Group B Streptococcus Remain Significant Threat to US Infants

MedicalResearch.com Interview with:

Dr. Nanduri Srinivas Acharya, MBBS, MD, MPH Respiratory Diseases Branch, National Center for Immunizations and Respiratory Diseases Centers for Disease Control and Prevention Roybal Campus Atlanta, GA 30333

Dr. Nanduri

Dr. Srinivas Acharya Nanduri, MBBS, MD, MPH
Respiratory Diseases Branch, National Center for Immunizations and Respiratory Diseases
Centers for Disease Control and Prevention
Roybal Campus
Atlanta, GA 3033

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

Response: Group B Streptococcus (GBS) is a leading cause of serious illness such as meningitis and sepsis in infants. Among infants, there are two main types of GBS disease. Early-onset GBS disease occurs during the first week of life and late-onset GBS disease occurs from the first week through three months of life. Rates of early-onset disease in the United States have decreased significantly since the 1990s through widespread implementation of intrapartum antibiotic prophylaxis (IAP) guidelines. However, IAP does not prevent late-onset disease. Maternal immunization represents a nonantibiotic strategy to prevent both early and late-onset disease. Multivalent polysaccharide-protein conjugate vaccines are under development against GBS capsular types, with candidate vaccines in phase I and II trials.

Active Bacterial Core surveillance (ABCs) conducts active surveillance for early and late-onset GBS disease among infants in select counties of 10 states, covering about 10% of live births across the United States. We analyzed data from early and late-onset GBS cases identified from ABCs between 2006 and 2015 to describe their epidemiology, incidence trends, and associated strain characteristics. Continue reading

All Travelers to Pakistan At Risk of Getting Drug Resistant Typhoid Fever

MedicalResearch.com Interview with:

Kevin Chatham-Stephens, MD, MPH, FAAP CDR U.S. Public Health Service

Dr. Chatham-Stephens

Kevin Chatham-Stephens, MD, MPH, FAAP
CDR U.S. Public Health Service

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

Response: Typhoid fever is a life-threatening disease caused by Salmonella Typhi bacteria. It spreads when someone consumes food or water that has been contaminated with feces (poop) from someone carrying the bacteria. About 12–27 million cases of typhoid fever occur worldwide every year.

About 350 culture-confirmed cases of typhoid fever in the United States are reported to CDC each year. Most of these cases occur among international travelers.

Symptoms of typhoid fever often include high fever, weakness, stomach pain, cough, and loss of appetite. Some people have diarrhea or constipation. Typhoid fever can be prevented through vaccination and safe food and water practices. Typhoid fever is treated with antibiotics, although most infections diagnosed in the United States cannot be successfully treated with the class of antibiotics called fluoroquinolones.

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Over the Counter Pain Meds May Worsen C. difficile Gut Infections

MedicalResearch.com Interview with:

MedicalResearch.com Interview with: David M. Aronoff, MD, FIDSA, FAAM Professor & Addison B. Scoville Jr. Chair in Medicine Director, Division of Infectious Diseases Department of Medicine Vanderbilt University Medical Center     MedicalResearch.com:  What is the background for this study?  Response: Clostridium difficile infection (CDI) is a major cause of antibiotic-associated colitis and diarrhea and a leading cause of hospital-acquired infection. It is caused by the toxin-producing, anaerobic, spore-forming bacterium Clostridium difficile. Antibiotic use is a major risk factor for CDI but epidemiological studies suggest that other factors, some modifiable, some not, can also increase the risk for CDI. Older age is an example of a non-modifiable risk factor for CDI. Some epidemiological studies suggested that taking the prostaglandin synthesis inhibiting drugs called non-steroidal anti-inflammatory drugs (NSAIDs) might also increase the risk for CDI. NSAIDs include medications such as ibuprofen, naproxen, indomethacin, and others. Because NSAID use is so common, if it is a risk factor for the acquisition of, or severity of, CDI, that would be important because that would be a modifiable risk factor. We therefore sought to determine the impact of NSAID exposure on CDI severity in a mouse model of antibiotic-associated CDI. We also sought evidence for possible mechanisms whereby NSAIDs might increase the risk for CDI.   MedicalResearch.com: What are the main findings?   Response: Exposure of mice to indomethacin (an NSAID) for two days prior to infection with Clostridium difficile in antibiotic-exposed mice increased the severity of disease and this was associated with severe inflammation, changes to the bacterial populations in the colon and increased damage to the protective epithelial lining of the colon.    MedicalResearch.com: What should readers take away from your report?  Response: Our studies provide evidence in a mouse model of CDI that support human epidemiological studies linking NSAID use with CDI.       MedicalResearch.com: What recommendations do you have for future research as a result of this work?  Response: Studies in humans are needed to see if NSAID use is indeed a causal risk factor for CDI acquisition or severity.      MedicalResearch.com: Is there anything else you would like to add?  Response: This work was funded by the National Institutes of Health and the Crohn’s and Colitis Foundation of America. Dr. Aronoff has served as Consultant for Synthetic Biologics, Inc, Biocidium, NAEJA-RGM and BLC-USA on projects unrelated to this study. He also has research funding from Pfizer unrelated to this study.      Citation: Damian Maseda, Joseph P. Zackular, Bruno Trindade, Leslie Kirk, Jennifer Lising Roxas, Lisa M. Rogers, Mary K. Washington, Liping Du, Tatsuki Koyama, V. K. Viswanathan, Gayatri Vedantam, Patrick D. Schloss, Leslie J. Crofford, Eric P. Skaar, David M. Aronoff. Nonsteroidal Anti-inflammatory Drugs Alter the Microbiota and Exacerbate Clostridium difficile Colitis while Dysregulating the Inflammatory Response. mBio, 2019; 10 (1) DOI: 10.1128/mBio.02282-18      <span class="last-modified-timestamp">Jan 9, 2019 @ 3:25 pm</span>    The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.

Dr. Aronoff

David M. Aronoff, MD, FIDSA, FAAM
Professor & Addison B. Scoville Jr. Chair in Medicine
Director, Division of Infectious Diseases
Department of Medicine
Vanderbilt University Medical Center

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

Response: Clostridium difficile infection (CDI) is a major cause of antibiotic-associated colitis and diarrhea and a leading cause of hospital-acquired infection. It is caused by the toxin-producing, anaerobic, spore-forming bacterium Clostridium difficile. Antibiotic use is a major risk factor for CDI but epidemiological studies suggest that other factors, some modifiable, some not, can also increase the risk for CDI. Older age is an example of a non-modifiable risk factor for CDI. Some epidemiological studies suggested that taking the prostaglandin synthesis inhibiting drugs called non-steroidal anti-inflammatory drugs (NSAIDs) might also increase the risk for CDI. NSAIDs include medications such as ibuprofen, naproxen, indomethacin, and others. Because NSAID use is so common, if it is a risk factor for the acquisition of, or severity of, CDI, that would be important because that would be a modifiable risk factor.

We therefore sought to determine the impact of NSAID exposure on CDI severity in a mouse model of antibiotic-associated CDI. We also sought evidence for possible mechanisms whereby NSAIDs might increase the risk for CDI.

Continue reading

Scabies: For Community Control, Exam of Just Arms and Legs May Be Sufficient

MedicalResearch.com Interview with:
Michael Marks MRCP DTM&H PhD
Clinical Research Department, Faculty of Infectious & Tropical Diseases
London School of Hygiene and Tropical Medicine
Hospital for Tropical Diseases
London, United Kingdom
Twitter @dr_michaelmarks
Daniel Engelman MBBS; BMedSci; MPHTM; FRACP; PhD
Centre for International Child Health, University of Melbourne,
Tropical Diseases Research Group
Murdoch Children’s Research Institute
Melbourne, Australia
Twitter @Dan_Engelman

The lateral aspect of the left hand depicted here, reveals the presence of papules due to an infestation of the human itch mite, Sarcoptes scabiei var. hominis, in a case of what is commonly referred to as scabies.

The lateral aspect of the left hand depicted here, reveals the presence of papules due to an infestation of the human itch mite, Sarcoptes scabiei var. hominis, in a case of what is commonly referred to as scabies.CDC image

 

 

 

 

 

 

 

 

 

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

MM: Scabies is extremely common. Globally in the region of 100-200 million people are believed to be affected by scabies annually.

Recently the WHO has recognised Scabies as a ‘Neglected Tropical Disease’ in response to this burden of disease. There has been increasing interest in using Mass Drug Administration (treating whole communities) as a strategy to control scabies in communities. In order to make this practical countries need an easy mechanism for establishing if scabies is a significant problem in their communities. In general when treating an individual, clinicians would conduct a full body examination to diagnose scabies – however this may not be practical or necessary when making decisions about whether to treat whole communities.

DE: Despite the fact that Scabies is a very common condition that causes a great deal of health problems, it has been largely neglected by health, research and funding agencies – but pleasingly, the WHO has now started to take action on scabies control, starting with the recognition of scabies as a “Neglected Tropical Disease”

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Steroids Associated With Reduced Mortality in Adults with Sepsis

MedicalResearch.com Interview with:

Dr. Jianguo Xu, MD West China Hospital, Sichuan University Chengdu, Sichuan, China

West China Hospital Sichuan University

Dr. Jianguo Xu, MD
West China Hospital, Sichuan University
Chengdu, Sichuan, China

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

Response: Since the mid-20th century, corticosteroids have been used as adjuvant therapy in the context of sepsis. Although evaluated in numerous randomized clinical trials and meta-analyses, both the safety and efficacy of corticosteroids remain controversial.

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Timing of Immunotherapy Crucial to Outcomes

MedicalResearch.com Interview with:

Tatiana Garcia-Bates, Ph.D. Research Assistant Professor Department of Infectious Diseases and Microbiology Graduate School of Public Health University of Pittsburgh

Dr. Garcia-Bates

Tatiana Garcia-Bates, Ph.D.
Research Assistant Professor
Department of Infectious Diseases and Microbiology
Graduate School of Public Health
University of Pittsburgh

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

Response: Human immunodeficiency virus (HIV) infection is now a manageable disease with the advent and availability of highly effective, combination antiretroviral therapy (ART). Unfortunately, as soon as ART is interrupted, the virus quickly rebounds to high levels and again targets the immune system. Therefore, new immunotherapeutic treatments are sought to re-program the immune system to control the virus after ART interruption.

In many ways, chronic HIV infection, even when controlled, resembles cancer in how it impacts the immune system. Both conditions for example are associated with immune dysfunction, where the immune cells (specifically T cells) that are supposed to protect our bodies against invading microorganisms or cancers become exhausted and fail to respond effectively. In cancer, effective immunotherapies have been developed to reverse this immune exhaustion to extend the fighting capacity of the T cells.

An example of this is drugs that target immune checkpoints, or “shut down” proteins, expressed on activated T cells, such as the programmed death-1 (PD-1) receptor. When engaged, PD-1 sends a negative signal to deactivate the T cell, and this contributes to the immune exhaustion seen in both cancer and in chronic infections. Some cancers express the ligand or the “trigger” for this shut down receptor, called PD-1 ligand (PD-L1). When this interaction between PD-1 and PD-L1 is interrupted, for example by using a blocking antibody, T cells can regain their killing capacity and destroy infected cells or cancer cells. This anti-PD-1 therapy has demonstrated high success against a variety of tumors.

Therefore, we tested this approach in the context of HIV infection using a well-characterized cohort of HIV-positive individuals to see if we could improve their T cell responses to HIV in a laboratory setting.

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Chemo and Some Cancers Raise Risk of Shingles

MedicalResearch.com Interview with:

Herpes Zoster - Shingles on chest Wikipedia image

Herpes Zoster – Shingles
on chest
Wikipedia image

Jiahui Qian, MPH
School of Public Health and Community Medicine
University of New South Wales
Sydney Australia

 

 

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

Response: Herpes zoster is a neurocutaneous disease caused by the reactivation of latent varicella zoster virus and its risk is related to the cell-mediated immunity. Previous studies have reported a higher zoster risk among patients with haematological cancer and cancer patients receiving chemotherapy. However, the role of the cancer itself and the receipt of cancer treatment is not clearly separated, we therefore started this study and tried to separate the risk of zoster associated with the cancer itself from cancer treatment.  Continue reading

Prions of Creutzfeldt-Jakob Disease Detected Throughout Eye Tissues

MedicalResearch.com Interview with:
Top, retina of a control patient. Bottom, retina from a patient with CJD. Arrowheads point to abnormal prions in the outer plexiform layer (opl), and the asterisk (*) marks more diffuse prions in the inner plexiform layer (ipl).Orrù et al., mBio
Byron Caughey, Ph.D.
Senior Investigator
Chief, TSE/prion Biochemistry Section
Laboratory of Persistent Viral Diseases
NIH/NIAID Rocky Mountain Laboratories
Hamilton, MT 59840 USA 

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

Response: Corneal transplants have caused the transmission of Creutzfeldt-Jakob disease (CJD) in at least two cases, and pathological prion protein has been detected in the retinas of the eyes of sporadic CJD cases. To build on these previous indications of prions in eye tissue, we tested the distribution of prions in various components of eyes from 11 sCJD decedents.

We applied a highly sensitive surrogate test for prions (RT-QuIC) that indicated that all of the sCJD cases had prions in multiple parts of their eye, including the cornea and sclera, which is the white outer surface of the eye. Retinas were usually contained the highest levels, in some cases approaching levels in the brain. Some other parts such as the cornea, lens and vitreous had much lower, but detectable, levels. 

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Marked Increase in Infected Heart Valves Due to Injected Opioids

MedicalResearch.com Interview with:

Asher Schranz, MD Division of Infectious Disease Department of Medicine UNC School of Medicine

Dr. Schranz

Asher Schranz, MD
Division of Infectious Disease
Department of Medicine
UNC School of Medicine

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

Response: The opioid crisis has led to several major infectious diseases concerns, including HIV and Hepatitis C.

Drug use-associated infective endocarditis (DUA-IE) is a less commonly discussed consequence of the opioid epidemic. DUA-IE is an infection of one or more heart valves that occurs from injecting drugs. It can be a severe, life-threatening infection and requires a long course of intravenous antibiotics as well as, in some cases, open heart surgery to replace an infected heart valve. Several studies over the past few years have shown that DUA-IE has been increasing.

Our study examined hospital discharges in North Carolina statewide from 2007 to 2017. We sought to update trends in DUA-IE and describe how much heart valve surgery was being performed for DUA-IE. We also aimed to report the demographics of persons who are undergoing heart valve surgery for DUA-IE and the charges, lengths of stay and outcomes of these hospitalizations.  Continue reading

Mother’s Milk and Microbiome Affect Babies’ Reaction to Diarrhea Disease from Rotavirus

MedicalResearch.com Interview with:

3D graphical representation of a number of Rotavirus virions: CDC image

3D graphical representation of a number of Rotavirus virions: CDC image

Sasirekha Ramani, PhD
Assistant Professor
Molecular Virology and Microbiology
Baylor College of Medicine
Houston, TX

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

Response: This work pertains to Rotavirus, a leading cause of diarrhea and vomiting in children under the age of 5 years. In this paper, we described our work with a rotavirus strain that almost exclusively causes neonatal infections. For many years, we have been trying to understand why this strain primarily infects newborns and why infection in some babies is associated with gastrointestinal symptoms while others are asymptomatic. A few years ago, we showed that this particular virus binds to developmentally-regulated glycans (sugars) in the gut as receptors. As the baby grows, these sugars get modified, and that potentially explains why infection with this virus is primarily restricted to neonates. However, we didn’t really have to answer to why there are differences in association with clinical presentations.

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What is Risk of Sexual Transmission of HIV With Treatment-Suppressed Low Viral Load?

MedicalResearch.com Interview with:

"HIV infecting a human cell" by NIH Image Gallery is licensed under CC BY 2.0

HIV Infecting T Cell

Rachel Rodin
Centre for Communicable Diseases and Infection Control
Public Health Agency of Canada

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

Response: On December 1, 2016 (World AIDS Day), the Honourable Jody Wilson-Raybould, federal Minister of Justice, committed to working with provinces and territories, affected communities, and medical professionals to examine the criminal justice system’s response to non-disclosure of HIV status in the context of sexual relations.

To this end, Justice Canada worked with the Public Health Agency of Canada (PHAC), provincial and territorial public health and justice counterparts, and a variety of other stakeholders to develop a comprehensive report on the issue of HIV non-disclosure. As part of this work, Justice Canada asked PHAC to provide an assessment of the most recent medical science on sexual HIV transmission risk.

In collaboration with external peer reviewers, PHAC undertook a systematic review of the full body of scientific evidence on sexual HIV transmission risk. The review found that the risk of sexual transmission of HIV is negligible when an individual is taking antiretroviral therapy as prescribed and maintains a suppressed viral load. The review also concluded that the risk remains low when the individual is on antiretroviral therapy with varying viral load, or is not on antiretroviral therapy but uses condoms.    Continue reading

CDC Identifies Most Serious Norovirus Strains

MedicalResearch.com Interview with:
"Day 19: Norovirus (stomach flu) visits our home." by Loren Kerns is licensed under CC BY 2.0Rachel M. Burke, PhD, MPH
Epidemiologist, Viral Gastroenteritis Branch
Centers for Disease Control and Prevention
Atlanta, GA 30329

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

Response: Noroviruses are the leading cause of vomiting and diarrhea from acute gastroenteritis (inflammation of the stomach or intestines) among people of all ages in the United States. Each year in the United States, norovirus illness is responsible for an estimated 19 to 21 million cases of acute gastroenteritis, and contributes to 56,000 to 71,000 hospitalizations and 570 to 800 deaths, mostly among children and the elderly.

CDC linked information from two different surveillance systems to analyze 3,747 norovirus outbreaks reported by health departments from 2009 to 2016. Our study provides a comprehensive description of norovirus outbreaks from the epidemiology and laboratory perspectives, using the National Outbreak Reporting System (NORS) and CaliciNet, respectively. 

Norovirus outbreaks caused by GII.4 strains occurred more often in healthcare settings, affected older adults, and caused more severe illness, leading to hospitalization or death.

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Cystic Fibrosis Patients May Need Higher Doses of Antibiotics To Clear Lung Infections

MedicalResearch.com Interview with:

Andrea Hahn, M.D., MS Infectious disease specialist and lead study author Children's National Health System

Dr. Hahn

Andrea Hahn, M.D., MS
Infectious disease specialist and lead study author
Children’s National Health System

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

Response: People who have the genetic disease cystic fibrosis have increased sticky secretions in their lungs that put them at risk for repeated bacterial infections. They often will receive courses of intravenous antibiotics to treat more severe or difficult-to-treat infections associated with decreased lung function. However, not all patients fully recover their lung function after antibiotic treatment, despite directing antibiotic therapy toward the specific bacteria thought to be causing the infection. The goal of this study was to determine if the pharmacokinetics of commonly used antibiotics was associated with recovery of lung function.

First, we found that patients with therapeutic blood levels of beta-lactam antibiotics had better lung recovery than patients with sub-therapeutic levels of these antibiotics.

Second, we found that using higher antibiotic dosing according to Cystic Fibrosis Foundation guidelines was not sufficient to predict which patients would have therapeutically meaningful blood levels of antibiotics. Continue reading

New Drug Class Holds Promise Against Antibiotic Resistant Gonorrhea

MedicalResearch.com Interview with:

Intracellular Gram-negative, Neisseria gonorrhoeae diplococcal bacteria, - CDC image

Intracellular Gram-negative, Neisseria gonorrhoeae diplococcal bacteria, – CDC image

Edward W. Hook, III, MD
University of Alabama at Birmingham
Medicine / Infectious Diseases
Birmingham, AL

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

Response: Zoliflodacin represents a new class of antibiotics (spiropyrimidinetriones) with in vitro activity against Neisseria gonorrhoeae, as well as other STD  pathogens (Chlamydia trachomatis and Mycoplasma genitalium).  Because of this promising data and the fact that the manufacturer (Entasis Pharmaceuticals) was willing to pursue the possibility of using this drug to treat gonorrhea, a Phase II trial was conducted which showed he drug to be 96% effective for genital or rectal infections.  The drug was well tolerated as well making it a promising drug for gonorrhea treatment which might help to combat the increasing problem of antibiotic resistant gonorrhea.  Continue reading

Tens of Thousands Worldwide Die of Antibiotic-Resistant Bacteria

MedicalResearch.com Interview with:
"Antibiotics" by Michael Mortensen is licensed under CC BY-SA 2.0Dr Alessandro Cassini MD

Epidemiologist, European Centre for Disease Prevention and Control
Solna, Sweden

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

Response: We published an ECDC study estimating attributable deaths and disability-adjusted life-years caused by infections with antibiotic-resistant bacteria in the European Union and the European Economic Area (EU/EEA). This study is based on 2015 data from the European Antimicrobial Resistance Surveillance Network (EARS-Net).

The study was developed by experts at ECDC and the Burden of AMR Collaborative Group, and published in The Lancet Infectious Diseases.

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Study Supports Antibiotic Prophylaxis Before Dental Procedures in High Risk Patients

MedicalResearch.com Interview with:

Martin H. Thornhill MBBS, BDS, PhD, MSc, FDSRCS(Edin), FDSRCSI, FDSRCS(Eng) Professor of Translational Research in Dentistry Academic Unit of Oral & Maxillofacial Medicine Surgery & Pathology, University of Sheffield School of Clinical Dentistry 

Prof. Thornhill

Martin H. Thornhill MBBS, BDS, PhD, MSc, FDSRCS(Edin), FDSRCSI, FDSRCS(Eng)
Professor of Translational Research in Dentistry
Academic Unit of Oral & Maxillofacial Medicine Surgery & Pathology,
University of Sheffield School of Clinical Dentistry 

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

Response: Infective endocarditis is an infection of the heart valves that has a high death rate (around 30% in the first year). It requires intensive treatment often involving replacement of affected heart valves and frequently results in serious long-term illness and disability in those who survive as well as an increased risk of re-infection and high healthcare costs.

In ~40% of cases, bacteria from the mouth are implicated as the causal organism. Because of this, guideline committees around the world recommended that all those at risk of infective endocarditis should receive antibiotic prophylaxis before undergoing invasive dental procedures. Due to a lack of evidence for efficacy, however, guideline committees started to limit the use of antibiotic prophylaxis. And in 2007, the American Heart Association (AHA) guideline committee recommended that antibiotic prophylaxis should continue for those at high-risk but should cease for those at moderate risk of endocarditis. Most guideline countries around the world followed suite. Except in the UK, where the National Institute for Health and Care Excellence (NICE) recommended that the use of antibiotic prophylaxis should completely stop in 2008.

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CDC Reports Decrease in Some Hospital Acquired Infections

MedicalResearch.com Interview with:
"Hospital Room" by Kyle Taylor is licensed under CC BY 2.0Dr. Shelley Magill, MD

Medical Officer and CDC lead
for the hospital HAI (hospital acquired infections) and antimicrobial use prevalence survey

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

Response: The prevalence survey effort began in 2009. The goal was to obtain a snapshot of all healthcare-associated infections affecting hospital patients, not limited to those commonly reported to the National Healthcare Safety Network. We conducted our first full-scale hospital prevalence survey in 2011, in collaboration with the Emerging Infections Program, a network of 10 state health departments and academic and other partners. Data from that survey showed that about four percent of patients had a healthcare-associated infection—or, on any given day, about 1 in 25 patients. We repeated the survey in a similar group of hospitals in 2015 to see whether changes had occurred.

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FDA Approves Single Dose XOFLUZA™ For Uncomplicated Flu

MedicalResearch.com Interview with:

Mark D. Eisner, MD, MPH Vice President, Product Development Immunology Infectious Disease and Ophthalmology Genentech 

Dr. Mark Eisner

Mark D. Eisner, MD, MPH
Vice PresidentProduct Development Immunology, Infectious Disease and Ophthalmology Genentech

Dr. Eisner discusses the announcement that the FDA has approved XOFLUZA™ (baloxavir marboxil) for the treatment of acute, uncomplicated influenza.

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

Response: Each year, an estimated 3-11 percent of the U.S. population gets the flu, and it can be very serious, resulting in hospitalization or even death. Since 2010, the Centers for Disease Control and Prevention (CDC) estimates that the flu has resulted annually in 9.2 to 35.6 million illnesses, 140,000 to 900,000 hospitalizations and 12,000 to 80,000 deaths. The severity of last year’s flu season underscores the need for new medical options beyond currently available antivirals.

XOFLUZA was granted Priority Review in June 2018 based on results from the Phase III CAPSTONE-1 study of a single dose of XOFLUZA compared with placebo or oseltamivir 75 mg, twice daily for five days, in otherwise healthy people with the flu, as well as results from a placebo-controlled Phase II study in otherwise healthy people with the flu.

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Gene Signature Blood Test Can Diagnose TB and Treatment Response

MedicalResearch.com Interview with:
"Mycobacterium tuberculosis Bacteria, the Cause of TB" by NIAID is licensed under CC BY 2.0Purvesh Khatri, Ph.D.
Associate Professor
Stanford Institute for Immunity, Transplantation and Infection (ITI)
Stanford Center for Biomedical Informatics Research (BMIR)
Department of Medicine
Stanford University
Stanford, CA 94305

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

Response: We have previously described a 3-gene signature for distinguishing patients with active tuberculosis (ATB) from those with other diseases, latent mycobacterium tuberculosis (LTB) infection, and healthy controls (Sweeney et al. Lancet Respir Med 2016).

The current study in JAMA Network Open is a follow up study to validate the 3-gene signature in 3 additional independent cohorts that were prospectively collected.

Using these 3 cohorts we have now showed that the 3-gene signature

(1) can identify patients with LTB that will progress to ATB about 6 months prior to diagnosis of active tuberculosis.

(2) can identify patients with ATB in active screening, and

(3) can identify patients with ATB at diagnosis that have higher likelihood of persistent lung inflammation due to subclinical ATB at the end of treatment.  Continue reading

Successful Trial of Cefiderocol For Resistant & Complicated Urinary Tract Infections

MedicalResearch.com Interview with:
https://www.shionogi.com/Simon Portsmouth, MD

Senior Medical Director
Shionogi Inc.

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

Response: Antibiotics for multidrug resistant  Gram-negative infections are desperately needed. Cefiderocol is the first siderophore antibiotic to reach patients.

Siderophore antibiotics bind to free iron and use the bacterial active iron transport channels to cross the outer membrane of Gram-negative bacteria. Laboratory studies have shown that cefiderocol is active against multi-drug resistant Gram-negative bacteria, often where no other antibiotics are active. It is able to overcome most types of antibiotic resistance due to its active transport into cells and stability against all carbapenemases.

The need for antibiotics for carbapenem resistant Gram-negative infections is described as a critical need by the WHO. This trial was the first in humans with serious infections and demonstrated excellent efficacy in a complicated patient population where almost ¼ were over 75 years of age. Additionally cefiderocol did not appear to have any safety problems, and was well tolerated.

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Nose-Picking Can Spread Pneumonia

MedicalResearch.com Interview with:
"still picking her nose" by quinn norton is licensed under CC BY 2.0Dr Victoria Connor 

Clinical Research Fellow
Liverpool School of Tropical Medicine and Royal Liverpool Hospital 

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

Response: Pneumococcus is a bacteria which is very common and causes lots of different infections (pneumococcal disease). Infections can be non-invasive or invasive. Non-invasive diseases include middle ear infections, sinusitis and bronchitis. Invasive infections including chest infection (pneumonia), infections of brain and spinal cord (meningitis) and blood infections (sepsis).

Invasive pneumococcal infections is a major cause of death around the world and in the UK, is estimated that is responsible for 1.3 million deaths in children under 5 annually. Pneumococcal disease causes more deaths in low and middle income countries where approximately 90% of pneumonia deaths occur.

Pneumococcus also is commonly carried (colonises) the nose/throat of children and adults. This colonisation is important to understand as it is the main source of the bacterial transmission and is also the first step in pneumococcal infections.

The understanding of transmission of pneumococcus is currently poor. It is generally thought that transmission occurs through breathing in the respiratory sections of someone carrying pneumococcus in their nose which are infected with pneumococcus.

However more recently studies especially in mice have shown that there may be a role of hands or other objects as vehicles for the transmission of pneumococcus.

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Dual Stain More Accurate & Efficient for Detecting Cervical Precancers in HPV-Positive Women

MedicalResearch.com Interview with:

Megan Clarke, PhD, MHS Cancer Prevention Fellow Clinical Genetics Branch Division of Cancer Epidemiology & Genetics National Cancer Institute Rockville, MD 20892

Dr. Clarke

Megan Clarke, PhD, MHS
Cancer Prevention Fellow
Clinical Genetics Branch
Division of Cancer Epidemiology & Genetics
National Cancer Institute
Rockville, MD 20892 

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

  • Infection with high-risk human papillomavirus (hrHPV) is the primary cause of cervical cancer. While hrHPV infection is common, most infections are benign and clear on their own without causing cervical cancer. However, some women develop persistent hrHPV infections and are at risk for cervical cancer and its precursors (i.e., precancer).
  • The United States Preventative Services Task Force recommends screening every 3 years with cervical cytology (i.e. Pap) alone, every 5 years with hrHPV testing alone, or with a combination of hrHPV testing and cytology (co-testing) for women aged 30 to 65 years.
  • Screening with hrHPV testing is highly sensitive for detecting cervical precancer but requires additional triage tests to identify HPV-positive women at high-risk of developing cancer who should undergo colposcopy (visualization of the cervix) and biopsy from those at low-risk who can be safely monitored.
  • Currently, Pap cytology is recommended as a triage test for women testing HPV-positive, but this approach requires frequent re-testing at short intervals because the risk of cervical precancer is not low enough in HPV-positive women who test cytology negative to provide long-term reassurance against future risk. In most settings, women who test HPV-positive, cytology-negative are referred to repeat screening within one year.
  • The p16/Ki-67 dual stain assay is a molecular test that measures two specific proteins, p16 that is strongly linked with hrHPV infection, and Ki-67, a marker of cell proliferation that is common in precancers and cancers.
  • Studies have shown that the dual stain test has greater accuracy for detecting cervical precancers in HPV-positive women compared with cytology.
  • In order to determine the optimal screening intervals for the dual stain test, long-term prospective studies are needed to determine how long HPV-positive women who test dual stain negative can be safely reassured of a low precancer risk.

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Mandated Audit-and-Feedback Did Not Improve Hospital Hand Hygiene

MedicalResearch.com Interview with:
"Hand Washing" by Anthony Albright is licensed under CC BY-SA 2.0Dr. Daniel J. Livorsi, MD
Assistant Professor
INFECTIOUS DISEASE SPECIALIST
University of Iowa

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

Response: One of the Joint Commission’s standards is that hospitals audit and provide feedback on hand hygiene compliance among healthcare workers. Audit-and-feedback is therefore commonly practiced in US hospitals, but the effective design and delivery of this intervention is poorly defined, particularly in relation to hand hygiene improvement.

We studied how 8 hospitals had implemented audit-and-feedback for hand hygiene improvement. We found that hospitals were encountering several barriers in their implementation of audit-and-feedback. Audit data on hand hygiene compliance was challenging to collect and was frequently questioned. The feedback of audit results did not motivate positive change. 

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Probiotic May Eliminate Staph Bacteria Colonizations

MedicalResearch.com Interview with:
"staph aureus on blood agar" by Iqbal Osman is licensed under CC BY 2.0Pipat Piewngam
Postdoctorol fellow
Pathogen Molecular Genetics Section,
Laboratory of Bacteriology,
NIAID/NIH
Bethesda, MD, USA 20892 

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

Response: Our team at National Institutes of health, Mahidol University and Rajamangala University of Technology in Thailand has reported that the consumption of probiotic Bacillus bacteria comprehensively abolishes colonization with the dangerous pathogen, Staphylococcus aureus.

We hypothesized that the composition of the human gut microbiota affects intestinal colonization with S. aureus. We collected fecal samples from 200 healthy individuals from rural populations in Thailand and analyzed the composition of the gut microbiome by 16S rRNA sequencing. Surprisingly, we did not detect significant differences in the composition of the microbiome between S. aureus carriers and non-carriers. We then sampled the same 200 people for S. aureus in the gut (25 positive) and nose (26 positive). Strikingly, we found no S. aureus in any of the samples where Bacillus were present.

In mouse studies, we discovered S. aureus Agr quorum-sensing signaling system that must function for the bacteria to grow in the gut. Intriguingly, all of the more than 100 Bacillus isolates we had recovered from the human feces efficiently inhibited that system. Then, we discovered that the fengycin class of Bacillus lipopeptides achieves colonization resistance by inhibiting that system.

To further validate their findings, we colonized the gut of mice with S. aureus and fed them B. subtilis spores to mimic probiotic intake. Probiotic Bacillus given every two days eliminated S. aureus in the guts of the mice. The same test using Bacillus where fengycin production had been removed had no effect, and S. aureus grew as expected. This is one of the first study that provide human evidence supporting the biological significance of probiotic bacterial interference and show that such interference can be achieved by blocking a pathogen’s signaling system. Continue reading

Single Dose Baloxavir marboxil (Xofluza) Has Potential To Improve Treatment of High-Risk Flu

MedicalResearch.com Interview with:

Mark D. Eisner, MD, MPH Vice President, Product Development Immunology Infectious Disease and Ophthalmology Genentech 

Dr. Eisner

Mark D. Eisner, MD, MPH
Vice President, Product Development Immunology
Infectious Disease and Ophthalmology
Genentech 

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

Response: CAPSTONE-2 is a Phase III multicenter, randomized, double-blind study that evaluated the efficacy and safety of a single dose of baloxavir marboxil compared with placebo and oseltamivir in people 12 years and older who are at a high risk of complications from the flu. The Centers for Disease Control and Prevention (CDC) defines people at high risk for serious flu complications to include adults 65 years of age or older, or those who have conditions such as asthma, chronic lung disease, morbid obesity or heart disease.

A total of 2,184 participants enrolled in the study and were randomly assigned to receive a single, oral dose of 40 mg or 80 mg of baloxavir marboxil (according to body weight), placebo or 75 mg of oseltamivir twice daily for five days. The primary objective of the study evaluated the efficacy of a single dose of baloxavir marboxil compared with placebo by measuring the time to improvement of influenza symptoms. Key secondary endpoints compared outcomes in baloxavir marboxil versus placebo or oseltamivir – these included time to resolution of fever, time to cessation of viral shedding, infectious virus detection in swabs of the nose and throat, prescription of antibiotics and influenza-related complications.

Genentech announced initial results from the study on July 16, 2018 but the full data was presented for the first time during a late-breaking oral presentation at the annual IDWeek meeting in San Francisco, CA on October 6, 2018.

Baloxavir marboxil is a first-in-class, single-dose investigational oral medicine with a novel proposed mechanism of action designed to target the influenza A and B viruses, including oseltamivir-resistant strains and avian strains (e.g. H7N9, H5N1). Baloxavir marboxil is the first potential influenza treatment to demonstrate a clinically meaningful benefit for people highly vulnerable to serious influenza complications in clinical trials.

The FDA accepted a New Drug Application (NDA) and granted Priority Review to baloxavir marboxil as a single-dose, oral treatment for acute, uncomplicated influenza in people 12 years and older. The NDA was based on results from the Phase III CAPSTONE-1 study of a single dose of baloxavir marboxil compared with placebo or oseltamivir 75 mg, twice daily for five days, in otherwise healthy people with the flu. Results from a placebo-controlled Phase II study in otherwise healthy people with the flu were included as supporting data in the NDA. The FDA is expected to make a decision on approval by December 24, 2018. Continue reading