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Cease and Persist?

After a bacterial infection is established, a small percentage of the bacteria slow their metabolism in response to environmental stressors. This semi-dormant state affords increased tolerance to antibiotics, especially aminoglycosides, lending these bacteria the name persisters. Over time, and often upon completion of a course of antibiotics, the persisters reactivate, leading to recurrent, chronic, and increasingly aggressive infections. Persistence is one of many mechanisms contributing to increasing rates of antibiotic resistance in modern healthcare.

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Biofilms: Skimming the Surface

A biofilm is a thin layer of microorganisms that have adhered to a surface and formed a complex, multicellular, three-dimensional structure. The National Institute of Health (NIH) reports that biofilms account for 80% of microbial infections in humans and have the ability to affect every organ in the body. Biofilms can form on living tissues, but also on artificial surfaces like catheters, prosthetics, pacemakers, and other medical devices. Pathogenic bacteria known to form biofilms include Escherichia coli, Staphylococcus aureus, and Salmonella species.

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Trick and Treat Bacteria

What do the ancient Greeks and a group of modern-day researchers have in common? Scientists at the University of Washington School of Medicine are using a “Trojan Horse” strategy to trick and treat (Happy Halloween!) antibiotic-resistant bacteria. Pseudomonas aeruginosa, a superbug that can cause serious wound and lung infections, relies on the uptake of iron to survive and spread. Microbiologists discovered that gallium, a metal similar to iron, tricks the bacteria by mimicking the essential nutrient. However, once inside, gallium fails to nourish the bacteria in the way iron does – and it actually harms them.

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E. coli in Retail Poultry May Cause UTIs

Foodborne bacteria are a common cause of gastrointestinal infection, but a recent study found that a strain of E. coli in retail chicken and turkey may be transmitted to humans and cause other infections. Researchers conducted a one-year study of urine and blood isolates from hospital patients in Flagstaff, AZ and compared these cultures to chicken, turkey, and pork from major grocery chains in the same city. E. coli was found in 72% of the patient samples and about 80% of the meat samples. The poultry samples, in particular, contained a specific strain called ST131-H22 which causes urinary tract infections (UTIs) in people. ST131 can also travel from the bladder to the blood, resulting in more serious infections and even death.

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Synergistic Combination Therapy Against Resistant Pathogens

Due to increasing rates of antimicrobial resistance, scientists are researching the potential of combination therapy (two or more drugs used together) to restore activity against resistant pathogens. In a recent study, investigators screened 19 antibiotics with colistin and observed high rates of synergy, where the efficacy of the combination therapy was greater than the sum of their separate effects. “It was remarkable to see two drugs, each of which is inactive on its own against these bacteria, inhibiting them in combination,” noted a doctor leading the study.

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Trained Dog Can Detect C. difficile

The nose knows! A dog in British Columbia, Canada has been trained to detect Clostridium difficile. C. difficile has a very particular odor, and a springer spaniel named Angus has been trained to sniff it out just as bomb dogs can identify explosives. Angus can detect the bacteria from several feet away and indicate the source to his trainer, who then provides a treat.

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NDM-1 and Drug Resistance

NDM-1 is a gene that codes for New Delhi metallo-beta-lactamase 1, an enzyme that provides resistance to multiple classes of antibiotics, including carbapenems, cephalosporins, and penicillins. Pathogens carrying this gene typically carry other resistance genes as well, classifying them as superbugs because the infections are extremely hard to treat with commonly used antibiotics.

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Preclinical Research in Drug Development

Preclinical studies provide data about drug safety and efficacy in animals to determine if the drug should proceed to clinical testing in humans. Three important factors to consider when conducting preclinical research are pharmacodynamics, pharmacokinetics, and toxicology.

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Economic Forecast for Preclinical CROs

Research and development (R&D), as well as manufacturing, are often outsourced from big pharma to smaller contract research organizations (CRO) with more resources and specialized expertise. As the global pharmaceutical market grows, so too does the need for contract service providers. Market research reports indicate a trend toward increasing capital spent on contract services, with a projected annual expenditure of $56.24 billion by 2023 (up $17.04 billion from $39.13 billion in 2018).

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These Pathogens Can ESKAPE Most Antibiotics

Antimicrobial resistance poses an ever-increasing healthcare threat, with pathogens evolving resistance faster than novel therapies are being developed. ESKAPE pathogens are just six of the many bacteria which have acquired the ability to escape the actions of current antibiotics.

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