Impact of daptomycin resistance on Staphylococcus aureus virulence.

Daptomycin resistance (DAP(R)) in Staphylococcus aureus is associated with mutations in genes that are also implicated in staphylococcal pathogenesis. Using a laboratory-derived series of DAP exposed strains, we showed a relationship between increasing DAP MIC and reduced virulence in a Galleria mellonella infection model. Point mutations in walK and rpoC led to cumulative reductions in virulence and simultaneous increases in DAP MIC.

Towards squalamine mimics: synthesis and antibacterial activities of head-to-tail dimeric sterol-polyamine conjugates.

Four dimeric sterol-polyamine conjugates have been synthesized from the homo- and hetero-connection of monomeric sterol-polyamine analogs in a head-to-tail manner. These dimeric conjugates show strong antibacterial activity against a broad spectrum of Gram-positive bacteria, whereas their corresponding activities against Gram-negative bacteria are relatively moderate. Though no significant difference was observed in the activities of these conjugates, cholic acid-containing dimeric conjugates generally exhibit higher activities than the corresponding deoxycholic acid-derived analogs.

Serine/threonine phosphatase Stp1 contributes to reduced susceptibility to vancomycin and virulence in Staphylococcus aureus.

The genetic mechanisms that contribute to reduced susceptibility to vancomycin in Staphylococcus aureus are complex and heterogeneous. In addition, debate is emerging as to the true effect of reduced susceptibility to vancomycin on staphylococcal virulence. To investigate this, comparative genomics was performed on a collection of vancomycin-exposed isogenic S.

Whole genome characterization of the mechanisms of daptomycin resistance in clinical and laboratory derived isolates of Staphylococcus aureus.

Background: Daptomycin remains one of our last-line anti-staphylococcal agents. This study aims to characterize the genetic evolution to daptomycin resistance in S. aureus.

MRSA: the first half century.

Fifty years ago methicillin-resistant Staphylococcus aureus (MRSA) first revealed themselves to the medical community, having been described in a landmark article published in the British Medical Journal. Among other things, their discovery set off a major response from the scientific and medical professions to control or even eliminate them as major human pathogens. Despite these efforts, however, MRSA have spread throughout the world and a half century after they burst upon the scene they continue to pose major challenges to research scientists and clinicians alike.

The problem of complicated skin and skin structure infections: the need for new agents.

Complicated skin and skin structure infections (cSSSIs) continue to pose a significant clinical challenge. The most frequent cause of these infections is Staphylococcus aureus, although other organisms, including Streptococcus pyogenes and, in certain circumstances, Enterobacteriaceae, are also involved. The relentless increase in methicillin resistance among S.

Discovering new antimicrobial agents.

Although there has been a relentless increase in resistance to antimicrobial agents amongst important bacterial pathogens throughout the world, it is well known that the number of new antimicrobial agents being brought to the market has undergone a steady decline in the past several decades. There are a number of reasons for this, which are detailed in this article, but there is also a great deal of continuing research to find new effective antimicrobials, much of it now being carried out in academic centres and especially in small biotechnology companies, rather than by large pharma. Whilst classic screening methods and chemical modification of known antimicrobial agents continue to produce potential leads for new antimicrobial agents, a number of other approaches are being investigated.

Lack of bactericidal antagonism or synergism in vitro between oxacillin and vancomycin against methicillin-susceptible strains of Staphylococcus aureus.

With the current high prevalence of infection caused by methicillin-resistant Staphylococcus aureus (MRSA) strains but in light of the general belief that beta-lactam antibiotics are more effective than vancomycin against infections caused by methicillin-susceptible S. aureus (MSSA) isolates, clinicians may utilize antistaphylococcal penicillins in combination with vancomycin for the empirical treatment of S. aureus infections.

Therapeutic monitoring of vancomycin in adults summary of consensus recommendations from the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists.

Vancomycin is a commonly used antibiotic due to its effectiveness in treating serious gram-positive infections caused by methicillin-resistant Staphylococcus aureus. As commercial drug assays and a multitude of pharmacokinetic data from a variety of patient populations are widely available, therapeutic monitoring of serum vancomycin concentrations is frequently performed by clinicians, with the expectation that targeting the concentrations within a relatively narrow range can minimize toxicity yet still achieve therapeutic success. Much debate exists, however, over the value of routine therapeutic monitoring of vancomycin levels because of conflicting evidence regarding the ability of serum concentrations to predict effectiveness or prevent toxicity.

Development of reduced vancomycin susceptibility in methicillin-susceptible Staphylococcus aureus.

Background: Most cases of reduced vancomycin susceptibility in Staphylococcus aureus reported in the literature have been in methicillin-resistant strains. We report the development of reduced vancomycin susceptibility in a series of clonally related, methicillin-susceptible S. aureus (MSSA) clinical isolates.

Competition of hospital-acquired and community-acquired methicillin-resistant Staphylococcus aureus strains in hospitals.

Recently, we [E.M.C.

Vancomycin therapeutic guidelines: a summary of consensus recommendations from the infectious diseases Society of America, the American Society of Health-System Pharmacists, and the Society of Infectious Diseases Pharmacists.

Practice guidelines for therapeutic monitoring of vancomycin treatment for Staphylococcus aureus infection in adult patients were reviewed by an expert panel of the Infectious Diseases Society of America, the American Society of Health-System Pharmacists, and the Society of Infectious Diseases Pharmacists. A literature review of existing evidence regarding vancomycin dosing and monitoring of serum concentrations, in addition to patient outcomes combined with expert opinion regarding the drug's pharmacokinetic, pharmacodynamic, and safety record, resulted in new recommendations for targeting and adjustment of vancomycin therapy.

Clinical consensus conference: survey on Gram-positive bloodstream infections with a focus on Staphylococcus aureus.

The increased incidence over the past decade of bloodstream infections (BSIs) caused by gram-positive bacteria, particularly methicillin-resistant Staphylococcus aureus, highlights the critical need for a consistent approach to therapy. However, there is currently no international consensus on the diagnosis and management of gram-positive BSIs. The Clinical Consensus Conference on Gram-Positive Bloodstream Infections was convened as a session at the 9th International Symposium on Modern Concepts in Endocarditis and Cardiovascular Infections held in 2007.

Galleria mellonella as a model system to study Acinetobacter baumannii pathogenesis and therapeutics.

Nonmammalian model systems of infection such as Galleria mellonella (caterpillars of the greater wax moth) have significant logistical and ethical advantages over mammalian models. In this study, we utilize G. mellonella caterpillars to study host-pathogen interactions with the gram-negative organism Acinetobacter baumannii and determine the utility of this infection model to study antibacterial efficacy.

Modeling the invasion of community-acquired methicillin-resistant Staphylococcus aureus into hospitals.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) has traditionally been associated with infections in hospitals. Recently, a new strain of MRSA has emerged and rapidly spread in the community, causing serious infections among young, healthy individuals. Preliminary reports imply that a particular clone (USA300) of a community-acquired MRSA (CA-MRSA) strain is infiltrating hospitals and replacing the traditional hospital-acquired MRSA strains.

Reduced susceptibility to vancomycin influences pathogenicity in Staphylococcus aureus infection.

In the present study, we demonstrated the utility of the nonmammalian model system Galleria mellonella for studying the pathogenesis of Staphylococcus aureus infection. By use of clinical and laboratory strains that had been exposed to vancomycin, we showed that both agr functional status and vancomycin minimum inhibitory concentration are determinants associated with the virulence of S. aureus in G.