In vitro activity of Iclaprim against Methicillin-resistant Staphylococcus aureus nonsusceptible to Daptomycin, Linezolid, or Vancomycin: A pilot study

Iclaprim is a bacterial dihydrofolate reductase inhibitor in Phase 3 clinical development for the treatment of acute bacterial skin and skin structure infections and hospital-acquired bacterial pneumonia caused by Gram-positive bacteria. Daptomycin, linezolid, and vancomycin are commonly used antibiotics for these indications. With increased selective pressure to these antibiotics, outbreaks of bacterial resistance to these antibiotics have been reported. This in vitro pilot study evaluated the activity of iclaprim against methicillin-resistant Staphylococcus aureus (MRSA) isolates, which were also not susceptible to daptomycin, linezolid, or vancomycin. Iclaprim had an MIC ≤ 1 µg/ml to the majority of MRSA isolates that were nonsusceptible to daptomycin (5 of 7 (71.4%)), linezolid (26 of 26 (100%)), or vancomycin (19 of 28 (66.7%)). In the analysis of time-kill curves, iclaprim demonstrated ≥ 3 log10 reduction in CFU/mL at 4–8 hours for tested strains and isolates nonsusceptible to daptomycin, linezolid, or vancomycin. Together, these data support the use of iclaprim in serious infections caused by MRSA nonsusceptible to daptomycin, linezolid, or vancomycin

Five-Year Longitudinal Assessment (2008 to 2012) of E-101 Solution Activity against Clinical Target and Antimicrobial-Resistant Pathogens

This study summarizes the topical E-101 solution susceptibility testing results for 760 Gram-positive and Gram-negative target pathogens collected from 75 U.S. sites between 2008 and 2012 and 103 ESKAPE pathogens. E-101 solution maintained potent activity against all bacterial species studied for each year tested, with MICs ranging from <0.008 to 0.25 μg porcine myeloperoxidase (pMPO)/ml. These results confirm that E-101 solution retains its potent broad-spectrum activity against U.S. clinical isolates and organisms with challenging resistance phenotypes

Prevalence of antimicrobial resistance in bacteria isolated from central nervous system specimens as reported by U.S. hospital laboratories from 2000 to 2002

BACKGROUND: Bacterial infections of the central nervous system, especially acute infections such as bacterial meningitis require immediate, invariably empiric antibiotic therapy. The widespread emergence of resistance among bacterial species is a cause for concern. Current antibacterial susceptibility data among central nervous system (CNS) pathogens is important to define current prevalence of resistance. METHODS: Antimicrobial susceptibility of pathogens isolated from CNS specimens was analyzed using The Surveillance Database (TSN(®)) USA Database which gathers routine antibiotic susceptibility data from >300 US hospital laboratories. A total of 6029 organisms derived from CNS specimen sources during 2000–2002, were isolated and susceptibility tested. RESULTS: Staphylococcus aureus (23.7%) and Streptococcus pneumoniae (11.0%) were the most common gram-positive pathogens. Gram-negative species comprised approximately 25% of isolates. The modal patient age was 1 or <1 year for most organisms. Prevalence of MRSA among S. aureus from cerebrospinal fluid (CSF) and brain abscesses were 29.9–32.9%. Penicillin resistance rates were 16.6% for S. pneumoniae, 5.3% for viridans group streptococci, and 0% for S. agalactiae. For CSF isolates, ceftriaxone resistance was S. pneumoniae (3.5%), E. coli (0.6%), Klebsiella pneumoniae (2.8%), Serratia marcescens (5.6%), Enterobacter cloacae (25.0%), Haemophilus influenzae (0%). Listeria monocytogenes and N. meningitidis are not routinely susceptibility tested. CONCLUSIONS: Resistance is commonly detected, albeit still at relatively low levels for key drugs classes such as third-generation cephalosporins. This data demonstrates the need to consider predominant resistance phenotypes when choosing empiric therapies to treat CNS infections

Emerging resistance among bacterial pathogens in the intensive care unit – a European and North American Surveillance study (2000–2002)

Background Globally ICUs are encountering emergence and spread of antibiotic-resistant pathogens and for some pathogens there are few therapeutic options available. Methods Antibiotic in vitro susceptibility data of predominant ICU pathogens during 2000–2 were analyzed using data from The Surveillance Network (TSN) Databases in Europe (France, Germany and Italy), Canada, and the United States (US). Results Oxacillin resistance rates among Staphylococcus aureus isolates ranged from 19.7% to 59.4%. Penicillin resistance rates among Streptococcus pneumoniae varied from 2.0% in Germany to as high as 20.2% in the US; however, ceftriaxone resistance rates were comparably lower, ranging from 0% in Germany to 3.4% in Italy. Vancomycin resistance rates among Enterococcus faecalis were ≤ 4.5%; however, among Enterococcus faecium vancomycin resistance rates were more frequent ranging from 0.8% in France to 76.3% in the United States. Putative rates of extended-spectrum β-lactamase (ESBL) production among Enterobacteriaceae were low, \u3c6% among Escherichia coli in the five countries studied. Ceftriaxone resistance rates were generally lower than or similar to piperacillin-tazobactam for most of the Enterobacteriaceae species examined. Fluoroquinolone resistance rates were generally higher for E. coli (6.5% – 13.9%), Proteus mirabilis (0–34.7%), and Morganella morganii (1.6–20.7%) than other Enterobacteriaceae spp (1.5–21.3%). P. aeruginosa demonstrated marked variation in β-lactam resistance rates among countries. Imipenem was the most active compound tested against Acinetobacter spp., based on resistance rates. Conclusion There was a wide distribution in resistance patterns among the five countries. Compared with other countries, Italy showed the highest resistance rates to all the organisms with the exception of Enterococcus spp., which were highest in the US. This data highlights the differences in resistance encountered in intensive care units in Europe and North America and the need to determine current local resistance patterns by which to guide empiric antimicrobial therapy for intensive care infections

Tracking the implementation of NCCLS M100-S12 expanded-spectrum cephalosporin MIC breakpoints for nonmeningeal isolates of Streptococcus pneumoniae by clinical laboratories in the United States during 2002 and 2003

BACKGROUND: The Performance Standards for Antimicrobial Susceptibility Testing, Twelfth Informational Supplement, M100-S12, published by the National Committee for Clinical Laboratory Standards (NCCLS) in January 2002 introduced distinct minimum inhibitory concentration (MIC) interpretative breakpoints for ceftriaxone, cefotaxime, and cefepime for nonmeningeal isolates of Streptococcus pneumoniae. Previously, a single set of interpretative breakpoints was used for both meningeal and nonmeningeal isolates. METHODS: To estimate the rate of adoption of the M100-S12 interpretive breakpoints by clinical laboratories, antimicrobial susceptibility test results for ceftriaxone and cefotaxime from nonmeningeal S. pneumoniae isolates were studied using data collected from January 2002 to June 2003 by The Surveillance Network(® )Database – USA (TSN(®)), an electronic surveillance database. RESULTS: Of the 262 laboratories that provided data that could be evaluated, 67.6% had adopted the M100-S12 breakpoints one and one-half years after they were published. CONCLUSIONS: The NCCLS M100-S12 recommendation to interpret MICs to expanded-spectrum cephalosporins using two distinct sets of breakpoints for meningeal and nonmeningeal isolates of S. pneumoniae was steadily implemented by clinical microbiology laboratories in the United States following their initial publication in January 2002. The use of these new breakpoints more accurately reflects the clinical activities of expanded-spectrum cephalosporins than did the single set of interpretative breakpoints previously used for both meningeal and nonmeningeal isolates

Prevalence and antimicrobial susceptibilities of bacteria isolated from blood cultures of hospitalized patients in the United States in 2002

BACKGROUND: Bloodstream infections are associated with significant patient morbidity and mortality. Antimicrobial susceptibility patterns should guide the choice of empiric antimicrobial regimens for patients with bacteremia. METHODS: From January to December of 2002, 82,569 bacterial blood culture isolates were reported to The Surveillance Network (TSN) Database-USA by 268 laboratories. Susceptibility to relevant antibiotic compounds was analyzed using National Committee for Clinical Laboratory Standards guidelines. RESULTS: Coagulase-negative staphylococci (42.0%), Staphylococcus aureus (16.5%), Enterococcus faecalis (8.3%), Escherichia coli (7.2%), Klebsiella pneumoniae (3.6%), and Enterococcus faecium (3.5%) were the most frequently isolated bacteria from blood cultures, collectively accounting for >80% of isolates. In vitro susceptibility to expanded-spectrum β-lactams such as ceftriaxone were high for oxacillin-susceptible coagulase-negative staphylococci (98.7%), oxacillin-susceptible S. aureus (99.8%), E. coli (97.3%), K. pneumoniae (93.3%), and Streptococcus pneumoniae (97.2%). Susceptibilities to fluoroquinolones were variable for K. pneumoniae (90.3–91.4%), E. coli (86.0–86.7%), oxacillin-susceptible S. aureus (84.0–89.4%), oxacillin-susceptible coagulase-negative staphylococci (72.7–82.7%), E. faecalis (52.1%), and E. faecium (11.3%). Combinations of antimicrobials are often prescribed as empiric therapy for bacteremia. Susceptibilities of all blood culture isolates to one or both agents in combinations of ceftriaxone, ceftazdime, cefepime, piperacillin-tazobactam or ciprofloxacin plus gentamicin were consistent (range, 74.8–76.3%) but lower than similar β-lactam or ciprofloxacin combinations with vancomycin (range, 93.5–96.6%). CONCLUSION: Ongoing surveillance for antimicrobial susceptibility remains essential, and will enhance efforts to identify resistance and attempt to limit its spread

A data mining approach to the SAR values over large MR image repositories

Purpose: In magnetic resonance imaging, the radiofrequency energy absorption arises as one of the main safety concerns, being mainly related with increased body temperature. Monitoring radiofrequency absorption is achieved by the estimation of specific absorption rate (SAR), whose implementation lies on equipment manufacturers, which in turn are not totally enlightening about its calculus. This work presents an exploratory approach of whole-body SAR values stored in DICOM metadata aiming to find correlation with body weight, body mass index (BMI), gender and pulse sequences for abdominal/pelvic (17.812 series) and head (29.907 series) studies. Methods and Materials: All studies were acquired in a 3 Tesla scanner with high-performance gradients. Data were extracted using Dicoogle, a DICOM metadata mining tool. Several DICOM tags were analysed (e.g. patient weight, height, gender, sequence name). For each study type, specifically weighted pulse sequences were related with weight, BMI and gender through boxplot diagrams, statistical and effect size analysis. Results: SAR limits were never exceeded. Generally, SAR values tended to decrease with increasing body weight and BMI values for abdominal/pelvic studies. On the other hand, head studies showed different trends regarding distinct pulse sequences. SAR values tend to be higher in male individuals (p<0,05). As expected, turbo spin echo sequences present the highest SAR values. The values found for echo gradient spoiled sequence (FLASH) were also high. Conclusion: It is confirmed that SAR estimates are related with the analysed variables. An individual examination of pulse sequences is recommended to observe trends regarding weight, BMI or gender.publishe

ZnSe Nanorods as Visible-Light Absorbers for Photocatalytic and Photoelectrochemical H2 Evolution in Water.

A precious-metal- and Cd-free photocatalyst system for efficient H2 evolution from aqueous protons with a performance comparable to Cd-based quantum dots is presented. Rod-shaped ZnSe nanocrystals (nanorods, NRs) with a Ni(BF4 )2 co-catalyst suspended in aqueous ascorbic acid evolve H2 with an activity up to 54±2 mmol H 2  gZnSe -1  h-1 and a quantum yield of 50±4 % (λ=400 nm) under visible light illumination (AM 1.5G, 100 mW cm-2 , λ>400 nm). Under simulated full-spectrum solar irradiation (AM 1.5G, 100 mW cm-2 ), up to 149±22 mmol H 2  gZnSe -1  h-1 is generated. Significant photocorrosion was not noticeable within 40 h and activity was even observed without an added co-catalyst. The ZnSe NRs can also be used to construct an inexpensive delafossite CuCrO2 photocathode, which does not rely on a sacrificial electron donor. Immobilized ZnSe NRs on CuCrO2 generate photocurrents of around -10 μA cm-2 in an aqueous electrolyte solution (pH 5.5) with a photocurrent onset potential of approximately +0.75 V vs. RHE. This work establishes ZnSe as a state-of-the-art light absorber for photocatalytic and photoelectrochemical H2 generation.Christian Doppler Research Association (Austrian Federal Ministry of Science, Research and Economy and the National Foundation for Research, Technology and Development), the OMV Group, the EPSRC NanoDTC, EPSRC Underpinning Multi-User Equipment Grant (EP/P030467/1), the Erasmus+ program (D.W.), the Erasmus program (A.S.) and the World Premier International Research Center Initiative, MEXT, Japa

Risk, Uncertainty, and the Perceived Threat of Terrorist Attacks: Evidence of Flight-to-Quality

© 2013 World Scientific Publishing Company and Midwest Finance Association. Information provided by the US Department of Homeland Security regarding potential terrorist attacks significantly affects US Treasury securities markets. When the government announces heightened terror alert levels, investors\u27 perceptions of risk increase and investors purchase 1-month and 1-year Treasury bills and 3-year, 5-year, 7-year, and 10-year US Treasuries in a flight-to-quality episode. Partial anticipation of increased threat level announcements is stronger than the anticipation of announcements regarding the federal funds rate during the 10 days prior to an announcement