Allergies, Author Interviews, Pediatrics / 07.09.2016 Interview with: Bryan L. Love, PharmD, BCPS-AQ ID Associate Professor Department of Clinical Pharmacy & Outcomes Sciences South Carolina College of Pharmacy University of South Carolina Columbia, South Carolina 29208-0001 What is the background for this study? Response: In the US, food allergy has become one of the more common childhood medical conditions diagnosed in young children. Antibiotics are frequently prescribed in young children, and research continues to reveal that as many as 30% of antibiotic prescriptions are not appropriate.* We sought to examine if there was an association between antibiotic prescription and food allergy diagnosis. (more…)
Author Interviews, Dermatology, Pharmacology / 15.08.2016 Interview with: Kin F. Chan, PhD Executive Vice President of Research and Technology BioPharmX Corporation What is the background for this study? What are the main findings? Response: There were two studies in this series.  The purpose is to get a better understanding of the blood plasma and skin levels of minocycline in a relevant animal model (minipig) for both the oral form of minocycline (Solodyn) and topical BPX-01, and to elucidate the same for oral minocycline only in a clinical study. The results provided valuable guidance and assurance to our upcoming Clinical Phase 2b dose-ranging study design. (more…)
Author Interviews, Infections, PLoS / 05.08.2016 Interview with: Dr Peter Monk BSc PhD Faculty Director of International Affairs Reader in Immunology Department of Infection, Immunity and Cardiovascular Disease Sheffield University Medical School What is the background for this study? What are the main findings? Response: The tetraspanin proteins are found on the surface of all mammalian cells. The cell surface is the place where cells 'socialise': they talk to each other to coordinate activities, stick to each other to form tissues and sometimes crawl across each other to get to where they need to go. Tetraspanins have an important job to do in the organisation of the cell surface, amongst other things enabling the formation of 'sticky patches' (tetraspanin-enriched microdomains or TEM) that cause cells to adhere together or provide traction to allow movement. Some bacteria have evolved ways of hijacking the TEM for their own ends, adhering to tightly to these structures so that the normal things that sweep bacteria away (such as blood, sweat and tears!) are no longer effective. At this point, infection begins. We have found that the TEM can be partly disrupted, by adding small parts of tetraspanins (peptides) to cells. The peptides seem to work by weakening the tetraspanin glue that holds the TEM together and causing the other components that give the 'stickiness' to the TEM to become more spaced out. We use the analogy of Velcro(TM), where the fabric hooks and loops are held together in woven material; loosen the weave and the hooks and loops fall apart, no longer able to engage strongly with the loops in the opposing piece of fabric. Using reconstructed human skin, we were able to show that the tetraspanin peptides were both safe and effective; they did not affect wound healing in burned skin, but they could lower the bacterial load in the wound by 50%. This would allow the immune system (including the fluid that 'weeps' from wounds) to deal with the remaining bacteria more easily. Unlike conventional antibiotics that tend to kill bacteria, our peptides simply cause them to get washed away, so not invoking the evolutionary selective mechanisms that lead to resistance. (more…)
Author Interviews, Infections, Pharmacology, Urinary Tract Infections / 25.06.2016 Interview with: Amanda Paschke, MD Director, Infectious Disease Clinical Research Merck Research Laboratories What is the background for this study? What are the main findings? Response: Relebactam is an investigational beta-lactamase inhibitor being developed as a fixed-dose combination with imipenem/cilastatin, which is a broad-spectrum antibiotic in the carbapenem class. In preclinical studies, this combination demonstrated antibacterial activity against a broad range of multidrug-resistant Gram-negative pathogens, including those producing extended-spectrum beta-lactamases such as Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae and AmpC-producing Pseudomonas aeruginosa. Many of the most concerning infections caused by “superbugs” are caused by Gram-negative bacteria. These bacteria have evolved to be resistant to commonly used antibacterials, and even to antibacterials used as “last resort” treatment, which is why finding ways to treat them has become urgent. The addition of relebactam to imipenem is designed to restore activity of imipenem against certain imipenem-resistant strains of Gram-negative bacteria known to cause serious infections among people who often have other underlying medical conditions, which complicates treatment. This was a Phase 2, multicenter, randomized, double-blind, non-inferiority study. The study looked at the use of relebactam plus imipenem versus imipenem alone for the treatment of adult patients with complicated urinary tract infections. The primary endpoint for the trial was microbiological response at the completion of IV study therapy. The study met its primary endpoint, demonstrating that the combination of relebactam with imipenem was as at least as effective as imipenem alone for the treatment of complicated urinary tract infections. The trial also demonstrated that the combination of relebactam plus imipenem is well-tolerated, with a safety profile similar to that of imipenem alone in this patient. (more…)
Antibiotic Resistance, Author Interviews, Gastrointestinal Disease, Infections / 16.05.2016 Interview with: Andreas J. Bäumler, Ph.D Editor, Infection and Immunity Associate Editor, PLOS Pathogens Section Editor, EcoSal Plus Professor, Department of Medical Microbiology and Immunology Vice Chair of Research University of California, Davis School of Medicine Davis, California What is the background for this study? What are the main findings? Dr. Bäumler: Antibiotics are generally beneficial for treating bacterial infection, but paradoxically a history of antibiotic therapy is a risk factor for developing Salmonella food poisoning.  Our study reveals the mechanism by which antibiotics increase susceptibility to Salmonella infection. Antibiotics deplete beneficial microbes from the gut, which normally provide nutrition to the cells lining our large bowel, termed epithelial cells. Depletion of microbe-derived nutrients causes our epithelial cells to switch their energy metabolism from respiration to fermentation, which in turn increases the availability of oxygen at the epithelial surface. The resulting increase in oxygen diffusion into the gut lumen drives a luminal expansion of Salmonella by respiration. Through this mechanism, antibiotics help Salmonella to breath in the gut. (more…)
Author Interviews, CDC, Infections, JAMA / 04.05.2016 Interview with: What is the background for this study? Dr. Fleming-Dutra: One of the most urgent public health threats of our time is the emergence of antibiotic-resistant bacteria. The use of antibiotics is the single most important factor leading to antibiotic resistance around the world.  Simply using antibiotics creates resistance.  To combat antibiotic resistance we have to use antibiotics appropriately — only when needed and, if needed, use them correctly.  In 2015, the White House released the National Action Plan for Combating Antibiotic-Resistant Bacteria (CARB), which set a goal for reducing inappropriate outpatient antibiotic use by 50% by 2020.  However, the amount of antibiotic use in the outpatient setting that is inappropriate was unknown. What are the main findings? Dr. Fleming-Dutra: In this study, we estimate that at least 30% of antibiotics prescribed in doctors’ offices, emergency departments and hospital-based clinics are unnecessary—meaning that no antibiotic was needed at all, which equates to 47 million unnecessary antibiotic prescriptions written annually in these outpatient settings.  Most of those unnecessary antibiotic prescriptions were written for acute respiratory conditions, a key driver of antibiotic overuse. Thus, in order to reach the White House goal of reducing inappropriate outpatient antibiotic use by 50%, a 15% reduction in overall antibiotic use in outpatient settings is needed by 2020. (more…)
Author Interviews, JAMA, Pediatrics, Surgical Research / 18.04.2016 Interview with: Thomas J. Sandora, M.D., M.P.H. Senior Associate Physician in Medicine; Hospital Epidemiologist; Medical Director, Infection Control Boston Children’s Hospital Associate Professor of Pediatrics, Harvard Medical School What is the background for this study? What are the main findings? Dr. Sandora: Giving antibiotics before certain types of operations results in lower rates of surgical site infections. However, there are limited data about which pediatric operations require antibiotic prophylaxis. We examined national variability in antibiotic prophylaxis for the 45 most commonly performed pediatric operations at children's hospitals in the U.S. We found that antibiotic use was considered appropriate for only 64.6% of cases, with a high degree of variability within procedures and between hospitals. (more…)
Antibiotic Resistance, Author Interviews, Nature / 12.04.2016 Interview with: Dr. Lingchong You PhD Paul Ruffin Scarborough Associate Professor of Engineering Duke University What is the background for this study? What are the main findings? Dr. You: Horizontal gene transfer (HGT) refers to the transfer of genes between organisms of the same or different species other than reproduction. In bacteria, ​Horizontal gene transfer can occur through conjugation (bacterial mating), transduction mediated by phage, or transformation. During conjugation, a donor cell makes a copy of a conjugal plasmid and passes it to a recipient cell, turning it into a transconjugant. It is well appreciated that HGT (particularly through conjugation) is the major mechanism underlying the wide spread of genes encoding antibiotic resistance.  Given this notion, it is tempting to assume that the use of antibiotics could increase the efficiency of horizontal gene transfer, creating a vicious cycle. Indeed, this has been speculated in the literature even though precise experimental measurements have been lacking. In our study, we find that antibiotics covering all major classes do not promote the probability of conjugation between donor and recipient cells. Instead, antibiotics modulate the final outcome of conjugation dynamics by imposing different degrees of selection on the donor cells, recipient cells, and the transconjugants. Depending on the antibiotic doses and how the antibiotic affects the three populations, the selection dynamics could lead to an increase or the decrease in the frequency of transconjugants. (more…)
Author Interviews, BMJ, Pediatrics / 14.03.2016 Interview with: Ashley Bryce, NIHR PhD student Centre for Academic Primary Care, University of Bristol (first author) Dr Céire Costelloe NIHR Health Protection Research Unit in Healthcare associated infections and AMR, Imperial College London (senior author) What is the background for this study? Response: Antimicrobial resistance is an internationally recognised threat to health. Previous antibiotic use has been shown to be a risk factor for antimicrobial resistance in adults. The contribution of primary healthcare is particularly important as this is where almost 80% of all antibiotics used within the health service are prescribed. Children receive a lot of primary healthcare services and, as such, receive a disproportionately high number of antibiotics compared with middle aged populations. Despite this, little research has been published describing the prevalence of bacterial resistance in children or the risk factors of importance in this group. What are the main findings? Response: Prevalence of resistance to commonly prescribed antibiotics in primary care in children with urinary tract infections caused by E coli is high, particularly in countries outside the OECD, where one possible explanation is the availability of antibiotics over the counter. This could render some antibiotics ineffective as first line treatments for urinary tract infection. Routine use of antibiotics in primary care contributes to antimicrobial resistance in children, which can persist for up to six months after treatment. (more…)
Author Interviews, JAMA, Ophthalmology / 14.03.2016 Interview with: Fanny Raguideau Evaluateur en pharmaco-épidémiologie Direction Scientifique et de la Stratégie Européenne Pôle Epidémiologie des produits de santé What is the background for this study? What are the main findings? Response: Retinal detachment (RD), including both exudative types often associated with systemic diseases that might be receiving antibiotics for related conditions as well as rhegmatogenous which require prompt surgical intervention to reduce the chance of irreversible severe vision loss, has an annual incidence rate of 1 per 10,000 in the general population. Rhegmatogenous is the most common type. Fluoroquinolones are one of the most commonly prescribed classes of antibiotics. Thanks to their broad-spectrum antibacterial coverage, they are effective in the treatment of a wide variety of community-acquired infections. What is the background for this study? What are the main findings? Response: Several studies have suggested that oral fluoroquinolone use increased the risk of Retinal detachment, however this association remains controversial. We conducted a nationwide self-matched design study to overcome limitations of previous studies. Our finding of a significant increased risk of  Retinal detachment, including both rhegmatogenous and exudative types, following use of oral fluoroquinolone strongly supports the existence of this association. (more…)
Author Interviews, Heart Disease / 11.03.2016 Interview with: Malin Inghammar, MD, PhD Department of Infectious Diseases Skåne University Hospital, Lund Sweden What is the background for this study? Dr. Inghammar: Fluoroquinolones are a class of antibiotics with a widespread use in the treatment of common infections. Agents of this drug are generally well tolerated and have few side effects but in some people fluoroquinolones can prolong the QT-interval. QT-prolongation is a sort of electrical disturbance in the heart that can, in rare instances, lead to potentially life-threatening arrhythmia. Some drugs are well known to cause QT-prolongation and to be able to trigger arrhythmia. Fluoroquinolones however, have only weak effect on the QT-time. There have been a few previous studies published reporting an increased risk. Some of these, compared fluoroquinolone treated patients with people who were not treated with antibiotics at all. In these studies, it can’t be ruled out that the infection itself, rather than the antibiotic treatment could have influenced the risk of arrhythmia. In some other previous studies, there have been indications that the patients receiving fluoroquinolones were of poorer general health than the comparison group, which could also have affected the results. Therefore it is not clear if oral fluoroquinolone treatment leads to an increased risk of serious cardiac arrhythmia in an everyday clinical situation. (more…)
Author Interviews, Hospital Acquired, Infections, Nature / 24.02.2016 Interview with: Ashootosh Tripathi, PhD Postdoctoral Research Fellow Life Sciences Institute I Sherman lab University of Michigan Ann Arbor, MI, USA MedicalResearch: What is the background for this study? What are the main findings? Dr. Tripathi: Acinetobacter baumannii is a nosocomial opportunistic and resistant pathogen that can spread epidemically among patients causing ventilator-associated pneumonia and bacteremia. The mortality rates associated with it can be as high as 60%, representing a paradigm of pathogenesis, transmission and resistance. In addition, numerous reports have shown the startling emergence of multidrug-resistant A. baumannii in hospitals as well as the identification of pan-drug-resistant strains at some locations. Among the  various reasons for the antibiotic resistance of this pathogenic microbe, perhaps the most significant is mediated by its tendency to form biofilms (a highly structured extracellular polymeric matrix), which provide the microbe with the alarming ability to colonize medical devices. Interestingly, despite the well-understood role of bacterial biofilm behind aggravating antimicrobial resistance, there are currently no drugs specifically targeting biofilms in clinical trials to date. The study sought to solve this problem through the development of a biofilm inhibitor as a precision medicine, directed towards vulnerable patients, to avoid potential life-threatening infections. A crystal-violet based high throughput in vitro screen was developed to identify inhibitors of A. baumannii biofilms against our natural products extract (NPE) library. The vast NPE library of ~42,000 extracts has been under constant development in Prof David H. Sherman laboratory at University of Michigan, Ann Arbor, for over the past decade, from a relatively underexplored marine microbiome collected from different part of world viz., Costa Rica, Panama, Papua New Guinea, etc., and is available for any research group with a robust high-throughput screening (HTS) assay ( The HTS assay that was queried against a library of 9,831 NPEs aimed to identify extracts inhibiting biofilm formation as a primary screening. Further secondary  screening and   activity  threshold optimization revealed the extract from Streptomyces gandocaensis (collected from Costa Rica) to be of particular interest due to its ability to inhibit biofilm formation and had a limited effect on A. baumannii growth. Activity based chromatographic separation and analysis of extracts derived from S. gandocaensis resulted in the discovery of three peptidic metabolites (cahuitamycins A–C),   with cahuitamycin  C  being   the   most effective biofilm inhibitor (IC50 =14.5 µM)   with  negligible A.  baumannii growth inhibition (an important trait for ideal biofilm inhibitor). Following up on the exciting discovery, we also completely characterized the biosynthetic machinery involved in making the active molecules by S. gandocaensis, using sophisticated bioinformatics and molecular biology techniques. The knock out analysis revealed that the biosynthesis of cahuitamycin C proceeds via a convergent biosynthetic pathway, with one of the steps apparently being catalyzed by an unlinked gene encoding a 6-methylsalicylate synthase. Efforts to assess starter unit diversification through selective mutasynthesis led to production of unnatural analogues cahuitamycins D and E with increased potency (IC50=8.4 and 10.5 µM) against A. baumannii biofilm. (more…)
Author Interviews, Hospital Acquired / 02.02.2016 Interview with: Leonard Mermel, DO, ScM, AM (Hon), FSHEA, FIDSA, FACP  Professor of Medicine, Warren Alpert Medical School of Brown University Medical Director, Dept. of Epidemiology & Infection Control, Rhode Island Hospital Adjunct Clinical Professor, University of Rhode Island College of Pharmacy  Medical Research: What is the background for this study? What are the main findings? Dr. Mermel:  There is increasing concern in the US and abroad regarding multi-drug resistant organisms (MDROs), particularly bacteria resistant to carbapenem antibiotics.  Concern has been raised about MDRO colonization in high-risk populations, such as nursing home patients and transmission between nursing home and acute care hospitals.  Little data exists concerning the incidence of GI tract colonization of such pathogens in nursing home patients at the time of acute care hospitalization.  We used rectal swabs on 500 hospital admissions from nursing homes to assess carriage of bacteria resistant to carbapenem antibiotics.  We found carbapenem-resistant or carbapenemase-producing gram-negative bacteria in 23 of the 500 (4.6%) hospital admissions from nursing homes, which included 7 carbapenemase-producing CRE bacteria (1.4%).  The latter bacteria produce an enzyme that breaks down the carbapenem antibiotic and the resistance genes are located on mobile genetic elements.  We also found that use of gastrostomy tubes was associated with fecal carriage of gram-negative bacteria with detectable carbapenem resistance. (more…)
Asthma, Author Interviews, Lancet, Pharmacology / 20.01.2016

More on Asthma on Interview with: Hans Bisgaard, MD, DMSc Professor of Pediatrics The Faculty of Health Sciences University of Copenhagen Head of the Copenhagen Prospective Studies on Asthma in Childhood University  of Copenhagen and Naestved Hospital Medical Research: What is the background for this study? Dr. Bisgaard: Childhood asthma is often preceded by recurrent asthma-like symptoms in relation to airway infections in the first years of life. Bacteria and viruses are equally associated with the risk of episodes of asthma-like symptoms in these children, suggesting antibiotics as a potential treatment for such episodes. Medical Research: What are the main findings? Dr. Bisgaard: Our study demonstrates a clinically significant shortening of symptom duration by 63% after intervention. The effect size increased with early initiation of treatment, showing a reduction in episode duration of 83% if treatment was initiated before day 6 of the episode. Azithromycin was effective in shortening the episodes even though no pathogenic bacteria was detected. This study is, to our knowledge, the first randomized trial of azithromycin treatment of acute episodes of asthma-like symptoms in young children with a history of recurrent episodes. (more…)
Author Interviews, Dermatology, Pharmacology / 22.12.2015 Interview with: Dr. Diana Lac, PhD Senior Scientist at BioPharmX Corporation. Dr. Lac received her PhD in Pharmacology and Toxicology from the University of California, Davis and currently focuses on the development of topical treatments for acne. MedicalResearch: What is the background for this study? What are the main findings? Dr. Lac: Acne affects almost 90% of people in western societies during their teenage years and may persist into adulthood. Currently, the oral tetracycline class of drugs dominates the acne treatment market. However, these treatments have been associated with a variety of adverse effects, such as headaches, dizziness, fatigue, nausea, photosensitivity, and severe itchiness. While a variety of acne treatments do exist, topical antibiotics particularly have had limited success due to formulation challenges. A topical minocycline formulation will provide a superior alternative for local treatment of acne, thereby limiting the amount of systemic exposure to the antibiotic and addressing the overall global antibiotic resistance problem. We believe that by directly delivering the drug to the skin we can decrease the amount of antibiotic exposure and also limit the off-target effects. We have developed a novel, stable minocycline gel formulation allowing for efficient delivery of minocycline directly to the pilosebaceous unit in the skin where Propionibacterium acnes typically reside. In this poster presentation we have demonstrated this effectively in live rats. A dose ranging study was conducted where drug delivery and safety of our novel formulation was assessed. A number of dose formulations were tested (up to 4% minocycline formulations) and were found to be non-irritating and safe for topical use. (more…)
Author Interviews, JAMA, Pediatrics, Respiratory / 17.11.2015 Interview with: Leonard B. Bacharier, MD Professor of pediatrics Clinical Director, Division of Allergy, Immunology and Pulmonary Medicine St Louis School of Medicine Washington University St Louis, Missouri  Medical Research: What is the background for this study? What are the main findings? Dr. Bacharier: Oral corticosteroids such as prednisone have become the standard of care for children whose colds tend to progress and lead to severe wheezing and difficulty breathing. “But there are some studies that suggest these treatments don’t consistently work for young children. That’s why we want to find ways to prevent upper respiratory infections from progressing to lower respiratory tract illnesses. Once the episode gets going, standard interventions are less effective than would be desired”​​​​​​​​​​​​​​​​, reported Dr. Bacharier. (more…)
Author Interviews, OBGYNE / 01.11.2015

Anick Bérard PhD FISPE Research chair FRQ-S on Medications and Pregnancy Director, Réseau Québécois de recherche sur le médicament (RQRM) Professor, Research Chair on Medications, Pregnancy and Lactation Faculty of Pharmacy, University of Montreal Director, Research Unit on Medications and Pregnancy Research Center CHU Interview with: Anick Bérard PhD FISPE Research chair FRQ-S on Medications and Pregnancy Director, Réseau Québécois de recherche sur le médicament (RQRM) Professor, Research Chair on Medications, Pregnancy and Lactation Faculty of Pharmacy, University of Montreal Director, Research Unit on Medications and Pregnancy Research Center CHU Ste-Justine Medical Research:  Should we have any reservations about prescribing these macrolides during pregnancy? Dr. Bérard: With penicillin, macrolides are amongst the most used medications in the general population and in pregnancy. However, debate remained on whether it is the infections or in fact the macrolides used to treat them that put women and their unborn child at greater risk of adverse pregnancy outcomes, including birth defects. Our study was performed within the Quebec Pregnancy Cohort, one of the largest pregnancy cohorts in the World, and did not find a statistically significant association between macrolide use (a widely used class of antibiotics) during pregnancy and the risk of malformations. When looking at specific types of macrolides, no association was found between azithromycin, clarithromycin or erythromycin use during the first trimester of pregnancy and the risk of major malformations or cardiac malformations. This is reassuring when treating infections during pregnancy. (more…)
Antibiotic Resistance, Author Interviews, Dermatology, NYU, Pharmacology / 30.10.2015 Interview with: Arielle Nagler MD Instructor, Department of Ronald O. Perelman Department of Dermatology NYU Langone Medical Center Medical Research: What is the background for this study of acne patient who eventually require isotretinoin? Dr. Nagler: Isotretinoin is a highly effective medication for the treatment of severe acne. In fact, it is the only medication that has been shown to provide patients with a durable cure for acne. However, its use is limited by its known teratogenicity as well as controversies regarding its relationship with psychiatric disturbances and inflammatory bowel disease. For many patients, systemic antibiotics provide an effective treatment for inflammatory acne. However, antibiotics do not provide the long term clearance that isotretinoin provides. Moreover, antibiotics are getting increasing attention due to fears of emerging bacterial resistance. There has been a recent emphasis on limiting antibiotic use in acne. As a result, this study sought to understand antibiotic use patterns amongst patients who eventually received isotretinoin.  (more…)
Author Interviews, Pediatrics, Weight Research / 24.10.2015 Interview with: Brian S. Schwartz, MD, MS Professor of Environmental Health Sciences, Epidemiology, and Medicine Co-director, Program on Global Sustainability and Health Senior Investigator, Geisinger Center for Health Research (Danville, PA) Johns Hopkins Bloomberg School of Public Health Baltimore, Maryland 21205 Medical Research: What is the background for this study? What are the main findings? Dr. Schwartz: Sub-therapeutic doses of antibiotics (not a high enough dose to treat an infection in the animal) have been added to animal feeds for decades to promote weight gain. An increasing number of studies of therapeutic uses of antibiotics in humans have reported weight gain, mostly in young children. Using electronic health record data on over 163,000 children between 3 and 18 years of age from the Geisinger Health System, our study was the first one to study the full childhood age range among mostly healthy children; to find effects of antibiotics on weight gain at all ages; to find that the more the cumulative number of antibiotics the greater the weight gain; and that some of the effects were progressive, in that the cumulative number of antibiotics caused an increasing divergence of the body mass index trajectory over time from the trajectory in children who had not received antibiotics. (more…)
Author Interviews, CDC, Health Care Systems, Infections, Outcomes & Safety / 12.10.2015 Interview with: James Baggs, PhD Division of Healthcare Quality Promotion Centers for Disease Control and Prevention Atlanta, GA Medical Research: What is the background for this study? Dr. Baggs: The National Action Plan for Combating Antibiotic Resistance Bacteria calls for annual reporting of antibiotic use in inpatient settings as well as the identification of variations at the provider or patient level that can assist in developing interventions. Antibiotic use varies among hospitals, but some portion of that variability is related to the type of patients admitted to the hospital and other hospital characteristics. We evaluated factors in a large cohort of US hospitals that may account for inter-facility variability in antibiotic use, so that we can more appropriately monitor antibiotic use in hospitals. Medical Research: What are the main findings? Dr. Baggs: We utilized data from the Truven Health MarketScan Hospital Drug Database (HDD), which contains detailed administrative records, including inpatient drug utilization data based on billing records, for all patients discharged from a convenience sample of over 500 US hospitals. We retrospectively estimated days of therapy (DOT)/1,000 patient days (PDs) by year from 2006-2012, and created a multivariable model that adjusts for hospital-specific location of antibiotic use (ICU vs. other), average patient age, average patient co-morbidity score, number of hospital beds, teaching status, urban or rural location, proportion of discharges with a surgical diagnosis related code, case mix index, and proportion of patient days with an infectious disease primary ICD-9-CM discharge code. We observed that DOT varied significantly between hospitals; the 10th to 90th percentile values for hospital days of therapy ranged from 546 to 998/1,000 PDs. The variables included in our model accounted for 47-53% of the inter-facility variability, depending on year. However, nearly all of this variability was explained by two predictors: proportion of PDs with an infectious disease diagnosis code and hospital location (ICU vs. other).  (more…)
AHRQ, Antibiotic Resistance, Author Interviews, Baylor College of Medicine Houston, JAMA, Urinary Tract Infections / 25.06.2015

Barbara W. Trautner, MD, PhD Houston Veterans Affairs Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center Section of Infectious Diseases, Department of Medicine Baylor College of Medicine, Houston, Interview with: Barbara W. Trautner, MD, PhD Houston Veterans Affairs Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center Section of Infectious Diseases Department of Medicine Baylor College of Medicine, Houston, Texas Medical Research: What is the background for this study? What are the main findings? Dr. Trautner: Reducing antimicrobial overuse, or antimicrobial stewardship, is a national imperative. If we fail to optimize and limit use of these precious resources, we may lose effective antimicrobial therapy in the future. CDC estimates that more than $1 billion is spent on unnecessary antibiotics annually, and that drug-resistant pathogens cause 2 million illnesses and 23,000 deaths in the U.S. each year. The use of antibiotics to treat asymptomatic bacteriuria (ASB) is a significant contributor to antibiotic overuse in hospitalized and nursing home patients, especially among patients with urinary catheters. In catheterized patients, ASB is very often misdiagnosed and treated as catheter-associated urinary tract infection (CAUTI). Therefore, we designed the “Kicking CAUTI: The No Knee-Jerk Antibiotics Campaign intervention” to reduce overtreatment of ASB and to reduce the confusion about distinguishing CAUTI from asymptomatic bacteriuria. This study evaluated the effectiveness of the Kicking CAUTI intervention in two VAMCs between July 2010 and June 2013. The primary outcomes were urine cultures ordered per 1,000 bed-days (inappropriate screening for ASB) and cases of ASB receiving antibiotics (overtreatment). The study included 289,754 total bed days, with 170,345 at the intervention site and 119,409 at the comparison site. Through this campaign, researchers were able to dramatically decrease the number of urine cultures ordered. At the intervention site, the total number of urine cultures ordered decreased by 71 percent over the course of the intervention. Antibiotic treatment of asymptomatic bacteriuria decreased by more than 75 percent during the study. No significant changes occurred at the comparison site over the same time period. Failure to treat catheter-associated urinary tract infection when indicated did not increase at either site. (more…)
Author Interviews, Microbiome, Pediatrics / 23.05.2015 Interview with: Ms. Pajau Vangay Graduate Research Fellow Biomedical Informatics and Computational Biology Vice President of Grants, Council of Graduate Students University of Minnesota Medical Research: What is the background for this study? What are the main findings? Response: Previous studies showed links between antibiotic use and unbalanced gut bacteria, and others showed links between unbalanced gut bacteria and adult disease. Over the past year we synthesized hundreds of studies and found evidence of strong correlations between antibiotic use, changes in gut bacteria, and disease in adulthood. (more…)
Antibiotic Resistance, Author Interviews, Infections, NEJM / 02.04.2015

Henri van Werkhoven PhD student | Julius Center for Health Sciences and Primary Care University Medical Center Utrecht, Utrecht, The Interview with: Henri van Werkhoven PhD student and Douwe-PostmaDouwe Postma PhD student Julius Center for Health Sciences and Primary Care University Medical Center Utrecht, Utrecht, The Netherlands Medical Research: What is the background for this study? What are the main findings? Response: Community-acquired pneumonia is an important cause of hospitalization and death worldwide. Recommendations for antibiotic treatment in patients hospitalized to a non-ICU ward vary widely between guidelines, because the optimal antibiotic strategy is unknown. Interpretation of the available evidence from clinical studies is complicated by the heterogeneity in designs and findings. In our study, we hypothesized that the most conservative strategy, beta-lactam monotherapy, would be non-inferior to strategies with a broader range of antibiotic coverage. The latter strategies are potentially related to increased antibiotic resistance. For this purpose, we randomized hospitals to follow three different strategies of preferred antibiotic treatment in consecutive periods of four months. Physicians were allowed to deviate from the preferred antibiotic treatment for medical reasons. We found that a strategy with beta-lactam monotherapy (e.g. amoxicillin) as the preferred treatment was non-inferior to the strategies with beta-lactam/macrolide combination therapy or fluoroquinolone monotherapy for 30 and 90-day all-cause mortality. Also there was no difference in length of hospitalization and rate of complications. (more…)
Antibiotic Resistance, Author Interviews, Infections / 26.01.2015

Dr. Thiago César Nascimento Assistant Professor, Department of Basic Nursing Laboratory of Bacterial Physiology and Molecular Genetics Institute of Biological Sciences Federal University of Juiz de Fora, Interview with: Dr. Thiago César Nascimento Assistant Professor, Department of Basic Nursing Laboratory of Bacterial Physiology and Molecular Genetics Institute of Biological Sciences Federal University of Juiz de Fora, Brazil Medical Research: What is the background for this study? What are the main findings? Response: Preliminarily, we observed a high incidence of coagulase-negative  Staphylococcus  strains (CoNS) recovered from the leachate of the health care waste in an untreated sanitary landfill. As Staphylococcus sp. especially oxacillin or methicillin-resistant CoNS remains as important putative pathogenic bacteria regarding human and other animals, in this study we investigated the antimicrobial susceptibility patterns and the occurrence of the  mecA  gene. In conclusion, our results raise issues related to the viability of putative pathogenic bacteria resistant to important antimicrobial drugs carrying important resistance markers in untreated healthcare waste in sanitary landfills.These risks regarding the potential spread of leachate from sanitary landfills due to human and animal activities, or even due to weather phenomena, such as torrential rains and floods, should be considered. Our results address a phenomenon related to the incorrect healthcare waste management in Brazil and in other geographical regions. Taking into account environmental health, more conscientious  policies should be considered by authorities to avoid the disposal of healthcare waste without any further treatment. (more…)
Author Interviews, Lancet, Stroke / 20.01.2015 Interview with: Prof. dr. Diederik van de Beek Department of Neurology, Academic Medical Center, University of Amsterdam The Netherlands What is the background for this study? What are the main findings? Dr. van de Beek: In adults with acute stroke, infections occur commonly and are associated with an unfavourable functional outcome. In the Preventive Antibiotics in Stroke Study (PASS) we aimed to establish whether or not preventive antimicrobial therapy with a third-generation cephalosporin, ceftriaxone, improves functional outcome in patients with acute stroke. PASS is an investigator-initiated, randomised, open-label, masked-endpoint trial that was undertaken between 2010 and 2014 in 30 Dutch centres and enrolled 2550 patients with ischaemic or haemorrhagic stroke. Randomly assigned in a 1:1 ratio to either preventive antibiotic therapy or a control group, all patients received standard stroke unit care. Starting within 24 h after stroke onset, patients in the preventive antibiotic group were given additional treatment with ceftriaxone administered intravenously at a dose of 2 g every 24 h for 4 days. The main findings were that preventive ceftriaxone did not improve 3-month functional outcome on the modified Rankin Scale (adjusted common odds ratio 0·95 [95% CI 0·82–1·09]); however, clinically diagnosed post-stroke infections were significantly reduced (adjusted odds ratio 0·55 [0·44–0·70]). Preventive antibiotic therapy with ceftriaxone is a safe treatment. (more…)
Antibiotic Resistance, Author Interviews, Infections, Science / 04.01.2015

Melanie Blokesch PhD Assistant Professor (tenure-track) Laboratory of Molecular Microbiology Global Health Institute, School of Life Sciences Swiss Federal Institute of Technology Lausanne (EPFL) Lausanne Interview with: Melanie Blokesch PhD Assistant Professor (tenure-track) Laboratory of Molecular Microbiology Global Health Institute, School of Life Sciences Swiss Federal Institute of Technology Lausanne (EPFL) Lausanne Switzerland Medical Research: What is the background for this study? What are the main findings? Dr. Blokesch: We have been studying the cholera-causing bacterium Vibrio cholerae for many years in my laboratory. Our main focus has always been on elucidating how this pathogen acquires new genetic material that allows it to evolve. This is often accomplished through a mechanism known as horizontal gene transfer (HGT). There are three main modes of horizontal gene transfer in bacteria and the one we are primarily interested in is called natural competence for transformation. When the bacterium enters the state of natural competence it can take up free genetic material from its surrounding and in case it recombines this new material into its own genome the bacterium is considered to be naturally transformed. Notably, natural competence/transformation was first described in 1928 by Fred Griffith, who showed that transformation can render harmless bacteria pathogenic. These early experiments can be considered a milestone in molecular biology as it later led to the discovery of DNA as the carrier of genetic information. Medical Research: What are the main findings? Dr. Blokesch: The main finding of our study is that the pathogen V. cholerae does not solely rely on free DNA floating around but that it actively kills neighbouring bacteria followed by the uptake of their DNA. Indeed, we were able to show that the two processes - killing of other bacteria and DNA uptake - are co-regulated by the same proteins within the bacterial cell. We also used imaging techniques to visualize the killing of other bacteria by V. cholerae, followed by the release of their genetic material, which the predator then pulled into its own cell. We further quantified these HGT events by following the transfer of an antibiotic resistance gene from the killed bacterium to the predatory V. cholerae cell. Notably, the spread of antibiotic resistances is a major health concern and HGT is a major driver of it. (more…)
Author Interviews, Heart Disease / 26.12.2014

Jiun-Ling Wang MD Associated professor at Medical school in I-Shou University infectious disease doctor at E-DA Hospital, Kaohsiung , Interview with: Jiun-Ling Wang MD Associated professor at Medical school in I-Shou University infectious disease doctor at E-DA Hospital, Kaohsiung , Taiwan Medical Research: What is the background for this study? What are the main findings? Dr. Wang: Some study showed increase cardiovascular death in azithromycin user. But there lacks of data in other antibiotics in the treatment for respiratory tract infections. So we used the Taiwan National Health Insurance Database to perform a nationwide, population-based study comparing the risks of ventricular arrhythmia and cardiovascular death among patients using these antibiotics. And we find azithromycin, and moxifloxacin were associated with higher risk of ventricular arrhythmia cardiovascular death than amoxicillin/clavunate. (more…)
Author Interviews, Heart Disease, Infections, Lancet / 24.11.2014 Interview with: Dr. Martin Thornhill PhD Department of Cardiology, Taunton and Somerset NHS Trust Taunton, Somerset, UK Medical Research: What is the background for this study? What are the main findings? Dr. Thornhill: In 2008 NICE introduced controversial new guidance recommending that antibiotic prophylaxis to prevent infective endocarditis should no longer be used. It was a rational decision, given the evidence for the effectiveness of antibiotic prophylaxis and potential concerns about costs, the development of antibiotic resistance and possible side effects from antibiotics, but it went against other guidelines from around the world that existed at the time. The main findings are that in England:
  1. There has been a large and significant decline in the use of antibiotic prophylaxis.
  2. There has been a significant increase in the number of cases of infective endocarditis, above the baseline trend, using hospital coding data, corrected for changes in the size of the English population.
Antibiotic Resistance, Author Interviews, Pharmacology, Rheumatology / 19.11.2014 Interview with: Dr. Daniel B Horton, MD Division of Pediatric Rheumatology Department of Pediatrics Nemours Dupont Pediatrics Wilmington, Delaware
Medical Research: What is the background for this study? What are the main findings? Dr. Horton: The reasons why children develop juvenile arthritis (JIA) are unclear. To date, genetic variation accounts for only a minority of disease incidence, and no environmental factor has consistently been associated with juvenile arthritis. There is growing understanding about the role of microbiome disturbance in the development of multiple diseases, including obesity, inflammatory bowel disease, and rheumatoid arthritis. Exposure to antibiotics, a known disruptor of the human microbiome, has been linked to pediatric conditions including inflammatory bowel disease, asthma, and obesity. We showed that antibiotic prescriptions are associated with the development of new JIA diagnosis in a large general pediatric population, after accounting for history of infection and other relevant factors. This association is stronger for those who have received multiple courses of antibiotics and appears specific for antibacterial antibiotics, such as penicillins and sulfa drugs. (more…)