Bacterial Appendage Offers New Target To Combat Antibiotic Resistance

MedicalResearch.com Interview with:

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

Dr. Thanassi

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.   Continue reading

Enzyme Key To Overcoming Antibiotic Resistance in Pseudomonas Infections

MedicalResearch.com Interview with:
"pseudomonas first bacteria to be patented. professor Chakrabarty" by adrigu is licensed under CC BY 2.0Dr 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.

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Antibiotics Increase Oxygen in Bowel, Allowing Salmonella To Thrive

MedicalResearch.com 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

Dr. Andreas Bäumler

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.

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Antibiotics Don’t Promote Resistance Gene Transfers Between Cells

MedicalResearch.com Interview with:

Dr. Lingchong You PhD Paul Ruffin Scarborough Associate Professor of Engineering Duke University

Dr. Lingchong You

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.

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Gonorrhea Still Treatable But Last Effective Antibiotic Remains Vulnerable to Resistance

Dr. Bob Kirkcaldy MD, MPH Epidemiologist, Division of STD Prevention CDCMedicalResearch.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.

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Earlier Isotretinoin Discussion May Decrease Long-Term Antibiotic Use For Acne

Arielle Nagler MD Instructor, Department of Ronald O. Perelman Department of Dermatology NYU Langone Medical Center

Dr. Nagler

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.  Continue reading

Coordinated Approach Could Decrease Infections and Deaths From Antibiotic Resistant Bacteria

MedicalResearch.com Interview with:
Rachel Slayton PhD
National Center for Emerging and Zoonotic Infectious Diseases
CDC

Medical Research: What is the background for this study? What are the main findings?

Dr. Slayton: Antibiotic-resistant bacteria cause more than 2 million illnesses and at least 23,000 deaths each year in the US. Additionally, Clostridium difficile caused close to half a million illnesses in 2011, and an estimated 15,000 deaths a year are attributable to C. difficile infections. Antibiotic resistance is a regional problem with inter-facility spread through movement of patients who are colonized or infected with these organisms.

In our first analysis we projected the national incidence of infections and deaths from Carbapenem-resistant Enterobacteriaceae (CRE), Clostridium difficile, invasive methicillin-resistant Staphylococcus aureus (MRSA), and multidrug-resistant Pseudomonas aeruginosa. With immediate implementation of national interventions combining infection control and antibiotic stewardship and, assuming similar effectiveness to that reported in other countries, an estimated 619,000 health care–associated infections and 37,000 deaths could be averted over 5 years.

Using CRE as an exemplar, we also estimated the effect of a coordinated approach in a network for the preventing the spread of antibiotic-resistance organisms among healthcare facilities that share patients. Our Carbapenem-resistant Enterobacteriaceae modeling was done in collaboration with Johns Hopkins Bloomberg School of Public Health, the University of Utah, and University of California Irvine School of Medicine. Both models clearly show that we could see fewer antibiotic-resistant infections if health care facilities and public health officials work together as a team. For example, five years after Carbapenem-resistant Enterobacteriaceae enters an area with 10 facilities that share patients, baseline activity alone resulted a prevalence of healthcare-associated CRE infection or colonization of 12.2% with 2,141 patients acquiring CRE. With independent facility-augmented efforts, we estimated that there would be an 8.6% prevalence with 1,590 patients acquiring Carbapenem-resistant Enterobacteriaceae. With a coordinated augmented approach, we estimated that there would be a 2.1% prevalence with 406 patients acquiring CRE. Using a 102-facility model of Orange County, California, we estimated that over 15 years countywide 19,271 patient acquisitions could be prevented with the coordinated augmented approach compared with independent-facility efforts. Continue reading

No Knee-Jerk Antibiotics Campaign Aims To Reduce Antibiotic Overusage

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, TexasMedicalResearch.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. Continue reading

The Infectious Diseases Society of America Comments on the 21st Century Cures Bill Including Antibiotic Development

Ms. Amanda Jezek Director of Government Relations Infectious Diseases Society Of AmericaMedicalResearch.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 Jezek has been Director of Government Relations at Infectious Diseases Society of America (ISDA) since July 2011. Ms. Jezek is “is responsible for policy development and advocacy on IDSA priority issues including antimicrobial resistance, antimicrobial and diagnositcs development, preparedness and federal funding’.

MedicalResearch: What are the main objectives of the 21st Century Cures bill? 

Ms. Jezek: This question goes far beyond IDSA’s work on the bill, so I would not be comfortable being quoted on this. The Energy and Commerce Committee’s website has more information.  Very generally, the bill seeks to advance the research and development of new cures for patients with a wide variety of diseases and conditions.

MedicalResearch: What health care needs and problems does it address? 

Ms. Jezek: I can only answer from IDSA’s perspective, keeping in mind that many sections of this bill go well beyond the field of ID.  IDSA is very pleased that the bill prioritizes the research and development of some of the most urgently needed new antibiotics to treat serious or life threatening infections with few or no current treatment options.  IDSA is also very pleased that the bill takes important steps to increase funding for NIH, which is urgently needed to ensure adequate investment in biomedical research and support for young people entering or thinking of pursuing research careers.

MedicalResearch: Does the proposed legislation address hospital-based infections, antibiotic resistance, pandemic detection and management, vaccine issues such as mandatory vaccination of school age children, or antibiotics in food sources? 

Ms. Jezek: The bill’s focus is really biomedical research and development and as these issues fall more into the public health sphere, they are not the specific focus of the bill.  However, the provisions aimed at antibiotic R&D also include language aimed at making sure the antibiotics are used appropriately and that their use is monitored, both of which are critical for addressing antibiotic resistance.

MedicalResearch: Does the legislation enable simplified access to clinical medical research trials or expedited review of new pharmaceuticals and medications

Ms. Jezek: I’m only answering from IDSA’s perspective, understanding that we are not involved in every provision in the bill and other provisions may address these issues.  One of the antibiotics provisions, which IDSA has been championing, would allow antibiotics to treat serious or life threatening infections with few or no current treatment options to be studied in smaller, more rapid clinical trials and approved only for the limited population of patients who need them.  This approach is needed because some of the most deadly, difficult to treat infections currently occur in small numbers of critically ill patients who are difficult to enroll in clinical trials, making it very difficult and sometimes impossible to populate traditional, large clinical trials.

MedicalResearch: How will patients benefit from bill?

Ms. Jezek: The bill will help enable the development of new safe and effective antibiotics to treat infections that could otherwise be lethal.  Such antibiotics could literally mean the difference between life or death for patients with these infections.

MedicalResearch: What should health care providers be aware of if the legislation passes?

Ms. Jezek: I think all of the components that IDSA is pursuing—specifically regarding antibiotic development and NIH funding—would be of great interest to providers given their potential impact on new treatment options for patients.

MedicalResearch: Is funding for implementation of the bill included in the legislation?

Ms. Jezek: As I understand it, the Committee is still working on some of this, so I can only provide a partial answer.  For the NIH funding-the bill would authorize new money for NIH for the next 3 years, but the Appropriations Committee in Congress would still need to actually appropriate that money.  However, the NIH Innovation Fund in the bill would provide mandatory funding for NIH for the next 5 years, and this would not have to be approved by the Appropriations Committee.  Some parts of the bill (such as the limited population antibiotic development provision discussed above) are not expected to require additional funding, as it is merely addressing a regulatory barrier.  Lastly, some funding items are still being worked out.

Citation:

(See a two-page Fact Sheet of H.R. 6 HERE. )

 

Ms. Amanda Jezek, Director of Government Relations, & Infectious Diseases Society Of America (2015). The Infectious Diseases Society of America Comments on the 21st Century Cures Bill Including Antibiotic Development 

NEJM Research Discusses Right Antibiotic Strategy For Community-Acquired Pneumonia in Adults

Henri van Werkhoven PhD student | Julius Center for Health Sciences and Primary Care University Medical Center Utrecht, Utrecht, The NetherlandsMedicalResearch.com 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.

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Travelers May Spread Antibiotic Resistance

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 "Photo taken by Leena Mattila/YLE/science"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.

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Health Care Waste in Landfills May Promote Antibiotic Resistance

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, BrazilMedicalResearch.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.

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Cholera Bacteria Kills Neighbors To Acquire Antibiotic Resistance Genes

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 SwitzerlandMedicalResearch.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.

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Antibiotics May Increase Risk of Juvenile Arthritis

MedicalResearch.com 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.
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New Ionic Liquids May Disrupt Pathogenic Biofilms, Enhance Antibiotic Delivery

MedicalResearch.com 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.
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Do Antibiotics Improve Post-Op Course Following Cholecystectomy?

Jean Marc Regimbeau
MedicalResearch.com Interview with :
Pr. Jean-Marc Regimbeau
Service de Chirurgie Digestive Oncologique et Métabolique,
CHU d’Amiens

 

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%.
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Genomic analysis of superbug provides clues to antibiotic resistance

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 at Houston (UTHealth) are published in the Sept. 8 issue of the New England Journal of Medicine.

Superbugs are bacteria that are resistant to multiple antibiotics and represent one of the most challenging health problems of the 21st century. Infections caused by these bacteria can lead to longer illnesses, extended hospital stays and in some instances death. Antibiotic resistance is on the rise and alternative treatments are frequently suboptimal.

Researchers focused on a superbug called vancomycin-resistant enterococci (VRE), which is an intestinal bacterium that is resistant to multiple antibiotics, particularly vancomycin, a drug that has been used for treatment of potentially lethal hospital-associated infections.

“It is the second most common bacterium isolated from patients in U.S. hospitals after staphylococci,” said Cesar Arias, M.D., Ph.D., the study’s lead author and principal investigator. He is an associate professor of medicine at the UTHealth Medical School.

“The problem is that VRE has become so resistant that we don’t have reliable antibiotics to treat it anymore,” Arias said. “Daptomycin is one of the few antibiotics left with activity against VRE and is usually used as a drug of last resort. Additionally, this particular superbug is frequently seen in debilitated patients such as those in critical care units, receiving cancer treatment and patients receiving transplants, among others; therefore the emergence of resistance during therapy is a big issue.”

VRE itself can develop resistance to daptomycin during treatment. To find out why, researchers compared the genomes of bacterial samples drawn from the blood of a patient with VRE bloodstream infection receiving daptomycin. The bacterium developed daptomycin resistance and the patient subsequently died.

By comparing the genetic makeup of the bacterium before and after it developed resistance to daptomycin, the researchers were able to identify changes in genes directly tied to antibiotic resistance. “Our research provides direct substantiation that changes in two bacterial genes are sufficient for the development of daptomycin resistance in VRE during therapy,” Arias said.

Barbara Murray, M.D., coauthor  and director of the Division of Infectious Diseases at the UTHealth Medical School, said, “These results lay the foundation for understanding how bacteria may become resistant to daptomycin, which opens immense possibilities for targeting the functions encoded by these mutated genes. This would be a step toward the development of much needed new drugs.  That is, once we understand the exact mechanism for resistance, one can start to develop strategies that block or attack the resistance mechanism.”

Murray, holder of the J. Ralph Meadows Professorship in Internal Medicine, added, “This study identified genes never before linked to antibiotic resistance in enterococci. The genomic approach used in the study is very powerful and was able to pinpoint exactly the specific genes and mutations within them that resulted in the failure of daptomycin (CUBICIN®) therapy and contributed to the fatal outcome of the patient.”

Arias’ laboratory is doing additional research needed to determine the precise mechanisms by which the gene changes allow the bacterium to defeat the antibiotic. “There are mutations that appear to alter the bacterial cell envelope, which is the target of the antibiotic. The modifications brought about by the gene mutations may change the cell envelope to avoid the killing by these antibiotics. We believe these changes are a general mechanism by which bacteria protect themselves,” Arias said.

Herbert DuPont, M.D., holder of the Mary W. Kelsey Distinguished Professorship in the Medical Sciences and director of the Center for Infectious Diseases at The University of Texas School of Public Health, said,  “Twenty years ago antibiotic-resistant bacteria more often caused hospital-acquired infections in people with underlying illness or advanced age. Now, resistant bacteria are often seen in the community in otherwise healthy people, making treatment very complicated.”

The study titled “Genetic Basis for In Vivo Daptomycin Resistance in Enterococci” received support from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.

Additional UTHealth Medical School researchers in the study include Diana Panesso, Ph.D.;  Lorena Diaz, Truc T. Tran, Pharm. D.; and Jung H. Roh, Ph.D. Coauthors from The University of Texas MD Anderson Cancer Center include Danielle M. McGrath, Ph.D.; E. Magda Barbu, Ph.D.; Renata Pasqualini, Ph.D.; and Wadih Arap, M.D., Ph.D. Others Houston-area contributors include: Xiang Qin, Ph.D., of Baylor College of Medicine; and Corwin Miller and Yousif Shamoo, Ph.D. of Rice University.

Other research contributors include Elizabeth Lobos, Ph.D., Erica Sodergren, Ph.D.  and George Weinstock, Ph.D., all from Washington University in St. Louis;  John P. Quinn, M.D., of the Chicago Infectious Disease Institute; Maria F. Mojica of the Center for Medical Research and Training (CIDEIM) in Cali, Colombia; and Sandra Rincon and Jinnethe Reyes of Universidad El Bosque, Bogota, Colombia.

Arap, DuPont, Murray and Pasqualini are on the faculty of The University of Texas Graduate School of Biomedical Sciences, which is overseen by UTHealth and the UT MD Anderson Cancer Center.

Arias leads the UTHealth Medical School Laboratory for Antimicrobial Research and the Universidad El Bosque, Molecular Genetics and Antimicrobial Resistance Unit in Colombia. Arias’ laboratories have collaborations with several Latin American countries to study specific types of antibiotic-resistant bacteria.

Press Release from University of Texas Health Science Center at Houston