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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 ...

Editorial Commentary: Surgical Therapy for Staphylococcus aureus Prosthetic Valve Endocarditis: Proceed With Caution (Caveat Emptor)

Adolf W. Karchmer 1 Arnold S. Bayer () 0 0 Harbor-UCLA Medical Center, David Geffen School of Medicine, University of California , Los Angeles 1 Beth Israel Deaconess Medical Center, Harvard Medical

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 ...

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 ...

Reduced Susceptibility to Host-Defense Cationic Peptides and Daptomycin Coemerge in Methicillin-Resistant Staphylococcus aureus From Daptomycin-Naive Bacteremic Patients

Background. We hypothesized that, for methicillin-resistant Staphylococcus aureus (MRSA), in vitro daptomycin susceptibility could be influenced by exposures to endogenous host defense peptides (HDPs) prior to clinical exposure to daptomycin. Methods. Two endovascular HDPs were used: thrombin-induced platelet microbicidal protein (tPMP) and human neutrophil defensin-1 (hNP-1) from ...

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 ...

Initial Low-Dose Aminoglycosides in Staphylococcus aureus Bacteremia: Good Science, Urban Legend, or Just Plain Toxic?

Arnold S. Bayer () 1 Barbara E. Murray 0 0 Division of Infectious Diseases and Center for the Study of Emerging and Re-emerging Pathogens, University of Texas Medical School at Houston 1 Department

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. ...

Factors Influencing Time to Vancomycin-Induced Clearance of Nonendocarditis Methicillin-Resistant Staphylococcus aureus Bacteremia: Role of Platelet Microbicidal Protein Killing and agr Genotypes

Background. Vancomycin susceptibility, the accessory gene global regulator (agr) genotype and function, staphylococcal cassette chromosome (SCC) mec type, and susceptibility to cationic thrombin-induced platelet microbicidal protein 1 (tPMP-1) have been individually predictive of duration of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. This investigation evaluated ...

Disparity in the In Vitro versus In Vivo Regulation of Fibronectin-Binding Proteins by 2 Global Regulators, saeRS and sigB, in Staphylococcus aureus

Fibronectin-binding protein A plays an important role in Staphylococcus aureus endovascular infections. We characterized the sigB-saeRS-fnbA expression network with fibronectin binding in vitro and in an experimental infective endocarditis (IE) model using parental strains RN6390 and SH1000 and their respective isogenic saeRS mutants. In contrast to the in vitro data, there was no ...

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 ...

Enhanced Expression of dltABCD Is Associated with the Development of Daptomycin Nonsusceptibility in a Clinical Endocarditis Isolate of Staphylococcus aureus

Using isogenic clinical bloodstream Staphylococcus aureus strains from a patient with relapsing endocarditis, we investigated the transcriptional profiles of the mprF and dlt genes in the context of cell-surface charge and daptomycin nonsusceptibility. As in prior studies, a point mutation within mprF was observed in the daptomycin-nonsusceptible strain. However, neither the ...

Influence of the Timing of Cardiac Surgery on the Outcome of Patients With Infective Endocarditis and Stroke

Background. The timing of cardiac surgery after stroke in infective endocarditis (IE) remains controversial. We examined the relationship between the timing of surgery after stroke and the incidence of in-hospital and 1-year mortalities. Methods. Data were obtained from the International Collaboration on Endocarditis–Prospective Cohort Study of 4794 patients with definite IE who ...

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 ...

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. ...