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Joshua Thomas Thaden

Associate Professor of Medicine
Medicine, Infectious Diseases
DUMC Box 102359, Durham, NC 27710
Rm 201 Alexander H. Sands Buil, 303 Research Drive, Durham, NC 27710

Selected Publications


Combination Therapy Is Not Associated with Decreased Mortality in Infectious Endocarditis: A Systematic Review and Meta-Analysis.

Journal Article Microorganisms · November 2, 2024 Untreated infective endocarditis (IE) is uniformly fatal. The practice of combination antibiotic therapy for IE is recommended by treatment guidelines but largely unsupported by high-quality evidence. This study aimed to assess the efficacy of combination ... Full text Link to item Cite

A microbiological and genomic perspective of globally collected Escherichia coli from adults hospitalized with invasive E. coli disease.

Journal Article J Antimicrob Chemother · September 3, 2024 OBJECTIVES: Escherichia coli can cause infections in the urinary tract and in normally sterile body sites leading to invasive E. coli disease (IED), including bacteraemia and sepsis, with older populations at increased risk. We aimed to estimate the theore ... Full text Link to item Cite

Persistent Gram-negative Bloodstream Infection Increases the Risk of Recurrent Bloodstream Infection With the Same Species.

Journal Article Clin Infect Dis · June 14, 2024 The association between persistent gram-negative bloodstream infection (GN-BSI), or ongoing positive cultures, and recurrent GN-BSI has not been investigated. Among 992 adults, persistent GN-BSI was associated with increased recurrent GN-BSI with the same ... Full text Link to item Cite

Clinical presentation and antimicrobial resistance of invasive Escherichia coli disease in hospitalized older adults: a prospective multinational observational study.

Journal Article Infection · June 2024 BACKGROUND: Clinical data characterizing invasive Escherichia coli disease (IED) are limited. We assessed the clinical presentation of IED and antimicrobial resistance (AMR) patterns of causative E. coli isolates in older adults. METHODS: EXPECT-2 (NCT0411 ... Full text Link to item Cite

Use of Transcriptional Signatures to Differentiate Pathogen-Specific and Treatment-Specific Host Responses in Patients With Bacterial Bloodstream Infections.

Journal Article J Infect Dis · May 15, 2024 BACKGROUND: Clinical outcomes in bacterial bloodstream infections (BSIs) are influenced by bacterial species, host immunity, and antibiotic therapy. The mechanisms by which such factors influence outcomes are poorly understood. We aimed to identify bacteri ... Full text Link to item Cite

Female Sex and Mortality in Patients with Staphylococcus aureus Bacteremia: A Systematic Review and Meta-analysis.

Journal Article JAMA Netw Open · February 5, 2024 IMPORTANCE: Staphylococcus aureus is the leading cause of death due to bacterial bloodstream infection. Female sex has been identified as a risk factor for mortality in S aureus bacteremia (SAB) in some studies, but not in others. OBJECTIVE: To determine w ... Full text Link to item Cite

In-patient evolution of a high-persister Escherichia coli strain with reduced in vivo antibiotic susceptibility.

Journal Article Proc Natl Acad Sci U S A · January 16, 2024 Gram-negative bacterial bloodstream infections (GNB-BSI) are common and frequently lethal. Despite appropriate antibiotic treatment, relapse of GNB-BSI with the same bacterial strain is common and associated with poor clinical outcomes and high healthcare ... Full text Link to item Cite

Serum susceptibility of Escherichia coli and its association with patient clinical outcomes.

Journal Article PLoS One · 2024 The innate immune system eliminates bloodstream pathogens such as Escherichia coli in part through complement protein deposition and subsequent bacterial death (i.e., "serum killing"). Some E. coli strains have developed mechanisms to resist serum killing, ... Full text Link to item Cite

Preclinical safety and efficacy characterization of an LpxC inhibitor against Gram-negative pathogens.

Journal Article Sci Transl Med · August 9, 2023 The UDP-3-O-(R-3-hydroxyacyl)-N-acetylglucosamine deacetylase LpxC is an essential enzyme in the biosynthesis of lipid A, the outer membrane anchor of lipopolysaccharide and lipooligosaccharide in Gram-negative bacteria. The development of LpxC-targeting a ... Full text Link to item Cite

Escherichia coli ST131 Associated with Increased Mortality in Bloodstream Infections from Urinary Tract Source.

Journal Article J Clin Microbiol · July 20, 2023 Escherichia coli sequence type 131 (ST131) is a globally dominant multidrug-resistant clone, although its clinical impact on patients with bloodstream infection (BSI) is incompletely understood. This study aims to further define the risk factors, clinical ... Full text Link to item Cite

Clinical and Molecular Analyses of Recurrent Gram-Negative Bloodstream Infections.

Journal Article Clin Infect Dis · February 8, 2023 BACKGROUND: The causes and clinical characteristics of recurrent gram-negative bacterial bloodstream infections (GNB-BSI) are poorly understood. METHODS: We used a cohort of patients with GNB-BSI to identify clinical characteristics, microbiology, and risk ... Full text Link to item Cite

Gram-negative bacteremia in solid organ transplant recipients: Clinical characteristics and outcomes as compared to immunocompetent non-transplant recipients.

Journal Article Transpl Infect Dis · December 2022 BACKGROUND: Outcomes from Gram-negative bacteremia (GNB) in solid organ transplant (SOT) recipients are poorly understood. METHODS: This is a single center prospective cohort study comparing the clinical characteristics and outcomes of SOT recipients with ... Full text Link to item Cite

Association of Follow-up Blood Cultures With Mortality in Patients With Gram-Negative Bloodstream Infections: A Systematic Review and Meta-analysis.

Journal Article JAMA Netw Open · September 1, 2022 IMPORTANCE: Obtaining follow-up blood cultures (FUBCs) in patients with Staphylococcus aureus bloodstream infection (BSI) is standard practice, although its utility in patients with gram-negative bacterial BSI (GN-BSI) is unclear. OBJECTIVE: To examine whe ... Full text Link to item Cite

Staphylococcus aureus Bacteremia Among Patients Receiving Maintenance Hemodialysis: Trends in Clinical Characteristics and Outcomes.

Journal Article Am J Kidney Dis · March 2022 RATIONALE & OBJECTIVE: Staphylococcus aureus (Saureus) bacteremia (SAB) is associated with morbidity and mortality in patients receiving maintenance hemodialysis (HD). We evaluated changes in clinical and bacterial characteristics, and their associations w ... Full text Open Access Link to item Cite

Survey of infectious diseases providers reveals variability in duration of antibiotic therapy for the treatment of Gram-negative bloodstream infections.

Journal Article JAC Antimicrob Resist · March 2022 BACKGROUND: Trials supporting shorter durations of antibiotic therapy for Gram-negative bloodstream infections (GN-BSI) have recently been published. However, adoption of these findings into practice is unclear given limited eligibility criteria and relati ... Full text Link to item Cite

Distribution of serotypes and antibiotic resistance of invasive Pseudomonas aeruginosa in a multi-country collection.

Journal Article BMC Microbiol · January 6, 2022 BACKGROUND: Pseudomonas aeruginosa is an opportunistic pathogen that causes a wide range of acute and chronic infections and is frequently associated with healthcare-associated infections. Because of its ability to rapidly acquire resistance to antibiotics ... Full text Link to item Cite

Variability in oral antibiotic step-down therapy in the management of Gram-negative bloodstream infections.

Journal Article Int J Antimicrob Agents · December 2021 There are important gaps in the literature regarding the role and timing of oral therapy for Gram-negative bloodstream infections (GN-BSIs). To better understand contemporary management practices involving oral step-down in GN-BSI, we conducted an internat ... Full text Link to item Cite

Bacteremia in solid organ transplant recipients as compared to immunocompetent patients: Acute phase cytokines and outcomes in a prospective, matched cohort study.

Journal Article Am J Transplant · June 2021 We undertook a prospective, matched cohort study of patients with Staphylococcus aureus bacteremia (SAB) and gram-negative bacteremia (GNB) to compare the characteristics, outcomes, and chemokine and cytokine response in transplant recipients to immunocomp ... Full text Open Access Link to item Cite

Human DNA methylation signatures differentiate persistent from resolving MRSA bacteremia.

Journal Article Proc Natl Acad Sci U S A · March 9, 2021 Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is life threatening and occurs in up to 30% of MRSA bacteremia cases despite appropriate antimicrobial therapy. Isolates of MRSA that cause antibiotic-persistent methicillin-resistant ... Full text Link to item Cite

Low-Avidity Autoantibodies against Bactericidal/Permeability-Increasing Protein Occur in Gram-Negative and Gram-Positive Bacteremia.

Journal Article Infect Immun · September 18, 2020 Antibody autoreactivity against bactericidal/permeability-increasing protein (BPI) is strongly associated with Pseudomonas aeruginosa infection in cystic fibrosis (CF), non-CF bronchiectasis (BE), and chronic obstructive pulmonary disease (COPD). We examin ... Full text Link to item Cite

Newly Named Klebsiella aerogenes (formerly Enterobacter aerogenes) Is Associated with Poor Clinical Outcomes Relative to Other Enterobacter Species in Patients with Bloodstream Infection.

Journal Article J Clin Microbiol · August 24, 2020 Enterobacter aerogenes was recently renamed Klebsiella aerogenes This study aimed to identify differences in clinical characteristics, outcomes, and bacterial genetics among patients with K. aerogenes versus Enterobacter species bloodstream infections (BSI ... Full text Link to item Cite

Temporal encoding of bacterial identity and traits in growth dynamics.

Journal Article Proc Natl Acad Sci U S A · August 18, 2020 In biology, it is often critical to determine the identity of an organism and phenotypic traits of interest. Whole-genome sequencing can be useful for this but has limited power for trait prediction. However, we can take advantage of the inherent informati ... Full text Link to item Cite

Positive follow-up blood cultures identify high mortality risk among patients with Gram-negative bacteraemia.

Journal Article Clin Microbiol Infect · July 2020 OBJECTIVES: The role of follow-up blood cultures (FUBCs) in the management of Gram-negative bacteraemia (GNB) is poorly understood. We aimed to determine the utility of FUBCs in identifying patients with increased mortality risk. METHODS: An observational ... Full text Open Access Link to item Cite

Case Report: Successful Rescue Therapy of Extensively Drug-Resistant Acinetobacter baumannii Osteomyelitis With Cefiderocol.

Journal Article Open Forum Infect Dis · May 2020 Cefiderocol is a novel catechol siderophore cephalosporin antibiotic developed to treat resistant gram-negative infections. We describe its successful use as rescue therapy, combined with surgical debridement, to treat a patient with osteomyelitis due to e ... Full text Link to item Cite

Environmental and genetic determinants of plasmid mobility in pathogenic Escherichia coli.

Journal Article Sci Adv · January 2020 Plasmids are key vehicles of horizontal gene transfer (HGT), mobilizing antibiotic resistance, virulence, and other traits among bacterial populations. The environmental and genetic forces that drive plasmid transfer are poorly understood, however, due to ... Full text Link to item Cite

The Diversity of Lipopolysaccharide (O) and Capsular Polysaccharide (K) Antigens of Invasive Klebsiella pneumoniae in a Multi-Country Collection.

Journal Article Front Microbiol · 2020 Klebsiella pneumoniae is a common cause of sepsis and is particularly associated with healthcare-associated infections. New strategies are needed to prevent or treat infections due to the emergence of multi-drug resistant K. pneumoniae. The goal of this st ... Full text Link to item Cite

Changing Characteristics of Staphylococcus aureus Bacteremia: Results From a 21-Year, Prospective, Longitudinal Study.

Journal Article Clin Infect Dis · November 13, 2019 BACKGROUND: We conducted a longitudinal study to evaluate changes in the clinical presentation and epidemiology of Staphylococcus aureus bacteremia (SAB) in an academic, US medical center. METHODS: Consecutive patients with monomicrobial SAB were enrolled ... Full text Link to item Cite

Genetic variation of DNA methyltransferase-3A contributes to protection against persistent MRSA bacteremia in patients.

Journal Article Proc Natl Acad Sci U S A · October 1, 2019 The role of the host in development of persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is not well understood. A cohort of prospectively enrolled patients with persistent methicillin-resistant S. aureus bacteremia (PB) and resolvin ... Full text Link to item Cite

Identifying determinants of persistent MRSA bacteremia using mathematical modeling.

Journal Article PLoS Comput Biol · July 2019 Persistent bacteremia caused by Staphylococcus aureus (SA), especially methicillin-resistant SA (MRSA), is a significant cause of morbidity and mortality. Despite susceptibility phenotypes in vitro, persistent MRSA strains fail to clear with appropriate an ... Full text Link to item Cite

Epidemiology and Mechanisms of Resistance of Extensively Drug Resistant Gram-Negative Bacteria.

Journal Article Antibiotics (Basel) · April 6, 2019 Antibiotic resistance has increased markedly in gram-negative bacteria over the last two decades, and in many cases has been associated with increased mortality and healthcare costs. The adoption of genotyping and next generation whole genome sequencing of ... Full text Link to item Cite

Protective immunity in recurrent Staphylococcus aureus infection reflects localized immune signatures and macrophage-conferred memory.

Journal Article Proc Natl Acad Sci U S A · November 20, 2018 Staphylococcus aureus is the leading cause of skin and skin structure infection (SSSI), a primary portal of entry for invasive infection. Our prior studies discovered a role for protective innate memory against recurrent methicillin-resistant S. aureus (MR ... Full text Link to item Cite

Pediatric Antibacterial and Antifungal Trials From 2007 to 2017.

Journal Article Pediatrics · September 2018 BACKGROUND AND OBJECTIVES: The impact of the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA) on pediatric antibacterial or antifungal drug trials is unknown. Our objective was to identify and characterize trials co ... Full text Open Access Link to item Cite

Salmonella Activation of STAT3 Signaling by SarA Effector Promotes Intracellular Replication and Production of IL-10.

Journal Article Cell Rep · June 19, 2018 Salmonella enterica is an important foodborne pathogen that uses secreted effector proteins to manipulate host pathways to facilitate survival and dissemination. Different S. enterica serovars cause disease syndromes ranging from gastroenteritis to typhoid ... Full text Link to item Cite

Seroconversion on preexposure prophylaxis: a case report with segmental hair analysis for timed adherence determination.

Journal Article AIDS · June 1, 2018 OBJECTIVE: We describe the third case report of seroconversion with multidrug resistant (MDR)-HIV despite pre-exposure prophylaxis (PrEP) with emtricitabine (FTC) and tenofovir (TFV) disoproxil (TDF). DESIGN: Case report. METHODS: PrEP adherence was assess ... Full text Link to item Cite

Results from a 13-Year Prospective Cohort Study Show Increased Mortality Associated with Bloodstream Infections Caused by Pseudomonas aeruginosa Compared to Other Bacteria.

Journal Article Antimicrob Agents Chemother · June 2017 The impact of bacterial species on outcome in bloodstream infections (BSI) is incompletely understood. We evaluated the impact of bacterial species on BSI mortality, with adjustment for patient, bacterial, and treatment factors. From 2002 to 2015, all adul ... Full text Link to item Cite

Role of newer and re-emerging older agents in the treatment of infections caused by carbapenem-resistant Enterobacteriaceae.

Journal Article Virulence · May 19, 2017 Antimicrobial resistance has been identified by the World Health Organization as "one of the three greatest threats to human health." Gram negative bacteria in particular drive this alarming trend. Carbapenem-resistant Enterobacteriaceae (CRE) such as Esch ... Full text Link to item Cite

Gram-Positive Bacterial Infections: Research Priorities, Accomplishments, and Future Directions of the Antibacterial Resistance Leadership Group.

Journal Article Clin Infect Dis · March 15, 2017 Antimicrobial resistance in gram-positive bacteria remains a challenge in infectious diseases. The mission of the Gram-Positive Committee of the Antibacterial Resistance Leadership Group (ARLG) is to advance knowledge in the prevention, management, and tre ... Full text Link to item Cite

Gram-Negative Bacterial Infections: Research Priorities, Accomplishments, and Future Directions of the Antibacterial Resistance Leadership Group.

Journal Article Clin Infect Dis · March 15, 2017 Antimicrobial resistance in pathogenic gram-negative bacteria is one of the most pressing challenges in the field of infectious diseases and is one of 4 key areas of unmet medical need identified by the Antibacterial Resistance Leadership Group (ARLG). The ... Full text Link to item Cite

Increased Costs Associated with Bloodstream Infections Caused by Multidrug-Resistant Gram-Negative Bacteria Are Due Primarily to Patients with Hospital-Acquired Infections.

Journal Article Antimicrob Agents Chemother · March 2017 The clinical and economic impacts of bloodstream infections (BSI) due to multidrug-resistant (MDR) Gram-negative bacteria are incompletely understood. From 2009 to 2015, all adult inpatients with Gram-negative BSI at our institution were prospectively enro ... Full text Open Access Link to item Cite

Evaluating genetic susceptibility to Staphylococcus aureus bacteremia in African Americans using admixture mapping.

Journal Article Genes Immun · March 2017 The incidence of Staphylococcus aureus bacteremia (SAB) is significantly higher in African American (AA) than in European-descended populations. We used admixture mapping (AM) to test the hypothesis that genomic variations with different frequencies in Eur ... Full text Link to item Cite

The Risk of Cardiac Device-Related Infection in Bacteremic Patients Is Species Specific: Results of a 12-Year Prospective Cohort.

Journal Article Open Forum Infect Dis · 2017 BACKGROUND: The species-specific risk of cardiac device-related infection (CDRI) among bacteremic patients is incompletely understood. METHODS: We conducted a prospective cohort study of hospitalized patients from October 2002 to December 2014 with a cardi ... Full text Open Access Link to item Cite

Increased in vitro phenol-soluble modulin production is associated with soft tissue infection source in clinical isolates of methicillin-susceptible Staphylococcus aureus.

Journal Article J Infect · March 2016 BACKGROUND: Phenol-soluble modulins (PSM) are amphipathic proteins produced by Staphylococcus aureus that promote virulence, inflammatory response, and biofilm formation. We previously showed that MRSA isolates from soft tissue infection (SSTI) produced si ... Full text Link to item Cite

Pseudomonas aeruginosa Bacteremic Patients Exhibit Nonprotective Antibody Titers Against Therapeutic Antibody Targets PcrV and Psl Exopolysaccharide.

Journal Article J Infect Dis · February 15, 2016 BACKGROUND: The type 3 secretion protein PcrV and Psl exopolysaccharide are promising therapeutic antibody targets against Pseudomonas aeruginosa. We examined P. aeruginosa bloodstream infection (BSI) isolates for the ability to express PcrV and Psl and ev ... Full text Link to item Cite

Increasing Incidence of Extended-Spectrum β-Lactamase-Producing Escherichia coli in Community Hospitals throughout the Southeastern United States.

Journal Article Infect Control Hosp Epidemiol · January 2016 OBJECTIVE To describe the epidemiology of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (ESBL-EC) and Klebsiella pneumoniae (ESBL-KP) infections DESIGN Retrospective cohort SETTING Inpatient care at community hospitals PATIENTS All patien ... Full text Link to item Cite

Respiratory Tract Infection Clinical Trials from 2007 to 2012. A Systematic Review of ClinicalTrials.gov.

Journal Article Ann Am Thorac Soc · December 2015 RATIONALE: Respiratory tract infections are highly prevalent and variable, and confer considerable morbidity and mortality. There is a growing need for new treatments for such infections, particularly in the setting of worsening antibacterial resistance. O ... Full text Link to item Cite

Survival Benefit of Empirical Therapy for Staphylococcus aureus Bloodstream Infections in Infants.

Journal Article Pediatr Infect Dis J · November 2015 BACKGROUND: The impact of early adequate empirical antibiotic therapy on outcomes of infants in the neonatal intensive care unit (NICU) who develop Staphylococcus aureus bloodstream infections (BSI) is unknown. METHODS: Infants with S. aureus BSI discharge ... Full text Link to item Cite

Clinical MRSA isolates from skin and soft tissue infections show increased in vitro production of phenol soluble modulins.

Journal Article J Infect · October 2015 BACKGROUND: Phenol-soluble modulins (PSMs) are amphipathic, pro-inflammatory proteins secreted by most Staphylococcus aureus isolates. This study tested the hypothesis that in vitro PSM production levels are associated with specific clinical phenotypes. ME ... Full text Link to item Cite

Neonatal Escherichia coli Bloodstream Infections: Clinical Outcomes and Impact of Initial Antibiotic Therapy.

Journal Article Pediatr Infect Dis J · September 2015 BACKGROUND: Escherichia coli is a common cause of bloodstream infections (BSIs) in infants and is associated with high mortality and morbidity among survivors. The clinical significance of antibiotic resistance and timing of appropriate antimicrobial thera ... Full text Link to item Cite

No survival benefit with empirical vancomycin therapy for coagulase-negative staphylococcal bloodstream infections in infants.

Journal Article Pediatr Infect Dis J · April 2015 BACKGROUND: Coagulase-negative Staphylococcus (CoNS) is the most common cause of bloodstream infections (BSI) in hospitalized infants. CoNS BSI is most reliably treated with vancomycin; however, concerns about side effects and promoting resistance often de ... Full text Link to item Cite

Characterization of alpha-toxin hla gene variants, alpha-toxin expression levels, and levels of antibody to alpha-toxin in hemodialysis and postsurgical patients with Staphylococcus aureus bacteremia.

Journal Article J Clin Microbiol · January 2015 Alpha-toxin is a major Staphylococcus aureus virulence factor. This study evaluated potential relationships between in vitro alpha-toxin expression of S. aureus bloodstream isolates, anti-alpha-toxin antibody in serum of patients with S. aureus bacteremia ... Full text Link to item Cite

Polymorphisms in Fibronectin Binding Proteins A and B among Staphylococcus aureus Bloodstream Isolates Are Not Associated with Arthroplasty Infection.

Journal Article PLoS One · 2015 BACKGROUND: Nonsynonymous single nucleotide polymorphisms (SNPs) in fibronectin binding protein A (fnbA) of Staphylococcus aureus are associated with cardiac device infections. However, the role of fnbA SNPs in S. aureus arthroplasty infection is unknown. ... Full text Open Access Link to item Cite

Rising rates of carbapenem-resistant enterobacteriaceae in community hospitals: a mixed-methods review of epidemiology and microbiology practices in a network of community hospitals in the southeastern United States.

Journal Article Infect Control Hosp Epidemiol · August 2014 OBJECTIVE: Describe the epidemiology of carbapenem-resistant Enterobacteriaceae (CRE) and examine the effect of lower carbapenem breakpoints on CRE detection. DESIGN: Retrospective cohort. SETTING: Inpatient care at community hospitals. PATIENTS: All patie ... Full text Link to item Cite

Dusp3 and Psme3 are associated with murine susceptibility to Staphylococcus aureus infection and human sepsis.

Journal Article PLoS Pathog · June 2014 Using A/J mice, which are susceptible to Staphylococcus aureus, we sought to identify genetic determinants of susceptibility to S. aureus, and evaluate their function with regard to S. aureus infection. One QTL region on chromosome 11 containing 422 genes ... Full text Open Access Link to item Cite

Virulence of endemic nonpigmented northern Australian Staphylococcus aureus clone (clonal complex 75, S. argenteus) is not augmented by staphyloxanthin.

Journal Article J Infect Dis · August 1, 2013 Staphylococcus aureus clonal complex 75 (herein referred to as S. argenteus) lacks the carotenoid pigment operon, crtOPQMN, responsible for production of the putative virulence factor, staphyloxanthin. Although a common cause of community-onset skin infect ... Full text Link to item Cite

Quorum-sensing regulation of a copper toxicity system in Pseudomonas aeruginosa.

Journal Article J Bacteriol · May 2010 The LasR/LasI quorum-sensing system in Pseudomonas aeruginosa influences global gene expression and mediates pathogenesis. In this study, we show that the quorum-sensing system activates, via the transcriptional regulator PA4778, a copper resistance system ... Full text Link to item Cite

Large-scale mapping and validation of Escherichia coli transcriptional regulation from a compendium of expression profiles.

Journal Article PLoS Biol · January 2007 Machine learning approaches offer the potential to systematically identify transcriptional regulatory interactions from a compendium of microarray expression profiles. However, experimental validation of the performance of these methods at the genome scale ... Full text Link to item Cite