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…)
Annals Internal Medicine, Author Interviews, Cost of Health Care, McGill / 18.11.2014 Interview with: Todd Lee MD MPH FRCPC Consultant in Internal Medicine and Infectious Diseases Assistant Professor of Medicine, McGill University Director, General Internal Medicine Consultation Service, Chief of Service, 6 Medical Clinical Teaching Unit, McGill University Health Centre Medical Research: What is the background for this study? What are the main findings? Dr. Lee: Antibiotics are often misused and overused in hospitalized patients leading to harms in terms of side effects, infections due to Clostridium dificile, the development of antibiotic resistance, and increased health care costs.  Antimicrobial stewardship is a set of processes which are employed to improve antibiotic use.  Through various techniques, stewardship seeks to ensure the patient receives the right drug, at the right dose, by the right route, for the right duration of therapy.  Sometimes this means that no antibiotics should be given. In implementing antimicrobial stewardship programs, some of the major challenges larger health care centers face include limitations in the availability of trained human resources to perform stewardship interventions and the costs of purchasing or developing information technology solutions. Faced with these same challenges, we hypothesized that for one major area of our hospital, our medical clinical teaching units, we could use our existing resources, namely resident and attending physicians, to perform "antimicrobial self-stewardship".  This concept tied the CDCs concept of antibiotic "time outs" (periodic reassessments of antibiotics) to a twice weekly audit using a locally developed checklist.  These audits were performed by our senior resident physicians in the context of providing their routine clinical care.  We also provided local antibiotic guidelines and regular educational sessions once a rotation. We demonstrated a significant reduction in antibiotic costs as well as improvement in two of the four major classes of antibiotics we targeted as high priority.  We estimated we saved between $140 and $640 in antibiotic expenses per hour of clinician time invested. Anecdotally, trainees felt the process to be highly valuable and believed they better understood the antibiotic use for their patients. (more…)
Anesthesiology, Author Interviews, Hepatitis - Liver Disease, Infections / 11.10.2014 Interview with: Sana Dastgheyb National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, MDDepartment of Orthopedic Surgery, Thomas Jefferson University, Philadelphia, PA and Dr. Noreen Hickok Department of Orthopedic Surgery Thomas Jefferson University, Philadelphia, PA Medical Research: What are the main findings of the study? Response: Physicians have long been resigned to the fact that staphylococcal joint infections are among the most challenging to treat. Our study points towards a definitive mechanism whereby bacteria become insensitive to antibiotics in the human joint environment. We added MRSA to synovial fluid and observed dense, biofilm-like aggregates, as well as a relative insensitivity to antibiotics as compared to ideal medium. Our findings suggest that serum/extracellular matrix proteins within synovial fluid contribute greatly to staphylococcal antibiotic insensitivity in synovial fluid. Furthermore, pre-treatment of synovial fluid with the enzyme plasmin, which degrades extracellular matrix proteins, significantly inhibits aggregate formation, and restores normal antibiotic sensitivity to MRSA. (more…)
Author Interviews, Infections, JAMA / 09.10.2014 Interview with: Dr. Nicolas Garin MD Division of General Internal Medicine, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland Division of Internal Medicine, Hôpital Riviera-Chablais, Monthey, Switzerland Medical Research: What are the main findings of the study? Dr. Garin: Empiric treatment with a betalactam drug (monotherapy) was not equivalent to the combination of a betalactam and a macrolide in patients hospitalized for moderate severity pneumonia (proportion of patients not having reached clinical stability at day 7 was 41.2 % in the monotherapy vs. 33.6 % in the combination therapy arm, between arm difference 7.6 %). This occurred despite systematic search for Legionella infection in the monotherapy arm. There was no difference in early or late mortality, but patients in the monotherapy arm were more frequently readmitted. Patients with higher severity of disease (in PSI category IV, or with a CURB-65 score higher than 1) seemed to benefit from combination therapy (HR 0.81 for the primary outcome of clinical instability at day 7), although it was statistically not significant. There was no difference in the primary outcome for patients in PSI category I to III. (more…)
Allergies, Author Interviews, Kaiser Permanente / 29.09.2014

Eric Macy, MS, MS Allergy & Immunology Kaiser Permanente Medical Interview with: Eric Macy, MS, MS Allergy & Immunology Kaiser Permanente Medical Group-Allergy   Medical Research: What are the main findings of the study? Dr. Macy:
  • Cephalosporins are currently widely and relatively safely used in individuals with a history of a penicillin "allergy" in their medical record.
  • Cephalosporin associated anaphylaxis is very rare, even in individuals with a history of penicillin "allergy".
  • Cephalosporin associated serious cutaneous adverse reactions are extremely rare.
  • Cephalosporin associated Clostridium difficile and serious nephropathy are relatively common. (more…)
Antibiotic Resistance, Author Interviews, PNAS / 05.09.2014 Interview with: David T. Fox, Ph.D. Scientist 3 Los Alamos National Laboratory andDavid T. Fox, Ph.D. Scientist 3 Los Alamos National Laboratory and Prof. Samir Mitragotri Center for Bioengineering and Department of Chemical Engineering University of California, Santa Barbara, CA 93106Prof. Samir Mitragotri Center for Bioengineering and Department of Chemical Engineering University of California, Santa Barbara, CA 93106 Medical Research: What are the main findings of this study? Answer: Our research team identified a molten salt, choline-geranate, that possessed multiple beneficial biological traits. Specifically, when mixed in a 1:2 ratio (choline:geranate) this solvent is able to effectively disrupt and neutralize 72-hour biofilms formed by both Pseudomonas aeruginosa and Salmonella enterica. Further, our studies demonstrated the same solvent exhibited minimal cytotoxicity effects to normal human bronchial epithelial (NHBE) cells and was able to deliver an antibiotic, cefadroxil, through the stratum corneum into the epidermis and dermis. Most importantly, the research culminated in demonstrating the molten salt was able to neutralize ~95% of the bacteria found within a 24-hour P. aeruginosa biofilm when grown on a skin wound model (MatTek)  and ~98% of the bacteria when formulated with the antibiotic, ceftazidime. When the biofilm was treated with only antibiotic in a saline solution, less than 20% of the bacteria were neutralized. (more…)
Author Interviews, Infections / 29.08.2014

Dr. Asha Bowen FRACP Menzies School of Health Research Charles Darwin University Darwin, NT, Interview with: Dr. Asha Bowen FRACP Menzies School of Health Research Charles Darwin University Darwin, NT, Australia Medical Research: What are the main findings of the study? Dr. Bowen: The Skin Sore Trial found that short courses (3 days of twice daily dosing or 5 days of once daily dosing) of oral co-trimoxazole worked just as well for treating impetigo in remote Indigenous Australian children as the standard treatment with an intramuscular injection of penicillin (BPG). Despite many randomised controlled trials (RCTs) on this common infection of childhood, few have been conducted where impetigo is severe and endemic and with over 100 million children affected at any one time, ongoing research is needed. This is only the second RCT to study impetigo in children where the problem is endemic and often severe. In our study, 70% of children had severe impetigo with a median of 3 body regions affected. BPG injections are painful and we knew from previous studies that not many children were receiving them. Our study confirmed that 30% of children had injection site pain 48 hours after receipt of the injection and 5 children ran away when they found out that they were randomised to the injection arm of the study. (more…)
Asthma, Author Interviews, Lancet, Pediatrics / 20.05.2014

Adnan Custovic DM MD PhD FRCP Professor of Allergy Institute of Inflammation and Repair University of Manchester University Hospital of South Manchester Manchester M23 9LT, Interview with: Adnan Custovic DM MD PhD FRCP Professor of Allergy Institute of Inflammation and Repair University of Manchester University Hospital of South Manchester Manchester M23 9LT, UK MedicalResearch: What are the main findings of the study? Dr. Custovic: In a longitudinal analysis of the data from our birth cohort study collected from birth to age eleven years, we demonstrated an association between early-life antibiotic prescription and development of wheezing, but not atopy. Furthermore, amongst children with wheezing, antibiotic prescription in infancy increases the risk of subsequent severe wheeze/asthma exacerbations and hospital admissions. This is the first demonstration that children who receive antibiotics in infancy have impaired antiviral immunity later in life, and that early-life antibiotic prescription is associated with variants on chromosome 17q21 locus (which is an asthma susceptibility locus). Our findings suggest that the association between antibiotics and childhood asthma reported in previous studies arises through a complex confounding by indication, in which hidden factors which increase the likelihood of both antibiotic prescription in early life and subsequent asthma development are increased susceptibility to virus infections consequent to impaired antiviral immunity, and genetic variants on 17q21. Our results raises an important issue that effects which are often attributed to environmental exposures may be a reflection of genetic predisposition. (more…)
Author Interviews, BMJ, McGill, Pediatrics / 16.04.2014 Interview with: Ethan K Gough, PhD candidate Department of Epidemiology Biostatistics and Occupational Health McGill University, Montreal, QC, Canada What are the main findings of the study? Answer: Antibiotic use produces significant gains toward expected growth in children, for their age and sex, from low- and middle-income countries. Children included in our study were generally smaller in height and weight than adequately nourished children of the same age, reflecting the spectrum of stunting and wasting malnutrition seen in low- and middle-income countries. Antibiotic use had a larger impact on weight than height, and the effect on weight was larger in populations who may be at greater risk of infections and early mortality, such as populations with a high prevalence of HIV infection or exposure, and a high prevalence of severe acute malnutrition. (more…)
Author Interviews, BMJ, Gastrointestinal Disease, Pediatrics / 26.03.2014 Interview with: Marie Lund MD, PhD student Department of Epidemiology Research København S | Denmark What are the main findings of the study? Dr. Lund: We found macrolide use in infants to be associated with a 30-fold increased risk of infantile hypertrophic pyloric stenosis (IHPS) with use during the first two weeks after birth and a lower, but significantly increased threefold risk with use during days 14 to 120. Similarly, there was a more than three-fold increased risk of IHPS associated with maternal macrolide use during the first two weeks after birth, but no increased risk with use thereafter. Finally, we found a possible modest association between maternal macrolide use during weeks 28 to birth and infantile hypertrophic pyloric stenosis. (more…)
Author Interviews, C. difficile, Infections, NEJM / 26.09.2013 Interview with: David W. Eyre, B.M., B.Ch. Nuffield Department of Clinical Medicine University of Oxford National Institute for Health Research (NIHR) Oxford Biomedical Research Centre John Radcliffe Hospital What are the main findings of this study? Dr. Eyre: All cases of Clostridium difficile in Oxfordshire were studied over 3 years. Isolates were characterized by whole genome sequencing and the data was linked to hospital databases allowing epidemiological relationships between patients at the level of the hospital ward, hospital specialty, and post code to be identified. For comparison, similar information was also available for all other patients with and without diarrhea.  Preliminary work on the genetic diversity of Clostridium difficile within individuals and between individuals within discrete outbreaks allowed reliable interpretation of transmission events using genomic data. This allowed a complete reconstruction of the pattern of transmission between affected cases in Oxfordshire to be made. The findings were: 1. Unexpectedly few cases (13%) appear to be acquired from direct ward based contact with other symptomatic cases (these have previously been thought to be the main source of infections, and the focus of prevention efforts). Another 6% were associated with other hospital contact and 3% had plausible community contacts. 2. In 13% of cases potential donors were identified gnomically but no contact, within hospitals or the community, were identified. This suggests that the existence of other modes of transmission of Clostridium difficile. 3. The sources of Clostridium difficile infections were highly genetically diverse, with 45% of cases having a genetically distinct origin - suggesting a diverse reservoir of disease, not previously appreciated 4. During the 3 years of the study the rate of Clostridium difficile in Oxfordshire fell.  Any improvement in infection control techniques would be expected to reduce the incidence of cases caused by within hospital transmission. Surprisingly, similar rates of fall occurred in both in secondary cases (considered to be acquired from hospital associated symptomatic cases) and for primary cases (cases not associated with transmission from symptomatic cases). (more…)