and gut tissues, with C. albicans being a major driver of this repertoire overlap. In patients with Crohn’s disease, C. albicans-specific Th17 cells with features of oral priming were enriched in intestinal tissues, where they retained their focused antigen specificity but acquired pathogenic Th17 cell traits. Together, our results reveal a stable, antigen-restricted C. albicans Th17 subset that is shared across mucosal sites and undergoes functional adaptation in the inflamed intestine. These cells represent a potential target for immune modulation in Crohn’s disease.

Candida auris is an often multidrug-resistant fungal pathogen notorious for persistent skin colonization and transmission in healthcare settings. However, the mechanisms driving its adherence to skin remain poorly understood. Here, we developed in vitro systems to allow for detailed analysis of early skin colonization events and identified critical host and pathogen mediators of attachment. Across multiple strains and clades of C. auris, we identified that Als4112, a conserved adhesin, is required for skin colonization via keratinocyte attachment and direct interactions with host extracellular matrix (ECM) proteins, especially basement membrane proteins such as laminin. In a murine epicutaneous infection and human skin explants, deletion of ALS4112 significantly reduced skin colonization, underscoring its essential role in establishing cutaneous persistence. Als4112 also contributes to systemic infection, highlighting the connection between adherence and pathogenicity in this organism. Finally, coating plastic and catheter surfaces with collagen I or III markedly inhibited C. auris attachment and biofilm formation, offering an approach to curb nosocomial transmission. Our study highlights the critical role of Als4112 in C. auris colonization and virulence in vivo, making it an attractive target for future vaccine development. This study also explores the potential of specific collagen coatings as a novel strategy to prevent C. auris adherence to abiotic surfaces, offering new therapeutic avenues to control the spread of C. auris in healthcare settings. ### Competing Interest Statement The authors have declared no competing interest.

Candida glabrata is the second most common cause of invasive candidiasis and is widely known to have reduced susceptibility to fluconazole relative to many other Candida spp. Upc2A is a transcription factor that regulates ergosterol biosynthesis gene expression under conditions of sterol stress such as azole drug treatment or hypoxia. Through an in vitro microevolution experiment, we found that loss-of-function mutants of the ATF/CREB transcription factor CST6 suppresses the fluconazole hyper-susceptibility of the upc2A triangle mutant. Here, we confirm that the cst6 triangle upc2A triangle mutants are resistant to fluconazole but not to hypoxia relative to the upc2A triangle mutant. Sterol analysis of these mutants indicates that this suppression phenotype is not due to restoration of ergosterol levels in the cst6 triangle upc2A triangle mutant. Furthermore, increased expression of CDR1, the efflux pump implicated in the vast majority of azole-resistant C. glabrata strains, does not account for the suppression phenotype. Instead, our data suggest that this effect is due in part to increased expression of the adhesin EPA3, which has been shown by others to reduce fluconazole susceptibility in C. glabrata. In addition, we find that loss of both UPC2A and CST6 reduces the expression of mitochondrial and respiratory genes and that this also contributes to the suppression phenotype as well as to the resistance of cst6 triangle to fluconazole. These latter data further emphasize the connection between mitochondrial function and azole susceptibility.

The increasing prevalence of candidemia and invasive candidiasis infections caused by Candida auris represents a global health risk. Such infections are difficult to treat as they are often multidrug-resistant and are linked to high rates of mortality. Rezafungin is a second-generation echinocandin with antifungal activity against a range of Candida species, including wild type, and azole- and some echinocandin-resistant isolates. Its stability and prolonged half-life permit less frequent dosing compared with other echinocandins, leading to high front-loaded exposures and potential earlier mycological clearance from infection sites. These properties make rezafungin a candidate for the treatment of candidemia and invasive candidiasis infections due to C. auris. Accordingly, this narrative review article describes available evidence for the activity and effectiveness of rezafungin against C. auris isolates and infections. To date, the activity of rezafungin against C. auris isolates and infections has been demonstrated in in vitro and in vivo non-clinical experiments, and in pharmacokinetic/pharmacodynamic target attainment estimations utilizing clinical data. With similar potency to other echinocandins, rezafungin demonstrates in vitro and in vivo activity that is comparable to or better than that seen with other echinocandins, and similar to that for rezafungin in other Candida species. Like other echinocandins, its activity is reduced in fks-mutant isolates. Although there is currently a dearth of data on the therapeutic activity of rezafungin against C. auris, it is reasonable that rezafungin may be a viable choice for treating candidemia and invasive candidiasis caused by C. auris. Further clinical investigations are necessary.

Screen of mutants from a mannosyltransferase family identified the importance of MNT5 for C. auris biofilm drug resistance and neutrophil evasion. Biochemical analysis of the mnt5∆ mutant matrix and cell wall identified alterations in the mannan structures. Resistance and matrix for mnt5∆ were restored with delivery of wild-type matrix via extracellular vesicles. Analysis of the mnt5∆ cell wall revealed a reduction in mannan and compensatory increase in cell surface glucan and chitin, suggesting a role for MNT5 in mannan masking of pathogen-associated molecular patterns. IMPORTANCE:C. auris recalcitrance is linked to biofilm drug resistance and immune evasion. The mannosyltransferase encoded by MNT5 is necessary for both phenotypes and may serve as a useful therapeutic target.

Recently expanded reports of multidrug-resistant fungal infections underscore the need to develop new and more efficient methods for antifungal drug discovery. A ubiquitous problem in natural product drug discovery campaigns is the rediscovery of known compounds or their relatives; accordingly, we have integrated Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS) for structural dereplication and Yeast Chemical Genomics for bioprocess evaluation into a screening platform to identify such compounds early in the screening process. We identified 450 fractions inhibiting Candida albicans and the resistant strains of C. auris and C. glabrata among more than 40,000 natural product fractions. LC-MS/MS and chemical genomics were then used to identify those with known chemistry and mechanisms of action. The parallel deployment of these orthogonal methods improved the detection of unwanted compound classes over the methods applied individually.

Biofilms of the fungal pathogen Candida albicans can form on implanted medical devices and contribute to fungal virulence and are recalcitrant to antifungal therapy. The transcription factor Ume6 directs hyphal cell elongation and thus promotes biofilm formation in C. albicans. However, how exactly this key biofilm and virulence regulator functions has remained unclear. Here RNA sequencing and chromatin immunoprecipitation with sequencing data show that Ume6 binds to and activates multiple biofilm-relevant genes. Ume6-associated sequence motifs correspond to binding sites for biofilm master regulators Efg1 and Ndt80, and hypoxic response regulator Upc2. Co-immunoprecipitation assays show the existence of Ume6-Efg1, Ume6-Ndt80 and Ume6-Upc2 protein complexes. Promoter binding of Ume6 is partially dependent upon Efg1, Ndt80 or Upc2, as is Ume6 target gene activation, thus indicating that the protein complexes function to drive Ume6-target gene interaction. Ume6 therefore acts as a bridge that connects the hyphal morphogenesis and adherence genes that shape biofilm architecture and the hypoxic response genes required for growth in the low-oxygen biofilm environment. These findings are vital for our understanding of the pathobiology of C. albicans and could open the way to new treatment options.

Since their discovery in 2007, there has been growing awareness of the importance of fungal extracellular vesicles (EVs) for fungal physiology, host-pathogen interactions and virulence. Fungal EVs are nanostructures comprising bilayered membranes and molecules of various types that participate in several pathophysiological processes in fungal biology, including secretion, cellular communication, immunopathogenesis and drug resistance. However, many questions remain regarding the classification of EVs, their cellular origin, passage across the cell wall, experimental models for functional and compositional analyses, production in vitro and in vivo and biomarkers for EVs. Here, we discuss gaps in the literature of fungal EVs and identify key questions for the field. We present the history of fungal EV discovery, discuss five major unanswered questions in fungal EV biology and provide future perspectives for fungal EV research. We primarily focus our discussion on human fungal pathogens, but also extend it to include knowledge of other fungi, such as plant pathogens. With this Perspective we hope to stimulate new approaches and expand studies to understand the biology of fungal EVs.

Candida auris is a fungal pathogen notorious for persistent skin colonization and transmission in healthcare settings. Here, we show that a C. auris conserved adhesin, Als4112, is required for skin colonization via keratinocyte attachment and direct interactions with host extracellular matrix proteins, especially basement membrane proteins such as laminin. Deletion of ALS4112 reduces skin colonization in mouse models of epicutaneous and systemic infection. In addition, coating plastic and catheter surfaces with collagen I or III inhibits C. auris attachment and biofilm formation. Our study highlights the critical role of Als4112 in C. auris colonization and virulence, and explores potential strategies to reduce the pathogen's adherence to abiotic surfaces and thus its spread in healthcare settings.

Candida biofilm matrix components are delivered to the extracellular space by vesicles where they deposit and confer biofilm-associated drug resistance. Here, we present evidence that drugs designed to inhibit mammalian exosome production exhibit similar effects on C. albicans extracellular vesicles, ultimately eliminating biofilm matrix assembly. We find that vesicle reduction renders biofilm communities susceptible to the antifungal fluconazole. Our findings argue that vesicle trafficking pathways represent a promising target to optimize for recalcitrant fungal biofilms.

Echinocandin drugs are the current first-line therapy for fungal infections caused by Candida spp. Most patients require once-daily intravenous (IV) administration in a hospital or outpatient setting for treatment, which may negatively impact their quality of life and stress healthcare resources. Similar to other echinocandins, the novel FDA-, EMA-, and Medical and Healthcare Products Regulatory Agency-approved echinocandin, rezafungin (CD101), exhibited strong antifungal activity against several fungal pathogens and a low drug-drug interaction liability, which are important for medically complex patients. A pharmacometric-based approach has been adopted throughout the development of rezafungin, which contrasts with older echinocandins where dosing regimens were largely derived empirically, and only recently based on pharmacometric guidance. This state-of-the-art approach used model-based simulations incorporating pre-clinical and clinical data as it became available to optimize the dosing regimen for rezafungin. The enhanced stability of the molecular structure and the safety profile of rezafungin allow for the administration of once-weekly IV doses, compared to the daily dosing requirement for other echinocandin drugs, with this distinctive pharmacokinetic profile of rezafungin resulting in a front-loaded dosing regimen with high exposures early in therapy for enhanced fungal killing. The long shelf-life of rezafungin makes this echinocandin more flexible in terms of storage and manufacturing. Demonstrated across clinical development, rezafungin may provide patients with next-generation first-line antifungal treatment for the treatment of candidaemia and invasive candidiasis.

Candida albicans is the most common cause of life-threatening fungal infection in the developed world but remains a therapeutic challenge. Protein kinases have been rewarding drug targets across diverse indications but remain untapped for antifungal development. Previously, screening kinase inhibitors against C. albicans revealed a 2,3-aryl-pyrazolopyridine, GW461484A (GW), which targets casein kinase 1 (CK1) family member Yck2. Here, we report optimization of GW via two complementary approaches, synthesis of bioisosteres possessing an imidazo[1,2-a]pyridine core, and R-group substitution of GW's pyrazolo[1,5-a]pyridine core. Characterization of compounds synthesized revealed two 6-cyano derivatives with improved pharmacological properties that retained whole-cell bioactivity and selectivity for fungal Yck2 compared to human CK1α. Efficacy studies in mice indicated both analogs possess single-agent activity against C. albicans resistant to first-line echinocandin antifungals and potentiate non-curative echinocandin treatment. Results validate Yck2 as an antifungal target and encourage further development of inhibitors acting by this previously unexploited mode of action.

Mucormycosis is a fungal infection caused by Mucorales fungi that cause severe disease and fatality, especially in immunocompromised individuals. Although vaccines and immunotherapeutics have been successful in combating viral and bacterial infections, approved antifungal immunotherapies are yet to be realized. To address this gap, monoclonal antibodies targeting invasive fungal infections have emerged as a promising approach, particularly for immunocompromised patients who are unlikely to maximally benefit from vaccines. The Mucorales spore coat (CotH) proteins have been identified as crucial fungal invasins that bind to glucose-regulated protein 78 (GRP78) and integrins of host barrier cells. Previously, we described a murine monoclonal antibody, anti-CotH C2, which protected diabetic ketoacidosis (DKA) and neutropenic mice from mucormycosis. Here, we advanced the development of the C2 immunoglobulin G1 (IgG1) by humanizing it, establishing a stable Chinese hamster ovary cell line producing the antibody at commercial yields, and carried out optimization of the upstream and downstream manufacturing processes. The resultant humanized IgG1 (VX-01) exhibited a 10-fold increase in binding affinity to CotH proteins and conferred comparable in vitro and in vivo efficacy when compared to C2 antibody. The mechanism of protection was reliant on prevention of angioinvasion and enhancing opsonophagocytic killing. VX-01 demonstrated acceptable safety profiles with no detectable damage to host cells in vitro and weak or moderate binding to only cytoplasmic proteins in ex vivo good laboratory practice-human tissue cross-reactivity studies. Our studies warrant continued development of VX-01 as a promising adjunctive immunotherapy.

Abstract Background Comparative pre-clinical studies examining humanized pharmacokinetic/pharmacodynamic (PK/PD) exposures of triazoles against A. fumigatus (AF), including clinical wild-type and cyp51 mutants, is lacking. These studies are important to set rational clinical breakpoints, predict clinical outcomes, and provide data to guide drug and dosing choice to optimize efficacy. The aim of this study was to compare target AUC/MIC exposures in the context of expected humanized exposures for posaconazole (P) and isavuconazole (I) against AF. Posaconazole AUC/MIC and Treatment Response in the Murine IPA Model Relationship between posaconazole free drug AUC/MIC and treatment response in the animal model. The dashed horizontal line is net stasis from the start of therapy. Overlaid with vertical lines are the expected humanized AUC/MIC exposures for various MIC values (range 0.25-2 mg/L). Organisms with MIC values of ≤1 mg/L would fall in the net cidal (i.e. log kill) area on the exposure response curve based on humanized AUC/MIC exposures. Methods A neutropenic murine model of IPA with 7 AF clinical strains (2 WT, 5 cyp51 mutants) were utilized. MICs were determined by CLSI methods. Plasma PK were determined after single oral doses (4 dose levels) of P or I at 7 time points. Infection was induced by nasal aspiration of 50ul of a 1x10^7 conidia/ml inoculum in anesthetized mice. Treatment doses in the mouse incorporated humanized AUC exposures to examine the PK/PD relationship in the context of MIC variation within clinical strains. The duration was 96 hours. Drug efficacy was determined by qPCR of AF DNA from lyophilized lung tissue. AUC/MIC and treatment effect was modelled using the sigmoid Emax equation. Isavuconazole AUC/MIC and Treatment Response in the Murine IPA Model Relationship between isavuconazole free drug AUC/MIC and treatment response in the animal model. The dashed horizontal line is net stasis from the start of therapy. Overlaid with vertical lines are the expected humanized AUC/MIC exposures for various MIC values (range 0.25-2 mg/L). Organisms with MIC values of <0.5 mg/L would fall in the net cidal (i.e. log kill) area on the exposure response curve based on humanized AUC/MIC exposures. Results P and I MIC ranged from 0.25-2 mg/L and 0.5-4 mg/L, respectively. The 96h AUC for both drugs was linear (R2 > 0.99). Increasing dose was associated with increased effect. A sigmoidal relationship between AUC/MIC and treatment effect was noted for both drugs. The median 96h free drug AUC/MIC target for net stasis was 1.61 for P and 4.18 for I (P = 0.001). The PK/PD curves for the animal model are shown in the figures. Overlaid are the expected humanized AUC/MIC exposures for various common MIC values. Conclusion P had comparatively lower free AUC/MIC target exposures than I. Moreover, P had more potency based on expected humanized exposures. The humanized AUC/MIC exposures for P would consistently fall in the cidal activity of the efficacy curve for strains with P MIC ≤ 1 mg/L; however, I was more heterogenous and humanized AUC/MIC exposures in the cidal portion of curve occur only at MIC values < 0.5 mg/L. This data will be integrated with human clinical PK variability, MIC distributions, and clinical outcome data based on MIC for target attainment analysis and breakpoint determination. Disclosures Brian D. VanScoy, B.S., Achaogen Inc.: Grant/Research Support|Adagio Therapeutics, Inc.: Grant/Research Support|AiCurtis Anti-infective Cures AG: Grant/Research Support|Albany Medical College: Grant/Research Support|AN2 Therapeutics: Grant/Research Support|Antabio SAS: Grant/Research Support|Apogee Biologics, Inc: Grant/Research Support|Arcutis Biotherapeutics, Inc.: Grant/Research Support|B. Braun Medical Inc.: Grant/Research Support|Basilea Pharmaceutica: Grant/Research Support|BioFire Diagnostics, LLC.: Grant/Research Support|Cidara Therapeutics Inc.: Grant/Research Support|Cipla USA: Grant/Research Support|Cumberland Pharmaceuticals Inc.: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Excalibur Pharmaceuticals Inc.: Grant/Research Support|Fedora Pharmaceuticals: Grant/Research Support|Genentech: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Global Antibiotic Research and Development Partnership: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|ICPD: Employee|Inotrem: Grant/Research Support|Insmed Inc: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience: Grant/Research Support|Lassen Therapeutics Inc.: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma Co., Ltd.: Grant/Research Support|Melinta Therapeutics: Grant/Research Support|Mutabilis: Grant/Research Support|Nabriva Therapeutics AG: Grant/Research Support|Novobiotic Pharmaceuticals LLC: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|Pfizer Inc: Grant/Research Support|Praxis Precision Medicines, Inc.: Grant/Research Support|PTC Therapeutics: Grant/Research Support|PureTech LYT 100 Inc.: Grant/Research Support|Qpex Biopharma: Grant/Research Support|Renibus Therapeutics: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Shionogi Inc.: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Spruce Biosciences Inc.: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co: Grant/Research Support|Theravance: Grant/Research Support|University of Wisconsin: Grant/Research Support|US Food and Drug Administration: Grant/Research Support|UT Southwestern: Grant/Research Support|ValanBio Therapeutics, Inc.: Grant/Research Support|VenatoRx: Grant/Research Support|Zogenix International: Grant/Research Support Catharine Vincent, Ph.D., Achaogen Inc.: Grant/Research Support|Adagio Therapeutics, Inc.: Grant/Research Support|AiCuris Anti-infective Cures AG: Grant/Research Support|Albany Medical College: Grant/Research Support|AN2 Therapeutics: Grant/Research Support|Antabio SAS: Grant/Research Support|Apogee Biologics, Inc.: Grant/Research Support|Arcutis Biotherapeutics, Inc.: Grant/Research Support|B. Braun Medical Inc.: Grant/Research Support|Basilea Pharmaceutica: Grant/Research Support|BioFire Diagnostics, LLC: Grant/Research Support|Cidara Therapeutics Inc.: Grant/Research Support|Cipla USA: Grant/Research Support|Cumberland Pharmaceuticals Inc.: Grant/Research Support|Entasis Therapeutics Inc.: Grant/Research Support|Excalibur Pharmaceuticals Inc.: Grant/Research Support|Fedora Pharmaceuticals: Grant/Research Support|Genetech: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Global Antibiotic Research and Development Partnership: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|Inotrem: Grant/Research Support|Insmed Inc.: Grant/Research Support|Institute for Clinical Pharmacodynamics, Inc.: Employee|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience: Grant/Research Support|Lassen Therapeutics Inc.: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma Co., Ltd.: Grant/Research Support|Melinta Therapeutics: Grant/Research Support|Mutabilis: Grant/Research Support|Nabriva Therapeutics AG: Grant/Research Support|Novobiotic Pharmaceuticals LLC.: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|Pfizer Inc.: Grant/Research Support|Praxis Precision Medicines, Inc.: Grant/Research Support|PTC Therapeutics: Grant/Research Support|PureTech Health LYT 100 Inc.: Grant/Research Support|Qpex Biopharma: Grant/Research Support|Renibus Therapeutics: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Shionogi Inc.: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Spruce Biosciences Inc.: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|Theravance: Grant/Research Support|University of Wisconsin: Grant/Research Support|US Food and Drug Administration: Grant/Research Support|ValanBio Therapeutics, Inc.: Grant/Research Support|VenatoRx: Grant/Research Support|Zogenix International: Grant/Research Support