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Avoiding the Perfect Storm: The Biologic and Clinical Case for Reevaluating the 7-Day Expectation for Methicillin-Resistant Staphylococcus aureus Bacteremia Before Switching Therapy

Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia (MRSAB) is associated with poor outcomes and serious complications. The MRSA guidelines define treatment failure and persistent bacteremia as lasting ≥7 days; however, this definition requires reevaluation. Aggressively reducing the bacterial inoculum promptly is critical because factors already in place ...

Alternative Mutational Pathways to Intermediate Resistance to Vancomycin in Methicillin-Resistant Staphylococcus aureus

Background. We used 2 in vitro experimental systems to compare phenotypic and genotypic changes that accompany selection of mutants of methicillin-resistant Staphylococcus aureus (MRSA) strain JH1 with low-level vancomycin resistance similar to the type found in vancomycin-intermediate S. aureus (VISA). Methods. The previously described MRSA strain JH1 and its ...

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 ...

Methicillin-Resistant Staphylococcus aureus (MRSA) Protocols Edited by Yinduo Ji New Jersey: Humana Press, 2007.264 pp., Illustrated. $99.50 (hardcover)

Ostrosky-Zeichner Laboratory of Mycology Research, University of Texas Medical School at Houston , Houston 1 George Sakoulas Department of Medicine, Division of Infectious Diseases, New York Medical College

Elevated Serum Interleukin-10 at Time of Hospital Admission Is Predictive of Mortality in Patients With Staphylococcus aureus Bacteremia

Background. Staphylococcus aureus bacteremia (SaB) carries considerable morbidity and mortality. We examined the predictive value of serum concentrations of interleukin (IL)–10, proinflammatory cytokines, and terminal complement on patient survival and SaB duration. Methods. Clinical information on consecutive patients with SaB at a tertiary medical center were collected ...

Staphylococcal Enterotoxin P Predicts Bacteremia in Hospitalized Patients Colonized With Methicillin-Resistant Staphylococcus aureus

Background. Methicillin-resistant Staphylococcus aureus (MRSA) colonization predicts later infection, with both host and pathogen determinants of invasive disease. Methods. This nested case-control study evaluates predictors of MRSA bacteremia in an 8–intensive care unit (ICU) prospective adult cohort from 1 September 2003 through 30 April 2005 with active MRSA surveillance and ...

Novel Bacterial Metabolite Merochlorin A Demonstrates in vitro Activity against Multi-Drug Resistant Methicillin-Resistant Staphylococcus aureus

Background We evaluated the in vitro activity of a merochlorin A, a novel compound with a unique carbon skeleton, against a spectrum of clinically relevant bacterial pathogens and against previously characterized clinical and laboratory Staphylococcus aureus isolates with resistance to numerous antibiotics. Methods Merochlorin A was isolated and purified from a marine-derived ...

Perspectives on Daptomycin Resistance, with Emphasis on Resistance in Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus infections are becoming more frequent and less easily treated by means of currently recommended agents. Vancomycin has been associated with decreased susceptibility in staphylococci and with treatment failures. Daptomycin is rapidly bactericidal; a dosage of 4 mg/kg daily is approved for treatment of skin and soft-tissue infections, and a ...

Increasing Antibiotic Resistance among Methicillin-Resistant Staphylococcus aureus Strains

George Sakoulas ) 1 Robert C. Moellering Jr. 0 0 Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School , Boston, Massachussetts 1 Division of Infectious Diseases

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 ...

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 ...

Comparative effectiveness of nafcillin or cefazolin versus vancomycin in methicillin-susceptible Staphylococcus aureus bacteremia

Background The high prevalence of methicillin-resistant S. aureus (MRSA) has led clinicians to select antibiotics that have coverage against MRSA, usually vancomycin, for empiric therapy for suspected staphylococcal infections. Clinicians often continue vancomycin started empirically even when methicillin-susceptible S. aureus (MSSA) strains are identified by culture. However, ...

Adaptation of Methicillin-Resistant Staphylococcus aureus in the Face of Vancomycin Therapy

For the past 2 decades, vancomycin has served as the cornerstone of therapy against serious methicillin-resistant Staphylococcus aureus infections. This role is increasingly challenged by questions of efficacy, including reduced efficacy against infections caused by glycopeptide-intermediate S. aureus strains. In an evaluation of clinical glycopeptide-intermediate S. aureus ...

Empiric Antibiotic Therapy for Staphylococcus aureus Bacteremia May Not Reduce In-Hospital Mortality: A Retrospective Cohort Study

Background Appropriate empiric therapy, antibiotic therapy with in vitro activity to the infecting organism given prior to confirmed culture results, may improve Staphylococcus aureus outcomes. We aimed to measure the clinical impact of appropriate empiric antibiotic therapy on mortality, while statistically adjusting for comorbidities, severity of illness and presence of virulence ...

Predicting and Defining Vancomycin Efficacy: Posttest and Program Evaluation

Sakoulas 4. Although precise and aggressive pharmacokinetic adjustments via repeated measuring of serum concentrations may not be necessary, monitoring of serum drug levels is often warranted for patients

Predicting and Defining Vancomycin Efficacy: Program Overview

Reference Center for Antibiotics, Institut 1 Robert C. Moellering, Jr., Patrice Courvalin, Ronald N. Jones , Donald P. Levine, Michael J. Rybak, Dennis L. Stevens, and George Sakoulas Release and Expiration ... unlabeled/investigational uses of a commercial product. George Sakoulas, MD (Assistant Professor of Medicine, Westchester Medical Center, Valhalla, NY), serves on the speakers’ bureaus of Aventis, Ortho

Comparison of Mortality Associated with Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus Bacteremia: A Meta-analysis

A meta-analysis was performed to summarize the impact of methicillin-resistance on mortality in Staphylococcus aureus bacteremia. A search of the MEDLINE database for studies published during the period of 1 January 1980 through 31 December 2000 and a bibliographic review identified English-language studies of S. aureus bacteremia. Studies were included if they contained the ...