Carbapenem-resistant Enterobacterales (CRE) are subject to intense global monitoring in an attempt to maintain awareness of prevalent and emerging resistance mechanisms and to inform treatment and ...infection prevention strategies. CRE and extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales are not usually examined collectively in regards to their shared pool of resistance determinants. Here, we genetically and phenotypically assess clinical isolates of CRE and extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales in the growing region of Central Texas, where CRE are emergent and occurrence of non-carbapenemase-producing-CRE (non-CP-CRE) infections is increasing.
CRE (n=16) and ESBL-producing Enterobacterales (n=116) isolates were acquired from a regional hospital in Central Texas between December 2018 and January 2020. Isolates were assessed genetically and phenotypically using antibiotic susceptibility testing, targeted PCR, and whole genome sequencing.
CRE infections are increasing in incidence in Central Texas, and
is causing the majority of these infections. Moreover,
sequence type (ST) 307 is commonly found among both non-CP-CRE and EBSL-producing strains. Isolates carry similar plasmids harboring the gene for the ESBL CTX-M-15 and belong to the global lineage, rather than the Texas lineage, of ST307. Antibiotic resistance profiles, sequence data, and clinical records suggest that porin mutations may promote the transition of ST307 isolates from ESBL-producing to non-CP-CRE. In addition to antibiotic resistance mechanisms, several CRE isolates harbor active colicinogenic plasmids, which might influence the competitiveness of these bacteria during patient colonization.
of the global ST307 lineage is circulating in Central Texas and is responsible for both non-CP CRE and ESBL-producing Enterobacterales infections. Enhanced surveillance is needed to understand the possible routes for the emergence of non-CP-CRE from EBSL-producing strains.
Presently marketed vaginal barrier agents are cytotoxic and damage the vaginal epithelium and natural vaginal flora with frequent use. Novel noncytotoxic agents are needed to protect women from ...sexually transmitted diseases. One candidate compound is a high-molecular-mass form of soluble poly(sodium 4-styrene sulfonate) (T-PSS). The antimicrobial activity of T-PSS was evaluated in primary culture systems and in a genital herpes murine model. Results obtained indicate that T-PSS is highly effective against herpes simplex viruses, Neisseria gonorrhoeae, and Chlamydia trachomatis in vitro. A 5% T-PSS gel protected 15 of 16 mice from vaginal herpes, compared with 2 of 16 mice treated with a placebo gel. Moreover, T-PSS exhibited little or no cytotoxicity and has an excellent selectivity index. T-PSS is an excellent candidate topical antimicrobial that blocks adherence of herpes simplex virus at low concentrations, inactivates virus at higher concentrations, and exhibits a broad spectrum of antimicrobial activity.
ABSTRACT
The spread of sexually transmitted infections (STIs) and limited methods for control of pregnancies presents high risks to the reproductive health of women. Methods controlled by women and ...directed toward disease prevention and contraception are needed. We report on preclinical studies of the biological properties of sodium cellulose sulfate (Ushercell) currently being developed for use as a topical contraceptive antimicrobial agent. Ushercell was evaluated with tests designed to identify its contraceptive and antimicrobial properties. Ushercell inhibits hyaluronidase (reversible; IC50 = 1.7 mg/mL), impairs sperm penetration of cervical mucus (approximately 70% inhibition at 1 mg/mL), and acts as a stimulus for acrosomal loss (IC50 = 52 ng/mL). It prevents conception in rabbits when added to spermatozoa (approximately 95% inhibition at 1 mg/mL) or when vaginally applied (complete contraception by 45 mg) before insemination. However, up to 50 mg/mL, Ushercell does not irreversibly immobilize spermatozoa, suggesting that Ushercell is not cytotoxic. Ushercell has a broad spectrum of antimicrobial activity in vitro. Inhibited microbes include human immunodeficiency viruses (different laboratory strains and clinical isolates; IC50 values range from 3 to 78 μg/mL), herpes viruses, HSV‐1 (IC50 = 59 ng/mL) and HSV‐2 (IC50 = 24 ng/mL), Neisseria gonorrhoeae (IC50 = 2 μg/mL), and Chlamydia trachomatis (IC50 = 78 μg/mL). In contrast, Ushercell does not inhibit growth of beneficial vaginal bacteria, Lactobacillus gasseri, at 5 mg/mL. These results suggest that the antimicrobial effects of Ushercell are selective, and not likely mediated by nonspecific cytotoxic mechanisms. These data provide the basis for further clinical development of Ushercell as a vaginal agent to prevent unplanned pregnancy and STIs.
A commercial preparation of a sodium polystyrene sulfonate (designated as N‐PSS; its molecular weight is 500000 daltons) was tested as an inhibitor of sperm function and as a preventive agent for ...conception and the transmission of sexually transmitted diseases. The polymer is an irreversible inhibitor of hyaluronidase and acrosin; its IC50 values are 5.7 μg/mL and 0.5 μg/mL, for hyaluronidase and acrosin, respectively. N‐PSS is also a stimulus of human sperm acrosomal loss. It produces maximal acrosomal loss at 2.5 μg/mL. Contraception in rabbits is nearly complete when rabbit spermatozoa are pretreated with 0.5 mg/mL of N‐PSS before artificial insemination; however, N‐PSS does not immobilize spermatozoa at concentrations as high as 50 mg/mL N‐PSS has broad spectrum antiviral and antibacterial activities. Infection by human immunodeficiency virus and herpes simplex virus are inhibited by N‐PSS; 3‐log reductions are produced by 7 μg/mL and 3 μg/mL, respectively. N‐PSS is active against Chlamydia trachomatis and Neisseria gonorrhoeae. At 1 mg/mL, N‐PSS inhibits chlamydial infectivity by more than 90%. N‐PSS produces a 3‐log reduction in gonococcal growth at 15 μg/mL. In contrast, N‐PSS (5 mg/mL) does not affect the growth of Lactobacillus (normal component of the vaginal flora). N‐PSS can be classified as a noncytotoxic contraceptive antimicrobial agent. These properties justify bringing a polystyrene sulfonate into clinical trials for its evaluation as a preventive agent for conception and several sexually transmitted diseases.
This article lists the top 25 most powerful businesspeople in the world. They are: 1. Steve Jobs of Apple, 2. Rupert Murdoch of News Corp, 3. Lloyd Blankfein of Goldman Sachs, 4. Eric Schmidt, Larry ...Page, and Sergei Brin of Google, 5. Warren Buffett of Berkshire Hathaway, 6. Rex Tillerson of Exxon Mobil, 7. Bill Gates of Microsoft and the Bill & Melinda Gates Foundation, 8. Jeff Immelt of GE, 9. Katsuaki Watanabe of Toyota, 10. A. G. Lafley of Procter & Gamble, 11. John Chambers of Cisco, 12. Li Ka-shing of Cheung Kong (Holdings) and Hutchison Whampoa, 13. Lee Scott of Wal-Mart, 14. Lakshmi Mittal of ArcelorMittal, 15. Jamie Dimon of JP Morgan Chase, 16. Mark Hurd of Hewlett-Packard, 17. James McNerney of Boeing, 18. Marius Kloppers of BHP Billiton, 19. Steve Schwarzman of Blackston, 20. Carlos Slim of TelMex and Carso Foundation, 21. Steve Feinberg of Cerberus, 22. Indra Nooyi of PepsiCo, 23. Ratan Tata of Tata Group, 24. Bob Iger of Walt Disney, and 25. Bernard Arnault of LVMH.
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