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Borrelia burgdorferi (Lyme disease agents)

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Researchers analyzing viruses taken from the first confirmed human case of H7N9 in 2013 determined that 35 percent were resistant to Oseltamivir and Zanamivir, antiviral drugs used to treat H7N9 cases in the past.  Lab testing also failed to detect the strains that were resistance, suggesting that using lab tests to monitor the development of resistance in H7N9 would be useless.  The loss of two front line therapeutic options for “Bird-flu” has public health official concerned.  mBio

Researchers from Sydney University in Australia have determined that drug-resistant cancer cells communicate with other cells using vesicles, or microparticles that are shed from the drug resistant cell’s surface.  The particles dock onto a drug-sensitive cancer cell and confer resistance within hours by pumping drugs out of a treated cell.  The microparticles also seem able to sequester cancer drugs from the bloodstream, rendering them useless.  SMH

Sequella, a clinical-stage pharmaceutical company commercializing novel antibiotics to treat life-threatening infectious diseases has licenses Pfizer Inc.’s exclusive worldwide rights to develop and commercialize sutezolis, a Phase 3 oxazolidinone antibiotic currently in development for the treatment of tuberculosis.  In addition to showing promise in the treatment of TB, Sutezolid also shows promise for antibiotic gram (+) infections such as staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). heraldonline

The FDA has granted Qualified Infectious Disease Product (QIDP) status to the antibiotic product candidate Eravacycline (Tetraphase Pharmaceuticals).  The QIDP designation granted for complicated intra-abdominal infection and complicated urinary tract infection will mean that the drug will benefit from certain incentives for development under the Generating Antibiotic Incentives Now Act (GAIN Act).  These incentives include priority review and eligibility for fast-tract status.  If approved as a drug by the FDA, Eravacycline will be eligible for an additional five-year extension of  Hatch-Waxman exclusivity Bezinga

Researcher from Cold Spring Harbor Laboratory have showed that there are molecules around the cancer cells in pancreatic tumors such as Connective Tissue Growth Factor (CTGF), that provide signals that overcome the killing power of chemotherapeutic drugs.  But the Researchers may have found a way to prevent this. The antibody FG-3019, a molecule that is now in phase 1/2 clinical investigation as a treatment option for pancreatic cancer, binds to CTGF and prevents it from providing cells with survival cues.  The Tuveson lab used a novel mouse model for pancreatic cancer to test FG-3019. Tumors in mice treated with FG-3019 in combination with the chemotherapeutic drug gemcitabine stopped growing. Inside the tumor there was an increase in the amount of cancer cells dying through apoptosis, which was associated with a decrease in levels of XIAP. Importantly, mice treated with both FG-3019 and gemcitabine also had an increased lifespan.  This suggests that overcoming resistance to medicines in cancer may be possible using combination therapy—co-administering molecules that help open up the tumor to drugs as well as other molecules that prevent cancer cell survival signals alongside the chemotherapeutics.  PNAS

Whole-genome sequencing of human malaria parasites has revealed genomic regions that are associated with resistance to artemisinin-based drugs. The findings may help to explain the origin and spread of this worrying trendNature

Researchers  at Sunnybrook Health Sciences Centre, in Toronto examined data from adult inpatients at 176 hospitals across Canada to evaluate the prevalence of Clostridium difficile, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus infections in Canadian hospitals.  Findings of the study revealed that the median (range) prevalence rates forMRSA and vancomycin-resistant Enterococcus(VRE) colonization or infection and C. difficileinfection were 4.2% (0%-22.1%), 0.5% (0%-13.1%) and 0.9% (0%-8.6%), respectively, according to the researchers.  Healio

A new study has found that cells in the placenta, called trophoblasts, are scattered throughout the placenta and limit the spread of viruses.  In the study, researchers found that primary human trophoblast (PHT) cells were resistant to a wide range of viruses like herpes simplex 1, poliovirus, and cytomegalovirus. The PHT cells were found to block the binding of viruses to them altogether, and so they could not be infected. As a result of their survival, the PHT cells send signals to other cells in the placenta so that they too can become resistant to infection by the virus. The signals can also cause infected cells to die quickly and prevent the spread of the virus.  PNAS

Basilea Pharmaceutica Ltd. (SIX: BSLN) reported today that new data on drug candidates from its development pipeline were presented at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) held in Berlin, Germany, from April 27 to 30.  Basilea is one of the few companies worldwide committed to address the problem of growing resistance against currently available antibiotics and antifungals. The data presented at ECCMID on the antifungal isavuconazole and the two antibiotics ceftobiprole and BAL30072 further substantiate the promising profiles of these innovative product candidates for addressing high unmet medical need.  ResearchViews

Surveying the genomes of malaria parasite populations can identify resistance to the frontline malaria drug artemisinin, a worldwide research collaboration has shown.  University of Oxford

Top officials from the World Health Organization (WHO) were in Phnom Penh on Thursday to launch a three-year, $400 million plan to prevent the “imminent threat” of an increasingly drug-resistant strain of malaria from escaping the region, a plan that puts Cambodia at its core.

Launched to coincide with World Malaria Day, the Emergency Response to Artemisinin Resistance in the Greater Mekong Sub-region aims to stop that resistance from spreading to Africa, where most of the world’s 216 million people infected each year by the malaria parasite live. The mosquito-borne disease kills more than 600,000 of them annually. WHO

Researchers at Duke University  have uncovered a previously unknown molecular network that regulates cell death.  The network was discovered during a 7-year study to understand how breast cancer cells resist treatment with the targeted therapy lapatinib.  The process of studying four different types of breast cancer They found that in each case, the drug resistance could be traced to the presence of high levels of MDM2, which was found to be blocking cell death signals independent of whether p53 was activated.  The findings suggest that other drugs targeting tyrosine kinases may be vulnerable to resistance using this same mechanism.  Science Signaling

In a study just published the Infectious Disease Society of America reports that only seven new drugs in clinical development for the treatment of infections caused by multidrug-resistant Gram-negative bacilli (GNB) and none that address the entire spectrum of clinically relevant GNB resistance. The report’s authors also found a dwindling number of pharmaceutical companies investing in antibiotic research and development (R&D), signaling an urgent need for action to address the problem as rates of multi-drug resistant pathogens continue to rise.  Clinical Infectious Disease

A new video from Extending the Cure is focused on educating the public that antibiotics are a shared resource in need of preservation. YouTube

 

Researchers from Penn State University have discovered a new antibiotic class that could be used to treat drug resistant tuberculosis, anthrax, and food poisoning.  The antibiotic targets the process called "trans-translation" helps bacteria to keep protein synthesis moving by removing faulty messenger RNA. By using a pharmaceutical chemical to use this system to gum up the works in bacterial production, tough-to-treat bacteria can be killed easily. The process does not exist in plants, animals, or humans, so a specifically-targeted chemical would not have significant effects on a person's cells.  

Further testing of the chemicals in infectious bacteria, such as Shigella, which is a large source of food-borne illness, and Bacillus anthracis, or anthrax, showed that only one molecule called KKL-35 was able to block the growth of distantly-related bacteria, making it "broad-spectrum." The tests showed that KKL-35 specifically blocked the trans-translation process. The research team then investigated the potency of the drug on the bacteria that causes tuberculosis, Mycobacterium tuberculosis, which is becoming drug resistant in many countries around the globe. The drug was more than 100-fold better at blocking bacterial growth than the currently used treatments.  PNAS

 
Researchers at Albert Einstein Medical College have conducted experiments suggesting that Vitamin C can be used to treat drug resistant tuberculosis.  Vitamin C, a compound known to drive the Fenton reaction, sterilizes cultures of drug-susceptible and drug-resistantMycobacterium tuberculosis, the causative agent of tuberculosis. While M. tuberculosis is highly susceptible to killing by vitamin C, other Gram-positive and Gram-negative pathogens are not. The bactericidal activity of vitamin C against M. tuberculosis is dependent on high ferrous ion levels and reactive oxygen species production, and causes a pleiotropic effect affecting several biological processes.  Nature Communications

NIH is funding the development of a clinical research network on antibacterial resistance.  Duke University, Durham, N.C., has been awarded $2 million to initiate a new clinical research network focused on antibacterial resistance. Total funding for the leadership group cooperative agreement award could reach up to $62 million through 2019. Funding is provided by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. 

Co-led by principal investigators Vance Fowler, M.D., of Duke University, and Henry Chambers, M.D., of the University of California, San Francisco, the leadership group will design, implement and manage the network's clinical research agenda. In addition to the two principal investigators, the leadership group will include a consortium of more than 20 investigators nationwide with experience in diverse areas related to antibacterial resistance. The scientific efforts the leadership group is expected to undertake include:

  • Conducting early-stage clinical evaluation of new antibacterial drugs 
  • Performing clinical trials to optimize currently licensed antibacterial drugs to reduce the risk of resistance 
  • Testing diagnostics 
  • Examining best practices in infection control programs to prevent the development and spread of resistant infections.  Eurekalert

A new study published online Wednesday by the New England Journal of Medicine demonstrates the effectiveness of using antimicrobial soap and ointment on all intensive-care unit (ICU) patients to reduce the burden of methicillin-resistant Staphylococcus aureus (MRSA), and decrease bloodstream infections. The Society for Healthcare Epidemiology of America (SHEA) says it is encouraged by the findings and hopes the study will help inform and advance evidence-based infection prevention practices and policies.  ICT

Representative Jim Matheson (D-UT) recently reintroduced the Strategies to Address Antimicrobial Resistance (STAAR) Act to provide urgently needed federal leadership to tackle growing antibacterial resistance. 

the STAAR Act provides direction and authority for the federal government to combat antimicrobial resistance by:

  1. Reauthorizing the Antimicrobial Resistance Task Force, establishing an Advisory Board of outside experts and an Antimicrobial Resistance Office in the Department of Health and Human Services whose director will coordinate government efforts to combat antimicrobial resistance;
  2. Building upon existing National Institutes of Health (NIH) efforts by creating an antimicrobial resistance strategic research plan and authorizing the Clinical Trials Network on Antibacterial Resistance;
  3. Building upon CDC’s programs by authorizing the Antimicrobial Resistance Surveillance and Laboratory Network and additional efforts to enhance the national capacity to prevent the transmission of resistant infections and the development of resistance; 
  4. Expanding current efforts to collect antimicrobial resistance and use data; 
  5. Developing and testing quality measures on antimicrobial use. ISDA

In March, 2013, a novel influenza A subtype H7N9 virus (A/H7N9) was detected in patients with severe respiratory disease in eastern China. Virological factors associated with a poor clinical outcome for this virus remain unclear.

The researchers said treating patients quickly with oseltamivir (Tamiflu, Roche) — within 2 days of disease onset — effectively reduced their viral load, but a mutation appeared in two patients, and that mutation helped lead to a viral rebound. Viral load was investigated sequentially in patients’ throat, stool, serum and urine specimens.  Lancet

Researchers at The Wistar Institute describe how they increase the effectiveness of anti-melanoma drugs by combining anticancer therapies with diabetes drugs.  Their studies, conducted in cell and animal models of melanoma, demonstrate that the combined therapy could destroy a subset of drug-resistant cells within a tumor.

"We have found that the individual cells within melanoma tumors are not all identical, and tumors contain a sub-population of cells that are inherently drug resistant, which accounts for the fact that advanced melanoma tumors return no matter how much the tumor is depleted," said Meenhard Herlyn, D.V.M., D.Sc., professor and director of Wistar's Melanoma Research Center. "We found that these slow-growing, drug-resistant cells are marked by a high rate of metabolism, which makes them susceptible to diabetes therapeutics."

"Our findings suggest a simple strategy to kill metastatic melanoma -- regardless of cell type within the tumor -- by combining anticancer drugs with diabetes drug," Herlyn said. "The diabetes drug puts the brakes on the cells that would otherwise repopulate the tumor, thus allowing the anticancer drug to be more effective."  Cancer Cell

The main drug used to cure TB (isoniazid) can also be used to prevent the acquisition of the disease.  Isoniazid is recommended for use by the World Health Organization (WHO) to prevent tuberculosis in HIV-infected individuals .  Recently, the WHO has recommended expanding this preventative treatment, Isoniazid preventative therapy (IPT) to entire communities.  In a recently published study, mathematical modeling suggests that while previous reviews did find an elevated risk of resistance among IPT treated individuals, there may be sufficient pressure in community-wide IPT to increase resistance. Science Translational Medicine

A new class of investigational medicines may help to treat patients with cancers driven by mutations in genes such as BRAF or KRAS/NRAS, including those patients who have become resistant to therapies that target BRAF directly.  Recent clinical trials with new drugs target ERK proteins that are components of the MAPK signaling pathways.  Preclinical results indicate the drugs induce tumor regression in mouse models. Oncotarget

Researchers have discovered that melanomas that develop resistance to anti-cancer drug Vemurafenib also become dependent on it, leading to the exploration of intermittent treatment with Vermurafenib as a management technique to preventing  drug resistance. Science Daily

A mixture od sequestration cuts is hindering the shift of American medicine from treatment to prevention of disease, leaving the population potentially more vulnerable to infectious disease.  GlobalData

Xellia, a pharmaceutical company focusing on global anti-infectives market has announced the development plans for new antibiotics targeting Gram-negative bacterial infections.  Based on a four year collaboration with SINTEF Materials and Chemistry and Statens Serum Institut (Copenhagen) the project is being supported by a $3 million grant from the Research Council of Norway. News Medical