Alzheimer's - Dementia, Author Interviews, Herpes Viruses / 20.07.2018

MedicalResearch.com Interview with: Prof Ruth Itzhaki Emeritus Professor Division of Neuroscience & Experimental Psychology The University of Manchester MedicalResearch.com: What is the background for this study? Response: The background arises from the unexpected discovery, made by my lab almost 30 years ago, that the DNA of the common virus, herpes simplex virus type 1 (HSV1), known as the "cold sore" virus, was present in a high proportion of autopsy brains from elderly humans. Subsequently, we found that HSV1, when in brain of people who have a specific genetic factor, APOE-e4, confers a strong risk of developing Alzheimer's disease. We found also a parallelism with cold sores in that APOE-e4 is a risk for the sores, which occur in about 25-40% of people infected with HSV1. We then looked for links between the effects of HSV1 infection of cells in culture and AD, and found some major associations between virus and disease. Firstly, HSV1 causes an increase in the formation of a small protein called beta amyloid, which is the main component of the abnormal "plaques" seen in Alzheimer's Disease brains. Secondly, we discovered that in AD brains, the viral DNA is located precisely within amyloid plaques, which suggests that the virus is responsible for the formation of these abnormal structures. Thirdly, we confirmed the finding of another lab that HSV1 causes the increased formation of an abnormal form of the protein known as tau, which is the main component of the other characteristic abnormality of Alzheimer's Disease brains - "neurofibrillary tangles". All these discoveries suggested that the damage caused by HSV1 leads eventually to the development of AD. Lastly, we showed that treating HSV1-infected cells in culture greatly reduces the formation of beta amyloid and abnormal tau. This suggests that antiviral agents might be used for treating Alzheimer's Disease patients. (more…)
Author Interviews, Biomarkers, Infections, NEJM, University of Pittsburgh / 19.07.2018

MedicalResearch.com Interview with: David T. Huang, MD, MPH Associate Professor, Critical Care Medicine, Emergency Medicine, Clinical and Translational Science Director, MACRO (Multidisciplinary Acute Care Research Organization) Director, CRISMA Administrative Core (Clinical Research, Investigation, and Systems Modeling of Acute illness) University of Pittsburgh MedicalResearch.com: What is the background for this study? Response: The overuse of antibiotics has become a serious threat to global public health, causing antibiotic resistance and increasing health care costs. Physicians have long known that antibiotics are usually unnecessary for acute bronchitis and for some other cases of lower respiratory tract infections, and that antibiotics treat only bacterial infections, not viral. But in daily practice, many physicians often prescribe them. Previous research had reported that using a biomarker blood test and following an antibiotic guideline tied to the test results could reduce antibiotic use in lower respiratory tract infections. In February 2017, the U.S. Food and Drug Administration approved the biomarker test that measures procalcitonin – a peptide that typically increases in bacterial infections, but not viral. We conducted the Procalcitonin Antibiotic Consensus Trial (ProACT) trial to evaluate whether a procalcitonin antibiotic prescribing guideline, implemented for the treatment of suspected lower respiratory tract infection with reproducible strategies, would result in less exposure to antibiotics than usual care, without a significantly higher rate of adverse events. The ProACT trial involved 14 predominately urban academic hospitals. We enrolled 1,656 adult patients who presented to the hospital emergency department and were initially diagnosed with a lower respiratory tract infection. All the patients were tested for their procalcitonin levels, but the results were shared only with the physicians of the patients randomly assigned to procalcitonin-guided antibiotic prescription. (more…)
Author Interviews, Infections, PLoS / 13.07.2018

MedicalResearch.com Interview with: Nine-banded armadillo image credit: Dr. Richard Truman, USPHS, Public Domain (2014)John S. Spencer, Ph.D. Colorado State University Fort Collins, Colorado MedicalResearch.com: What is the background for this study? Where can armadillos be found? What are the main findings?  Response: The ancient disease leprosy, a disease causing skin lesions, nerve damage, disfigurement and disability, is caused by the bacterium Mycobacterium leprae, and is mainly spread by aerosol infection (coughing and sneezing) from human to human. It is rare in the United States (less than 200 cases on average per year), while it is endemic in Brazil, where over 25,000 new cases were diagnosed last year. In addition, zoonotic transmission of leprosy by nine-banded armadillos (Dasypus novemcintus, pictured at left) has been shown to occur in the southern United States, mainly in Texas, Louisiana and Florida. Nine-banded armadillos originated from South America, and expanded their range from Mexico into Texas in the 1800’s, eventually spreading north and east throughout the gulf states. People in Brazil, particularly in rural areas, hunt and kill armadillos as a dietary source of protein. In the small town of Belterra in western Pará state in the Brazilian Amazon region, a survey of 146 residents showed that around 65% of people had some contact with armadillos, through hunting, preparing the meat for cooking, or by eating them. A group of individuals who ate armadillos most frequently (more than once per month and up to twice a week) had a significantly higher antibody titer towards the M. leprae-specific antigen PGL-I and an almost two-fold higher risk of being diagnosed with disease, a significant risk.   (more…)
Author Interviews, Infections / 10.07.2018

MedicalResearch.com Interview with: Thomas A Russo, MD, CM The Departments of Medicine, and Microbiology and Immunology The Witebsky Center for Microbial Pathogenesis University at Buffalo-State University of New York, and the Veterans Administration Western New York Healthcare System Buffalo, New York MedicalResearch.com: What is the background for this study? What is Klebsiella pneumoniae? Response: K. pneumoniae is an important bacterial pathogen that cause a number of different infections. Presently, two pathotypes exist that behave very differently. Classical K. pneumoniae, which is most common in North America and Europe primarily causes infections in the healthcare setting, usually in patients with co-morbidities. Also, it is becoming increasingly antimicrobial resistant, making treatment challenging. Hypervirulent K. pneumoniae, which is more common in the Asian Pacific Rim,  can cause infections in otherwise healthy individuals, often causes infection in multiple sites, and these sites are usually not infected by classical K. pneumonia, such as the eye, brain, and aggressive soft-tissue infection (necrotizing fasciitis). Hypervirulent K. pneumonia strains are also becoming antimicrobial resistant, albeit at a slower rate than classical K. pneumoniae at this time. There are some differences how infections due to these two pathotypes are managed. It would also be ideal to track the prevalence and relative antimicrobial resistance of these two pathotypes, but up until now this could not be reliably done because there was not a validated test that could differentiate them. The goal of this study was to identify biomarkers that could accurately differentiate classical from hypervirulent K. pneumoniae.  (more…)
Author Interviews, Beth Israel Deaconess, HIV, Lancet, Vaccine Studies / 08.07.2018

MedicalResearch.com Interview with: Dan Barouch, M.D., Ph.D. Professor of Medicine Harvard Medical School Ragon Institute of MGH, MIT, and Harvard Director, Center for Virology and Vaccine Research Beth Israel Deaconess Medical Center Boston, MA 02215 MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study demonstrates that the mosaic Ad26/Env HIV vaccine candidate induced robust and comparable immune responses in humans and monkeys. Moreover, the vaccine provided 67% protection against viral challenge in monkeys.    (more…)
Author Interviews, Infections, NEJM / 05.07.2018

MedicalResearch.com Interview with: Dr. Dennis E. Hruby PhD Chief Science Officer of SIGA Technologies Corvallis, OR MedicalResearch.com: What is the background for this study?  Response: Naturally occurring smallpox was declared eradicated in 1980 following coordinated decades-long global vaccination campaigns. However, there is a significant concern that smallpox, which is both highly contagious and highly lethal, could be used as a potential bioweapon. DNA synthesis technology and the possibility of unaccounted for smallpox stocks pose significant risks. While there are two publicly acknowledged stocks of smallpox virus held by the United States and Russia, some believe that additional stores of the virus could be in the hands of governments or organizations that might use them to cause harm. The DNA sequence of the smallpox genome is in the public domain and could potentially be synthesized in a laboratory from scratch or created by genetically modifying a similar virus. Currently, there are no therapies approved for the treatment of smallpox infection. A smallpox bioterror attack could be especially damaging because the majority of today’s population is not immune to the virus, as routine vaccination ended in the 1970s. It is estimated that without vaccination or treatment, each person infected with smallpox would infect 5 - 7 others. Rapid spread from person-to-person can occur through speaking, breathing or touching. Smallpox also can be transmitted by direct contact with infected fluids and contaminated objects. Furthermore, vaccination must occur within 3-5 days of exposure to smallpox, when patients are still asymptomatic, to be effective. These limitations underscore the need for an effective smallpox antiviral therapy, in addition to any available vaccine. (more…)
Author Interviews, Cost of Health Care, Hospital Acquired, Medicare / 02.07.2018

MedicalResearch.com Interview with: Michael S. Calderwood, MD, MPH, FIDSA Regional Hospital Epidemiologist Assistant Professor of Medicine Infectious Disease & International Health MedicalResearch.com: What is the background for this study?   Response: Prior work by Lee et al. (N Engl J Med 2012;367:1428–1437) found that the 2008 CMS Hospital-Acquired Conditions (HAC) policy did not impact already declining national rates of central line-associated bloodstream infections (CLABSIs) or catheter-associated urinary tract infections (CAUTIs). We studied why this policy did not have its intended impact by looking at coding practices and the impact of the policy on the diagnosis-related group (DRG) assignment for Medicare hospitalizations. The DRG assignment determines reimbursement for inpatient hospitalizations. (more…)
Author Interviews, Diabetes, Infections / 27.06.2018

MedicalResearch.com Interview with: Sandrine Levet PhD Preclinical Study Manager GeNeuro MedicalResearch.com: What is the background for this study? Response: Human endogenous retroviruses (HERVs), remnants of ancestral viral genomic insertions, are known to represent 8% of the human genome and are associated with several pathologies. In particular, the envelope protein of HERV-W family (HERV-W Env) has been involved in multiple sclerosis pathogenesis. A previous study published in JCI Insight revealed that HERV-W Env is also involved in Type 1 diabetes (T1D) pathogenesis. In this study, we observed that HERV-W-Env protein and RNA are detected respectively in sera and peripheral blood mononuclear cell (PBMC) of T1D patients. We also demonstrated that this pathogenic protein is expressed by acinar cells in human T1D pancreas and is associated with the recruitment of macrophages within the pancreas of these patients. HERV-W Env also displays direct pathogenic properties as it inhibits insulin secretion by human islets of Langerhans. (more…)
Author Interviews, CDC, HIV, University of Michigan / 26.06.2018

MedicalResearch.com Interview with: Rogério M. Pinto, LCSW, Ph.D. Associate Professor Associate Dean for Research School of Social Work University of Michigan Ann Arbor, Michigan MedicalResearch.com: What is the background for this study? Response: This research, published in Health Education & Behavior (https://doi.org/10.1177/1090198118760681),highlights the crucial role of providers of social and public health services in helping patients to access lifesaving HIV services. Before 2012, providers were encouraged and trained to link patients to behavioral interventions to help patients modify their behaviors to protect themselves against HIV transmission and infection. A shift in policy from targeting anyone at risk to those at highest risk (called “High Impact Prevention”) made these interventions less available (they were actually discontinued) and new policy dictated that providers should have as many people as possible access HIV testing and link them to HIV primary care in order to receive antiretroviral medication. (more…)
Author Interviews, Hospital Acquired, Infections / 22.06.2018

MedicalResearch.com Interview with: Richard Stanton, PhD Health Scientist, Division of Healthcare Quality Promotion Centers for Disease Control and Prevention MedicalResearch.com: What is the background for this study? Response: We used whole genome sequencing (WGS) to investigate an outbreak of carbapenem-resistant Enterobacteriaceae (CRE) that occurred in an acute care hospital in Kentucky over a six month period in late 2016. The outbreak included 18 cases of CRE. (more…)
AHA Journals, Allergies, Author Interviews, Infections, JAMA / 17.06.2018

MedicalResearch.com Interview with: “Lone Star Tick” by Katja Schulz is licensed under CC BY 2.0Jeffrey Wilson, MD, PhD Research Fellow, Allergy & Immunology University of Virginia  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Galactose-α-1,3-galactose (α-Gal) represents an oligosaccharide that is present in mammalian products and is the causal allergen in a syndrome of delayed red meat allergy (commonly called α-Gal syndrome). Sensitization to this allergen has been linked to tick bites, specifically the lone star tick in the United States. Thus, sensitization to α-Gal (and the prevalence of subjects with symptomatic red meat allergy) is relatively common where the lone star tick is common, i.e- the southeast. For a variety of reasons we hypothesized that specific immune sensitization (which relates to IgE antibody production) to α-Gal would be a risk factor for coronary artery disease. To address this possibility we measured IgE specific to α-Gal in 118 adults subjects from central Virginia who had undergone advanced cardiac imaging with a technique called intravascular ultrasound. Out of the cohort 26% of the subjects in the study had the sensitivity to α-Gal. The main finding was that subjects with the IgE sensitization to α-Gal had greater amounts of atherosclerosis, as well as atherosclerotic plaques with more unstable characteristics. This association was significant when controlled for traditional cardiovascular risk factors such as hypertension, diabetes and lipids levels. (more…)
Author Interviews, Environmental Risks, Infections, Zika / 17.06.2018

MedicalResearch.com Interview with: “Bromeliad” by Selena N. B. H. is licensed under CC BY 2.0André Wilke, Ph.D. Post Doctoral Associate Division of Environment & Public Health Department of Public Health Sciences University of Miami Miller School of Medicine Clinical Research Building Miami, Florida 33136 MedicalResearch.com: What is the background for this study? Response: As vector-borne diseases pose an increasing public health threat to communities in South Florida and elsewhere, a new study led by public health researchers at the University of Miami Miller School of Medicine has revealed that ornamental bromeliad plants contribute to breeding of the Aedes aegypti mosquito—a key culprit for the Zika outbreak that hit Miami-Dade County and other areas of Florida and the Americas in 2016. In addition to Zika, bites from the Aedes aegypti mosquito can cause dengue, yellow fever and chikungunya. Zika has been linked to microcephaly and other birth defects in unborn babies when pregnant women contract the disease. The family of diseases linked to the Aedes aegypti can cause other severe symptoms. Yellow fever can be fatal. (more…)
Author Interviews, Infections, OBGYNE, Pediatrics, Vaccine Studies / 17.06.2018

MedicalResearch.com Interview with: Sylvia Becker-Dreps, MD MPH Associate Professor, Department of Family Medicine Associate Director, Office of International Activities (Latin America Focus) Director, UNC Program in Nicaragua University of North Carolina at Chapel Hill Chapel Hill, NC 27599-7595 MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Pertussis (or whooping cough) is a respiratory infection caused by bacteria. It has been becoming more common in the US over the past two decades. Infants are more likely to be hospitalized and die of the disease. They are especially vulnerable in the first months of life because they have not yet had time to complete the DTaP vaccine series themselves. (Currently, infants receive 3 doses of DTaP at 2,4, and 6 months of age.) Immunizing mothers allows the mothers to pass antibodies against pertussis through the placenta and provide passive immunity to infants early in life. In early 2013, the CDC recommended that pregnant women receive a Tdap vaccine in every pregnancy. That recommendation was based on studies of the immune response to the vaccine, not real cases of pertussis. Our study examined clinical cases of pertussis in over 675,000 infants throughout the US. We found that in the first six months of life, infants of vaccinated mothers (those that received Tdap during pregnancy) had 75% less pertussis hospitalizations and 50% less pertussis cases overall.  (more…)
Author Interviews, Hand Washing, Infections, MRSA, Pediatrics / 15.06.2018

MedicalResearch.com Interview with: “Bart Infant” by Bart Everson is licensed under CC BY 2.0Gwen M. Westerling, BSN, RN, CIC Infection Preventionist Helen DeVos Children's Hospital MedicalResearch.com: What is the background for this study? Response: The setting of this study is a Level III Neonatal Intensive Care Unit (NICU) with 106 beds. In 2016, an increase in Hospital Acquired Infections (HAI) was noted in the Neonatal Intensive Care Unit (NICU) caused by Staphylococcus aureus (SA) through diligent Infection Prevention Surveillance. When we reviewed the literature we found the SA is a common skin colonizer and can be a problem for neonates with immature skin and immune systems. Staphylococcus aureus is easily transmitted through direct contact with skin, the contaminated hands of health care workers, the environment and equipment. We also found one study that listed skin to skin care as a risk factor for acquisition of SA. Before we saw the increase in infections some process changes occurred in our NICU that included increased skin to skin care, meaningful touch between neonates and parents, and two person staff care. We hypothesized that the process changes were exposing neonates to increased amounts of Staphylococcus aureus and contributing to the increase in infections. (more…)
Author Interviews, HIV, University of Michigan / 13.06.2018

MedicalResearch.com Interview with: Rogério M. Pinto, LCSW, Ph.D. Associate Professor Associate Dean for Research School of Social Work University of Michigan Ann Arbor, USA MedicalResearch.com: What is the background for this study? Response: This integrative review, published in the journal AIDS and Behavior, includes content from 47 peer-reviewed scholarly articles reporting multiple barriers to high-risk individuals trying to access pre-exposure prophylaxis (PrEP), the HIV drugs that reduce subsequent risk of infection. We found 31 potential solutions to 30 barriers at the patient, provider and health-system levels. In synthesizing this research from a multi-level perspective, based upon a socioecological model, our report contributes much-needed analysis to the rapidly expanding field of PrEP implementation research. At this stage in the scale-up of U.S. PrEP programs, it is important to systematically and comprehensively analyze and integrate knowledge about the successes of and the barriers to PrEP implementation. Our review provides a comprehensive analysis and informs the direction of PrEP implementation across a variety of settings. (more…)
Author Interviews, Health Care Systems, Infections, JAMA, Outcomes & Safety / 13.06.2018

MedicalResearch.com Interview with: Sarah L. Krein, PhD, RN Research Career Scientist VA Ann Arbor Healthcare System Ann Arbor, MI  Sarah L. Krein, PhD, RN Research Career Scientist VA Ann Arbor Healthcare System Ann Arbor, MI MedicalResearch.com: What is the background for this study? Response: We conducted this study to better understand the challenges faced by health care personnel when trying to follow transmission based precaution practices while providing care for hospitalized patients.  We already know from other studies that there are breaches in practice but our team was interested in better understanding why and how those breaches (or failures) occur so we can develop better strategies to ensure the safety of patients and health care personnel. (more…)
Author Interviews, Global Health, Infections / 12.06.2018

MedicalResearch.com Interview with: “Cholera Hospital 3” by Mark Knobil is licensed under CC BY 2.0Dr. Daihai He Assistant Professor Department of Applied Mathematics Hong Kong Polytechnic University   MedicalResearch.com: What is the background for this study? What are the main findings? Response: A large-scale cholera outbreak hit Yemen in 2017-2018 and caused an estimated 1,100,720 suspected cases and 2291 associated deaths between 27 April 2017 and 20 May 2018, thus a case fatality ratio 0.21%. (more…)
Annals Internal Medicine, Author Interviews, Cancer Research, HIV, Infections / 12.06.2018

MedicalResearch.com Interview with: Lesley S. Park, PhD, MPH Instructor, Medicine- Primary Care and Population Health BioStanford Center for Population Health Sciences (PHS) Associate Director, Research and Data Strategy; Director, PHS Postdoctoral Fellowship Veterans Aging Cohort Study (VACS) Cancer Core Co-Director MedicalResearch.com: What is the background for this study? What are the main findings?  Response: As the population of persons living with HIV/AIDS is aging, the overall burden of cancer is substantial and increasing; however, we have much to learn about the potential cancer prevention benefits of antiretroviral treatment (ART). Our study is the first to examine the effects of prolonged periods of viral suppression and potential cancer prevention benefits. While prior randomized clinical trials (RCTs) and observational studies have examined viral suppression and cancer risk, they mostly were limited to small numbers of cancer outcomes or were only focused on few specific cancer types. Our study demonstrated a benefit of the prevention of cancer development in AIDS-defining cancers (non-Hodgkin lymphoma, Kaposi sarcoma), which was expected, but also in some non-AIDS-defining cancer types (lung, larynx, melanoma, leukemia).  (more…)
Author Interviews, HIV, Infections, OBGYNE / 12.06.2018

MedicalResearch.com Interview with: Manish Sagar, MD Infectious Disease Physician at Boston Medical Center Boston MA  MedicalResearch.com: What is the background for this study? Response: Women compromise the majority of new infections in the world and most of them acquire the virus after sexual exposure.  The goal of the study was to understand how HIV establishes initial infection in the female genital tract. We obtained discarded vaginal tissue and isolated cells present in the outermost layer that contact the virus during exposure. (more…)
Author Interviews, Infections, Social Issues / 05.06.2018

MedicalResearch.com Interview with: rat- wikipedia imageMícheál de Barra, PhD Lecturer in Psychology Brunel University London MedicalResearch.com: What is the background for this study? What are the main findings? Response: Disgust has been called the "intuitive microbiologist"  - it tracks the sources of infection in our environment. But so far, there has been little attempt to link the sources of disgust to the sources of infectious disease in a comprehensive way. So we developed a method for developing stimuli based on a random sample illness. We basically asked ourselves what the kinds of cues that might be associated with that kind of disease risk and asked people to rate disgust responses. The main motive for this was to contribute to a debate in the literature about if there are "kinds of disgust" and if so, how many. I results were a little ambiguous there I'm afraid. (more…)
Author Interviews, CDC, JAMA, Neurological Disorders, Zika / 31.05.2018

MedicalResearch.com Interview with: Dr. Emilio Dirlikov, PhD Office of Epidemiology and Research, Puerto Rico Department of Health Epidemic Intelligence Service Division of Scientific Education and Professional Development CDC MedicalResearch.com: What is the background for this study? What are the main findings? Response: After reporting local Zika transmission in December 2015, the Puerto Rico Department of Health (PRDH), US Centers for Disease Control and Prevention (CDC), and University of Puerto Rico began identifying cases of Guillain-Barré syndrome (GBS), testing specimens, and conducting follow-up telephone interviews after patients left the hospital. Through these efforts, we were able to characterize acute clinical features and long-term disability of GBS associated with Zika infection by analyzing data from GBS patients with and without evidence of Zika infection. This investigation increases scientific and medical understanding of Guillain-Barré syndrome following Zika infection, provides insight into the disease processes involved in GBS following Zika infection, and adds to growing evidence of a causal association between Zika and GBS.  (more…)
Author Interviews, Infections / 21.05.2018

MedicalResearch.com Interview with: Christopher M. Waters PhD Departments of Microbiology and Molecular Genetics BEACON Center for The Study of Evolution in Actio Michigan State University East Lansing, MI  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Our research really centers on understanding and targeting bacterial biofilms. These are multicellular communities of bacteria encased in a slimy matrix that protects them from the immune system and antibiotic treatment during infections. One of the most common types of biofilm infections is in the lungs of cystic fibrosis by the bacterium Pseudomonas aeruginosa. CF patients can become chronically colonized by P. aeruginosa, and antibiotics are not able to clear these infections. Our idea was can we find other molecules that make antibiotics more effective at killing biofilms? To this end, we screened about 6,000 compounds for those that would make tobramycin more effective at killing P. aeruginosa biofilms, and one of the best hits we found was the antimicrobial triclosan that has been widely used for decades in hand sanitizers, soaps, and tooth paste. Although neither triclosan nor tobramycin can kill biofilms alone, the combination is 100X more effective against virtually every P. aeruginosa strain tested. It also worked against other bacteria that commonly infect cystic fibrosis lungs such as Staphylococcus aureus and Burkholderia cenocepacia. (more…)
Author Interviews, Infections, Leukemia, MD Anderson, Transplantation / 20.05.2018

MedicalResearch.com Interview with: Roy F. Chemaly, MD, MPH F.A.C.P., F.I.D.S.A. Department of Infectious Diseases Infection Control and Employee Health Division of Internal Medicine MD Anderson Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: CytomegalovirusCMV infection is a common cause of morbidity and mortality in allo-HCT recipients. Evidence suggests that CMV infection has not only an enormous clinical burden, but a substantial economic burden as well. We conducted this study at MD Anderson to determine the economic and clinical burden of preemptive therapy (PET) for CMV infection. Between 2012 and 2015, 100 consecutive patients hospitalized at our institution for allo-HCT who experienced reactivation of CMV and were treated pre-emptively, were enrolled. The majority of patients were men (55%), who had underlying leukemia (73%), and underwent matched unrelated donor transplant (59%). At the time of hospitalization, most patients had acute GvHD (62%), and were on steroids (58%) within 30 days of CMV reactivation which occurred at a median of 32 days post-HCT (2 -174). A total of 192 episodes of PET occurred in the 100 allo-HCT recipients within 1 year post-HCT. PET consisted of ganciclovir (41%), foscarnet (40%), and valganciclovir (38%). IVIG was also used as adjunct therapy in 20% of episodes. Progression to Cytomegalovirus disease occurred in 4 patients (4%) and mainly affected the GI tract. Mean length of stay for patients treated with ganciclovir or foscarnet was 32 days (2-141) and 41 days (1-177), respectively. The average direct cost per patient admitted for PET was $126,038 ($7,866-$641,841) and the mean cost of CMV antiviral drug per hospitalization was $6,096 for IVIG, $2,410 for foscarnet, $836 for ganciclovir, and $780 for valganciclovir. Serious side effects from PET were observed in 35% of patients on ganciclovir and 12% of patients on foscarnet. Total direct cost per encounter was significantly higher in patients who had serious side effects from foscarnet. All-cause mortality was 59% at 1 year post-transplant. (more…)
Author Interviews, Infections, Pain Research, PLoS, Urinary Tract Infections / 17.05.2018

MedicalResearch.com Interview with: Ingvild Vik MD Doctoral Research Fellow Department of General Practice Institute of Health and Society - UiO University of Oslo, Norway MedicalResearch.com: What is the background for this study? Response: Uncomplicated urinary tract infection (UTI) is the most common bacterial infection in women. It is painful and troublesome, and even though it is often self-limiting most women who see a doctor will be prescribed an antibiotic, as antibiotics provide quick symptom relief.  Antibiotic resistance is a growing, serious public health problem. Antibiotic use is the main contributor to antibiotic resistance, and to stop the rapid development it is crucial that we reduce unnecessary use of antibiotics. Antibiotics can cause unpleasant and potentially severe side effects, so avoiding unnecessary use is also beneficial for the individual patient. A small German trial published in 2010 by Bleidorn et al. suggested that ibuprofen was non-inferior to the antibiotic ciprofloxacin in achieving symptomatic cure in uncomplicated UTI. This inspired us to conduct a larger trial to compare the anti-inflammatory drug ibuprofen to antibiotics in the treatment of uncomplicated UTI.  (more…)
Author Interviews, Infections / 15.05.2018

MedicalResearch.com Interview with: Dr. Tom Lodise PharmD, Professor Albany College of Health Sciences, NY  MedicalResearch.com: What is the background for this study? Response: P. aeruginosa (PSA) is intrinsically resistant to many commercially available antibiotics and also has a remarkable capacity to develop resistance to commonly used antibiotics like carbapenems, aminoglycosides, and fluoroquinolones. The terms ‘multidrug resistant’ (MDR) and ‘pan-drug resistant’ are often used to characterize the different patterns of multiple drug resistance exhibited by PSA. Patients with MDR-PSA infections are at an increased risk for delayed receipt of appropriate antimicrobial therapy and ample studies indicated that receipt of delayed appropriate therapy results in substantial increases in morbidity, mortality, and healthcare resource utilization. Although risk factors for these types of infections have previously been identified in the literature, this study takes identification of risk factors further, and develops two clinical risk scores to estimate the probabilities of carbapenem and extensively beta-lactam non-susceptibility among hospitalized, adult patients with PSA infections based on covariates available on clinical presentation. We focused on these two PSA non-susceptible phenotypes as they represent infections at high risk of delayed appropriate therapy due to resistance against the current commonly prescribed empiric anti-pseudomonal antibiotics. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Infections, Merck / 10.05.2018

MedicalResearch.com Interview with: Dr. Elizabeth Rhee MD Director, Infectious Disease Clinical Research Merck MedicalResearch.com: What is the background for this study? What are the main findings? Response: High-risk patients, such as the critically ill, with suspected bacterial infections require prompt treatment with appropriate empiric therapy to improve survival. Given the high prevalence of multidrug-resistant (MDR) Pseudomonas aeruginosa in the ICU setting, new safe and broadly effective treatment options are needed for critically ill patients requiring antipseudomonal agents. Ceftolozane/tazobactam (C/T) is an antipseudomonal cephalosporin/beta-lactamase inhibitor combination with broad in vitro activity against Gram-negative pathogens, including MDR P. aeruginosa and many extended-spectrum beta-lactamase (ESBL) producers. It is FDA approved for complicated intra-abdominal and urinary tract infections in adults at 1.5g (1g/0.5g) q8h. C/T is currently being studied at 3g (2g/1g) q8h, for the treatment of ventilated nosocomial pneumonia, in the ASPECT-NP Phase 3 trial. This Phase 1 pharmacokinetic (PK) study investigated the penetration of a 3g dose of C/T in the epithelial lining fluid (ELF) of ventilated patients with proven or suspected pneumonia. This is the dose and patient population being evaluated in ASPECT-NP. ELF lines the alveoli, and investigators took samples in a group of 26 patients to see what amount of C/T was in the lung and what was circulating in the plasma during the dosing intervals. In mechanically ventilated critically ill patients, the 3g dose of C/T achieved ≥50% lung penetration (relative to free plasma) and sustained levels in ELF above the target concentrations for the entire dosing interval. These findings support the 3g dose that is included in the ASPECT-NP Phase 3 trial.  (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Infections, Merck / 10.05.2018

MedicalResearch.com Interview with: Becky Jayakumar, PharmD College of Pharmacy Assistant Professor of Pharmacy Practice Roseman University of Health Sciences MedicalResearch.com: What is the background for this study? What are the main findings? Response: Bacteremia (bloodstream infections) due to Gram-negative (GN) bacteria are a frequent cause of severe sepsis and pose serious therapeutic challenges due to multidrug-resistance (MDR). Ceftolozane/tazobactam (C/T) is a novel antipseudomonal cephalosporin combined with an established β-lactamase inhibitor. This retrospective, observational study evaluated the clinical outcomes of C/T real-world use in severely ill patients. Twenty-two patients with sepsis and/or bacteremia were included; 95% of whom had Pseudomonas aeruginosa that was resistant to almost all antibacterials with the exception of colistin. C/T successfully treated the majority of these complicated patients. In this real-world study, 77% of patients had a clinical response with C/T and 75% had a microbiological response. Clinical success rates were high and mortality rates were similar to other studies in this severely ill population. (more…)
Author Interviews, Critical Care - Intensive Care - ICUs, Infections, Merck / 10.05.2018

MedicalResearch.com Interview with: Amanda Paschke, MD, MSCE Senior principal scientist Infectious disease clinical research Merck Research Laboratories MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study sought to evaluate a new beta-lactam/beta-lactamase inhibitor antibacterial combination, imipenem/relebactam (IMI/REL), compared with colistin plus imipenem for the treatment of infections caused by resistant Gram-negative bacteria. Patients enrolled in the trial had hospital-acquired or ventilator-associated bacterial pneumonia (HABP/VABP), complicated intra-abdominal infections (cIAI), or complicated urinary tract infections (cUTI) caused by pathogens that were non susceptible to imipenem, a carbapenem antibacterial. In this study, the primary outcome was a favorable overall response to treatment, which was comparable between the IMI/REL vs colistin + IMI arms. Colistin (often combined with a carbapenem) is currently among the standard of care treatment regimens for MDR infections.  A key secondary endpoint of the study was safety.  IMI/REL was well tolerated; among all treated patients, drug-related adverse events (AEs) occurred in 16.1% of IMI/REL and 31.3% of colistin + IMI patients with treatment-emergent nephrotoxicity observed in 10% (3/29 patients) and 56% (9/16 patients), respectively (p=0.002). Results of the trial support the use of imipenem-relebactam (IMI/REL) as an efficacious and well-tolerated treatment option for carbapenem-resistant infections.  (more…)
FDA, Infections, Vaccine Studies / 08.05.2018

MedicalResearch.com Interview with: Lisa Danzig, MD Chief Medical Office PaxVax MedicalResearch.com: Would you briefly explain what is meant by Chikungunya infection?  Whom does it primarily affect?  How is it transmitted and what the  complications? Response: Chikungunya is caused by the chikungunya virus (CHIKV), an arthropod-borne virus (arbovirus) spread by infected mosquitos. Infection with chikungunya virus results in severe, often debilitating joint pain in infected patients, known as arthralgia. Symptoms can include intense discomfort in joints, such as the wrists, fingers, ankles, and feet, in the knees and in the hips or shoulders. Those affected can also frequently suffer from headaches, fever, and severe muscle pain, rashes on the torso and limbs and swelling in one or more cervical lymph nodes. Individuals who are at a higher risk for contracting chikungunya include infants, elderly and those with chronic conditions. The virus is a small, spherical, enveloped, positive-strand RNA virus. The virus is transmitted by the Aedes aegypti and Aedes albopictus mosquito, which originated in Africa, first spreading to Asia and recently expanding to the western hemisphere.  Outbreaks are rapid and widespread.  In February 2005 a major outbreak of chikungunya occurred in the islands of the Indian Ocean after which over 1.9 million cases have been reported in India, Indonesia, Maldives, Myanmar and Thailand. Chikungunya spread has been identified in 45 countries in the Americas alone with more than 1.7 million suspected cases reported to the Pan American Health Organization since 2015, increasing the incidence of the disease and risk to U.S. travelers. In 2016 there were approximately 60,000 cases of chikungunya across India. Beyond the Indian subcontinent, the Caribbean, Central America and South America, inhabitants and travelers visiting sub-Saharan Africa and Southeast Asia are also at risk. (more…)