Anthracimycin activity against contemporary methicillin-resistant Staphylococcus aureus.

Anthracimycin is a recently discovered novel marine-derived compound with activity against Bacillus anthracis. We tested anthracimycin against an expanded panel of Staphylococcus aureus strains in vitro and in vivo. All strains of S. aureus tested, including methicillin-susceptible, methicillin-resistant (MRSA) and vancomycin-resistant strains of S. aureus, were susceptible to anthracimycin at MIC values of ⩽0.25 mg l(-1). Although its postantibiotic effects were minimal, anthracimycin exhibited potent and rapid bactericidal activity, with a >4-log kill of USA300 MRSA within 3 h at five times its MIC. At concentrations significantly below the MIC, anthracimycin slowed MRSA growth and potentiated the bactericidal activity of the human cathelicidin, LL-37. The bactericidal activity of anthracimycin was somewhat mitigated in the presence of 20% human serum, and the compound was minimally toxic to human cells, with an IC50 (inhibitory concentration 50)=70 mg l(-1) against human carcinoma cells. At concentrations near the MIC, anthracimycin inhibited S. aureus nucleic acid synthesis as determined by optimized macromolecular synthesis methodology, with inhibition of DNA and RNA synthesis occurring in the absence of DNA intercalation. Anthracimycin at a single dose of 1 or 10 mg kg(-1) was able to protect mice from MRSA-induced mortality in a murine peritonitis model of infection. Anthracimycin provides an interesting new scaffold for future development of a novel MRSA antibiotic

Microdosing and other phase 0 clinical trials: facilitating translation in Drug Development

Increasing costs of drug development and ethical concernsabout the risks of exposing humans and animals to novelchemical entities favor limited exposure clinical trials suchas microdosing and other phase 0 trials. An increasing bodyof research supports the validity of extrapolation from thelimited drug exposure of phase 0 approaches to the full,therapeutic exposure. An increasing number of applicationsand design options demonstrate the versatility and exibilitythese approaches offer to drug developers

Low mass T Tauri and young brown dwarf candidates in the Chamaeleon II dark cloud found by DENIS

We define a sample designed to select low-mass T Tauri stars and young brown dwarfs using DENIS data in the Chamaeleon II molecular cloud. We use a star count method to construct an extinction map of the Chamaeleon II cloud. We select our low-mass T Tauri star and young brown dwarf candidates by their strong infrared colour excess in the I-J/J-K_s colour-colour dereddened diagram. We retain only objects with colours I-J>2, and spatially distributed in groups around the cloud cores. This provides a sample of 70 stars of which 4 are previously known T Tauri stars. We have carefully checked the reliability of all these objects by visual inspection on the DENIS images. Thanks to the association of the optical I-band to the infra-red J and K_s bands in DENIS, we can apply this selection method to all star formation regions observed in the southern hemisphere. We also identify six DENIS sources with X-ray sources detected by ROSAT. Assuming that they are reliable low-mass candidates and using the evolutionary models for low-mass stars, we estimate the age of these sources between 1 Myr and < 10 Myr.Comment: 7 Pages, including 3 PostScript figures. Accepted for publication in Astronomy & Astrophysic

Racial Bias Beliefs Related to COVID-19 Among Asian Americans, Native Hawaiians, and Pacific Islanders: Findings From the COVID-19 Effects on the Mental and Physical Health of Asian Americans and Pacific Islanders Survey Study (COMPASS)

Background: During the COVID-19 pandemic, there have been increased reports of racial biases against Asian American and Native Hawaiian and Pacific Islander individuals. However, the extent to which different Asian American and Native Hawaiian and Pacific Islander groups perceive and experience (firsthand or as a witness to such experiences) how COVID-19 has negatively affected people of their race has not received much attention. Objective: This study used data from the COVID-19 Effects on the Mental and Physical Health of Asian Americans and Pacific Islanders Survey Study (COMPASS), a nationwide, multilingual survey, to empirically examine COVID-19-related racial bias beliefs among Asian American and Native Hawaiian and Pacific Islander individuals and the factors associated with these beliefs. Methods: COMPASS participants were Asian American and Native Hawaiian and Pacific Islander adults who were able to speak English, Chinese (Cantonese or Mandarin), Korean, Samoan, or Vietnamese and who resided in the United States during the time of the survey (October 2020 to May 2021). Participants completed the survey on the web, via phone, or in person. The Coronavirus Racial Bias Scale (CRBS) was used to assess COVID-19-related racial bias beliefs toward Asian American and Native Hawaiian and Pacific Islander individuals. Participants were asked to rate the degree to which they agreed with 9 statements on a 5-point Likert scale (ie, 1=strongly disagree to 5=strongly agree). Multivariable linear regression was used to examine the associations between demographic, health, and COVID-19-related characteristics and perceived racial bias. Results: A total of 5068 participants completed the survey (mean age 45.4, SD 16.4 years; range 18-97 years). Overall, 73.97% (3749/5068) agreed or strongly agreed with ≥1 COVID-19-related racial bias belief in the past 6 months (during the COVID-19 pandemic). Across the 9 racial bias beliefs, participants scored an average of 2.59 (SD 0.96, range 1-5). Adjusted analyses revealed that compared with Asian Indians, those who were ethnic Chinese, Filipino, Hmong, Japanese, Korean, Vietnamese, and other or multicultural had significantly higher mean CRBS scores, whereas no significant differences were found among Native Hawaiian and Pacific Islander individuals. Nonheterosexual participants had statistically significant and higher mean CRBS scores than heterosexual participants. Compared with participants aged ≥60 years, those who were younger (aged \u3c30, 30-39, 40-49, and 50-59 years) had significantly higher mean CRBS scores. US-born participants had significantly higher mean CRBS scores than foreign-born participants, whereas those with limited English proficiency (relative to those reporting no limitation) had lower mean CRBS scores. Conclusions: Many COMPASS participants reported racial bias beliefs because of the COVID-19 pandemic. Relevant sociodemographic contexts and pre-existing and COVID-19-specific factors across individual, community, and society levels were associated with the perceived racial bias of being Asian during the pandemic. The findings underscore the importance of addressing the burden of racial bias on Asian American and Native Hawaiian and Pacific Islander communities among other COVID-19-related sequelae

Cost of hospitalised patients due to complicated urinary tract infections: a retrospective observational study in countries with high prevalence of multidrug-resistant Gram-negative bacteria: the COMBACTE-MAGNET, RESCUING study

OBJECTIVE: Complicated urinary tract infections (cUTIs) impose a high burden on healthcare systems and are a frequent cause of hospitalisation. The aims of this paper are to estimate the cost per episode of patients hospitalised due to cUTI and to explore the factors associated with cUTI-related healthcare costs in eight countries with high prevalence of multidrug resistance (MDR). DESIGN: This is a multinational observational, retrospective study. The mean cost per episode was computed by multiplying the volume of healthcare use for each patient by the unit cost of each item of care and summing across all components. Costs were measured from the hospital perspective. Patient-level regression analyses were used to identify the factors explaining variation in cUTI-related costs. SETTING: The study was conducted in 20 hospitals in eight countries with high prevalence of multidrug resistant Gram-negative bacteria (Bulgaria, Greece, Hungary, Israel, Italy, Romania, Spain and Turkey). PARTICIPANTS: Data were obtained from 644 episodes of patients hospitalised due to cUTI. RESULTS: The mean cost per case was €5700, with considerable variation between countries (largest value €7740 in Turkey; lowest value €4028 in Israel), mainly due to differences in length of hospital stay. Factors associated with higher costs per patient were: type of admission, infection source, infection severity, the Charlson comorbidity index and presence of MDR. CONCLUSIONS: The mean cost per hospitalised case of cUTI was substantial and varied significantly between countries. A better knowledge of the reasons for variations in length of stays could facilitate a better standardised quality of care for patients with cUTI and allow a more efficient allocation of healthcare resources. Urgent admissions, infections due to an indwelling urinary catheterisation, resulting in septic shock or severe sepsis, in patients with comorbidities and presenting MDR were related to a higher cost

Catheter Colonization and Abscess Formation Due to Staphylococcus epidermidis with Normal and Small-Colony-Variant Phenotype Is Mouse Strain Dependent

Coagulase-negative staphylococci (CoNS) form a thick, multilayered biofilm on foreign bodies and are a major cause of nosocomial implant-associated infections. Although foreign body infection models are well-established, limited in vivo data are available for CoNS with small-colony-variant (SCV) phenotype described as causative agents in implant-associated infections. Therefore, we investigated the impact of the Staphylococcus epidermidis phenotype on colonization of implanted PVC catheters and abscess formation in three different mouse strains. Following introduction of a catheter subcutaneously in each flank of 8- to 12-week-old inbred C57BL/6JCrl (B6J), outbred Crl:CD1(ICR) (CD-1), and inbred BALB/cAnNCrl (BALB/c) male mice, doses of S. epidermidis O-47 wild type, its hemB mutant with stable SCV phenotype, or its complemented mutant at concentrations of 106 to 109 colony forming units (CFUs) were gently spread onto each catheter. On day 7, mice were sacrificed and the size of the abscesses as well as bacterial colonization was determined. A total of 11,500 CFUs of the complemented mutant adhered to the catheter in BALB/c followed by 9,960 CFUs and 9,900 CFUs from S. epidermidis wild type in BALB/c and CD-1, respectively. SCV colonization was highest in CD-1 with 9,500 CFUs, whereas SCVs were not detected in B6J. The minimum dose that led to colonization or abscess formation in all mouse strains was 107 or 108 CFUs of the normal phenotype, respectively. A minimum dose of 108 or 109 CFU of the hemB mutant with stable SCV phenotype led to colonization only or abscess formation, respectively. The largest abscesses were detected in BALB/c inoculated with wild type bacteria or SCV (64 mm2 vs. 28 mm2). Our results indicate that colonization and abscess formation by different phenotypes of S. epidermidis in a foreign body infection model is most effective in inbred BALB/c followed by outbred CD-1 and inbred B6J mice