Antibiotic Resistance Common In Infections After Ocular Surgery

MedicalResearch.com Interview with:

Dr-Penny Asbell

Dr. Asbell

Penny Asbell, MD
Icahn School of Medicine
Mt. Sinai, New York City.

MedicalResearch.com: What is the background for this study?

─     Bacterial endophthalmitis is a serious, although infrequent, complication of ocular surgery, typically caused by perioperative introduction of bacterial flora from the patient’s own conjunctiva and skin.

─     Prophylactic measures such as perioperative antibiotic treatment may minimize the risk for endophthalmitis, but can be complicated by antibiotic resistant bacteria.

─     The ongoing Antibiotic Resistance Monitoring in Ocular micRoorganisms (ARMOR) study is the only nationwide antibiotic resistance surveillance program specific to ocular pathogens.

─     The purpose of this presentation is to report on the antibiotic susceptibility profiles of bacterial isolates from the vitreous and aqueous humor collected in the ARMOR study expanding upon earlier findings.

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Antibiotic-Resistant Organisms Affect Majority of Long-Term Care Patients

MedicalResearch.com Interview with:
Susan S. Huang, MD
Professor, Infectious Disease
School of Medicine
Medical Director, Epidemiology and Infection Prevention
UCI

MedicalResearch.com: What is the background for this study? What are the main findings?

Response:  The SHIELD Orange County Project is a CDC-initiated public health collaborative among nursing homes, long-term acute care (LTAC) facilities, and hospitals in the 6th largest U.S. County (Orange County, California). The 38 facilities (18 nursing homes, 3 LTACs, 17 hospitals) received targeted invitations based upon their high degree of shared patients with one another. The goal of the collaborative is to reduce multi-drug resistant organisms throughout the county using a decolonization strategy.

As part of the baseline assessment, we swabbed 50 adult patients in each facility to assess the frequency that patients had multi-drug resistant organisms (MDRO) on their body. Nursing home and LTAC patients were sampled from the entire population while hospital sampling involved only adults in contact precautions. We found that an alarmingly high percent of patients had an MDRO, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), extended-spectrum beta-lactamase producers (ESBLs), and carbapenem-resistant enterobacteriaceae (CRE).

  • For nursing homes, 64% of residents have an antibiotic resistant bacteria on their body. Almost all of these are not known to the nursing home.
  • For LTACs, 80% of patients have an antibiotic resistant bacteria on their body. 7 in 10 patients have an MDRO that is not known to the LTAC.
  • For hospitalized patients on contact precautions, 64% have an antibiotic-resistant bacteria on their body. One third have an antibiotic-resistant bacteria that is not known to the hospital.
  • Having one MDRO is highly associated with having another one/

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MRSA Contamination of Home and Pets May Contribute To Reinfection and Resistance

MedicalResearch.com Interview with:

Mr-Jonathan-Shahbazian

Mr. Shahbazian

Mr. Jonathan Shahbazian, MPH
Johns Hopkins Bloomberg School of Public Health
Baltimore

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Our study was designed to investigate risk factors for drug resistance in MRSA found in dust on surfaces in the home. We undertook this investigation because we were concerned first that people living in the home could pick up MRSA from these surfaces, and second, that if they picked up drug-resistant MRSA, it would be more difficult to treat them.

Our main finding was that use of antibiotics by either people or pets in the home, as well as use of biocidal cleaning products, was associated with multidrug resistance (MDR) in home MRSA. This study is the first to report that use clindamycin in either humans or domestic animals was not associated with risk of MDR in the home environment.

We also found that mupirocin treatment was associated with a slight increase in mupirocin resistance in the household environment, which could complicate decolonization efforts that rely on use of nasal mupirocin ointment. We found that 100% of our MRSA isolates from rural homes were MDR, suggesting living in a rural household may be a risk factor. We also found the presence of domestic pets was associated with MDR MRSA in the home environment while the presence of unwanted pests, such as mice or cockroaches, was associated with non-MDR MRSA strains at the three-month visit.

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New Test for TB Can Detect Antibiotic Resistant Strains

MedicalResearch.com Interview with:

Susan E. Dorman, M.D Associate Professor of Medicine, Division of Infectious Diseases Johns Hopkins University School of Medicine, Baltimore

Dr. Dorman

Susan E. Dorman, M.D
Associate Professor of Medicine, Division of Infectious Diseases
Johns Hopkins University School of Medicine, Baltimore

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Tuberculosis, also called “TB” is one of the top 10 causes of death worldwide, according to the World Health Organization.  TB is caused by bacteria called Mycobacterium tuberculosis.  In 2015, over 10 million people became sick from TB and 1.8 million people died from TB.  This is a lot of people – diagnosing and treating TB to improve their health is important.  Because TB usually involves the lungs, it can be passed from person to person through the air, and thus, diagnosing and treating TB is critical to  reduce the spread of TB.   Drug-resistant TB — TB caused by bacteria that are resistant to commonly used TB antibiotics — is a serious problem.  In 2015 an estimated 480,000 people had multidrug-resistant TB.

We have been working to develop better, faster ways to diagnose TB and drug-resistant TB.  A new test was developed as a partnership between Rutgers University and Cepheid (Sunnyvale, CA), and development was supported by the US National Institutes of Health (NIH).  The new test was designed to detect Mycobacterium tuberculosis bacteria in sputum, and to simultaneously detect whether the bacteria are resistant to several of the main antibiotics (isoniazid, fluoroquinolones, and aminoglycosides) used to treat TB.  The test takes about two hours from sample to result.

The NEJM article describes the results of a study that was undertaken in China and South Korea to understand how well the new test works, compared against gold standard tests.

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New Drug May Protect Gut From Antibiotic-Resistance Genes

MedicalResearch.com Interview with:

Synthetic Biologics, Inc.

Synthetic Biologics, Inc.

Sheila Connelly, PhD
Vice President, Research
Synthetic Biologics, Inc.

MedicalResearch.com: What is the background for this study?

Response: Synthetic Biologics, Inc. is focused on the protection and preservation of the gut microbiome which is the diverse collection of microorganisms that live in the intestinal tract. We are learning that the gut microbiome plays a key role in health. Negative changes to the microbiome, called dysbiosis, are linked to disease states including allergies, autism, and obesity, among a rapidly growing list of other conditions. A consequence of using antibiotics is that, in addition to fighting the bacterial infection being treated, they also kill the gut microbiota. The space left in the gut by the dead bacteria allows other surviving bacteria, many times opportunistic pathogens or microbes that are resistant to multiple antibiotics, to overgrow and fill the open niches. Exposure to antibiotics, particularly broad-spectrum antimicrobials, such as penicillins and cephalosporins, is a major risk factor for acquiring a potentially deadly Clostridium difficile infection.

Dr-Sheila-Connelly.jpg

Dr. Sheila Connelly

Another consequence of antibiotic use is the emergence of antibiotic-resistant organisms. Widespread use of antibiotics provides selective pressure for the evolution of lethal, multi-drug resistant pathogens, termed “nightmare bacteria”. The gut microbiome acts as a reservoir of antibiotic resistance that can be triggered, by antibiotic exposure, to acquire and propagate resistance genes.

A way to protect the microbiome and reduce antibiotic resistance is to limit exposure of the gut microbiota to antibiotics. To this end, we developed an antibiotic inactivation strategy using a beta-lactamase enzyme to degrade beta-lactam antibiotics in the GI tract before they can harm the gut microbiome. Beta-lactamases are naturally-occurring bacterial enzymes that confer resistance to beta-lactams, the most widely used broad spectrum antibiotics, and their presence is normally considered an obstacle to efficacious infection control. We took advantage of the highly efficient antibiotic degradation activity of a beta-lactamase and developed SYN-004 (ribaxamase). Ribaxamase is a beta-lactamase engineered to inactivate penicillins and most cephalosporins, formulated for oral delivery, and intended for use with IV beta-lactam antibiotics to degrade the antibiotics in the GI tract to protect the microbiome.

Ribaxamase was demonstrated to significantly reduce the occurrence of C. difficile disease in a recently completed Phase 2b clinical study. The study met its primary endpoint by demonstrating that ribaxamase, when delivered orally with IV ceftriaxone, significantly reduced C. difficile disease in patients treated for a respiratory tract infection. Ribaxamase also resulted in a significant reduction in new colonization by vancomycin-resistant enterococcus (VRE).

For the current study, pig models of antibiotic-mediated gut dysbiosis were established using three classes of beta-lactam antibiotics, a cephalosporin, ceftriaxone, a penicillin, amoxicillin, and a carbapenem, ertapenem. The ceftriaxone model was used to evaluate the protective effect of ribaxamase on the microbiome and the amoxicillin and ertapenem models are intended for evaluation of pipeline products.

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Cures of Multidrug Resistant Tuberculosis Probably Underestimated Under Current WHO Guidelines

MedicalResearch.com Interview with:
Dr. Heinke Kunst, M.D.
Queen Mary University Hospital, London, United Kingdom

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Multidrug resistant tuberculosis (MDR-TB) has been on the increase worldwide over the past decade. Many patients who have been identified with MDR-TB live in the European region. Despite treatment with expensive second-line drug regimens, curing MDR TB remains a challenge and cure rates were thought to be very low. As part of the EU Commission funded TB-PANNET project 380 patients with MDR-TB were observed at 23 TB centers in countries of high, intermediate and low TB burden in Europe over a period of 5 years. Observation started from the time of diagnosis and lasted until one year after the end of the treatment.

The TBNET proposed new definitions for “cure” and “failure” of MDR-TB treatment based on the sputum culture status at 6 month after the initiation of therapy and whether patients were free from disease recurrence one year after the end of therapy. The researchers found that the WHO criterion for “cure” could not be applied in the majority of patients, simply because most patients who were being treated successfully were not able to produce sputum after 8 months of therapy. The TB-PANNET study showed much higher cure rates using a new definition of cure and failure of treatment for MDR TB in the European region. (61% cure rates compared to only 31% when using WHO criteria.)

The study also demonstrates that the results for “cure” from MDR-TB correlate very well with the level of drug resistance and the time to culture conversion that means the time when TB bacilli are no longer detectable in sputum. The new definitions are also independent of the total duration of treatment and can be applied to the standard 20 months MDR-TB regimen as well as to the 9-12 months shorter course MDR-TB treatment that was recently proposed by the WHO.

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Newly Discovered Phages Can Target Antibiotic Resistance

MedicalResearch.com Interview with:

Paul E. Turner Chair of Ecology and Evolutionary Biology, Yale University Microbiology Faculty, Yale School of Medicine New Haven, CT 06520

Dr. Paul Turner

Paul E. Turner Ph.D
Chair of Ecology and Evolutionary Biology,
Yale University
Microbiology Faculty,
Yale School of Medicine
New Haven, CT 06520

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Turner:  Our study concerned the problem of multi-drug resistance in the opportunistic pathogen Pseudomonas aeruginosa, especially the search for promising bacteriophage candidates with biological properties to effectively target these bacteria. We tested whether the binding of phage to outer membrane proteins of multidrug efflux pumps would exert selection for bacteria to avoid virus attack by compromising pump performance – thus suffering increased sensitivity to traditional antibiotics. We discovered a naturally occurring phage that forced the desired evolutionary trade-off; we showed that clinical isolates of P. aeruginosa gained phage resistance, while simultaneously becoming susceptible to several antibiotics that are ordinarily useless in controlling these MDR pathogens.

MedicalResearch.com: What should readers take away from your report?

Dr. Turner: Newly discovered phages can be highly effective at targeting antibiotic resistance mechanisms in MDR bacteria, causing these pathogens to become antibiotic sensitive. Medical use of such resistance targeting phages could greatly improve clinical outcomes by reversing antibiotic resistance in MDR bacterial pathogens.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Dr. Turner: We recommend utilizing a ‘rational drug design’ approach to combating antibiotic resistance, especially use of phages to target efflux pump systems in MDR bacteria. This approach could greatly reduce the burden to rely on drugs of last resort and would extend the lifetime of our current antibiotic library.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Benjamin K. Chan, Mark Sistrom, John E. Wertz, Kaitlyn E. Kortright, Deepak Narayan, Paul E. Turner. Phage selection restores antibiotic sensitivity in MDR Pseudomonas aeruginosa. Scientific Reports, 2016; 6: 26717 DOI:10.1038/srep26717

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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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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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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Antibiotic Resistant Bacteria Increase in South East US Community Hospitals

MedicalResearch.com Interview with:
Dr Joshua Thaden MD, PhD
Duke University Division of Infectious Diseases
Durham, North Carolina

Medical Research: What are the main findings of the study?

Dr. Thaden: The primary findings of the study are that

  • The rate of detection of particularly antibiotic resistant bacteria — the carbapenem-resistant Enterobacteriaceae (CRE) — has increased 5-fold in a set of community hospitals in the southeastern United States, and that
  • This increase is due to both changes in how we detect CRE and in increased endemicity (i.e., there are just more CRE around).

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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