Severe Clostridium difficile Infections May Be Better Treated With Vancomycin

MedicalResearch.com Interview with:

Vanessa W. Stevens, PhD IDEAS 2.0 Center, Veterans Affairs (VA) Salt Lake City Health Care System Division of Epidemiology, Department of Internal Medicine University of Utah School of Medicine Salt Lake City, Utah

Dr. Vanessa Stevens

Vanessa W. Stevens, PhD
IDEAS 2.0 Center, Veterans Affairs (VA) Salt Lake City Health Care System
Division of Epidemiology, Department of Internal Medicine
University of Utah School of Medicine
Salt Lake City, Utah

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

Response: Although metronidazole remains the most commonly used drug to treat Clostridium difficile infection (CDI), there is mounting evidence that vancomycin is a better choice for some patients. Most previous studies have focused on primary clinical cure, but we were interested in downstream outcomes such as disease recurrence and mortality. We found that patients receiving metronidazole and vancomycin had similar rates of recurrence, but patients who were treated with vancomycin had lower risks of all-cause mortality. This was especially true among patients with severe Clostridium difficile.

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Childhood Antibiotic Use Linked To Higher BMI At Age 3

MedicalResearch.com Interview with:

Melissa N. Poulsen, PhD, MPH</strong> Postdoctoral Fellow Johns Hopkins Bloomberg School of Public Health Geisinger Center for Health Research

Dr. Melissa N. Poulsen

Melissa N. Poulsen, PhD, MPH
Postdoctoral Fellow
Johns Hopkins Bloomberg School of Public Health
Geisinger Center for Health Research

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

Response: Several past studies report positive associations between early childhood antibiotic use (particularly in the first year of life) and body mass index (BMI) later in childhood. Studies have also observed positive associations with prenatal antibiotic use and BMI, but without information on childhood antibiotics, such studies cannot rule out an underlying causal relationship between prenatal antibiotic exposure and early childhood antibiotic use.

No study to date has concurrently evaluated prenatal and early childhood antibiotic exposure. We used mother-child linked electronic health record data to determine whether prenatal and childhood antibiotic use are independently associated with BMI at age 3 years.

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Infections in Infancy, Not Antibiotics Associated With Childhood Obesity

MedicalResearch.com Interview with:

De-Kun Li, MD, PhD Senior Research Scientist Division of Research Kaiser Foundation Research Institute Kaiser Permanente Oakland, CA 94612

Dr. De-Kun Li,

De-Kun Li, MD, PhD
Senior Research Scientist
Division of Research
Kaiser Foundation Research Institute
Kaiser Permanente
Oakland, CA 94612

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

Response: The composition of gut microbia (microbiome) has emerged as a key contributor to human disease risk. The external influence on the composition of microbiome in early childhood, especially in infancy, has been linked to increased risk of childhood obesity. Several studies have examined use of antibiotics in infancy and reported an association between use of antibiotics and increased risk of childhood obesity. This has caused a great uncertainty among both pediatricians and parents regarding treatment of infant infections. However, the previous studies failed to separate the effect of underlying infections for which antibiotics were used from the effect of the antibiotics itself. The contribution of our study was to examine the effects of infections and antibiotic use separately.

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33% Rise In ‘Last-Resort’ Antibiotics Use in Hospitals

MedicalResearch.com Interview with:

James Baggs, PhD CDC

Dr. James Baggs

James Baggs, PhD
Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention
Atlanta, Georgia

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

Response: We used medical claims data to estimate the amount of antibiotics used in US hospitals from 2006 – 2012. Data came from the Truven Health MarketScan Hospital Drug Database, which included about 300 hospitals and more than 34 million discharges. Antibiotic use in hospitals was very common with more than half of patients receiving at least one antibiotic during their hospital stay. Overall rates of antibiotic use in U.S. hospitals did not change over time; however, there were significant changes in the types of antibiotics prescribed.

Importantly, the types of antibiotics with the largest increases in use were the types of antibiotics often considered to be the most powerful. Of particular concern, there was a 37% rise in the use of carbapenems, commonly referred to as “last resort” antibiotics.

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Food Allergies May Be Higher In Children Who Receive Antibiotics During First Year

MedicalResearch.com Interview with:

Bryan L. Love, PharmD, BCPS-AQ ID Associate Professor Department of Clinical Pharmacy & Outcomes Sciences South Carolina College of Pharmacy - University of South Carolina Columbia, South Carolina 29208-0001

Dr. Bryan Love

Bryan L. Love, PharmD, BCPS-AQ ID
Associate Professor
Department of Clinical Pharmacy & Outcomes Sciences
South Carolina College of Pharmacy
University of South Carolina
Columbia, South Carolina 29208-0001

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

Response: In the US, food allergy has become one of the more common childhood medical conditions diagnosed in young children. Antibiotics are frequently prescribed in young children, and research continues to reveal that as many as 30% of antibiotic prescriptions are not appropriate.* We sought to examine if there was an association between antibiotic prescription and food allergy diagnosis.
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Study of Topical Minocycline For Acne Demonstrates No Phototoxicity or Absorption

MedicalResearch.com Interview with:
Kin F. Chan, PhD

Executive Vice President of Research and Technology
BioPharmX Corporation

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

Response: There were two studies in this series.  The purpose is to get a better understanding of the blood plasma and skin levels of minocycline in a relevant animal model (minipig) for both the oral form of minocycline (Solodyn) and topical BPX-01, and to elucidate the same for oral minocycline only in a clinical study.

The results provided valuable guidance and assurance to our upcoming Clinical Phase 2b dose-ranging study design.

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Preventing Bacteria From Sticking Would Eliminate Need For Antibiotics

MedicalResearch.com Interview with:

Dr Peter Monk BSc PhD Faculty Director of International Affairs Reader in Immunology Department of Infection, Immunity and Cardiovascular Disease Sheffield University Medical School

Dr. Peter Monk

Dr Peter Monk BSc PhD
Faculty Director of International Affairs
Reader in Immunology
Department of Infection, Immunity and Cardiovascular Disease
Sheffield University Medical School

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

Response: The tetraspanin proteins are found on the surface of all mammalian cells. The cell surface is the place where cells ‘socialise’: they talk to each other to coordinate activities, stick to each other to form tissues and sometimes crawl across each other to get to where they need to go. Tetraspanins have an important job to do in the organisation of the cell surface, amongst other things enabling the formation of ‘sticky patches’ (tetraspanin-enriched microdomains or TEM) that cause cells to adhere together or provide traction to allow movement. Some bacteria have evolved ways of hijacking the TEM for their own ends, adhering to tightly to these structures so that the normal things that sweep bacteria away (such as blood, sweat and tears!) are no longer effective. At this point, infection begins.

We have found that the TEM can be partly disrupted, by adding small parts of tetraspanins (peptides) to cells. The peptides seem to work by weakening the tetraspanin glue that holds the TEM together and causing the other components that give the ‘stickiness’ to the TEM to become more spaced out. We use the analogy of Velcro(TM), where the fabric hooks and loops are held together in woven material; loosen the weave and the hooks and loops fall apart, no longer able to engage strongly with the loops in the opposing piece of fabric.

Using reconstructed human skin, we were able to show that the tetraspanin peptides were both safe and effective; they did not affect wound healing in burned skin, but they could lower the bacterial load in the wound by 50%. This would allow the immune system (including the fluid that ‘weeps’ from wounds) to deal with the remaining bacteria more easily. Unlike conventional antibiotics that tend to kill bacteria, our peptides simply cause them to get washed away, so not invoking the evolutionary selective mechanisms that lead to resistance.

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Phase 2 Study of New Combination Antibiotics Successfully Treats Complicated UTIs

MedicalResearch.com Interview with:

Amanda Paschke, MD Director, Infectious Disease Clinical Research Merck Research Laboratories

Dr. Amanda Paschke

Amanda Paschke, MD
Director, Infectious Disease Clinical Research
Merck Research Laboratories

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

Response: Relebactam is an investigational beta-lactamase inhibitor being developed as a fixed-dose combination with imipenem/cilastatin, which is a broad-spectrum antibiotic in the carbapenem class. In preclinical studies, this combination demonstrated antibacterial activity against a broad range of multidrug-resistant Gram-negative pathogens, including those producing extended-spectrum beta-lactamases such as Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae and AmpC-producing Pseudomonas aeruginosa. Many of the most concerning infections caused by “superbugs” are caused by Gram-negative bacteria. These bacteria have evolved to be resistant to commonly used antibacterials, and even to antibacterials used as “last resort” treatment, which is why finding ways to treat them has become urgent. The addition of relebactam to imipenem is designed to restore activity of imipenem against certain imipenem-resistant strains of Gram-negative bacteria known to cause serious infections among people who often have other underlying medical conditions, which complicates treatment.

This was a Phase 2, multicenter, randomized, double-blind, non-inferiority study. The study looked at the use of relebactam plus imipenem versus imipenem alone for the treatment of adult patients with complicated urinary tract infections. The primary endpoint for the trial was microbiological response at the completion of IV study therapy. The study met its primary endpoint, demonstrating that the combination of relebactam with imipenem was as at least as effective as imipenem alone for the treatment of complicated urinary tract infections. The trial also demonstrated that the combination of relebactam plus imipenem is well-tolerated, with a safety profile similar to that of imipenem alone in this patient.

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Antibiotics Increase Oxygen in Bowel, Allowing Salmonella To Thrive

MedicalResearch.com Interview with:

Andreas J. Bäumler, Ph.D Editor, Infection and Immunity Associate Editor, PLOS Pathogens Section Editor, EcoSal Plus Professor, Department of Medical Microbiology and Immunology Vice Chair of Research University of California, Davis School of Medicine Davis, California

Dr. Andreas Bäumler

Andreas J. Bäumler, Ph.D
Editor, Infection and Immunity
Associate Editor, PLOS Pathogens
Section Editor, EcoSal Plus
Professor, Department of Medical Microbiology and Immunology
Vice Chair of Research
University of California, Davis School of Medicine
Davis, California

 

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

Dr. Bäumler: Antibiotics are generally beneficial for treating bacterial infection, but paradoxically a history of antibiotic therapy is a risk factor for developing Salmonella food poisoning.  Our study reveals the mechanism by which antibiotics increase susceptibility to Salmonella infection.

Antibiotics deplete beneficial microbes from the gut, which normally provide nutrition to the cells lining our large bowel, termed epithelial cells. Depletion of microbe-derived nutrients causes our epithelial cells to switch their energy metabolism from respiration to fermentation, which in turn increases the availability of oxygen at the epithelial surface. The resulting increase in oxygen diffusion into the gut lumen drives a luminal expansion of Salmonella by respiration. Through this mechanism, antibiotics help Salmonella to breath in the gut.

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CDC Estimates 47 Million Unnecessary Antibiotic Prescriptions Among US Outpatients Annually

MedicalResearch.com Interview with:

Dr. Fleming-Dutra MD CDC Dr. Fleming-Dutra MD is a medical epidemiologist with the Office of Antibiotic Stewardship in the Division of Healthcare Quality Promotion at the Centers for Disease Control and Prevention (CDC). She is also a pediatrician and pediatric emergency medicine physician and has focused on infectious diseases epidemiology and antibiotic stewardship in the outpatient setting in her career at CDC.

Dr. Fleming Dutra

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

Dr. Fleming-Dutra: One of the most urgent public health threats of our time is the emergence of antibiotic-resistant bacteria. The use of antibiotics is the single most important factor leading to antibiotic resistance around the world.  Simply using antibiotics creates resistance.  To combat antibiotic resistance we have to use antibiotics appropriately — only when needed and, if needed, use them correctly.  In 2015, the White House released the National Action Plan for Combating Antibiotic-Resistant Bacteria (CARB), which set a goal for reducing inappropriate outpatient antibiotic use by 50% by 2020.  However, the amount of antibiotic use in the outpatient setting that is inappropriate was unknown.

MedicalResearch.com: What are the main findings?

Dr. Fleming-Dutra: In this study, we estimate that at least 30% of antibiotics prescribed in doctors’ offices, emergency departments and hospital-based clinics are unnecessary—meaning that no antibiotic was needed at all, which equates to 47 million unnecessary antibiotic prescriptions written annually in these outpatient settings.  Most of those unnecessary antibiotic prescriptions were written for acute respiratory conditions, a key driver of antibiotic overuse. Thus, in order to reach the White House goal of reducing inappropriate outpatient antibiotic use by 50%, a 15% reduction in overall antibiotic use in outpatient settings is needed by 2020.

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No Consensus on Antibiotic Prophylaxis Prior To Pediatric Surgery

MedicalResearch.com Interview with:

Thomas J. Sandora, M.D., M.P.H. Senior Associate Physician in Medicine; Hospital Epidemiologist; Medical Director, Infection Control Boston Children’s Hospital Associate Professor of Pediatrics, Harvard Medical School

Dr. Thomas Sandora

Thomas J. Sandora, M.D., M.P.H.
Senior Associate Physician in Medicine; Hospital Epidemiologist; Medical Director, Infection Control
Boston Children’s Hospital
Associate Professor of Pediatrics, Harvard Medical School

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

Dr. Sandora: Giving antibiotics before certain types of operations results in lower rates of surgical site infections. However, there are limited data about which pediatric operations require antibiotic prophylaxis. We examined national variability in antibiotic prophylaxis for the 45 most commonly performed pediatric operations at children’s hospitals in the U.S. We found that antibiotic use was considered appropriate for only 64.6% of cases, with a high degree of variability within procedures and between hospitals.

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Antibiotics Don’t Promote Resistance Gene Transfers Between Cells

MedicalResearch.com Interview with:

Dr. Lingchong You PhD Paul Ruffin Scarborough Associate Professor of Engineering Duke University

Dr. Lingchong You

Dr. Lingchong You PhD
Paul Ruffin Scarborough Associate Professor of Engineering
Duke University

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

Dr. You: Horizontal gene transfer (HGT) refers to the transfer of genes between organisms of the same or different species other than reproduction. In bacteria, ​Horizontal gene transfer can occur through conjugation (bacterial mating), transduction mediated by phage, or transformation. During conjugation, a donor cell makes a copy of a conjugal plasmid and passes it to a recipient cell, turning it into a transconjugant.

It is well appreciated that HGT (particularly through conjugation) is the major mechanism underlying the wide spread of genes encoding antibiotic resistance.  Given this notion, it is tempting to assume that the use of antibiotics could increase the efficiency of horizontal gene transfer, creating a vicious cycle. Indeed, this has been speculated in the literature even though precise experimental measurements have been lacking.

In our study, we find that antibiotics covering all major classes do not promote the probability of conjugation between donor and recipient cells. Instead, antibiotics modulate the final outcome of conjugation dynamics by imposing different degrees of selection on the donor cells, recipient cells, and the transconjugants. Depending on the antibiotic doses and how the antibiotic affects the three populations, the selection dynamics could lead to an increase or the decrease in the frequency of transconjugants.

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