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Search: authors:"Arnold S. Bayer"

27 papers found.
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Evolving Resistance Among Gram-positive Pathogens

Antimicrobial therapy is a key component of modern medical practice and a cornerstone for the development of complex clinical interventions in critically ill patients. Unfortunately, the increasing problem of antimicrobial resistance is now recognized as a major public health threat jeopardizing the care of thousands of patients worldwide. Gram-positive pathogens exhibit an immense ...

MgrA Activates Expression of Capsule Genes, but Not the α-Toxin Gene in Experimental Staphylococcus aureus Endocarditis

Background. Staphylococcus aureus produces numerous virulence factors but little is known about their in vivo regulation during an infection. Methods. The production of capsule and α-toxin, and the expression of their respective genes, cap5 and hla, were analyzed by comparing CYL11481 (derivative of Newman) and its isogenic regulatory mutants in vitro. The temporal expression of ...

Phenotypic and Genotypic Characterization of Daptomycin-Resistant Methicillin-Resistant Staphylococcus aureus Strains: Relative Roles of mprF and dlt Operons

Development of in vivo daptomycin resistance (DAP-R) among Staphylococcus aureus clinical isolates, in association with clinical treatment failures, has become a major therapeutic problem. This issue is especially relevant to methicillin-resistant S. aureus (MRSA) strains in the context of invasive endovascular infections. In the current study, we used three well-characterized and ...

Failure of High-Dose Daptomycin for Bacteremia Caused by Daptomycin-Susceptible Enterococcus faecium Harboring LiaSR Substitutions

High-dose daptomycin (DAP) therapy failed in a neutropenic patient with bloodstream infection caused by a DAP-susceptible Enterococcus faecium (minimum inhibitory concentration, 3 µg/mL) harboring genetic changes associated with DAP resistance, with persistent bacteremia and selection of additional resistances. Daptomycin monotherapy should be used cautiously against ...

Increased Cell Wall Teichoic Acid Production and D-alanylation Are Common Phenotypes among Daptomycin-Resistant Methicillin-Resistant Staphylococcus aureus (MRSA) Clinical Isolates

Multiple mechanisms have been correlated with daptomycin-resistance (DAP-R) in Staphylococcus aureus. However, one common phenotype observed in many DAP-R S. Aureus strains is a thickened cell wall (CW). The first evidence for an impact of CW-linked glycopolymers on this phenotype was recently demonstrated in a single, well-characterized DAP-R methicillin-susceptible S. aureus ...

Staphylococcus aureus Bacteremia at 5 US Academic Medical Centers, 2008–2011: Significant Geographic Variation in Community-Onset Infections

Background. The incidence of community-onset (CO) methicillin-resistant Staphylococcus aureus (MRSA) bacteremia rose from the late 1990s through the 2000s. However, hospital-onset (HO) MRSA rates have recently declined in the United States and Europe. Methods. Data were abstracted from infection prevention databases between 1 January 2008 and 31 December 2011 at 5 US academic ...

Daptomycin Resistance in Enterococci Is Associated with Distinct Alterations of Cell Membrane Phospholipid Content

Background The lipopeptide antibiotic, daptomycin (DAP) interacts with the bacterial cell membrane (CM). Development of DAP resistance during therapy in a clinical strain of Enterococcus faecalis was associated with mutations in genes encoding enzymes involved in cell envelope homeostasis and phospholipid metabolism. Here we characterized changes in CM phospholipid profiles ...

Emergence of Daptomycin Resistance in Daptomycin-Naïve Rabbits with Methicillin-Resistant Staphylococcus aureus Prosthetic Joint Infection Is Associated with Resistance to Host Defense Cationic Peptides and mprF Polymorphisms

Background Previous studies of both clinically-derived and in vitro passage-derived daptomycin–resistant (DAP-R) Staphylococcus aureus strains demonstrated the coincident emergence of increased DAP MICs and resistance to host defense cationic peptides (HDP-R). Methods In the present investigation, we studied a parental DAP-susceptible (DAP-S) methicillin-resistant Staphylococcus ...

Divergent Responses of Different Endothelial Cell Types to Infection with Candida albicans and Staphylococcus aureus

Endothelial cells are important in the pathogenesis of bloodstream infections caused by Candida albicans and Staphylococcus aureus. Numerous investigations have used human umbilical vein endothelial cells (HUVECs) to study microbial-endothelial cell interactions in vitro. However, the use of HUVECs requires a constant supply of umbilical cords, and there are significant ...

Use of Antistaphylococcal β-Lactams to Increase Daptomycin Activity in Eradicating Persistent Bacteremia Due to Methicillin-Resistant Staphylococcus aureus: Role of Enhanced Daptomycin Binding

We used daptomycin plus antistaphylococcal β-lactams (ASBL) to clear refractory MRSA bacteremia. In vitro studies showed enhanced daptomycin bactericidal activity, increased membrane daptomycin binding, and decrease in positive surface charge induced by ASBLs against daptomycin nonsusceptible MRSA. Addition of ASBLs to daptomycin may be of benefit in refractory MRSA bacteremia. ...

Bacteriophage Lysin Mediates the Binding of Streptococcus mitis to Human Platelets through Interaction with Fibrinogen

The binding of bacteria to human platelets is a likely central mechanism in the pathogenesis of infective endocarditis. We have previously found that platelet binding by Streptococcus mitis SF100 is mediated by surface components encoded by a lysogenic bacteriophage, SM1. We now demonstrate that SM1-encoded lysin contributes to platelet binding via its direct interaction with ...

Virulence of Endemic Nonpigmented Northern Australian Staphylococcus aureus Clone (Clonal Complex 75, S. argenteus) Is Not Augmented by Staphyloxanthin

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 infections among Indigenous populations in northern Australia, this clone is infrequently isolated from hospital-based patients with ...

Role of mgrA and sarA in Methicillin-Resistant Staphylococcus aureus Autolysis and Resistance to Cell Wall-Active Antibiotics

Background. We have previously shown the importance of mgrA and sarA in controlling autolysis of Staphylococcus aureus, with MgrA and SarA both being negative regulators of murein hydrolases.Methods. In this study, we analyzed the effects of mgrA and sarA on antibiotic-mediated lysis in vitro and on the responses to cell wall-active antibiotic therapy in an experimental ...

Phenotypic and Genotypic Characteristics of Persistent Methicillin-Resistant Staphylococcus aureus Bacteremia In Vitro and in an Experimental Endocarditis Model

Background. Persistent MRSA bacteremia (PB) represents an important subset of Staphylococcus aureus infections and correlates with poor clinical outcomes. Methods. We profiled relevant in vitro phenotypic and genotypic characteristics of MRSA isolates from 39 persons with bacteremia (21 had PB and 18 had resolving bacteremia [RB]). We also compared the intrinsic virulence and ...

The Bacterial Defensin Resistance Protein MprF Consists of Separable Domains for Lipid Lysinylation and Antimicrobial Peptide Repulsion

Many bacterial pathogens achieve resistance to defensin-like cationic antimicrobial peptides (CAMPs) by the multiple peptide resistance factor (MprF) protein. MprF plays a crucial role in Staphylococcus aureus virulence and it is involved in resistance to the CAMP-like antibiotic daptomycin. MprF is a large membrane protein that modifies the anionic phospholipid ...

Regulation of Staphylococcus aureus α-Toxin Gene (hla) Expression by agr, sarA and sae In Vitro and in Experimental Infective Endocarditis

BackgroundThe Staphylococcus aureus global regulators—agr, sarA and sae—coordinately control α-toxin gene (hla) expression in vitro. However, their relative in vivo contributions to hla expression, particularly in endovascular infections, have not been defined MethodsA plasmid-based hla-promoter:green fluorescent protein reporter system was constructed in 2 genetically related S. ...

Combination Antibiotic Therapy for Infective Endocarditis

Despite the availability of new and potent antibiotics, modern echocardiography, and advanced surgical techniques, infective endocarditis (IE) is still associated with high morbidity and mortality rates. Use of synergistic antibiotic combinations is an appealing way to optimize therapy for IE. This review focuses on evidence-based recommendations for combination antimicrobial ...

Inhibition of Intracellular Macromolecular Synthesis in Staphylococcus aureus by Thrombin-Induced Platelet Microbicidal Proteins

Thrombin-induced platelet microbicidal proteins (tPMP-1 and tPMP-2) are believed to initiate their staphylocidal effects via cytoplasmic membrane perturbation. The aim of the present study was to investigate the role of subsequent inhibition of macromolecular synthesis in the staphylocidal mechanisms of tPMP-1 and tPMP-2 in an isogenic tPMP-susceptible and -resistant strain pair ...