Showing papers by "Robert C. Moellering published in 2005"
TL;DR: An association was identified between loss of agrII function and the emergence of hetero-GISA phenotype during either in vitro or in vivo vancomycin exposure and these events were associated with defective lysis and reduced susceptibility to tPMP.
Abstract: Loss of agr function, vancomycin exposure, and abnormal autolysis have been linked with both development of the GISA phenotype and low-level resistance in vitro to thrombin-induced platelet microbicidal proteins (tPMPs). We examined the potential in vitro interrelationships among these parameters in well-characterized, isogenic laboratory-derived and clinical Staphylococcus aureus isolates. The laboratory-derived S. aureus strains included RN6607 (agrII-positive parent) and RN6607V (vancomycin-passaged variant; hetero-GISA), RN9120 (RN6607 agr::tetM; agr II knockout parent), RN9120V (vancomycin-passaged variant), and RN9120-GISA (vancomycin passaged, GISA). Two serial isolates from a vancomycin-treated patient with recalcitrant, methicillin-resistant S. aureus (MRSA) endocarditis were also studied: A5937 (agrII-positive initial isolate) and A5940 (agrII-defective/hetero-GISA isolate obtained after prolonged vancomycin administration). In vitro tPMP susceptibility phenotypes were assessed after exposure of strains to either 1 or 2 mug/ml. Triton X-100- and vancomycin-induced lysis profiles were determined spectrophotometrically. For agrII-intact strain RN6607, vancomycin exposure in vitro was associated with modest increases in vancomycin MICs and reduced killing by tPMP, but no change in lysis profiles. In contrast, vancomycin exposure of agrII-negative RN9120 yielded a hetero-GISA phenotype and was associated with defects in lysis and reduced in vitro killing by tPMP. In the clinical isolates, loss of agrII function during prolonged vancomycin therapy was accompanied by emergence of the hetero-GISA phenotype and reduced tPMP killing, with no significant change in lysis profiles. An association was identified between loss of agrII function and the emergence of hetero-GISA phenotype during either in vitro or in vivo vancomycin exposure. In vitro, these events were associated with defective lysis and reduced susceptibility to tPMP. The precise mechanism(s) underlying these findings is the subject of current investigations.
163 citations
TL;DR: The comparative in vitro potency of XRP2868, a new oral semisynthetic streptogramin antibiotic, was evaluated against gram-positive bacteria and was fourfold more potent than quinupristin-dalfopristin against Staphylococcus aureus and Enterococcus faecium.
Abstract: The comparative in vitro potency of XRP2868, a new oral semisynthetic streptogramin antibiotic, was evaluated against gram-positive bacteria. XRP2868 inhibited all staphylococci at ≤1 μg/ml and all nonpneumococcal streptococci at ≤0.25 μg/ml and was fourfold more potent than quinupristin-dalfopristin against Staphylococcus aureus and Enterococcus faecium.
16 citations
TL;DR: A 28-year-old patient that presented to the emergency room initially with upper respiratory symptoms that rapidly progressed to become critically ill with a necrotizing pneumonia, leukopenia, thrombocytopenia, and renal failure is presented.
Abstract: There have been increasing reports of methicillin-resistant Staphylococcus aureus (MRSA) infections developing in the community setting in patients without traditional risk factors for MRSA infection. We present a case ofa 28-year-old patient that presented to the emergency room initially with upper respiratory symptoms that rapidly progressed to become critically ill with a necrotizing pneumonia, leukopenia, thrombocytopenia, and renal failure. The patient subsequently grew a MRSA isolate from bronchoalveolar lavage samples, which was found to carry SCCmec IV and to contain the Panton-Valentine leukocidin genes. We present this case to review the virulence, unique genomic characteristics, distinct antimicrobial susceptibility pattern, and potential complications associated with these community-associated MRSA isolates. As seen in our patient, community-associated MRSA infections often present with skin and soft tissue infections and may cause severe necrotizing pneumonia as well as other serious infections including fatal bacteremia.
11 citations
TL;DR: The papers in this Current Topic review a number of the important aspects of the dissemination and clinical impact of multiply resistant gram-positive bacteria.
Abstract: Antimicrobial resistance is an unwelcome companion of the successful clinical deployment of antimicrobial agents during the past 70 years. Despite sometimes heroic efforts to identify and deal with this problem, resistant organisms and the clinical problems associated with them continue to multiply throughout the world. Among bacteria, resistance to antimicrobial agents is seen in all species. In recent years, however, some of the most dramatic increases and problems associated with resistance have come from methicillin-resistant Staphylococcus aureus (MRSA), multiply resistant Streptococcus pneumoniae, and vancomycin-resistant enterococci (VRE). These organisms, which are fully virulent (and in some cases appear to be associated with even higher mortality rates than their more susceptible brethren), represent a major challenge for the clinician. Their continued spread and dissemination has not been effectively stopped by our best efforts at infection control, although, as will be seen in the papers in this Current Topic, we now have a much better understanding of methods that can be used to interdict their spread, at least in the hospital setting. Problems with these organisms have arisen, in large part, from our inability to control the inappropriate use of antimicrobial agents, and this represents a major challenge in curtailing further evolution and spread of antimicrobial resistance. The papers in this Current Topic review a number of the important aspects of the dissemination and clinical impact of multiply resistant gram-positive bacteria. The problem of multiply resistant pneumococci is addressed in the paper by Fuller et al. [1]. They note that although there has been an alarming increase in the incidence of infections caused by pneumococci resistant to penicillins, macrolides, and, more recently, fluoroquinolones, these agents are still used as first-line empiric therapy in the outpatient setting. There are numerous reasons for this, including the diagnostic uncertainty that often accompanies the therapy of outpatient respiratory tract infections. In addition, there has, until recently, been a failure of studies to demonstrate the clinical relevance of resistance. Moreover, clinicians often fail to recognize clinical treatment failures. The information provided in Fuller et al.'s excellent review of pneumococci provides clear-cut data on the clinical significance of resistance to beta-lactam agents, macrolides, and fluoroquinolones, with a more than adequate demonstration of the clinical failures that can result from discordant therapy with any of these agents. They also provide valuable information to enable the clinician to quantify the risk of infection due to resistant pneumococci so that therapy can be appropriately tailored. Penicillin-resistant S. aureus represents perhaps an even greater challenge. These organisms are fully virulent; indeed, infections with these organisms are likely associated with increased mortality [2]. Methicillin-resistant staphylococci are a worldwide problem, but there are some striking differences in the frequency with which they cause nosocomial infections. For instance, intensive infection control measures appear to be responsible for the low prevalence of infections with these organisms in northern Europe. This has not, however, allowed for effective control of methicillin-resistant staphylococci in the USA, southern Europe, or much of Asia. A striking exception to the “northern Europe rule” is the UK. The reasons for this are beautifully outlined in the article by I.M. Gould [3]. He notes that failures to control MRSA in the UK are presently causing a “huge public and political concern”. He then provides a detailed explanation for the apparent failure to control this epidemic in the UK—an explanation that should serve as a lesson to all parts of the world where nosocomial infections with MRSA continue to be a major plague. Gould goes on to point out that the control of this organism in settings where its prevalence has been allowed to increase will require a multifaceted approach, with considerable monetary expenditure for improvement of Presented at the 2nd International symposium on resistant grampositive infections, Berlin, Germany, 10–12 December 2004.
10 citations
7 citations