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Warren Rose

· ProfessorVerified

University of Wisconsin-Madison · Pharmacology

Active 1951–2026

h-index45
Citations6.0k
Papers20056 last 5y
Funding$2.1M
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About

Warren Rose is an Associate Professor at the University of Wisconsin-Madison, affiliated with the School of Pharmacy. He holds credentials including a PharmD and MPH. His research focuses on glyco/lipopeptide synergy with older antimicrobials, biofilm and virulence production during antimicrobial exposures, and investigating biomarkers of S. aureus bacteremia in patients. His work aims to enhance understanding of antimicrobial interactions, biofilm formation, and infection biomarkers, contributing to the development of more effective antimicrobial therapies and diagnostic tools.

Research topics

  • Microbiology
  • Intensive care medicine
  • Medicine
  • Biology
  • Internal medicine
  • Bioinformatics
  • Pharmacology
  • Chemistry
  • Genetics
  • Biochemistry
  • Cell biology

Selected publications

  • Unlocking the secret to <i>Staphylococcus aureus</i> survival in serum

    mSystems · 2026-04-29

    articleOpen access1st authorCorresponding

    ABSTRACT Staphylococcus aureus bloodstream infections remain a major clinical challenge. A key knowledge gap is how S. aureus adapts to the hostile, nutrient-limited environment of human serum, where immune pressures, such as complement, antimicrobial peptides, and nutritional immunity, restrict bacterial survival. Recent investigations integrating transcriptomic, proteomic, and metabolomic data across five clinically relevant S. aureus lineages revealed coordinated serum-specific metabolic and stress-response adaptations (W. Mujchariyakul, C. J. Walsh, S. Giulieri, C. Cramond, et al., mSystems 11:e01183-25, 2026, https://doi.org/10.1128/msystems.01183-25 ). Serum triggered increased gluconeogenic and TCA-cycle activity, expanded carbohydrate, amino acid, and lipid utilization, and induction of iron-acquisition systems, nucleotide biosynthesis, and oxidative-stress defenses, while suppressing ribosome biogenesis. Functional validation confirmed key roles for carbon-metabolism genes ( gapdhB, sucA ), siderophore and iron-uptake systems ( sirA, sstD ), and the peroxide regulator perR . These findings highlight the metabolic resourcefulness and stress resilience that enable S. aureus survival and persistence despite antibiotic therapy. This work underscores the importance of multiomic approaches across pathogens and physiologic models to reveal new therapeutic targets for bloodstream infections.

  • Elevated urinary glycosaminoglycans in Staphylococcus aureus bacteraemia with endovascular source

    Journal of Medical Microbiology · 2026-05-21

    articleOpen accessSenior author

    The differentiation of endovascular sources of Staphylococcus aureus bacteraemia from non-endovascular infection carries significant prognostic information that can be used to therapeutically stratify patients. The endovascular glycocalyx is a protective barrier composed of glycosaminoglycans (GAGs) that can be degraded and excreted in the urine from endothelial injury occurring in endovascular infections, but not in non-endovascular infections. To determine whether patients who had S. aureus endovascular infections, including endocarditis, had increased urinary glycocalyx shedding suggestive of endothelial damage, urine samples from 55 patients with bacteraemia caused by S. aureus were assessed for GAG content. Patients with endovascular source bacteraemia were compared to those from non-vascular source bacteraemia (e.g. prosthetic joint infections, pyomyositis and cellulitis) for GAG content. As expected, patients with S. aureus bacteraemia stemming from endovascular foci of infection showed increased GAG content in the urine (24.11±4.9 g GAG/mol creatinine, n =22) compared to those with non-vascular infections (13.65±1.6 g GAG/mol creatinine, n =33, P =0.024). Further analysis of GAG composition in urine revealed differential presence of GAGs between these two groups. In the first pilot study of its kind, we found that the measurement of GAG in the urine of patients with S. aureus bacteraemia shows promise for clinical risk stratification to identify high-risk endovascular infections in order to guide clinical diagnostic and therapeutic decision-making. Larger studies will be needed to determine relevant quantitative cut-off values.

  • A national survey of the infectious diseases and antimicrobial stewardship pharmacist workforce in the United States: work settings, characteristics, employment activities, resources and needs

    Antimicrobial Stewardship & Healthcare Epidemiology · 2026-01-01

    articleOpen access

    Purpose: This national survey aimed to describe the work settings, characteristics, employment activities, scope, functions, and challenges of the pharmacist workforce responsible for infectious diseases (ID) and antimicrobial stewardship (AMS)-related tasks in the U.S. Methods: survey was distributed to 22,749 unique individuals with potential ID or AMS job responsibilities via email listservs for three national pharmacy organizations, and was open from 9/25/2024 to 10/24/2024. A respondent was considered engaged in ID/AMS activities if they reported involvement in at least one of 14 activities directly related to ID/AMS. Results: A total of 796 pharmacists with ID or AMS job responsibilities responded (3.5% response rate), with 607 working clinically or administratively in ID or AMS further categorized in four mutually exclusive groups based on formal and informal ID/AMS responsibilities. Respondents were predominantly female (66%), less than 40 years of age (59%) and white (82%). ID-specific training was completed by 41.8%, and 74% reported having student loan debt at graduation. Work-related activities were diverse and most frequently included: staffing or taking calls on weekends related to ID/AMS, AMS, educating learners or healthcare providers about ID-related topics, precepting learners, and conducting ID-related research and/or quality improvement projects. Respondents frequently indicated they lacked adequate job resources. Conclusions: The results highlight the extensive responsibilities placed on ID/AMS pharmacists to fulfill multiple roles. Pharmacists frequently lack ID-specific training or dedicated time for AMS responsibilities. The workforce is young, suggesting a need for both increased capacity for training programs and strategies for workforce retention.

  • Impact on Daptomycin-Resistance Using Combination of Daptomycin Plus Ceftaroline in Daptomycin-Susceptible and -Resistant <i>Staphylococcus aureus</i>

    FEMS Microbes · 2026-03-05

    articleOpen accessSenior author

    Abstract Persistent Staphylococcus aureus infections treated with prolonged daptomycin (DAP) can select for DAP resistance (DAP-R), reinforcing the need for combination strategies that both improve killing and constrain resistance evolution. Prior work suggests the DAP+ceftaroline (CPT) combination can deliver synergistic killing, prevent emergence of DAP-R, and resensitize DAP-R subpopulations toward a DAP-susceptible (DAP-S) phenotype. Here, using a clinically derived, MSSA isogenic DAP-S (616)/DAP-R (703) strain pair, we evaluated DAP+CPT activity across in vitro assays, ex vivo models, and an in vivo experimental infective endocarditis (IE) model, and integrated ultra-deep targeted sequencing to link phenotypic responses to genomic adaptation. DAP+CPT produced enhanced killing of both strains in vitro and ex vivo, improved target-tissue clearance of the DAP-R strain in vivo, prevented emergence of DAP-R in the DAP-S parental strain in vitro and ex vivo, and resensitized the DAP-R strain toward a DAP-S phenotype ex vivo. Genomically, ultra-deep sequencing of resistance loci (thousands-fold coverage) identified fixed background divergence versus the N315 reference and revealed regimen-dependent selection in membrane-stress pathways, including a high-frequency mixed mprF subpopulation consistent with DAP-driven heterogeneity under monotherapy, contrasted by distinct locus-level changes under combination exposure. In addition, coverage profiling detected a large, combination-associated mobile-element/prophage gene-content event in the 703 background affecting an immune-evasion/β-hemolysin–converting region, highlighting that antibiotic pressure can couple resistance dynamics with pathogenesis-relevant genome remodeling. Together, these data show that DAP+CPT provides potent activity beyond synergistic killing—improving clearance while constraining or reshaping resistance evolution—and they define genomic signatures that help explain divergent evolutionary trajectories under DAP alone versus DAP+CPT.

  • Genetic Correlates of Synergy Mechanisms of Daptomycin Plus Fosfomycin in Daptomycin-Susceptible and -Resistant Methicillin-Resistant Staphylococcus aureus (MRSA)

    Microorganisms · 2025-06-30

    articleOpen access1st author

    This study elucidates potential genetic determinants and mechanisms involved in the synergistic effects of daptomycin (DAP) + fosfomycin (FOF) combination therapy. Among 33 clinically derived DAP-susceptible (S)/DAP-resistant (R) isogenic strain pairs, mutations in the mprF gene occurred in 30/33 DAP-R strains, including polymorphisms of L826F (33%) or T345A/L/I (15%). Strain variants of DAP-S CB1483 serially passaged in vitro for 10 days in DAP +/− FOF identified a key non-synonymous mutation in mprF (L826F) only in the DAP monotherapy arm. Interestingly, passage in FOF alone or DAP + FOF prevented the emergence of this mprF mutation following 10-day passage. This L826F mprF polymorphism, associated with a “gain-in-function” phenotype, exhibited increased amounts of lysyl-phosphatidylglycerol (L-PG) in the cell membrane (CM). Transcriptomics revealed a relatively modest number (~10) of distinct genes that were significantly up- or downregulated (≥2 log fold) in both the DAP-S and DAP-R strain pairs upon DAP + FOF exposures (vs. DAP or FOF alone). Of note, DAP + FOF decreased expression of lrgAB and sdrE and increased the expression level of fosB. In a rabbit infective endocarditis (IE) model, the DAP-R CB185 strain treated with DAP +/− FOF showed significantly reduced lrgB expression in vegetations compared with DAP treatment alone. Overall, these findings indicate that DAP + FOF therapy impacts MRSA through multiple specific mechanisms, enhancing bacterial clearance.

  • Rapid valve sterilization with meropenem plus ceftolozane/tazobactam combination therapy for <i>Pseudomonas aeruginosa</i> prosthetic valve endocarditis

    JAC-Antimicrobial Resistance · 2025-04-29 · 2 citations

    articleOpen access

    Abstract Background Pseudomonas aeruginosa infective endocarditis (IE) presents a significant clinical challenge, leading to high rates of treatment failure and mortality. Even with the use of antipseudomonal β-lactams combined with aminoglycosides or fluoroquinolones, these therapies often fail to provide clinical resolution and are frequently accompanied by severe adverse effects. Methods We report a case of P. aeruginosa prosthetic valve endocarditis successfully treated with a combination of meropenem and ceftolozane/tazobactam. To investigate the synergistic effects of this combination, we conducted checkerboard, time-kill, human whole blood killing, and biofilm assays, as well as a simulated endocardial vegetation (SEV) model. Results Meropenem plus ceftolozane/tazobactam combination therapy successfully bridged the patient to cardiac surgery, achieving rapid microbiological clearance and sterile intraoperative valve cultures. While checkerboard assays showed additivity, time-kill assays with subtherapeutic antibiotic concentrations did not demonstrate synergy in standard media. However, significant synergy was observed in human whole blood and biofilm environments, with modestly improved activity in the SEV model. Conclusions The combination of meropenem and ceftolozane/tazobactam demonstrates promising synergy in physiologically relevant conditions, offering a potentially safer alternative for treating P. aeruginosa IE and stabilizing complex patients prior to cardiac surgery. Further clinical investigation is needed to evaluate its efficacy and safety profile in severe Pseudomonas infections, including IE.

  • Bicarbonate Within: A Hidden Modulator of Antibiotic Susceptibility

    Antibiotics · 2025-01-16 · 2 citations

    reviewOpen access

    Since its standardization, clinical antimicrobial susceptibility testing (AST) has relied upon a standard medium, Mueller-Hinton Broth/Agar (MHB/A), to determine antibiotic resistance. However, this microbiologic medium bears little resemblance to the host milieu, calling into question the physiological relevance of resistance phenotypes it reveals. Recent studies investigating antimicrobial susceptibility in mammalian cell culture media, a more host-mimicking environment, demonstrate that exposure to host factors significantly alters susceptibility profiles. One such factor is bicarbonate, an abundant ion in the mammalian bloodstream/tissues. Importantly, bicarbonate sensitizes methicillin-resistant Staphylococcus aureus (MRSA) to early-generation β-lactams used for the treatment of methicillin-susceptible S. aureus (MSSA). This “NaHCO3-responsive” phenotype is widespread among US MRSA USA300/CC8 bloodstream and skin and soft tissue infection isolates. Translationally, β-lactam therapy has proven effective against NaHCO3-responsive MRSA in both ex vivo simulated endocarditis vegetation (SEV) and in vivo rabbit infective endocarditis (IE) models. Mechanistically, bicarbonate appears to influence mecA expression and PBP2a production/localization, as well as key elements for PBP2a functionality, including the PBP2a chaperone PrsA, components of functional membrane microdomains (FMMs), and wall teichoic acid (WTA) synthesis. The NaHCO3-responsive phenotype highlights the critical role of host factors in shaping antibiotic susceptibility, emphasizing the need to incorporate more physiological conditions into AST protocols.

  • Multi-omic signatures of host response associated with presence, type, and outcome of enterococcal bacteremia

    mSystems · 2025-01-21

    articleOpen accessSenior author

    ABSTRACT Despite the prevalence and severity of enterococcal bacteremia (EcB), the mechanisms underlying systemic host responses to the disease remain unclear. Here, we present an extensive study that profiles molecular differences in plasma from EcB patients using an unbiased multi-omics approach. We performed shotgun proteomics and metabolomics on 105 plasma samples, including those from EcB patients and healthy volunteers. Comparison between healthy volunteer and EcB-infected patient samples revealed significant disparities in proteins and metabolites involved in the acute phase response, inflammatory processes, and cholestasis. Several features distinguish these two groups with remarkable accuracy. Cross-referencing EcB signatures with those of Staphylococcus aureus bacteremia revealed shared reductions in cholesterol metabolism proteins and differing responses in platelet alpha granule and neutrophil-associated proteins. Characterization of Enterococcus isolates derived from patients facilitated a nuanced comparison between EcB caused by Enterococcus faecalis and Enterococcus faecium, uncovering reduced immunoglobulin abundances in E. faecium cases and features capable of distinguishing the underlying microbe. Leveraging extensive patient metadata, we now have identified features associated with mortality or survival, revealing significant multi-omic differences and pinpointing histidine-rich glycoprotein and fetuin-B as features capable of distinguishing survival status with excellent accuracy. Altogether, this study aims to culminate in the creation of objective risk stratification algorithms—a pivotal step toward enhancing patient management and care. To facilitate the exploration of this rich data source, we provide a user-friendly interface at https://gonzalezlab.shinyapps.io/EcB_multiomics/ . IMPORTANCE Enterococcus infections have emerged as the second most common nosocomial infection, with enterococcal bacteremia (EcB) contributing to thousands of patient deaths annually. To address a lack of detailed understanding regarding the specific systemic response to EcB, we conducted a comprehensive multi-omic evaluation of the systemic host response observed in patient plasma. Our findings reveal significant features in the metabolome and proteome associated with the presence of infection, species differences, and survival outcome. We identified features capable of discriminating EcB infection from healthy states and survival from mortality with excellent accuracy, suggesting potential practical clinical utility. However, our study also established that systemic features to distinguish Enterococcus faecalis from Enterococcus faecium EcB show only a moderate degree of discriminatory accuracy, unlikely to significantly improve upon current diagnostic methods. Comparisons of differences in the plasma proteome relative to healthy samples between bacteremia caused by Enterococcus and Staphylococcus aureus suggest the presence of bacteria-specific responses alongside conserved inflammatory reactions.

  • Telehealth: The Way for Efficient, Comprehensive, and Equitable Antimicrobial Stewardship in the US Healthcare System

    Open Forum Infectious Diseases · 2025-11-25 · 1 citations

    articleOpen accessSenior author

    Rural and critical access hospitals serve 15% of the United States population and utilize antibiotics at similar rates and spectrum as larger urban hospitals, making them a priority for antimicrobial stewardship. However, barriers such as insufficient personnel, limited electronic health record capabilities, and financial constraints limit stewardship initiatives. Telestewardship partnerships with urban hospitals offer a promising solution; however, a structured process to develop and implement such programs is not established. This perspective focuses on unmet needs in rural hospitals to provide future direction for improved patient care in these settings. In 2024, UW Health engaged leaders of small and rural hospitals to design a telestewardship program that meets regulatory requirements (ie, Joint Commission Standards). Despite these requested services, financial barriers hindered implementation of telestewardship partnerships. This work underscores the opportunities and challenges faced by rural hospitals and the ongoing need for state and national funding to support these communities.

  • Monthly dalbavancin dosing for suppressive therapy: a pharmacokinetic estimation analysis and case series

    Antimicrobial Agents and Chemotherapy · 2025-12-19 · 1 citations

    articleOpen access

    ABSTRACT Retained hardware/prosthetic infections frequently require antimicrobial suppression therapy. Treatment options are often limited by resistance, allergies, and dosing frequencies. Dalbavancin (DAL) is a potentially attractive option for suppression of gram-positive infections given its potential for infrequent dosing. However, optimal DAL suppression dosing is unknown. An in silico pharmacokinetic/pharmacodynamic simulation was performed to assess the predicted dalbavancin concentration resulting from suppressive regimens. Serum levels were deemed adequate if the f AUC 24 /MIC was above the PK target of 27.1. Patients at a U.S. medical center receiving DAL as suppressive therapy were reviewed. PK simulation of DAL dosed 1,500 mg monthly resulted in free serum concentrations above the PK target. Because many clinicians opt to initiate these regimens with two doses given 1 week apart, the next modeled regimen included this load, before initiating 1,500 mg monthly. This initial load did not significantly alter total drug exposure. The final simulated regimen was 1,000 mg monthly. With this simulation, the lower 95% CI f AUC 24 /MIC fell just below the PK target for an isolate at the breakpoint. Nine patients who received dalbavancin 1,500 mg monthly as suppressive therapy were reviewed. All had retained hardware and received DAL for a median 591 days, with 7 patients still receiving treatment and no reported suppressive therapy failure. Monthly 1500 mg dalbavancin dosing for suppressive therapy is supported by this case series and PK simulation data. An initial weekly loading dose appears unnecessary. Reducing the monthly dose to 1000 mg may also be appropriate for certain patients, though clinical data is needed to support this practice.

Recent grants

Frequent coauthors

  • Michael J. Rybak

    Wayne State University

    114 shared
  • George Sakoulas

    University of California, San Diego

    69 shared
  • Glenn W. Kaatz

    Wayne State University

    47 shared
  • Arnold S. Bayer

    UCLA Medical Center

    28 shared
  • Victor Nizet

    University of California, San Diego

    23 shared
  • Lucas Schulz

    University of Wisconsin Health

    23 shared
  • Ryan Tewhey

    Jackson Laboratory

    22 shared
  • Andrew D. Berti

    Wayne State University

    22 shared

Education

  • Ph.D., Pharmacy

    University of Wisconsin–Madison

    1990
  • M.S., Pharmacy

    University of Wisconsin–Madison

    1986
  • B.S., Pharmacy

    University of Wisconsin–Madison

    1984
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