Author Interviews, Infections / 21.05.2018 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 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 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 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 Interview with: Ingvild Vik MD Doctoral Research Fellow Department of General Practice Institute of Health and Society - UiO University of Oslo, Norway 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 Interview with: Dr. Tom Lodise PharmD, Professor Albany College of Health Sciences, NY 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 Interview with: Dr. Elizabeth Rhee MD Director, Infectious Disease Clinical Research Merck 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 Interview with: Becky Jayakumar, PharmD College of Pharmacy Assistant Professor of Pharmacy Practice Roseman University of Health Sciences 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 Interview with: Amanda Paschke, MD, MSCE Senior principal scientist Infectious disease clinical research Merck Research Laboratories 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 Interview with: Lisa Danzig, MD Chief Medical Office PaxVax 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…)
Author Interviews, Emory, Infections, JACC, Orthopedics / 26.04.2018 Interview with: Robert Taylor, MD, PhD Marcus Chair in Vascular Medicine Executive Vice Chair, Medicine Director, Division of Cardiology Professor of Medicine and Biomedical Engineering Emory University School of Medicine What is the background for this study? What are the main findings? Response: The early identification and localization of bacterial infections is a critical step for initiating effective treatment.   This is particularly challenging in the setting of infections associated with implanted medical devices.  We have developed a highly specific probe for bacteria that is based on the fact that bacteria have a specific system for taking up maltodextrins which are polysaccharides that mammalian cells cannot take up directly.  We can label this probe with either a fluorescent of radioactive tag that allows visualization of the bacteria. In the current article, we have used an animal model of implantable cardiac devices to demonstrate that our probe is very specific and sensitive for detecting bacterial infections.  It is worth noting that these are subclinical infections that could not be detected by any other means except for surgical removal. (more…)
Author Interviews, Environmental Risks, Infections, Pediatrics, Respiratory / 18.04.2018 Interview with: Benjamin D. Horne, PhD Director of Cardiovascular and Genetic Epidemiology Intermountain Heart Institute Intermountain Medical Center Salt Lake City, Utah What is the background for this study? Response: Evidence suggests that short-term elevations (even for just a few days) of fine particulate matter air pollution (PM2.5, which is particulate matter less than 2.5 um or about one-thirtieth the diameter of a human hair) is associated with various poor health outcomes among adults, including myocardial infarction, heart failure exacerbation, and worsening of chronic obstructive pulmonary disease symptoms. Studies of long-term exposure to moderately elevated levels of PM2.5 indicate that chronic daily air pollution exposure may contribute to death due to pneumonia and influenza. Research regarding the association of short-term elevations in PM2.5 has provided some limited evidence of a possible association between short-term PM2.5 increases and infection with respiratory syncytial virus (RSV) or bronchiolitis in children, but scientifically these reports have been weak and unreliable, probably because they have only looked at a period of a few days to a week after short-term PM2.5 elevations. An evaluation of a very large population in a geographic location that provides a wide variation in PM2.5 levels from lowest to highest levels and that examines longer periods of time after the PM2.5 elevations is needed to determine whether a PM2.5 association with lower respiratory infection exists. (more…)
Author Interviews, Infections, Nature, NIH, PLoS, Rheumatology / 16.04.2018 Interview with: John B. Harley, MD, PhD Professor and Director David Glass Endowed Chair Center for Autoimmune Genomics and Etiology (CAGE) Department of Pediatrics University of Cincinnati Cincinnati Children’s Hospital Medical Center Cincinnati, Ohio 45229 What is the background for this study? Response: Previous work has shown that Epstein-Barr virus infection is associated with systemic lupus erythematosus and studies of the origins of the autoimmune response have also suggested that the autoimmunity of this disease may originate with the immune response against this virus. In the meantime, many investigators have been studying the genetics of lupus over the past 25 years. They have found about 100 convincing genes that alter the risk of developing lupus. (more…)
Author Interviews, Infections, Lipids / 11.04.2018 Interview with: Børge G. Nordestgaard, MD, DMSc Professor, University of Copenhagen Chief Physician, Dept. Clinical Biochemistry Herlev and Gentofte Hospital Copenhagen University Hospital, Denmark What is the background for this study? Response: For decades research into the role and function of high-density lipoprotein (HDL) has revolved around the believe that HDL protects against atherosclerotic cardiovascular disease. However, results from large genetic studies and from large randomized clinical trials with HDL cholesterol elevating drugs have all indicated that there is no causal association between HDL cholesterol and risk of atherosclerotic cardiovascular disease. Given the hitherto strong focus on cardiovascular disease, little is known about the possible role of HDL in other aspects of human health and disease. Preclinical evidence has indicated that HDL might be of importance for normal function of the immune system and susceptibility to infectious disease, but it had never previously been investigated if levels of HDL cholesterol is associated with the risk of infectious disease in individuals from the general population. In the present study we tested this hypothesis in more than 100.000 Danes from the population at large. (more…)
Author Interviews, Global Health, Infections, Pediatrics / 10.04.2018 Interview with: Georgies Mgode PhD Sokoine University of Agriculture Pest Management Centre African Centre of Excellence for Innovative Rodent Pest Management and Biosensor Technology Development Morogoro, Tanzania What is the background for this study? Response: The background of this study is the APOPO and Sokoine University of Agriculture together with NIMR and NTLP interest to explore a cheap, reliable and sustainable means of addressing TB problem in high-burden countries with limited access to advanced sensitive tests. This refers to countries where to-date TB diagnosis is mainly by microscopy that is less sensitive leaving majority of patients undetected. We were driven to explore how these rats can contribute to diagnosis of TB in children that is known to be difficult and rats are known to have a better and advanced sense of smell. According to WHO " an estimated 1 million children became ill with TB and 250 000 children died of TB in 2016 and the actual burden of TB in children is likely higher given the challenge in diagnosing childhood TB.  (more…)
Author Interviews, Infections, Orthopedics, Surgical Research / 09.04.2018 Interview with: Dr Setor Kunutsor PhD Research Fellow Musculoskeletal Research Unit Bristol Medical School What is the background for this study? Response: Hip replacement is a very common operation that is effective at providing pain relief and improving mobility. Infection is a fortunately infrequent but devastating complication that can occur following joint replacement. Currently, two main types of surgical procedures are used in treating these infections – one-stage and two-stage revision strategies. In the two-stage procedure, the existing artificial joint is removed in one operation and the patient is treated for several months with antibiotics. A new joint is then inserted in a second operation. In the one-stage procedure, the artificial joint is removed along with all infected tissue and a new one inserted in the same operation. The two-stage procedure has been in use for decades and was regarded as the most effective treatment. There has been an increase in the use of the one-stage procedure as it has also been claimed to be very effective at treating infection. There has been a lot of controversy among orthopaedic surgeons as to which is the best way to treat infected hip replacements. Several studies have been conducted on the topic, but the findings have been inconsistent. Some claim the two-stage to be more effective and others claim the one-stage procedure is. Currently the majority of studies claim the two-stage is better; but no study has been conducted that compares these procedures head-to-head to decide if one is better or if they achieve the same results. Due to the lack of evidence, some surgeons are reluctant to use the one-stage strategy. There was therefore a need to compare the effectiveness of the two surgical strategies using an appropriate study design. We conducted a study which involved collecting and bringing all previous data together under one umbrella. The process is known as “Individual Participant Data meta-analysis”. It involved communicating with surgeons in different countries all over the world and inviting them to contribute data. We called the name of the group “The Global Infection Orthopaedic Management (INFORM) Collaboration”. (more…)
Author Interviews, Infections, Science, Vaccine Studies / 05.04.2018 Interview with: Matthieu Domenech de Cellès PhD Department of Ecology and Evolutionary Biology University of Michigan, Ann Arbor, MI, USA. Biostatistics, Biomathematics, Pharmacoepidemiology, and Infectious Diseases Unit Institut Pasteur, Inserm, University of Versailles St-Quentin-en-Yvelines, Versailles, France. What is the background for this study? What are the main findings?   Response: Our main motivation was to elucidate an apparent paradox: Why has the US experienced a resurgence of pertussis (whooping cough) since the mid-1970s, despite persistently high vaccine coverage? A variety of hypotheses have been proposed to explain this resurgence, but most attention has focused on the potential shortcomings of the new generation of pertussis vaccines (called acellular pertussis vaccines). However, there remains considerable uncertainty about the degree and the mechanisms of protection conferred by pertussis vaccines. Via a collaboration with the local department of public health, we used detailed surveillance data in the state of Massachusetts to test a number of hypotheses about pertussis vaccines. We found that, although pertussis vaccines are imperfect (in the sense that they do not provide lifelong, 100% protection to 100% of children vaccinated), they are still highly efficacious. Specifically, we estimated that vaccine protection wanes over time, but slowly, with about 85% of children still protected 10 years after vaccination. Despite this high vaccine efficacy, we showed that the resurgence of pertussis was, in fact, to be expected. What happens is that the introduction of routine vaccination leads to an overall reduction in transmission, not only in vaccinated children but also in the population at large. Accordingly, those who escaped vaccination as children (as a consequence of incomplete vaccine coverage or imperfect vaccine protection) increasingly age having also avoided natural infection. As a result, the number of individuals susceptible to contract pertussis gradually increases. Because such people are the “fuel” of epidemics, this sets the stage for pertussis’ resurgence, with increasing incidence among older individuals. This overall effect is called the “end-of-honeymoon” and means that resurgence is therefore a predictable consequence of incomplete vaccination with efficacious, but imperfect, vaccines. Importantly, these results show that recent trends do not necessarily reflect recent changes in the epidemiology of pertussis. Rather, they may be interpreted as a legacy of past immunization practices, with long-to-manifest effects. This is a significant shift of perspective about pertussis epidemiology.  (more…)
Author Interviews, CDC, HIV, Sexual Health / 29.03.2018 Interview with: Sonia Singh, PhD, Epidemiologist Division of HIV/AIDS Prevention CDC What is the background for this study? What are the main findings? Response: HIV infection is a persistent health concern in the United States, particularly for people at high risk of infection such as gay and bisexual men. We used data from the National HIV Surveillance System to estimate HIV incidence and prevalence and the percentage of undiagnosed HIV infections overall and among gay and bisexual men. Estimated HIV incidence declined nearly 15% overall in the U.S. from an estimated 45,200 infections in 2008 to 38,500 in 2015. Estimated HIV incidence declined for both males (9%) and females (33%) over this period. Estimated HIV incidence declined 32% among heterosexuals, 42% among people who inject drugs and 20% among gay and bisexual men who also inject drugs. Estimated HIV incidence remained relatively stable among gay and bisexual men; however, it increased over 25% among Latino gay and bisexual men, almost 45% among gay and bisexual men ages 25 to 34 and 30% among gay and bisexual men ages 55 and older. The percentage of undiagnosed HIV infections decreased nearly 20%, from 18.1% in 2008 to 14.5% in 2015. The percentage of undiagnosed HIV infections among gay and bisexual men declined 21.6%, from 21.3% in 2008 to 16.7% in 2015. In 2015, the percentage of undiagnosed HIV infections was highest among gay and bisexual males ages 13-24 (52.2%) compared to other age groups and higher among Latino (20.1%) and African American (19.6%) gay and bisexual men, as well as Asian gay and bisexual men (20.5%), compared to white gay and bisexual men (11.9%). (more…)
Author Interviews, CDC, Infections, JAMA / 26.03.2018 Interview with: Dr. Katherine Fleming-Dutra, MD, senior author Deputy Director Office of Antibiotic Stewardship CDC What is the background for this study? What are the main findings? Response: As noted in a previous study, antibiotics are prescribed more for sinus infections than any other illness in the United States. We found that almost 70% of antibiotic prescriptions were for 10 days or longer, whereas 5-7 days is recommended for most patients when antibiotics are needed. In addition, more than 20% of antibiotic prescriptions for sinus infections were for 5 days of azithromycin, even though guidelines recommend against prescribing azithromycin for sinus infections. (more…)
Author Interviews, Dermatology, Global Health, NEJM, Zika / 15.03.2018 Interview with: Professor Bruno Hoen, M.D., Ph.D Dept of Infectious Diseases, Dermatology, and Internal Medicine University Medical Center of Guadeloupe What is the background for this study? Response: Zika virus (ZIKV) infection during pregnancy has been identified only recently to cause severe birth defects, including microcephaly, other brain defects, and the congenital Zika syndrome. However, the magnitude of this risk was not clearly defined, with discrepancies between observational data from Brazil and the U.S. Zika Pregnancy Registry. We implemented a cohort study of pregnant women who have been exposed to ZIKV throughout the outbreak that hit the Caribbean in 2016. (more…)
Author Interviews, Flu - Influenza, Infections, Mental Health Research, Primary Care, Roche / 14.03.2018 Interview with: James W. Antoon, MD, PhD, FAAP Assistant Professor of Clinical Pediatrics University of Illinois at Chicago Associate Medical Director, Pediatric Inpatient Unit Children's Hospital, University of Illinois Hospital & Health Sciences System Chicago, IL 60612 What is the background for this study? What are the main findings? Response: Oseltamivir, commonly known as Tamiflu, is the only commercially available medication FDA approved to treat the flu.  Since the 2009 H1N1 flu epidemic pediatric prescriptions for Tamiflu have soared.  In the United States, about 40% of Tamiflu prescriptions are given to children less than 16 years of age.  Following reports of abnormal behavior, such as hallucinations, self-injury and suicide attempts in adolescents on Tamiflu, the FDA placed a new warning about these neuropsychiatric symptoms on the drug label.  Whenever the FDA puts out label warning about a drug, doctors and the public take notice. Whether Tamiflu truly causes these side effects is unclear.  For this study we chose to focus on the most consequential of those reports: suicide. The potential link between a drug and suicide is a particularly difficult topic to study for a number of reasons. There are things that happen together or at the same time that can influence someone to attempt suicide and it is very difficult to know which thing is actually having an affect. In our study, other things that can influence suicide are socioeconomic status, mental health, trauma, abuse, among others.  Separating the effects of these confounders can be difficult. It is also possible that the disease itself, which in this case is the flu, causes the effect of suicide. Finally, and luckily, suicide is rare. Our database had 12 million children per year and over five year 21,000 attempted suicide. Of those, only 251 were taking Tamiflu. To get past these issues, we took advantage of a growing drug safety research collaboration between the Departments of Pediatrics and Pharmacy at our institution.  Previous studies have compared those on Tamiflu to those not on Tamiflu to see if there are more side effects in the Tamiflu group.  Our team utilized a novel study method called a case-crossover design. What’s different about this study is that we used each patient as their own comparison.  In other words, we compared each patient to themselves rather than a different group of people.  We essentially studied how patients behaved when the Tamiflu was in their system compared to other l periods where they were not on Tamiflu.  This allowed use to account for the personal differences noted above like mental health and socioeconomic status.   We also compared those children with flu who got Tamiflu and those with flu who did not get Tamiflu to see if the infection itself could be associated with increased suicide. After accounting for all these variables, we did not find any an association between Tamiflu exposure and suicide. Our findings suggest that Tamiflu does NOT increase the risk of suicide in children or teenagers. (more…)
Author Interviews, JAMA, University of Michigan, Urinary Tract Infections / 12.03.2018 Interview with: Keith SKayeMD, MPH Professor of Medicine, Division of Infectious Diseases University of Michigan Medical School Ann Arbor MI What is the background for this study? Response: Complicated complicated urinary tract infections (cUTI), including acute pyelonephritis, are a major cause of hospital admissions, and are associated with significant morbidity and mortality and can be difficult to treat. While the most common pathogen is Escherichia coli, the more problematic pathogens are multidrug-resistant (MDR) gram-negative organisms including other Enterobacteriaceae species. The prevalence of cUTI due to MDR gram-negative bacteria has risen. In some instances, MDR gram-negative bacteria isolated from the urinary tract can cause bacteremia. Vabomere was approved by the U.S. Food and Drug Administration (FDA) in August 2017 for the treatment of adult patients with cUTI, including pyelonephritis, caused by designated susceptible Enterobacteriaceae: Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae species complex.   Vabomere is a fixed-dose (2g/2g) combination product of a carbapenem and a β-lactamase inhibitor with potent in vitro activity against Klebsiella pneumoniae carbapenemase (KPC)-producing carbapenem-resistant Enterobacteriaceae (CRE), an important MDR organism associated with serious infections. The Targeting Antibiotic Non-susceptible Gram-negative Organisms (TANGO I) trial was the pivotal Phase 3 study that compared the efficacy and safety of Vabomere to piperacillin-tazobactam in the treatment of patients with cUTI and acute pyelonephritis. (more…)
Author Interviews, Infections / 12.03.2018 Interview with: Michael Durkin, MD MPH Washington University School of Medicine St. Louis What is the background for this study? What are the main findings? Response: The aim of this study was to evaluate overall national outpatient antibiotic prescribing trends using a pharmacy benefits manager (Express Scripts). We wanted to evaluate if antibiotic prescribing had decreased as a result of increase physician awareness of antibiotic prescribing. Specifically, the ABIM choosing wisely campaign overlapped with our study period. We did not see any significant reductions in antibiotic prescribing during the 3-year study period. This is a little disappointing given that the CDC estimates that 30% of outpatient antibiotic prescriptions are inappropriate. We also saw some seasonal variation in antibiotic prescribing. This isn’t particularly novel. But it is important to note, as some of these prescriptions represent providers writing antibiotics for likely viral conditions. (more…)
Author Interviews, GSK, Herpes Viruses, Infections, Vaccine Studies / 10.03.2018 Interview with: Anthony. L. Cunningham, MD The Westmead Institute for Medical Research Westmead, NSW University of Sydney, Sydney, What is the background for this study? What are the main findings? Response: This study examines the reasons why the HZ subunit vaccine candidate (HZ/su vaccine) consisting of a single viral protein, varicella-zoster glycoprotein E, and and adjuvant (immunostimulant) combination AS01B is so effective as a vaccine to prevent shingles (>90%), especially in those over the age of 70 years and 80 years, as published in recent trials i.e. it combats the declining immunity in the aging which usually restricts vaccine efficacy to under 60% in these age groups.  (more…)
Author Interviews, Infections / 09.03.2018 Interview with: Chih-Chi Andrew Hu, Ph.D. Associate professor in Microenvironment & Metastasis Program Wistar Institute What is the background for this study? What are the main findings?  Response: To help our body fight infections, B cells need to differentiate into plasma cells so that they can produce abundant antibodies against pathogens. Antibodies are folded and assembled in the endoplasmic reticulum (ER). Only those perfectly manufactured antibodies are allowed to be released from the ER and delivered to the outside of B cells to fight against the pathogens. IRE1 is a sensor protein that sits on the membrane of the ER, and can respond to B cell differentiation by activating the transcription factor called XBP1s. Activation of XBP1s allows B cells to expand the size of the ER and produce necessary chaperone proteins to help B cells manufacture perfect antibodies. By studying B cells that lack XBP1s, we discovered that these B cells produced dramatically increased levels of IRE1, and such IRE1 acquired phosphorylation at its serine 729 (S729).  (more…)
Author Interviews, Gastrointestinal Disease, Infections / 08.03.2018 Interview with: Esther Bullitt, Ph.D. Associate Professor Dept. of Physiology & Biophysics Boston University School of Medicine Boston, MA  02118-2526 What is the background for this study? Response:      We know that saliva has properties that allow us to swallow easily, and to help prevent gum disease and infections in the mouth. But is that really the only use for the 1-2 liters (1-2 quarts) of saliva we produce every day?  We decided to test whether a component of saliva, Histatin-5, can help prevent diarrheal disease (Traveler’s Diarrhea by Enterotoxigenic Escherichia coli (ETEC)) that is caused by bacteria commonly found in contaminated food and water. ETEC are bacteria that have hundreds of thin hair-like fibers on their surface, called pili. These bacteria bind specifically to the surface of the gut using these pili, and the bacteria need to stay bound long enough to initiate disease. Studies by Mike Levine’s group in the 1970’s showed that pili are necessary for enterotoxigenic Escherichia coli (ETEC) to cause disease. No adhesion, no disease. One aid to remaining bound is the unwinding and rewinding of the pili. These helical fibers can unwind up to 8 times their original length, acting as shock absorbers during fluid flow.   (more…)
Author Interviews, Biomarkers, Neurological Disorders, University Texas, Zika / 07.03.2018 Interview with: Slobodan Paessler, D.V.M., Ph.D. Professor, Department of Pathology; Director, Galveston National Laboratory Preclinical Studies Core; Director, Animal Biosafety Level 3, Institute for Human Infections and Immunity; Member, Center for Biodefense & Emerging Infectious Diseases University of Texas Medical Branch Galveston, TX What is the background for this study? What are the main findings? Response: Zika virus infection is associated with various developmental issues for human embryos such as reduced head growth, reduced brain tissue growth, and damage to brain or eyes. We wanted to better understand if some of these birth defects are caused directly by the Zika virus or maybe by the host response to infection. In our study we demonstrate that the Zika virus infection induces autoimmune response against the C1q protein. This protein is a very important immune protein as well as one of the essential proteins for healthy brain development. Attacking the C1q protein upon exposure with the Zika virus could contribute to the development of autoimmune disorders and birth defects.  (more…)
Author Interviews, Flu - Influenza / 02.03.2018 Interview with: Ishanu Chattopadhyay, PhD Assistant Professor, Department of Medicine Section of Hospital Medicine Institute for Genomics and Systems Biology University of Chicago What is the background for this study? What are the main findings? Response: It is estimated that flu kills thousands every year in US, some estimates put the yearly death toll to around 30,000 -- that is just in US, and that is irrespective of whether a new virus emerges. But why do waves of the disease sweep the globe every year, as if on a schedule? It had been suggested before that the trigger is a specific change in weather conditions, specifically, when normally humid air turns dry. In this new study, we explore this question in much greater detail than was possible before, bringing to bear massive amounts data, such as 150 million individual medical histories recorded over the last decade, along with massive climate datasets. What we found was both fascinating, and consequential -- no single factor is responsible wholly, and it requires a complex, yet precise, mix of weather conditions, demographic makeup, socio-economic variables, vaccination coverage, antigenic drift states of the virus, and human traveling habits, among others, to trigger the seasonal epidemic waves. Quite surprisingly, long range air-travel is far less important compared to short range ground travel. This work attempts to finally settle the lack of consensus in the scientific community on which factors are responsible, as well as each factor’s relative importance. (more…)
Author Interviews, HIV, NYU, PLoS, Zika / 23.02.2018 Interview with: Maite Sabalza Ph.D Post Doctoral Associate Department of Basic Science and Craniofacial Biology College of Dentistry, New York University New York, NY 10010 What is the background for this study? What are the main findings?  Response: With previous NIH funding we were able to develop an automated “dual assay” (able to detect both host antibodies and viral RNA) for HIV. In relatively short time, we were able to migrate those findings into the new assay for ZIKA Virus. (more…)
Author Interviews, Education, Infections, Pediatrics / 23.02.2018 Interview with: Ole Köhler-Forsberg, PhD Student Department of Clinical Medicine - Psychosis Research Unit Aarhus University What is the background for this study? What are the main findings? Response: Prior studies have demonstrated that serious illnesses, for example severe infections such as measles, rubella or meningitis, which we vaccinate against, affect the brain and thereby the child's ability to learn. From this we know that illnesses and in particular infections to some degree have an influence on our brains. In this study, we decided to look at how children perform following the less severe infections that many of them frequently experience during their childhood. After all, this is the largest group of children, but this has not been studied previously in such a large population. Basically, we found that among 598,553 Danes born 1987-1997, the less severe infections treated with anti-infective agents during childhood did not affect the child´s ability to perform well in school, nonetheless whether 5, 10 or 15 prescriptions had been prescribed. On the other hand, we found that children who had been admitted to hospital as a result of severe infections had a lower chance of completing 9th grade. The decisive factor is therefore the severity of the disease, but not necessarily the number of sick days.   (more…)
Author Interviews, Infections, Pediatrics, Vaccine Studies / 23.02.2018 Interview with: Professor Julie Bines Inaugural Victor and Loti Smorgon Professor of Paediatrics and Deputy Head of Department of Paediatrics University of Melbourne. Murdoch Childrens Research Institute What is the background for this study? Would you briefly explain the significance of Rotavirus infections? Diarrhoea is one of the leading causes of child illness and death, and rotavirus is the most common cause of severe diarrhoea. Globally rotaviruses cause approximately 215,000 deaths in children under five years. This disease doesn’t discriminate – it infects children worldwide under the age of five – irrespective of what environment you live in. The rotavirus vaccines that are currently available work very well in places like Australia, the US and Europe but they don’t seem to work as well in low income settings in Africa and Asia where severe gastroenteritis is common and many children die. In a world-first clinical trial conducted in Indonesia, the oral RV3-BB vaccine was administered to babies within their first five days of life. Current rotavirus vaccines can only be administered to children older than six weeks, which leaves newborn babies particularly vulnerable to rotavirus infection. In lower resource settings, birth is often the best contact between mother, baby and health services. The oral RV3-BB vaccine was developed from the human neonatal rotavirus strain RV3 identified in the stool of healthy newborn babies. It does not naturally cause diarrhoea like other rotaviruses. The RV3-BB vaccine program aims to take advantage of the characteristics of this novel strain to target a birth dose vaccination strategy.  (more…)
Author Interviews, PLoS, Sexual Health, Zika / 16.02.2018 Interview with: Yogy Simanjuntak PhD Postdoctoral Research Fellow Institute of Biomedical Sciences Academia Sinica, Taiwan What is the background for this study? What are the main findings? Response: Despite the low case fatality, Zika virus infection has been associated with microcephaly in infants and Guillain-Barré syndrome. Primarily transmitted by Aedes species mosquitoes, Zika also can be sexually transmitted in humans. By August 2016, the sexual transmission of Zika had been documented in 11 countries worldwide and most of the cases were from male to female. Infectious Zika in semen has been reported. Moreover, unlike in serum or urine samples, Zika RNA can still be detected in semen up to 188 days after the onset of symptoms. In the absence of approved antiviral drugs or vaccines for Zika infection, preventing the disease transmission is critical. We observed Zika progressively damaged testes by gaining access to testicular cells including sperm. Notably, Zika caused signs of increased testicular oxidative stress and inflammation, characterized by high levels of reactive oxygen species and pro-inflammatory cytokines. Our data indicate that these factors may contribute to testicular damage as well as successful sexual transmission of Zika; thus, we speculate antioxidants might display beneficial effects to alleviate these disease outcomes. We found that antioxidant ebselen both alleviated testicular damage and prevented sexual transmission of Zika via sperm from infected male mice to uninfected female mice. (more…)