FDA Approves BAXDELA™ (Delafloxacin) For Skin Infections

MedicalResearch.com Interview with:

Dr. Sue Cammarata, MD Chief Medical Officer Melinta Therapeutics

Dr. Cammarata

Dr. Sue Cammarata, MD
Chief Medical Officer
Melinta Therapeutics

MedicalResearch.com:   Would you explain what is meant by MRSA?

Response: MRSA is methicillin-resistant Staphylococcus aureus, a type of staph bacteria that is  resistant to many antibiotics. MRSA is noted by the CDC as one of the top 18 drug-resistant bacteria threats to the United States.  (from CDC https://www.cdc.gov/drugresistance/biggest_threats.html  ) 

MedicalResearch.com:   Why is infection with MRSA so serious?

Response:  MRSA can cause skin infections, lung infection and other issues.

If left untreated, MRSA infections can become severe and cause sepsis – a life-threatening reaction to severe infection in the body – and even death.  MRSA can also cause major issues, such as bloodstream infectionspneumonia and surgical site infections in a healthcare setting, such as a hospital or nursing home. “Resistance to first-line drugs to treat infections caused by Staphlylococcus aureus—a common cause of severe infections in health facilities and the community—is widespread. People with MRSA (methicillin-resistant Staphylococcus aureus) are estimated to be 64% more likely to die than people with a non-resistant form of the infection.”  (quote from WHO website http://www.who.int/mediacentre/factsheets/fs194/en/  )   Continue reading

Animal Visitation Programs Can Raise Infection Risks In Health Care Facilities

MedicalResearch.com Interview with:

Deborah Linder, DVM, MS, DACVN</strong> Research assistant professor Cummings School of Veterinary Medicine Tufts University and Associate director of the Tufts Institute for Human-Animal Interaction

Dr. Linder

Deborah Linder, DVM, MS, DACVN
Research assistant professor
Cummings School of Veterinary Medicine
Tufts University and
Associate director of the Tufts Institute for Human-Animal Interaction

MedicalResearch.com: What is the background for this study?

Response: In our experience with our own therapy animal program, Tufts Paws for People, we have seen facilities and organizations put animals and people at risk by not following rigorous health and safety policies, and this certainly was confirmed by the results of our study. Lax health and safety policies typically aren’t intentional but occur as a result of enthusiasm for therapy animal programs without being aware of potential risks and what questions to ask. Also, it’s not just obvious problems that can occur, such as bites or allergies. It also can be an animal spreading infections due to diet or inadequate grooming, or unwanted stress on the animal.

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How Does HPV Virus Lead To Skin Cancer?

MedicalResearch.com Interview with:
Prof. Dr. med. Sigrun Smola
Institute of Virology, Saarland University
Homburg/Saar, Germany

MedicalResearch.com: What is the background for this study?

Response: Non-melanoma skin cancer (NMSC), the most common cancer in humans, is caused by UV-irradiation. The potential co-factor role of cutaneous genus beta-human papillomaviruses (beta-HPV) in skin carcinogenesis, particularly in immunosuppressed patients, has become a major field of interest. However, the underlying mechanisms were unclear.

The skin has natural mechanisms providing protection against UV-induced damage. One important factor suppressing UV-induced skin carcinogenesis is the transcription factor C/EBPα belonging to the CCAAT/enhancer binding protein family. C/EBPα can induce cellular differentiation and is regarded as a tumor suppressor in various tissues. When C/EBPα expression is blocked in these tissues, tumorigenesis is enhanced.

Another important factor is the microRNA-203. It has been shown to control “stemness” in normal skin by suppressing a factor called p63. In many tumors miR-203 expression is shut off releasing this “brake”.

In our study we demonstrate that cutaneous beta-HPV interferes with both protective factors providing an explanation how cutaneous beta-HPV enhances the susceptibility to UV-induced carcinogenesis. Moreover, we provide evidence that these viruses regulate miR-203 via C/EBPα.

We have investigated this mechanism in Epidermodysplasia verruciformis (EV) patients that serve as a human model disease for studying the biology of genus beta-HPVs. They are highly susceptible to persistent genus beta-HPV infection, such as HPV8, and have an increased risk to develop non-melanoma skin cancer at sun-exposed sites.

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Efficacy of Recombinant Flu Vaccine in Adults 50 Years of Age or Older 

MedicalResearch.com Interview with:

Lisa M. Dunkle, M.D. Chief Medical Officer Protein Sciences Corporation 1000 Research Parkway Meriden, CT 

Dr. Dunkle

Lisa M. Dunkle, M.D.
Chief Medical Officer
Protein Sciences Corporation
1000 Research Parkway
Meriden, CT

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The first and only recombinant protein influenza vaccine (RIV, Flublok) was approved in 2013 as a trivalent formulation for use in adults 18 years of age and older. This approval was based on demonstration of clinical efficacy (full approval) in adults 18-49 years of age and accelerated approval was granted for adults 50 years of age and older. Two clinical trials were conducted in 2014-2015 with RIV4 (Flublok Quadrivalent), of which the trial reported in the current NEJM is one.

These studies supported full approval of Flublok in adults 50 years of age and older and approval of Flublok Quadrivalent in all adults 18 years of age and older. The second trial of immunogenicity of Flublok Quadrivalent in adults 18-49 years of age will be the subject of another publication in the near future.

The main findings of the current trial are well summarized in the Conclusion of the Abstract: “RIV4 provided better protection than standard-dose IIV4 against confirmed influenza-like illness in older adults.”

Additionally, the recombinant vaccine (RIV4, Flublok Quadrivalent) demonstrated significantly less injection site pain and tenderness following vaccination. Based on the characteristics of the study participants, one can conclude that RIV4 is safe and effective in most individuals with underlying chronic diseases

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The President’s Malaria Initiative Reduced All-Cause Childhood Mortality

MedicalResearch.com Interview with:

Alexsandra Jakubowski

Aleksandra Jakubowski MPH

Aleksandra Jakubowski, MPH PhD candidate
Department of Health Policy and Management
Gillings School of Global Public Health
University of North Carolina at Chapel Hill

MedicalResearch.com: What is the background for this study?

Response: The US President’s Malaria Initiative (PMI) provides approximately $600 million annually to fund implementation of key evidence-based malaria prevention and treatment interventions, including insecticide treated nets (ITNs), artemisinin-based combination therapy (ACT), and indoor residual spraying (IRS) to populations in 19 recipient countries in sub-Saharan Africa (SSA). Despite this considerable investment, no study to date has evaluated the impact of PMI on population health outcomes. Previous evaluations have noted improved health outcomes in PMI countries, but comparison groups are needed to establish whether these changes were beyond the declining trends in mortality observed in the rest of the region. Our study sought to generate objective evidence for policy makers about the role this US-funded malaria aid program may have played in curbing child mortality in SSA.

We used a quasi-experimental design known as difference-in-differences to compare trends in health outcomes in PMI-recipient vs. PMI non-recipient countries. We analyzed publicly-available data from 32 countries in SSA spanning a period that included about ten years before and after the introduction of the program.

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Legionnaires’ Disease Is Widespread and Deadly in US Health Care Facilities

MedicalResearch.com Interview with:
Elizabeth A. Soda, MD
Epidemic Intelligence Service
Divison of Bacterial Diseases
National Center of Immunization and Respiratory Diseases
CDC

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Legionella is a waterborne bacterium responsible for Legionnaires’ disease, an often severe pneumonia. Legionnaires’ disease primarily affects certain groups of individuals such as those ≥50 year of age, current or former smokers, and those with chronic diseases or weakened immune systems. Health care facilities often have large and complex water systems and care for vulnerable populations that are susceptible to developing Legionnaires’ disease. Thus preventing hospitalized patients from developing Legionnaires’ disease is the ultimate goal. This analysis aimed to describe health care-associated Legionnaires’ disease in 2015 from the 21 U.S. jurisdictions that completely reported their health care-associated Legionnaires’ disease cases to the CDC’s Supplemental Legionnaires’ Disease Surveillance System (SLDSS).

Over 2,800 cases of Legionnaires’ disease cases were reported to SLDSS by the 21 jurisdictions, and 553 (20%) were considered health care associated. The analysis showed 16 of the 21 (76%) jurisdictions had at least one case of Legionnaires’ disease definitely related to a stay in a hospital or long-term care facility. In total there were 85 (3%) definite health care-associated Legionnaires’ disease cases (as defined by continuous exposure to a hospital or long-term facility for the entire 10 days before symptom onset) that resulted from 72 different health care facilities.

Additionally, 20 of 21 jurisdictions (95%) reported 468 (17%) possible health care-associated Legionnaires’ disease cases (as defined by any exposure to a health care facility for a portion of the 10 days before symptom onset) that resulted from approximately 415 different health care facilities.

While approximately 9% of Legionnaires’ disease cases overall are fatal, this report showed a case fatality of 25% for definite health care-associated cases.

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Outcomes of Hospital-Onset Multidrug Resistant Pseudomonas aeruginosa

MedicalResearch.com Interview with:

Sanjay Merchant, PhD Executive Director Center for Observational and Real-world Evidence (CORE) Merck

Dr. Merchant

Sanjay Merchant, PhD
Executive Director
Center for Observational and Real-world Evidence (CORE)
Merck

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In February, the World Health Organization (WHO) published its first ever list of antibiotic-resistant “priority pathogens” that pose the greatest threat to human health. The list highlights in particular the threat of gram-negative bacteria that are resistant to multiple antibiotics, referred to as multidrug-resistant (MDR) bacteria, which have built-in abilities to find new ways to resist treatment. MDR Pseudomonas aeruginosa (MDR PsA) is listed as one of the pathogens in the Critical category in terms of need for new therapies. It poses an urgent threat.

We set out to better understand the clinical and economic burden associated with hospital-onset MDR PsA so that appropriate treatment strategies can be employed to mitigate resistance. Our findings were presented at ASM Microbe 2017.

Mortality rates for hospital-onset MDR PsA patients (20.1%) were almost twice as high compared to patients who did not have MDR PsA (11.5%). The MDR PsA patient group had a significantly higher odds ratio for mortality even after controlling for various factors that may impact mortality.

Hospital-onset MDR PsA patients spent six additional days in the hospital when compared to patients who did not have MDR PsA infectionsThese findings highlight the public health threat of MDR PsA among hospitalized patients and the need for timely and effective therapy.

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Handwashing Effectiveness Not Affected By Water Temperature

MedicalResearch.com Interview with:

Donald Schaffner, PhD Extension Specialist in Food Science and Distinguished Professor Rutgers-New Brunswick

Dr. Schaffner

Donald Schaffner, PhD
Extension Specialist in Food Science and Distinguished Professor
Rutgers-New Brunswick

MedicalResearch.com: What is the background for this study?

Response: We been interested in handwashing and cross-contamination research for more than 15 years. About 10 years after I started as a faculty member I was approached about doing research in this area. The first paper republished has turned into my most highly cited paper. I think it was mostly a matter of being in the right place at the right time, with the right idea.

This latest bit of research came out of my ongoing participation in the Conference for Food Protection. This is an unusual meeting, and unlike any other scientific conference. It’s a group of industry scientists, government regulators, and academics would get together every two years to help the FDA Center for Food Safety and Applied Nutrition update a document called the Model Food Code. The code has no regulatory standing, but it is used by state health agencies as the basis for state food codes that regulate restaurants, supermarkets, and other food service establishments.

There are several provisions in the code that we wanted to try to impact with our research. The code currently states that hands must be washed in warm water. The plumbing section of the code also states that hand wash sinks must be capable of dispensing water at 100°F. We wanted to explore whether there was any scientific basis statements.

In some recent survey-based research, graduate student that is also the first author on this manuscript surveyed the Internet for the kind of advice was offered on handwashing posters that provide advice on how to wash your hands. He found that the recommendations varied widely including recommendations on how long to wash your hands.

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Study Finds Single Antibiotic Cephalexin Alone Is Appropriate Outpatient Treatment For Cellulitis

MedicalResearch.com Interview with:
Gregory John Moran, MD, FACEP
Emergency Medicine Dept. & Infectious Diseases Service
UCLA Medical Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The bacterial etiology of cellulitis is difficult to determine because there is usually no material for culture, but streptococci are believed to be the most common etiology. Since the emergence of MRSA as a common cause of skin infections in the community, many clinicians add a second antibiotic with MRSA activity to an oral cephalosporin, such as a combination of cephalexin plus trimethoprim-sulfamethoxazole. It is unknown if there is an additional benefit to adding MRSA activity for treatment of cellulitis. This randomized, blinded trial compared cephalexin plus placebo to cephalexin plus trimethoprim-sulfamethoxazole for outpatient treatment of cellulitis without an abscess or wound.

Bottom line: We did not find a benefit from addition of trimethoprim-sulfamethoxazole.

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Opioid Agonist Therapy Found Cost Effective In Preventing HIV in People Who Inject Drugs

MedicalResearch.com Interview with:

Cora Bernard, MS, PhD candidate Pre-doctoral Student in Management Science and Enginnering Affiliate, Center for Health Policy and the Center for Primary Care and Outcomes Research Stanford Health Policy

Cora Bernard

Cora Bernard, MS, PhD candidate
Pre-doctoral Student in Management Science and Enginnering
Affiliate, Center for Health Policy and the Center for Primary Care and Outcomes Research
Stanford Health Policy

MedicalResearch.com: What is the background for this study?

Response: The US opioid epidemic is leading to an increase in the US drug-injecting population, which also increases the risks of HIV transmission. It is critical to public health that the US invests in a coherent and cost-effective suite of HIV prevention programs. In our model-based analysis, we considered programs that have the potential both to prevent HIV and to improve long-term health outcomes for people who inject drugs. Specifically, we evaluated opioid agonist therapy, which reduces the frequency of injection; needle and syringe exchange programs, which reduce the frequency of injecting equipment sharing; enhanced HIV screening and antiretroviral therapy programs, which virally suppress individuals and decrease downstream transmission; and oral HIV pre-exposure prophylaxis (PrEP), which is taken by an uninfected individual and lowers the risk of infection.

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Study Finds No Link Between First Trimester Influenza Vaccination and Major Structural Birth Defects

MedicalResearch.com Interview with:

Dr. Elyse Olshen Kharbanda, MD MPH HealthPartners Institute Minneapolis, MN

Dr. Kharbanda

Dr. Elyse Olshen Kharbanda, MD MPH

HealthPartners Institute
Minneapolis, MN

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Pregnant women who get the flu are at an increased risk for severe illness. To protect pregnant women, the Advisory Committee on Immunization Practices recommends women receive inactivated influenza vaccine (IIV) during any trimester of their pregnancy.

This study used data from the Vaccine Safety Datalink to evaluate if there was an increased risk for selected major structural birth defects for infants whose mothers received IIV in the first trimester of pregnancy versus infants who were unexposed to IIV. Among over 425,000 live births, including 52,856 whose mothers received IIV during first trimester, we evaluated risks for major structural birth defects.  In this large observational study, we did not observe increased risks for major structural birth defects in offspring following first trimester maternal inactivated influenza vaccine exposure.

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Directly Observed Therapy Linked To Lower Mortality In Multi-Drug Resistant TB

MedicalResearch.com Interview with:
Dr. Jorge Salinas MD
Epidemic intelligence service officer
Division of Tuberculosis Elimination
Centers for Disease Control and Prevention 

MedicalResearch.com: What is the background for this study?

Response: Because multidrug-resistant TB (MDR TB) treatment regimens are less effective, more complex, and are more likely to have side effects that are difficult to tolerate than regimens for drug-susceptible TB, patients with MDR TB are at a higher risk of dying. Directly observed therapy (a therapy by which patients meet with a healthcare worker at a regularly scheduled time and place so the healthcare worker can observe the patient taking their TB medication) is recommended to treat all forms of TB disease, including MDR TB.

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Could a Strep Throat Increase Risk of OCD?

MedicalResearch.com Interview with:
Sonja Orlovska MD, PhD student

Mental Health Centre Copenhagen
Denmark

MedicalResearch.com: What is the background for this study?

Response: This Danish register-based study is the largest study so far investigating the hypothesis PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections) which describes a possible link between streptococcal throat infection and the subsequent development of OCD and tic disorders in children. PANDAS is in thread with research in mental health in recent years, suggesting that infections and immune activation might increase the risk of mental disorders.

MedicalResearch.com: What are the main findings?

Response: Out of the 1,1 million individuals <18 years of age born in the study period, we found that the 349,982 individuals tested positive for a streptococcal throat infection by their GP had an increased risk of mental disorders by 18% and the risk of specifically OCD and tic disorders was increased with respectively 51% and 35%, compared to individuals who had never been tested. This seems to confirm PANDAS which speaks in favor of a specific link between strep throat and the development of OCD and tic disorders. However, we also found that non-streptococcal throat infection increased the risk of mental disorders, even though the risk of OCD and all mental disorders was larger after a strep throat. The study was performed at the Mental Health Centre Copenhagen together with Senior researcher Michael Eriksen Benros.

MedicalResearch.com: What should readers take away from your report?

Response: Our results indicate that the brain might be affected by the immunological activation caused by a streptococcal infection possibly due to streptococcal antibodies cross-reacting with brain tissue causing psychiatric symptoms which is the theory of PANDAS. However, it seems as if the immunological response caused by other types of throat infections might also have a damaging effect in some individuals. Nevertheless, it cannot be ruled out that the results to some extent might be driven by a medical care-seeking behavior in some parents bringing their child to the GP more often in spite of only few symptoms of throat infection leading to testing for strep throat and also more frequent examination and diagnosis by a psychiatrist.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Even though our study supports some elements of the PANDAS hypothesis, more research is needed to fully confirm PANDAS. The research field would benefit from larger clinical studies following children with PANDAS over a longer period of time with frequent follow-ups in order to establish if streptococcal throat infections cause and worsen neuropsychiatric symptoms of OCD and tic disorders.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Orlovska S, Vestergaard CH, Bech BH, Nordentoft M, Vestergaard M, Benros ME. Association of Streptococcal Throat Infection With Mental DisordersTesting Key Aspects of the PANDAS Hypothesis in a Nationwide Study. JAMA Psychiatry. Published online May 24, 2017. doi:10.1001/jamapsychiatry.2017.0995

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

More Medical Research Interviews on MedicalResearch.com

Injectable Cabotegravir Holds Promise as HIV Prevention Stategy

MedicalResearch.com Interview with:

Martin Markowitz MD Clinical Director and Staff Investigator Aaron Diamond AIDS Research Center Aaron Diamond Professor at The Rockefeller University

Dr. Markowitz

Martin Markowitz MD
Clinical Director and Staff Investigator
Aaron Diamond AIDS Research Center
Aaron Diamond Professor at The Rockefeller University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Cabotegravir ((CAB) is an inhibitor of HIV-1 integrase and is amenable to formulation in both oral and long acting injectable forms. In preclinical studies injectable CAB protected against low dose intrarectal challenge using an HIV-like virus in the rhesus macaque model.

These results support the clinical development of CAB as prevention. This study was a first attempt to establish a dosing regimen and evaluate safety and acceptability of intramuscular injections of CAB. The study was a placebo controlled blinded study of approximately 120 subjects with a 5:1 randomization active/placebo. Subjects received 800mg CAB given as 2 2mL injections or placebo every 12 weeks for 3 injections after a 4 week safety lead in of oral therapy. Safety acceptability and PK were assessed.

The main findings were that injections were associated with injection site reactions in the vast majority of participants that were mild to moderate and of short duration. Only 4 subjects who entered the injection phase discontinued due to injection intolerance. There were no additional safety signals and the participants considered the injections acceptable when asked to complete questionnaires. PK analysis found that despite modeling that suggested that the 800mg q 12 week dose would be adequate, this was not the case. More rapid uptake and release from the depot resulted in lower than anticipated drug levels at trough. Alternate dosing regimens are under study.

Another finding is that there were participants (14%) who had detectable drug in plasma detected at 52 weeks after last injection suggesting the presence of a tail in some individuals.

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In Accordance With Guidelines, Fewer Low Risk Patients Receiving Antibiotics Before Dental Procedures

MedicalResearch.com Interview with:

Daniel C. DeSimone, M.D.</strong> Infectious Diseases Fellowship, Year 2 Mayo Clinic

Dr. DeSimone

Daniel C. DeSimone, M.D.
Infectious Diseases Fellowship, Year 2
Mayo Clinic

MedicalResearch.com: What is the background for this study?

Response: For over 50 years, the American Heart Association (AHA) has recommended antibiotics to be given to patients with certain cardiac conditions prior to invasive dental procedures (dental cleanings, extractions, root canals) with the hope to prevent infective endocarditis–a potentially deadly infection of the heart valves. Prevention of this infection was preferred to treatment of an established infection due to its high morbidity and mortality rates. However, in 2007, experts found that there was very little, if any, evidence that showed antibiotics prophylaxis prevented infective endocarditis prior to invasive dental procedures. Given this, the AHA revised its guidelines, significant reducing the number of patients where antibiotic prophylaxis would be given–as routine daily activities such as chewing food, tooth brushing, and flossing were much more likely to cause infective endocarditis than a single dental procedure.

For over 50 years, patients with cardiac conditions that placed them at “moderate risk” and/or “high risk” were to receive antibiotics prior to dental procedures. In 2007, the “moderate risk” group were to no longer receive antibiotic prophylaxis. This is a significantly large proportion of patients–approximately 90% of all patients who would have received antibiotic prophylaxis. Given the drastic changes made in 2007, there was concern among the medical and dental communities about whether we were leaving patients “unprotected” and at risk for infective endocarditis. Thankfully, several population based studies from our group and others across the United States have not shown an increase in the rate of infective endocarditis. However, the question remained, “Are providers following the 2007 AHA guidelines?” and “Are patients still receiving antibiotics prior to dental procedures when its no longer indicated by the guidelines?”.

This was the main focus of our paper. We were able to go into the local dental offices and at the same time, have full access to their medical records. Every dental visit between 2005 and 2015 at their dental office was reviewed; the type of dental visit, whether they received antibiotic prophylaxis or not. In addition, we could confirm their cardiac conditions that would place them at “moderate risk” or “high risk” compared to the general population.

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Antibiotic Failure in Community Acquired Pneumonia Surprisingly Common

MedicalResearch.com Interview with:

Dr. James A. McKinnell, MD LA BioMed Assistant Professor of Medicine David Geffen School of Medicine at UCLA

Dr. McKinnell

Dr. James A. McKinnell, MD
LA BioMed
Assistant Professor of Medicine
David Geffen School of Medicine at UCLA

MedicalResearch.com: What is the background for this study?

Response: Pneumonia is the leading cause of death from infectious disease in the United States. We conducted this study because current community-acquired pneumonia guidelines from the American Thoracic Society and the Infectious Disease Society America, published in 2007, provide some direction about prescribing antibiotics for community-acquired pneumonia. But large-scale, real-world data are needed to better understand and optimize antibiotic choices and to better define clinical risk factors that may be associated with treatment failure. Antibiotic failure for community-acquired pneumonia is associated with substantial morbidity and mortality and results in significant medical expenditures.

We examined databases containing records for 251,947 adult patients who were treated between 2011 and 2015 with a single class of antibiotics (beta-lactam, macrolide, tetracycline, or fluoroquinolone) following a visit to their physician for treatment for community-acquired pneumonia. We defined treatment failure as either the need to refill antibiotic prescriptions, antibiotic switch, ER visit or hospitalization within 30 days of receipt of the initial antibiotic prescription.

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Synthetic Human Angiotensin II for the Treatment of Vasodilatory Shock

MedicalResearch.com Interview with:

Ashish Khanna, MD, FCCP Assistant Professor of Anesthesiology, Cleveland Clinic Lerner College of Medicine Staff Intensivist Center for Critical Care and Department of Outcomes Research Cleveland Clinic, Cleveland

Dr. Khanna

Ashish Khanna, MD, FCCP
Assistant Professor of Anesthesiology, Cleveland Clinic Lerner College of Medicine
Staff Intensivist
Center for Critical Care and Department of Outcomes Research
Cleveland Clinic, Cleveland

MedicalResearch.com: How did you become interested in this topic?

Response: Anesthesia forms the basis of my training but I also completed a fellowship in critical care and, at the present time, I do more work in critical care than anesthesia. About 75% of my time is spent in the Cleveland Clinic critical care units, including the Medical and surgical ICUs (Intensive Care Units).

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Rory’s Regulations: Faster Is Better When It Comes To Sepsis Care

MedicalResearch.com Interview with:

Christopher W. Seymour, M.D., M.Sc. Assistant professor of Critical Care Medicine and Emergency Medicine, and member of Clinical Research Investigation and Systems Modeling of Acute Illness University of Pittsburgh

Dr. Seymour

Christopher W. Seymour, M.D., M.Sc.
Assistant professor of Critical Care Medicine and Emergency Medicine, and member of Clinical Research Investigation and Systems Modeling of Acute Illness
University of Pittsburgh

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Following the tragic and widely publicized death of Rory Staunton, 12, from undiagnosed sepsis in 2012, New York became the first state to require that hospitals follow a protocol to quickly identify and treat the condition. The mandate led to widespread controversy in the medical community as to whether such steps would have saved Rory or anyone else’s life.

Rory’s Regulations require hospitals to follow protocols for early identification and treatment of sepsis, and submit data on compliance and outcomes. The hospitals can tailor how they implement the protocols, but must include a blood culture to test for infection, measurement of blood lactate (a sign of tissue stress) and administration of antibiotics within three hours of diagnosis—collectively known as the “three-hour bundle.”

We analyzed data from nearly 50,000 patients from 149 New York hospitals to scientifically determine if  Rory’s Regulations worked. We found that they did – 83 percent of the hospitals completed the bundle within the required three hours, overall averaging 1.3 hours for completion. For every hour that it took clinicians to complete the bundle, the odds of the patient dying increased by 4 percent.

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EHRs Can Facilitate Rapid Detection and Treatment of Sepsis

MedicalResearch.com Interview with:

Faheem Guirgis MD  Assistant Professor of Emergency Medicine Department of Emergency Medicine Division of Research UF Health Jacksonville

Dr. Guirgis

Faheem Guirgis MD
Assistant Professor of Emergency Medicine
Department of Emergency Medicine
Division of Research
UF Health Jacksonville

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Sepsis is quite prevalent among hospitals and the incidence is increasing. It is a life-threatening disease that can lead to poor outcomes if patients are not recognized and treated promptly. We recognized that our institution needed a strategic approach to the problem of sepsis, therefore the Sepsis Committee was created with the goal of creating a comprehensive sepsis program.

We developed a system for sepsis recognition and rapid care delivery that would work in any area of the hospital. We found that we reduced overall mortality from sepsis, the number of patients requiring mechanical ventilation, intensive care unit length and overall hospital length of stay, and the charges to the patient by approximately $7000 per patient.

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Toward A Real Cure for HIV: Abivax’s ABX464 Reduced HIV Reservoir in Phase 2 Trial

MedicalResearch.com Interview with:
AbivaxJean-Marc Steens, M.D.

Chief Medical Officer of Abivax

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Antiretroviral therapy (ART) has had an enormous impact on the HIV pandemic since its introduction almost 20 years ago. Most patients treated with ART achieve undetectable or near undetectable plasma levels of the virus. This means that although HIV is controlled, it is not completely eliminated. The virus remains in the body, usually contained in dormant cells (known as the HIV reservoir) that are widely distributed, including to the central nervous system, the gut mucosa, the lymph nodes and other sites. If ART is stopped, the virus rebounds. The goal of any curative therapy would be to eliminate the virus or ensure there is sustained remission in the absence of ART, which until now have been unsuccessful.

Abivax’s Phase 2 clinical study with ABX464 demonstrated, for the first time, a reduction in HIV reservoirs in chronically infected HIV patients as measured by total HIV DNA detected in peripheral blood mononuclear cells (PBMCs).

In the ABX464-004 trial, 30 HIV patients received either ABX464 or matching placebo in addition to their current antiretroviral treatment over 28 days. The viral load at the start of the study was well controlled with boosted darunavir. After the 28-day treatment period, all treatments were interrupted until viral load rebound. Baseline and day 28 blood samples were taken to assess the potential effect of ABX464 on the HIV reservoir in PBMCs.

Safety was the primary endpoint in the trial. ABX464 was well tolerated, with no severe adverse events in the treatment group. Amongst evaluable patients (4 placebo and 14 ABX464-treated patients), a reduction in viral DNA copies/mPBMCs was observed in 7/14 treated patients (mean change of -40%, ranging from -27% to -67%) and no responders were observed in the placebo group. Responders were defined as patients who had a decrease greater than 25% in total HIV DNA in PBMCs and a reduction of at least 50 copies.

Total HIV DNA in PBMC has been validated as a widely accepted biomarker for measuring the HIV reservoir. Specifically, in untreated patients, total HIV DNA load influences the course of the infection and is therefore clinically relevant. In addition, a correlation exists between the pool of HIV-1 DNA and the replication-competent reservoir.

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PaxVax Commences Trial to Modernize Adenovirus Vaccine

MedicalResearch.com Interview with:

Nima Farzan Chief Executive Officer & President of PaxVax

Nima Farzan

Nima Farzan
Chief Executive Officer & President of PaxVax

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: PaxVax is developing a new and improved version of the vaccine, known as the Modernized Production Adenovirus Vaccine (MPAV) Prototype A. The Company was chosen as the Small Business Innovation Research and Regulatory Sponsor for the development of the Modernized Production Adenovirus Vaccine (MPAV) Prototype A due to the company’s prior experience working with multiple strains of Adenovirus. An Investigational New Drug (IND) application for MPACV was submitted to the U.S. Food and Drug Administration (FDA) on January 30, 2017. The Phase I clinical trial has been initiated and will be conducted at the Larner College of Medicine at the University of Vermont and Cincinnati Children’s Hospital. PaxVax expects to see results of the Phase I clinical trial in early 2018.

Complications of adenovirus 4/7 can include headache, pneumonia, sore throat and eye infections. In severe cases, adenovirus can lead to acute respiratory distress syndrome and other serious complications related to organ system damage (including GI tract and bladder) that can result in death, if left untreated.

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New Drug May Protect Gut From Antibiotic-Resistance Genes

MedicalResearch.com Interview with:

Synthetic Biologics, Inc.

Synthetic Biologics, Inc.

Sheila Connelly, PhD
Vice President, Research
Synthetic Biologics, Inc.

MedicalResearch.com: What is the background for this study?

Response: Synthetic Biologics, Inc. is focused on the protection and preservation of the gut microbiome which is the diverse collection of microorganisms that live in the intestinal tract. We are learning that the gut microbiome plays a key role in health. Negative changes to the microbiome, called dysbiosis, are linked to disease states including allergies, autism, and obesity, among a rapidly growing list of other conditions. A consequence of using antibiotics is that, in addition to fighting the bacterial infection being treated, they also kill the gut microbiota. The space left in the gut by the dead bacteria allows other surviving bacteria, many times opportunistic pathogens or microbes that are resistant to multiple antibiotics, to overgrow and fill the open niches. Exposure to antibiotics, particularly broad-spectrum antimicrobials, such as penicillins and cephalosporins, is a major risk factor for acquiring a potentially deadly Clostridium difficile infection.

Dr-Sheila-Connelly.jpg

Dr. Sheila Connelly

Another consequence of antibiotic use is the emergence of antibiotic-resistant organisms. Widespread use of antibiotics provides selective pressure for the evolution of lethal, multi-drug resistant pathogens, termed “nightmare bacteria”. The gut microbiome acts as a reservoir of antibiotic resistance that can be triggered, by antibiotic exposure, to acquire and propagate resistance genes.

A way to protect the microbiome and reduce antibiotic resistance is to limit exposure of the gut microbiota to antibiotics. To this end, we developed an antibiotic inactivation strategy using a beta-lactamase enzyme to degrade beta-lactam antibiotics in the GI tract before they can harm the gut microbiome. Beta-lactamases are naturally-occurring bacterial enzymes that confer resistance to beta-lactams, the most widely used broad spectrum antibiotics, and their presence is normally considered an obstacle to efficacious infection control. We took advantage of the highly efficient antibiotic degradation activity of a beta-lactamase and developed SYN-004 (ribaxamase). Ribaxamase is a beta-lactamase engineered to inactivate penicillins and most cephalosporins, formulated for oral delivery, and intended for use with IV beta-lactam antibiotics to degrade the antibiotics in the GI tract to protect the microbiome.

Ribaxamase was demonstrated to significantly reduce the occurrence of C. difficile disease in a recently completed Phase 2b clinical study. The study met its primary endpoint by demonstrating that ribaxamase, when delivered orally with IV ceftriaxone, significantly reduced C. difficile disease in patients treated for a respiratory tract infection. Ribaxamase also resulted in a significant reduction in new colonization by vancomycin-resistant enterococcus (VRE).

For the current study, pig models of antibiotic-mediated gut dysbiosis were established using three classes of beta-lactam antibiotics, a cephalosporin, ceftriaxone, a penicillin, amoxicillin, and a carbapenem, ertapenem. The ceftriaxone model was used to evaluate the protective effect of ribaxamase on the microbiome and the amoxicillin and ertapenem models are intended for evaluation of pipeline products.

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Phase 2 Trial of Takeda’s Dengue Vaccine Demonstrates Immune Response Against All 4 Strains

MedicalResearch.com Interview with:

Dr Vianney Tricou DPhil Takeda Vaccines Singapore

Dr. Vianney Tricou

Dr Vianney Tricou DPhil
Takeda Vaccines
Singapore

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Dengue fever is a painful, debilitating mosquito-borne disease caused by any one of four closely related dengue virus serotypes, and persons living in dengue endemic regions may be affected by dengue more than once in their lifetime. Some individuals with dengue fever are hospitalized and may need intensive therapy to prevent shock and death, and severe dengue is a leading cause of hospitalization and death among children and adults in some Asian and Latin American countries. About half of the world’s population lives under the threat of dengue and the disease has a significant medical and economic impact in the tropical and subtropical regions of the world where dengue is endemic.

Takeda is committed to improving global public health and to developing a life-saving dengue vaccine candidate for people around the world. Takeda’s tetravalent dengue vaccine candidate (TAK-003) is based on a live-attenuated dengue serotype 2 virus (DENV-2), which provides the genetic ‘backbone’ for all four attenuated dengue virus serotypes present in the vaccine. Takeda’s Phase 1 and Phase 2 clinical study program includes 8 studies to date that assess the safety and/or immunogenicity of this candidate, before moving into Phase 3.

Takeda’s ongoing Phase 2 DEN-204 study is designed to assess the safety and immunogenicity of one- and two-dose schedules of TAK-003 in 1,794 healthy children and adolescents ages two through 17 years living in dengue-endemic countries in Latin America and Asia.

As published in The Lancet Infectious Diseases in March 2017, an interim analysis of DEN-204 data indicated that TAK-003 elicited antibody responses to all four dengue serotypes in the population studied, regardless of whether they had previous dengue exposure.

A second TDV dose improved antibody responses against DENV-3 and DENV-4 in children who were seronegative before vaccination. In this study, the safety profile was consistent with that observed in earlier Phase 1 and 2 studies.
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Study Compares Zinc Lozenges Used to Treat the Common Cold

MedicalResearch.com Interview with:

Dr-Harri-Hemilae.jpg

Dr. Harri Hemilae

Harri Hemilä, MD, PhD
Department of Public Health
University of Helsinki

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Some zinc lozenges intended for treating the common cold have contained zinc acetate and some others have contained zinc gluconate. There have been proposals that zinc acetate might be more optimal salt for lozenges than zinc gluconate.
Therefore I compared the randomized trials that have used zinc acetate with zinc gluconate to see if there is difference between the lozenges. Although the average effect in 3 studies with zinc acetate lozenges was greater (40%) than the average effect in 4 studies with zinc gluconate lozenges (28%), that difference was explained by random variation.

I also analyzed the dose dependency of the effect and found that 2 studies that used 192 and 207 mg per day elemental zinc did not find greater benefit than 5 studies that used 80 to 92 mg per day zinc. The overall average effect of zinc lozenges was 33% reduction in common cold duration and that effect seems to be reached with doses less than 100 mg per day.

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Some Antibiotics Linked To Increased Risk of Miscarriage

MedicalResearch.com Interview with:

Anick Bérard PhD FISPE Research chair FRQ-S on Medications and Pregnancy and Director, Réseau Québécois de recherche sur le médicament (RQRM) and Professor, Research Chair on Medications, Pregnancy and Lactation Faculty of Pharmacy University of Montreal and Director, Research Unit on Medications and Pregnancy Research Center CHU Ste-Justine

Dr. Anick Bérard

Anick Bérard PhD FISPE
Research chair FRQS on Medications and Pregnancy
Director, Réseau Québécois de recherche sur le médicament (RQRM)
Professor, Research Chair on Medications, Pregnancy and Lactation
Faculty of Pharmacy, University of Montreal
Director, Research Unit on Medications and Pregnancy
Research Center, CHU Ste-Justine

MedicalResearch.com: The Danish study you cite reported a connection between antibiotics and miscarriage – why was further research of this topic necessary?

Response: Given that a single study will assess an association, repetition of findings are essential in order to assess causality. For example, we were able to conclude that smoking was causing lung cancer after 10 years of observational research on the topic showing concordant associations.

In addition, antibiotic prescription patterns vary from country to country, hence the importance of studying the research question in various patient populations.

Finally, our cohort has validated exposure status, gestational age (first day of pregnancy) and miscarriage cases – our study was also able to look at types of antibiotics.

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Community Targeting of High Risk Minority Males Improves HIV Detection and Treatment

MedicalResearch.com Interview with:

Robin Lin Miller, Ph.D. Professor, Ecological-Community Psychology Co-Director, MA in Program Evaluation Chair, Graduate Program in Ecological-Community Psychology Michigan State University East Lansing, MI 48824

Dr. Miller

Robin Lin Miller, Ph.D.
Professor, Ecological-Community Psychology
Co-Director, MA in Program Evaluation
Chair, Graduate Program in Ecological-Community Psychology
Michigan State University
East Lansing, MI 48824
MedicalResearch.com: What is the background for this study?

Response: We wanted to identify promising strategies for providing access to HIV-testing for gay and bisexual male youth. We were especially interested in testing strategies to reach gay and bisexual male youth of color, as they bear a disproportionate burden of the HIV epidemic and are the least likely to be aware of their HIV status. We also wanted to explore approaches to successfully link these youth with HIV-negative test results to diverse HIV prevention services, including pre-exposure prophylaxis, when warranted.

Although some argue that the ideal place to test adolescents and young adults is via emergency rooms and in routine medical care visits, we found that we were able test many more youth with previously undiagnosed HIV-infection through intensive, targeted community outreach efforts. We also tested a much higher proportion of young men of color through targeted outreach.

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Outbreak of Severe Fungal Eye Infections Linked To IV Opioid Epidemic

MedicalResearch.com Interview with:
Aubrey Tirpack, PGY3

New England Eye Center
Tufts Medical Center 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Intravenous drug abuse is a known risk factor for the development of endogenous fungal endophthalmitis (EFE), a severe intraocular infection cause by the seeding of mycotic organisms to the eye.

Our institution noted a marked increase in cases of EFE beginning in May 2014, which correlates to increasing rates of opioid abuse throughout the New England region. Ten patients were found to have intravenous drug abuse related EFE over the two year time period studied. The most common presenting symptoms were floaters, decreased vision, and pain. All patients were treated with systemic antifungals and nine patients underwent intravitreal antifungal injection. All patients were ambulatory at presentation and the majority were without systemic signs of infection.

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Rapid Tests For Foodborne Infections Can Provide Faster Treatment But Curtail Important Outbreak Data

MedicalResearch.com Interview with:

Ms. Ellyn Marder MPH</strong> Surveillance Epidemiologist, CDC Centers for Disease Control and Prevention Atlanta, Georgia

Ellyn Marder

Ms. Ellyn Marder MPH
Surveillance Epidemiologist, CDC
Centers for Disease Control and Prevention
Atlanta, Georgia

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: CDC’s Foodborne Diseases Active Surveillance Network (FoodNet) report provides the most up-to-date information about foodborne illnesses in the United States. Each year, FoodNet publishes a report that includes preliminary data compared with data from the previous three years. FoodNet has been monitoring illness trends since 1996 and collects data on about 15 percent of the U.S. population.

Campylobacter and Salmonella caused the most reported bacterial foodborne illnesses in 2016, according to preliminary data. FoodNet sites alone reported 24,029 foodborne infections, 5,512 hospitalizations, and 98 deaths in 2016. The numbers of reported illnesses by germ are: Campylobacter (8,547), Salmonella (8,172), Shigella (2,913), Shiga toxin-producing E. coli (1,845), Cryptosporidium (1,816), Yersinia (302), Vibrio (252), Listeria (127) and Cyclospora (55).

This is the first time the report also includes in the total number of infections those foodborne bacterial infections diagnosed only by rapid diagnostic tests in FoodNet sites. Previously, the report counted foodborne bacterial infections confirmed only by traditional culture-based methods in the total numbers.

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Low CD4 Count Linked To Heart Failure in HIV Patients

MedicalResearch.com Interview with:
Matthew S Freiberg, MD, MSc
Associate Professor of Medicine, Division of Cardiovascular Medicine
Vanderbilt Translational and Clinical Cardiovascular Research Center

MedicalResearch.com: What is the background for this study?

Response:  HIV infected people are living longer and are at risk for cardiovascular diseases. While acute myocardial infarction has been studied and the increased risk of Acute Myocardial Infarction (AMI) among HIV+ people compared to uninfected people is well documented, there are less data describing the risk of HIV and different types of heart failure, including reduced and preserved ejection fraction heart failure. Understanding more about the link between HIV and different types of HF is important because reduced and preserved ejection fraction heart failure differ with respect to underlying mechanism, treatment, and prognosis. Moreover, as cardiovascular care has improved, HIV infected people who experience an AMI are likely to survive but may live with a damaged heart. Understanding more about the link between HIV and heart failure may help providers and their patients prevent or reduce the impact of HF on the HIV community.

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Potential Drug-Binding Site Against Zika Virus Identified

MedicalResearch.com Interview with:

Dr. Jikui Song PhD Assistant professor of biochemistry University of California, Riverside.

Dr. Jikui Song

Dr. Jikui Song PhD
Assistant professor of biochemistry
University of California, Riverside.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Recent outbreak of Zika virus (ZIKV) has become a wordwide health concern. However, no vaccines or antiviral drugs against ZIKV are currently available. To explore potential druggable sites for ZIKV, we set out to determine the crystal structure of full-length ZIKV NS5, the molecular machinery responsible for the genomic replication of ZIKV.

The major findings of our study include the identification of a conserved domain conformation within flavivirus NS5 family, which may be important for functional regulation of flavivirus NS5. Furthermore, our structural analysis revealed a potential drug-binding site of ZIKV NS5, providing basis for future development of novel antivirals against ZIKV.

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Antibiotics in Pregnancy Increase Children’s Risk of Otitis Media and Ventilation Tubes

MedicalResearch.com Interview with:
Hans Bisgaard, MD, DMSc

Professor of Pediatrics
The Faculty of Health Sciences
University of Copenhagen
Copenhagen University Hospital, Gentofte
Copenhagen, Denmark

MedicalResearch.com: What is the background for this study?

Response: The consumption of antibiotics is increasing worldwide. Antibiotics alter the maternal bacterial colonization and by vertical transmission this can affect the offspring. An unfavorable microbiome may increase the disease propensity of the offspring.
Otitis media is one of the most common infections in early childhood. We hypothesized that antibiotic consumption in pregnancy can increase the children’s risk of otitis media.
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Promising New Drug Can Stop Malaria After Mosquito Bite

MedicalResearch.com Interview with:

Dr Mihály Sulyok MD Eberhard Karls University Institute of Tropical Medicine, Tübingen, Germany

Dr Mihály Sulyok

Dr Mihály Sulyok MD
Eberhard Karls University
Institute of Tropical Medicine,
Tübingen, Germany

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: New antimalarials are desperately needed, not just for treatment, but also for prophylaxis. DSM265, a novel antimalarial compound that selectively inhibits the plasmodial dihydroorotate dehydrogenase has a promising pharmacokinetic profile characterized by a long elimination half-life.

We performed a study at the Institute of Tropical Medicine, Eberhard Karls University (Tübingen, Germany) to investigate safety, tolerability and efficacy of DSM265 using controlled human malaria infection. In the first cohort, 400mg of DSM265 was administered orally to five healthy, malaria naive individuals one day before direct venous inoculation of an established infective dose of P. falciparum sporozoites (PfSPZ Challenge). Placebo was administered to two volunteers. The study was randomized and double blinded. In this cohort all placebo participants developed malaria, whereas all DSM265 participants were protected.

In a second cohort, 400mg DSM265 was administered 7 days before the sporozoite inoculation for six participants, two participants recieved placebo. In this cohort, the two placebo and three of six DSM265 volunteers developed thick blood smear positive malaria. The remaining three DSM265 volunteers developed transient submicroscopic parasitemia without symptoms or thick blood smear positivity. The only possible DSM265-related adverse event was a slight transient elevation in serum bilirubin in one volunteer.

The study was funded by the Global Health Innovative Technology Fund, Wellcome Trust, Bill & Melinda Gates Foundation through Medicines for Malaria Venture, and the German Center for Infection Research.

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Comparison Zika Outbreaks in French Polynesia, Colombia and the State of Bahia in Brazil

MedicalResearch.com Interview with:

Daihai He PhD Department of Applied Mathematics The Hong Kong Polytechnic University Hung Hom, Kowloon Hong Kong (SAR), China

Dr. Daihai He

Daihai He PhD
Department of Applied Mathematics
The Hong Kong Polytechnic University
Hung Hom, Kowloon
Hong Kong (SAR), China

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Zika virus disease has large outbreaks in many Pacific and American countries in 2016, and the outbreaks are still on-going. Our work is conducted against this background. We compared data from three localities: French Polynesia in 2013-2014, Colombia and Brazil in 2016. We found that in French Polynesia the infection attack rate (i.e. the proportion of the population who got infected) is about 3/4, which matched previous serological studies. We then make estimation for the other two place. We found that the infection attack rate in Colombia in 2016 was most likely less than 50%. For Bahia province of Brazil, we did not arrive at a very accurate estimation, as the confidence interval is wide, and our best estimate is 30%. The relatively low infection attack rate in Colombia and Brazil implies that future outbreaks of Zika virus diseases are still possible. Thus control and surveillance efforts should be continued.

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Quadrivalent HPV Vaccination and the Risk of Adverse Pregnancy Outcomes

MedicalResearch.com Interview with:
Anders Hviid

Senior Investigator, M.Sc.,Dr.Med.Sci.
Department of Epidemiology Research
Division of National Health Surveillance & Research

MedicalResearch.com: What is the background for this study?

Response: HPV vaccination targeting girls and young women has been introduced in many countries throughout the world. HPV vaccines are not recommended for use in pregnancy, but given the target group, inadvertent exposure will occur in early unrecognized pregnancies. However, data on the safety of HPV vaccination in pregnancy is lacking.
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Patients With Clostridium difficile Infections Should Have Need For Gastric Acid Suppression Reassessed

MedicalResearch.com Interview with:

Sahil Khanna,

Dr. Sahil Khanna

Sahil Khanna, M.B.B.S. MS
Division of Gastroenterology and Hepatology
Mayo Clinic, Rochester, Minnesota

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Clostridium difficile infection (CDI) is the most common cause of hospital-acquired diarrhea and has recently shown increasing incidence especially in the community. Novel risk factors for CDI development include the use of gastric acid suppression medication, presence of systemic comorbid conditions, C difficile carriage in water and food sources, amongst others.

Gastric acid suppression medications such as proton-pump inhibitors (PPIs) and histamine-2 receptor blockers (H2Bs) are commonly prescribed and consumed over the counter for gastroesophageal reflux disease, peptic ulcer disease, or functional dyspepsia, but they are also sometimes prescribed for unnecessary indications, which leads to overuse of these medications. Recurrent CDI after a primary infection is a major problem, with the risk being as high as 50% to 60% after 3 or more Clostridium difficile infections. Data on the association between acid suppression and recurrent CDI are conflicting and therefore we performed a systematic review and meta-analysis to study the association between the use of gastric acid suppression medications and the risk of recurrent CDI.

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Adolescents Perinatally Infected with HIV Are At Increased Risk of Serious Physical and Mental Health Problems

MedicalResearch.com Interview with:

Anne M Neilan, MD,MPH Assistant In Medicine, Massachusetts General Hospital Research Fellow, Harvard Medical School Department: Medicine Service Division: Infectious Disease Department: Pediatric Service Massachusetts General Hospital Boston, MA 02114

Dr. Neilan

Anne M Neilan, MD,MPH
Assistant in Medicine and Pediatrics
Massachusetts General Hospital
Instructor at Harvard Medical School
Department: Medicine Service
Division: Infectious Disease
Department: Pediatric Service
Massachusetts General Hospital
Boston, MA 02114

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Adolescents infected with HIV – either at birth or later in life – experience poorer health outcomes compared to adults with HIV in nearly every respect. This study found that U.S. youth infected with HIV around the time of their birth are at higher risk throughout their adolescence and young adulthood for experiencing serious health problems, poor control of the HIV virus (having high levels of HIV virus in their bodies and fewer CD4 immune cells which protect the body from infection), or death. The study also found that among those with good HIV control, serious health problems are rare.

By combining data from two large, long-term U.S. studies – the Pediatric HIV/AIDS Cohort Study (PHACS, www.phacsstudy.org) and the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT, www.impaactnetwork.org) Network – we were able to study the health of more than 1,400 perinatally HIV-infected children, adolescents and young adults ages 7 to 30 years between 2007 and 2015. The study found that youth ages 13 to 30 were most likely to have poor HIV control AIDS-related illnesses, and death compared to younger participants. Among 18 – 30 year-olds, the study found that poor control of the HIV virus – meaning higher levels of HIV virus and lower levels of CD4 immune cells which protect the body from infection –35 percent of the time, increasing the risk that these youth would stop responding to certain HIV medications and could transmit HIV to others. These findings are consistent with other U.S. and European reports. Despite being engaged in health care, the number of deaths among youth born with HIV in the U.S. is 6 to12 times higher than for youth without HIV of the same age, sex and race.

Along with HIV-related health problems, the most commonly reported health conditions concerned mental health and brain and nervous system development. Many women in the study also had sexually transmitted infections, which was found to be associated with lower CD4 immune cell counts. This may suggest a biological mechanism or may reflect that patients who have difficulty with their medications are also engaging in more frequent risky sexual behaviors.

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High Risk Individuals Are Testing For HIV More Frequently

MedicalResearch.com Interview with:
Qian An, PhD

Epidemiologist/statistician
Division of HIV/AIDS Prevention
CDC

MedicalResearch.com: What is the background for this study?

Response: Since 2006, the Centers for Disease Control and Prevention (CDC) has recommended HIV testing for all persons aged 13-64 years old. Persons at high risk for HIV infection should be tested more frequently. Among sexually active men who have sex with men (MSM), repeat testing is recommended at least annually. An analysis in 2011 suggested that MSM might benefit from more frequent than annual testing.(1)

Among non-MSM, repeat testing is recommended at least annually for persons at high risk, including persons who inject drugs (PWID) and their sex partners, those who have sex in exchange for money or drugs, heterosexuals who have had more than one sex partner since their most recent HIV test, and those whose partners are living with HIV..

Using statistical models based on renewal theory, we estimate the mean HIV inter-test interval (ITI) — meaning the average time period (in months) between two successive HIV tests — to describe temporal trends in HIV testing frequency among MSM, PWID and high-risk heterosexuals (HRH) and differences in testing frequency by age and race/ethnicity. A decrease in ITI means individuals are testing more frequently.

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Human Placenta May Be Most Vulnerable To Zika In First Trimester

MedicalResearch.com Interview with:

R. Michael Roberts

Dr. R. Michael Roberts

R. Michael Roberts PhD
Curators’ Distinguished Professor
240b Bond Life Sciences Center
Columbia, Missouri 65211-7310

MedicalResearch.com: What is the background for this study?

Response: My background in placental biology and in communication between the embryo and the mother in early pregnancy made me curious about how the zika virus (ZIKV) crossed the placenta in early pregnancy to cause microcephaly. My group had been working on a laboratory model for placental trophoblast for over 10 years. We generate trophoblast from human pluripotent cells (embryonic stem cells and induced pluripotent stem cells) by exposing them to the growth factor BMP4 and two pharmaceuticals that inhibit the signaling pathways necessary to maintain pluripotency. I was curious to determine whether or not ZIKV could infect these cells, replicate, and release infectious virus, because work from my collaborator Yoel Sadovsky at the University of Pittsburgh indicated that the mature placenta was likely to be resistant to infection.

MedicalResearch.com: What are the main findings?

Response: There are, I believe two striking outcomes from this work.

One is that the results indicate that the human placenta is likely most vulnerable to infection by Zika during the first trimester. We also suggest that women whose fetus is affected from an infection occurring later in pregnancy likely had a past dengue infection. The second striking result is that the African strain of Zika may have greater virulence towards early placenta than the Asian strains, such as the ones that have spread in the New World.

The work with the virus only began when we realized that term trophoblasts lacked expression of the genes that encode the protein factors that promote flavivirus infection (ZIKV is a flavivirus, like dengue, West Nile virus), e.g. TYRO3, AXL, MERTK, and also had a poised innate immune system that would counteract virus replication. Conversely, the trophoblasts we create from embryonic stem cells had the factors that would promote virus uptake, but seemed ill-prepared to counteract virus replication once infection occurred. In other words, the early placental trophoblasts were potentially more susceptible to infection. We confirmed this hypothesis with two strains of ZIKV (an Asian strain related to the one encountered in Brazil, and an African strain often considered to be relatively benign). What was unexpected was the African strain appeared to be more virulent than the Asian strain.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Whether the early placenta could be protected by some sort of immune therapy or by prior vaccination of the mother is clearly uncertain at present. Vaccination programs have not been altogether successful when used to protect against Dengue, which is a virus related to ZIKV.

There is evidence that the early placenta is also permissive to other viruses, such as Rubella. Also there is a very interesting paper in the Journal of the American medical Association by Honein et al. that was published on December 15, 2016. In this study, the overall risk for microcephaly and other brain abnormalities in infants born to a large cohort of U.S. women exposed to ZIKV while traveling (n = 442) was 5.9 % (18), and, of these, there were no cases noted among the women known to have been infected during their second or third trimesters. In Brazil, women appear to be at risk for fetal infections by ZIKV throughout their pregnancies but this may be because they had experienced an earlier infection by Dengue. I have discussed this puzzle in the paper.

I have no disclosures to make, nor conflicts of interest regarding the research or this response to your queries.

Citation:

PNAS Plus – Biological Sciences – Applied Biological Sciences:
Megan A. Sheridan, Dinar Yunusov, Velmurugan Balaraman, Andrei P. Alexenko, Shinichiro Yabe, Sergio Verjovski-Almeida, Danny J. Schust, Alexander W. Franz, Yoel Sadovsky, Toshihiko Ezashi, and R. Michael Roberts
Vulnerability of primitive human placental trophoblast to Zika virus PNAS 2017 114 (9) E1587-E1596; published ahead of print February 13, 2017, doi:10.1073/pnas.1616097114

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Frozen Fecal Transplant in Pill Form Found To Reverse C. Diff Infection

MedicalResearch.com Interview with:

Dr. H. L. DuPont MD Director, Center for Infectious Diseases, UTHealth School of Public Health Mary W. Kelsey Chair in the Medical Sciences, McGovern Medical School at UTHealth Professor, Department of Epidemiology, Human Genetics and Environmental Sciences UTHealth School of Public Health Houston, TX 77030

Dr. DuPont

Dr. H. L. DuPont MD
Director, Center for Infectious Diseases, UTHealth School of Public Health
Mary W. Kelsey Chair in the Medical Sciences, McGovern Medical School at UTHealth
Professor, Department of Epidemiology, Human Genetics and Environmental Sciences
UTHealth School of Public Health
Houston, TX 77030

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Many diseases and disorders are associated with “dysbiosis,” where the intestinal microbiota diversity is reduced. This contributes to disease and to the acquisition of antibiotic resistance. Fecal microbiota transplantation (FMT) is successful in conditions with pure dysbiosis (e.g. C diff infection) and a single dose of FMT is curative in most cases.

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Hospital Floors May Be Underappreciated Source Of Hospital Infections

MedicalResearch.com Interview with:

Curtis J. Donskey, MD Geriatric Research, Education, and Clinical Center Cleveland Veterans Affairs Medical Center Cleveland, OH 44106

Dr. Curtis J. Donskey

Curtis J. Donskey, MD
Geriatric Research, Education, and Clinical Center
Cleveland Veterans Affairs Medical Center
Cleveland, OH 44106

MedicalResearch.com: What is the background for this study? 

Response: Many hospitals are making efforts to improve cleaning to reduce the risk for transmission of infection from contaminated environmental surfaces. Most of these efforts focus on surfaces like bed rails that are frequently touched by staff and patients. Despite the fact that floors have consistently been the most heavily contaminated surfaces in hospitals, they have not been a focus of cleaning interventions because they are rarely touched. However, it is plausible that bacteria on floors could picked up by shoes and socks and then transferred onto hands. In a recent study, we found that when a nonpathogenic virus was inoculated onto floors in hospital rooms, it did spread to the hands of patients and to surfaces inside and outside the room. Based on those results, we assessed the frequency of floor contamination in 5 hospitals and examined the potential for transfer of bacteria from the floor to hands.

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Frequent Cause of Infertility, Pelvic Inflammatory Disease, Often Goes Unrecognized

Dr. Kirsten Kreise

Dr. Kristen Kreisel

MedicalResearch.com Interview with:
Dr. Kristen Kreisel PhD
Epidemiologist at Centers for Disease Control and Prevention
Centers for Disease Control and Prevention

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Pelvic inflammatory disease (PID), an infection of the female reproductive tract often associated with STDs, is putting millions of women at risk for infertility, ectopic pregnancy and chronic pelvic pain. Our study looked at data from the National Health and Nutrition Examination Survey to estimate the national burden of PID. Findings show an estimated 4.4 percent of sexually-experienced women aged 18-44, or approximately 2.5 million woman nationwide reported a history of PID.

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Flu Treatment With Neuraminidase Inhibitors During Pregnancy Not Linked To Birth Defects

MedicalResearch.com Interview with:

Dr. Sophie Graner Department of Women's and Childrens Health Karolinska Institute, Stockholm, Sweden

Dr. Graner

Dr. Sophie Graner
Department of Women’s and Childrens Health
Karolinska Institute, Stockholm, Sweden

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Pregnant women are at increased risks of severe disease and death due to influensa infection, as well as hospitalization. Also influenza and fever increase the risk of adverse pregnancy outcomes for their infants such as intrauterine death and preterm birth. Due to this, the regulatory agencies in Europe and the US recommended post exposure prophylaxis and treatment for pregnant women with neuraminidase inhibitors during the last influenza pandemic 2009-10. Despite the recommendations, the knowledge on the effect of neuraminidase inhibitors on the infant has been limited. Previously published studies have not shown any increased risk, but they have had limited power to assess specific neonatal outcomes such as stillbirth, neonatal mortality, preterm birth, low Agar score, neonatal morbidity and congenital malformations.
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SWORD Study Demonstrates Two-Drug Control of HIV

MedicalResearch.com Interview with:

Kati Vandermeulen Senior Director, Global Regulatory Leader and Compound Development Team Lead IDV Janssen

Kati Vandermeulen

Kati Vandermeulen
Senior Director, Global Regulatory Leader and Compound Development Team Lead
IDV Janssen

MedicalResearch.com: What is the background for this study? What are the main findings?

Response:  SWORD is the first large trial program specifically conducted to look at the combination of dolutegravir and rilpivirine as a complete, two-drug antiretroviral regimen. Results of the two identical Phase III SWORD studies have been positive and demonstrate that the two-drug regimen of dolutegravir and rilpivirine is as effective, with comparable tolerability, to traditional three- or four-drug (integrase inhibitor-, non-nucleoside reverse transcriptase inhibitor-, or boosted protease inhibitor-based) antiretroviral regimens for the maintenance treatment of HIV.
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Human Genetics Contributes To Zika-Induced Brain Damage

MedicalResearch.com Interview with:

Ping Wu, MD, PhD John S. Dunn Distinguished Chair in Neurological Recovery Professor, Department of Neuroscience & Cell Biology University of Texas Medical Branch Galveston, TX 77555-0620

Dr. Ping Wu

Ping Wu, MD, PhD
John S. Dunn Distinguished Chair in Neurological Recovery
Professor, Department of Neuroscience & Cell Biology
University of Texas Medical Branch
Galveston, TX 77555-0620

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Zika viral infection poses a major global public health threat, evidenced by recent outbreaks in America with many cases of microcephaly in newborns and other neurological impairments. A critical knowledge gap in our understanding is the role of host determinants of Zika-mediated fetal malformation. For example, not all infants born to Zika-infected women develop microcephaly, and there is a wide range of Zika-induced brain damage. To begin to fill the gap, we infected brain stem cells that were derived from three human donors, and found that only two of them exhibited severer deficits in nerve cell production along with aberrant alterations in gene expression.

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Educating Religious Leaders Improves Uptake of Male Circumcision in Tanzania

MedicalResearch.com Interview with:

Jennifer A. Downs, M.D., Ph.D. Assistant Professor of Medicine and Microbiology & Immunology Department of Medicine Weill Cornell Medicine Center for Global Health New York, NY 10065

Dr. Jennifer Downs

Jennifer A. Downs, M.D., Ph.D.
Assistant Professor of Medicine and Microbiology & Immunology
Department of Medicine
Weill Cornell Medicine
Center for Global Health
New York, NY 10065

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Between 2002 and 2006, three large randomized controlled trials in sub-Saharan Africa demonstrated that male circumcision reduces new HIV infections in men by approximately 60%. Based on these findings, the World Health Organization recommended male circumcision as an HIV prevention strategy in countries with high levels of HIV and a low prevalence of male circumcision. This led to prioritization of 14 countries in Eastern and Southern Africa for massive scale-up of male circumcision beginning in 2011.

In many of these countries, the uptake of male circumcision was lower than expected. In northwest Tanzania, where we work, there are a number of barriers to male circumcision. Some of these barriers are cultural, tribal, economic, and religious. We conducted focus group interviews in 2012 that showed that many Christian church leaders and church attenders in our region in Tanzania had major concerns about whether male circumcision was compatible with their religious beliefs. This led us to hypothesize that the uptake of male circumcision could be increased when religious leaders were taught about male circumcision, with the goal that they would then be equipped to discuss this issue with their congregations.
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Ibalizumab Immunotherapy Decreased Viral Load In Resistant HIV

MedicalResearch.com Interview with:

Brinda Emu MD Assistant Professor of Medicine (Infectious Diseases Yale University New Haven, CT

Dr. Brinda Emu

Brinda Emu MD
Assistant Professor of Medicine (Infectious Diseases
Yale University
New Haven, CT 

MedicalResearch.com: What is the background for this study?

Response: Ibalizumab is a fully humanized monoclonal antibody that targets the CD4 receptor.  This Phase III registrational study enrolled individuals with HIV infection that harbor high levels of multi-drug resistance, with limited treatment options.  At IDWeek in October, 2016, data was presented that demonstrated patients experienced a significant decrease in viral load after receiving a single loading dose of ibalizumab 2,000 mg intravenously (IV) in addition to their failing antiretroviral therapies (ART) (or no therapy). Seven days after this loading dose, 83% of patients achieved a ≥ 0.5 log10 decrease from baseline compared with 3% during the seven-day control period .These results were statistically significant (p<0.0001).

At CROI, additional data on the Week 24 results from this study are now presented.

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Persistence of Zika Virus in Body Fluids — Preliminary Report

MedicalResearch.com Interview with:
Gabriela Paz-Bailey MD PhD

Senior Epidemiologist
Centers for Disease Control and Prevention 

MedicalResearch.com: What is the background for this study?

Response: Zika virus is recognized as a cause of microcephaly and other severe birth defects when a woman is infected during pregnancy. Additionally, it has been associated with potentially fatal complications, such as Guillain-Barré syndrome. It is not well understood how often Zika virus particles can be detected in semen and other body fluids and for how long they remain detectable. Existing evidence is based on case reports and cross-sectional observations, primarily from returning travelers. A more comprehensive description of the dynamics of the early stages of Zika virus infection, observed within infected people over time, is needed to inform diagnostic testing as well as prevention recommendations and interventions.
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Vitamin D May Have Protective Role Against Respiratory Infections

MedicalResearch.com Interview with:
Dr. Adrian R Martineau
B Med Sci DTM&H MRCP PhD
Clinical Professor of Respiratory Infection and Immunity
Centre for Primary Care and Public Health.
Blizard Institute, Barts and The London School of Medicine and Dentistry
Queen Mary, University of London

MedicalResearch.com: What is the background for this study?

Response: In addition to its well-known effects on bone, Vitamin D has also been shown to boost immune responses to viruses and bacteria that cause respiratory infections in lab experiments.

In order to see whether these effects translate into a health benefit, a total of 25 clinical trials of vitamin D supplementation to prevent various respiratory infections have been carried out in around 11,000 people living in 14 different countries over the last decade.

These trials have yielded conflicting results: in some, vitamin D reduced the risk of infections, but in others it did not.

The reason why vitamin D ‘worked’ in some trials, but not in others, has been the subject of much debate.

In order to answer this question, we assembled an international consortium of investigators and compiled the raw data from every trial into a single database containing information from 10,933 people in total. This allowed us to run sub-group analyses to determine whether particular groups of people benefit more from vitamin D supplementation than others.

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Intestinal E. coli Linked to Arthritis in Inflammatory Bowel Disease

MedicalResearch.com Interview with:

Randy Longman, M.D. / Ph.D. Assistant Professor of Medicine Jill Roberts Center and Institute for Research in Inflammatory Bowel Disease Weill Cornell Medicine Division of Gastroenterology and Hepatology Joan and Sanford I. Weill Department of Medicine Department of Microbiology and Immunology New York, NY 10021

Dr. Randy Longman

Randy Longman, M.D. / Ph.D.
Assistant Professor of Medicine
Jill Roberts Center and Institute for Research in Inflammatory Bowel Disease
Weill Cornell Medicine
Division of Gastroenterology and Hepatology
Joan and Sanford I. Weill Department of Medicine
Department of Microbiology and Immunology
New York, NY 10021 

MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Inflammatory bowel disease is not limited to intestinal inflammation.  Up to 1/3 of patients with active disease suffer from extra-intestinal manifestations.

The most common extra-intestinal manifestations in IBD is joint inflammation or spondyloarthritis.  Peripheral joint spondyloarthritis  carries a prevalence of 20% in Crohn’s Disease and 10% in Ulcerative Colitis, predominantly affecting joints of the lower limbs.  It has long been suggested that gut bacteria can drive this systemic joint inflammation, but microbial targets have not been characterized.

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Aspirin Promotes Growth of Staph aureus in Nose

MedicalResearch.com Interview with:
Dr. Fernanda Buzzola

IMPaM, UBA-CONICET

MedicalResearch.com: What is the background for this study?

Response: Staphylococcus aureus represents a serious problem to public health due to methicillin-resistance and the bacterial persistence over a long period of time in the host. Approximately the 20% of the human population is at risk to acquire an endogenous infection by S. aureus as a consequence of its asymptomatic nasal colonization.

Aspirin, the main source of salicylic acid in the human host, is currently taken by millions of human beings worldwide without medical prescription and widely indicated for defined purposes, including prevention of coronary thrombosis. Salicylic acid is a plant hormone known too for its use as a key ingredient in anti-acne preparations and medications for skin conditions. We also consume mild doses of salicylic acid when we eat fruits and vegetables. Iron is an important trace element for the human body and plays an essential role in blood formation. The metabolism of many bacteria, including S. aureus, also depends on the availability of iron molecules. Salicylic acid forms complexes with iron ions in the blood and so deprives not only us but also the staphylococcal bacteria of this element. S. aureus modifies its metabolism if the iron content is insufficient. The microorganism reacts to the changed – from its perspective, negative – conditions through the intensified formation of a biofilm, a sort of layer of slime formed by the aggregation of individual bacteria. The enhanced biofilm production allows the bacteria to survive for an even longer period under unfavourable living conditions.

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