Vancomycin-resistant enterococci outside the health-care setting: prevalence, sources, and public health implications.

Although nosocomial acquisition and subsequent colonization of vancomycin-resistant enterococci (VRE), an emerging international threat to public health, has been emphasized in the United States, colonization among nonhospitalized persons has been infrequently documented. In contrast, in Europe, colonization appears to occur frequently in persons outside the health-care setting. An important factor associated with VRE in the community in Europe has been avoparcin, a glycopeptide antimicrobial drug used for years in many European nations at subtherapeutic doses as a growth promoter in food-producing animals. In Europe, evidence suggests that foodborne VRE may cause human colonization. Although avoparcin has never been approved for use in the United States, undetected community VRE transmission may be occurring at low levels. Further studies of community transmission of VRE in the United States are urgently needed. If transmission with VRE from unrecognized community sources can be identified and controlled, increased incidence of colonization and infection among hospitalized patients may be prevented

Maintaining Fluoroquinolone Class Efficacy: Review of Influencing Factors

Previous experience with antimicrobial resistance has emphasized the importance of appropriate stewardship of these pharmacotherapeutic agents. The introduction of fluoroquinolones provided potent new drugs directed primarily against gram-negative pathogens, while the newer members of this class demonstrate more activity against gram-positive species, including Streptococcus pneumoniae. Although these agents are clinically effective against a broad range of infectious agents, emergence of resistance and associated clinical failures have prompted reexamination of their use. Appropriate use revolves around two key objectives: 1) only prescribing antimicrobial therapy when it is beneficial and 2) using the agents(s) with optimal activity against the expected pathogens(s). Pharmacodynamic principles and properties can be applied to achieve the latter objective when prescribing agents belonging to the fluoroquinolone class. A focused approach emphasizing “correct-spectrum” coverage may reduce development of antimicrobial resistance and maintain class efficacy

Dead Bugs Don’t Mutate: Susceptibility Issues in the Emergence of Bacterial Resistance

The global emergence of antibacterial resistance among common and atypical respiratory pathogens in the last decade necessitates the strategic application of antibacterial agents. The use of bactericidal rather than bacteriostatic agents as first-line therapy is recommended because the eradication of microorganisms serves to curtail, although not avoid, the development of bacterial resistance. Bactericidal activity is achieved with specific classes of antimicrobial agents as well as by combination therapy. Newer classes of antibacterial agents, such as the fluoroquinolones and certain members of the macrolide/lincosamine/streptogramin class have increased bactericidal activity compared with traditional agents. More recently, the ketolides (novel, semisynthetic, erythromycin-A derivatives) have demonstrated potent bactericidal activity against key respiratory pathogens, including Streptococcus pneumoniae, Haemophilus influenzae, Chlamydia pneumoniae, and Moraxella catarrhalis. Moreover, the ketolides are associated with a low potential for inducing resistance, making them promising first-line agents for respiratory tract infections

The Human Nasal Microbiota and Staphylococcus aureus Carriage

BACKGROUND: Colonization of humans with Staphylococcus aureus is a critical prerequisite of subsequent clinical infection of the skin, blood, lung, heart and other deep tissues. S. aureus persistently or intermittently colonizes the nares of approximately 50% of healthy adults, whereas approximately 50% of the general population is rarely or never colonized by this pathogen. Because microbial consortia within the nasal cavity may be an important determinant of S. aureus colonization we determined the composition and dynamics of the nasal microbiota and correlated specific microorganisms with S. aureus colonization. METHODOLOGY/PRINCIPAL FINDINGS: Nasal specimens were collected longitudinally from five healthy adults and a cross-section of hospitalized patients (26 S. aureus carriers and 16 non-carriers). Culture-independent analysis of 16S rRNA sequences revealed that the nasal microbiota of healthy subjects consists primarily of members of the phylum Actinobacteria (e.g., Propionibacterium spp. and Corynebacterium spp.), with proportionally less representation of other phyla, including Firmicutes (e.g., Staphylococcus spp.) and Proteobacteria (e.g. Enterobacter spp). In contrast, inpatient nasal microbiotas were enriched in S. aureus or Staphylococcus epidermidis and diminished in several actinobacterial groups, most notably Propionibacterium acnes. Moreover, within the inpatient population S. aureus colonization was negatively correlated with the abundances of several microbial groups, including S. epidermidis (p = 0.004). CONCLUSIONS/SIGNIFICANCE: The nares environment is colonized by a temporally stable microbiota that is distinct from other regions of the integument. Negative association between S. aureus, S. epidermidis, and other groups suggests microbial competition during colonization of the nares, a finding that could be exploited to limit S. aureus colonization

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

The Isogeny Problem in the Post-Quantum World

Quantum computers represent an existential threat to current techniques in cryptography. However, systems such as Supersingular Isogeny Diffie-Hellman (SIDH) and Commutative-SIDH (CSIDH) are potential working solutions that are believed to be resistant to quantum attacks, and as viable candidates, it is important to study the efficiency and security of such systems. Both protocols rely on the computational complexity of solving the isogeny problem. This problem corresponds to finding a path between two known vertices in a large well-connected graph known as the isogeny graph. We investigate the isogeny graphs related to SIDH and CSIDH systems. We then consider the adjacency matrices associated with these graphs and establish the correspondence between standard operations on an adjacency matrix and the effects on the associated isogeny graph. With this insight, we can understand the isogeny problem from a new perspective, and we demonstrate the utility of such a viewpoint. Additionally, we investigate the endomorphism ring of the elliptic curves used in CSIDH. Specifically, we compute the probability the class number of the order associated with the endomorphism ring is smooth. A low probability is important, as it would preclude the Pohlig-Hellman attack on the CSIDH system