Dr. Fangjian Guo[/caption]
Fangjian Guo, MD, PhD
Department of Obstetrics and Gynecology
Center for Interdisciplinary Research in Women’s Health
University of Texas Medical Branch
Galveston TX
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The identification of BRCA1/BRCA2 pathogenic variants in women susceptible to breast or ovarian cancer in the 1990s created an opportunity for targeted, individualized cancer prevention. BRCA testing in young women before cancer onset enables early detection of those with increased cancer risk and creates an opportunity to offer life-saving prophylactic procedures and medication.
We used insurance claims data to assess the use of BRCA testing in unaffected young women <40 years of age between 2006 and 2017 and found that BRCA testing among cancer-free women under 40 has more than doubled in recent years. However, only about 25% of all BRCA testing done in 2017 was performed in unaffected young women under 40.
Dr. Thanassi[/caption]
David G. Thanassi, Ph.D.
Professor and Interim Chair
Department of Molecular Genetics & Microbiology
Center for Infectious Diseases
Stony Brook University
Stony Brook, NY 11794-5222
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Pathogenic bacteria such as Escherichia coli use hair-like surface appendages termed pili to colonize tissues within the host and initiate infection. Together with our collaborators - the group of Huilin Li at the Van Andel Research Institute - we used an advanced imaging technique termed cryo-electron microscopy to determine snapshots of bacterial pili as they are being assembled. The pili we studied are critical for uropathogenic strains of E. coli to colonize the urinary tract and cause urinary tract infections. Our work revealed a new stage in the pilus assembly process and new details about how these structures are built on the bacterial surface.
Dr Dorival Martins
Department of Microbiology and Immunology
Meakins-Christie Laboratories, Research Institute
McGill University Health Centre
Montreal Canada.
MedicalResearch.com: What is the background for this study?
Response: Antibiotic tolerance, together with drug resistance, makes bacteria refractory to antibiotics and can cause treatment failure in subacute and chronic bacterial infections.
Pseudomonas aeruginosa, a major health concern worldwide, can cause severe chronic infections that are refractory to antibiotic treatments due to tolerance. Since the discovery of new antibiotics has been drastically diminished over the last decades, overcoming tolerance could be a strategy to enhance the efficacy of currently available antibiotic treatments. However, very little is known about the mechanism of tolerance, even though this phenomenon has been observed over 60 years ago.
Dr. Andreas Bäumler[/caption]
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
MedicalResearch.com: 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.
Dr. Lingchong You[/caption]
Dr. Lingchong You PhD
Paul Ruffin Scarborough Associate Professor of Engineering
Duke University
MedicalResearch.com: 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.
MedicalResearch.com Interview with:
Dr. Bob Kirkcaldy MD, MPH
Epidemiologist, Division of STD Prevention
CDC
Medical Research: What is the background for this study? What are the main findings?
Dr. Kirkcaldy: Gonorrhea is a common sexually transmitted disease that, if untreated, can cause severe reproductive health complications. While gonorrhea is very common, it is often symptomless and many may not realize they have it. 333,004 cases were diagnosed in 2013, but more than 820,000 are estimated to occur annually. Because antibiotic resistance has jeopardized treatment for gonorrhea, CDC’s Gonoccocal Isolate Surveillance Project (GISP) monitors antimicrobial susceptibility and tracks patterns of resistance among antibiotics currently used to treat gonorrhea. From 2006-2009, susceptibility to the oral cephalosporin antibiotic cefixime declined in GISP, threatening the effectiveness of this drug. Continued use of cefixime in the face of declining susceptibility could theoretically foster broad resistance to the cephalosporin class (including ceftriaxone, the last treatment option). So in 2012, CDC changed its treatment recommendations to recommend only dual gonorrhea treatment with injectable ceftriaxone plus oral azithromycin.
The most recent data from GISP analyzed urethral gonorrhea samples of men from STD clinics in 34 cities from 2006-2014 and found resistance to cefixime increased in 2014 after two years of dramatic decreases. While CDC’s STD Treatment Guidelines suggest cefixime should only be considered as an alternative treatment for gonorrhea when ceftriaxone is not available, trends of cefixime susceptibility have historically been a precursor to trends in ceftriaxone so it’s important to continue monitoring cefixime to be able to anticipate what might happen with other drugs in the future. GISP data also found that resistance remained stable for ceftriaxone and resistance levels remain highest among men who have sex with men (MSM).
We’re concerned about the increase in resistance for cefixime; however, more years of data are needed to know if the 2014 increase is the beginning of a new trend.
Dr. Nagler[/caption]
MedicalResearch.com 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.
MedicalResearch.com 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.
MedicalResearch.com Interview with: Ms. Amanda Jezek Director of Government Relations Infectious Diseases Society Of America Editor's Note: The Infectious Diseases Society of America Comments on the 21st Century Cures bill, a bill desigend “to help modernize and personalize health care, encourage greater innovation, support research” including important issues surrounding antimicrobial resistance and antibiotic development. Ms. Amanda...
MedicalResearch.com Interview with:
Henri van Werkhoven
PhD student and
Douwe 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.
MedicalResearch.com Interview with:
Anu Kantele, MD PhD
Associate Professor, Department of Medicine, University of Helsinki Specialist of Infectious Diseases, Helsinki University Hospital Head of Travel Clinic, Aava Medical Centre
Medical Research: What is the background for this study? What are the main findings?
Dr. Kantele: Increasing antimicrobial resistance is considered a serious global threat for modern medicine. Resistance is rapidly surging in regions with poor hygiene and uncontrolled use of antibiotics. Resistant bacteria are gradually spreading from there to countries in which the prevalence has thus far been low.
Our study was conducted among 430 healthy Finnish travelers visiting warm countries (tropical /subtropical regions). The volunteers provided stool samples before and after travel and filled in questionnaires. The stools were analyzed for multidrugresistant bacteria (not only so called ESBL bacteria but also CPE bacteria which are even more resistant).
None of the travelers had CPE strains in their stools before or after their journey. 1% carried ESBL before travel, and 21% acquired a strain while overseas. The risk was greatest in the Indian subcontinent and almost similar in Southeast Asia. In Africa, it proved to be increased but did not reach such a high level. Two factors amplified the risk significantly: travellers’ diarrhea and use of antibiotics. Among the entire study population, ESBL was found in 11% of those staying healthy, 22% of those with diarrhea, and 37% of those who took antibiotics for their diarrhea. In the Indian subcontinent, the respective figures were 23%, 47%, and 80%, and in Southeast Asia 14%, 32%, and 69%.
Medical Research: Why do antibiotics predispose to contracting resistant bacteria from the surroundings?
Dr. Kantele: The effects of antibiotics cannot be restricted to killing merely the bugs we wish them to kill. When doing their job they also wipe out a huge number of our own intestinal bacteria, thereby opening the door for newcomers’ invasion. If antibiotics are taken in an environment exposing people to a multitude of resistant bacteria, part of these newcomers are likely to be resistant ones. Antibiotics may, in fact, kill the sensitive newcomers and favor the resistant ones.
MedicalResearch.com 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.
MedicalResearch.com 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.
David 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 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.
MedicalResearch.com Interview with :
Pr. Jean-Marc Regimbeau
Service de Chirurgie Digestive Oncologique et Métabolique,
CHU dAmiens
Medical Research : What are the main findings of the study?
Answer: In our study we found that the absence of postoperative administration of amoxicillin plus clavulanic acid did not improve the occurrence of postoperative infections in patients with mild or moderate acute calculous cholecystitis. The bile cultures were pathogen free in 60.9% of case. Moreover we show that less than 2 percent of the overall population presented a major complication defined according to the Clavien Dindo Classification (Clavien score ≥3a). After cholecystectomy the readmission rate was 6%.
HOUSTON - (Sept. 7, 2011) - An analysis of the genome of a superbug has yielded crucial, novel information that could aid efforts to counteract the bacterium’s resistance to an antibiotic of last resort. The results of the research led by scientists from The University of Texas Health Science Center...