The number of deaths caused by resistant bacteria is expected to reach 10 million by 2025, according to the Centers of Disease Control and Prevention. A highly resistant bacteria found in hospitals – Klebsiella pneumoniae – is now a big global threat, according to a recent (April, 2019) study published by researchers from University College London. Researchers have issued a warning that more stringent cleaning of infectious wards and new air disinfection protocols are key to battling the bug. This is because this bacteria possesses the ability to change genetically at an alarming rate, adapting and essentially nullifying the effect of all current antibiotics.
MedicalResearch.com Interview with:
Lona Mody, MBBS, MSc
Associate Division Chief, Clinical and Translational Research
Associate Director, Clinical Programs, VA GRECC
Associate Professor, Internal Medicine
Research Associate Professor, Institute of Gerontology
University of Michigan Geriatrics Ann Arbor, MI
Medical Research: What is the background for this study? What are the main findings?
Response: Over 1.5 million residents live in 15,600 Nursing Homes in the US. The acuity of illness in this population has increased substantially in the last decade, as has the risk of acquiring new infections. Multi-drug resistant organisms, also known as MDROs, are endemic in this setting with prevalence estimates upwards of 35% and surpassing those in the hospitals. Nursing homes historically have had few infection prevention resources, which contributes to these high rates. Patients with indwelling devices such as urinary catheters and feeding tubes present an attractive habitat for these ‘superbugs’ and thus carry the added burden of device-related infections.
The authors examined the effect of a targeted infection program, or TIP, to reduce the prevalence of Multi-drug resistant organisms and new catheter or feeding tube infections among patients with indwelling devices. The TIP intervention was three-fold:
- Surveillance for infections and Multi-drug resistant organism colonization with regular feedback to facilities;
- Extensive and interactive staff education using adult learning theory about key infection prevention practices and hand hygiene; and
- Use of gowns and gown when providing assistance to patients for high-risk activities such as bathing and grooming.
Staff education emphasized precautionary measures against the spread of infection and included mock game shows, songs and dances. Hands were cultured for bacteria before and after hand washing. Outcomes were measured by results of the cultures taken for each patient and monitoring infection rates.
A team of researchers from the University of Michigan and the Veterans Affairs Ann Arbor Health System has demonstrated that simple measures might be all it takes to push back at the spread of Multi-drug resistant organisms or ‘superbugs’ in nursing homes as well as reduce infections. In their study of patients with indwelling devices, MDROs were reduced by 23 percent among 418 residents in six southeast Michigan nursing homes who participated over the course of the three-year study. The numbers of catheter-associated urinary tract infections and MRSA acquisitions also decreased, 46 percent and 22 percent respectively.
The trial examined the relationship between acquisition of antimicrobial resistance among nursing home and assisted living facility residents with the use of devices by adapting new methodological approaches and study designs to study infection prevention interventions including the use of cluster-randomized study design for infection prevention interventions, adopting adult learning practices to engage frontline healthcare personnel and using multi-anatomic site sampling to demonstrate effectiveness of the program.
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