Combating drug-resistant superbugs

Antibiotic resistance

Antibiotics have been used for the last 80 years to treat patients with bacterial infections. While antibiotics have greatly reduced illness and death resulting from these infections, their use has been so prevalent that microbes have adapted to them, eliminating their effectiveness. These microbes are named antibiotic-resistant superbugs. Superbugs can acquire resistance genes either by a transfer of DNA from a bacterium that is already resistant or through a genetic mutation that helps the bacteria survive. Genetic mutations can enable bacteria to produce antibiotic-inactivating enzymes like carbapenemase, or to express efflux systems that remove the drug from the cells. Mutations can also modify the drug’s target site or activate an alternative metabolic pathway.

In recent years, there has been an alarming increase in infections and mortality due to antibiotic-resistant pathogens. In particular, hospital-acquired infections (HAIs) are a major challenge to patient welfare. HAIs are most commonly associated with invasive medical devices or surgical procedures. Typically, patients that are the most susceptible are exposed at a greater rate to these superbugs. The CDC reports that each year in the United States, at least 2 million people are infected with antibiotic-resistant bacteria, and at least 23,000 people die each year as a direct result of these infections. The pathogens that cause the majority of U.S. HAIs include Enterococcus faecium, Staphylococcus aureus, Klebsiella sp., Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter sp., also known as the “ESKAPE” pathogens. A major concern is the rise of gram-negative bacteria developing resistance to the carbapenem antibiotics, particularly the carbapenem-resistant enterobacteriaceae (CRE). Antibiotic-resistant enterobacteriaceae infections can lead to opportunistic infections such as pneumonia. CRE are resistant to almost all available antibiotics, except colistin, which is a last resort drug used to treat patients with multi-drug resistant infections.

In March of 2015, President Obama released the National Action Plan for Combating Antibiotic Resistant Bacteria. This plan outlined critical actions to be taken by key federal agencies to combat the rise of antibiotic-resistant bacteria. A year and a few months later, a report of a superbug resistant to colistin has emerged.

As part of a surveillance program, researchers at the Walter Reed Army Institute of Research and the Walter Reed National Military Medical Center began testing drug-resistant Escherichia coli bacteria isolated from U.S. patients treated at various institutions. During their testing last month, they identified the first instance of mcr-1-mediated colistin resistance in bacteria in the U.S. (1). The sample was collected from a woman treated for a urinary tract infection in late April at an outpatient military medical center. The discovery has elicited concern because emerging resistance to colistin is a serious hazard to patient health. Bacteria have exhibited colistin resistance in the past; however, the resistance genes were located on DNA that could not be easily shared among bacteria. Unfortunately, that is no longer the case.

In a study published last year, researchers determined that mcr-1 was circulating among animals and people in China and was located on a plasmid, an independent, circular, self-replicating DNA molecule that carries only a few genes (2). This is alarming because plasmids are capable of easily moving between bacterial species. Researchers in Denmark and France have also confirmed the presence of the mcr-1 gene in stored samples of bacteria obtained from patients and poultry meat (3, 4).

Now, thanks to the McGann et al.’s finding, we know that the mcr-1 gene is in the United States. The woman in whom the mcr-1 gene was detected has since recovered because she was given other antibiotics to clear the infection. But what if the mcr-1 gene is picked up by other multi-drug resistant bacteria such as CRE? We would then be dealing with a pan-drug-resistant bacteria. The potential for such bacteria demonstrates the severity of the rise of antibiotic-resistant bacteria and the need for better surveillance in both animals and people.

 

Are you currently testing or planning to test for antibiotic resistance genes in your research samples? QIAGEN offers a convenient way for you to detect the presence of antibiotic resistance genes that may be in isolated bacterial colonies, bacteria from blood culture, metagenomic samples and other sample types. Find out how other researchers have used the Antibiotic Resistance Genes Microbial DNA qPCR Array to test their samples for antibiotic resistance genes.

Vandini, A. et al. (2014) Hard surface biocontrol in hospitals using microbial-based cleaning products. PLoS One. 9, 9. (link)

This study determined the efficacy of a probiotic-based cleaning procedure by assessing the presence and survival of a number of bacteria (Staphylococcus aureus, coliform bacteria, Clostridium difficile and Candida albicans) responsible for HAIs on hard surfaces in a hospital setting. The study was conducted in three different hospitals with nearly 20,000 microbial surface samples collected. The researchers used the Antibiotic Resistance Genes Microbial DNA qPCR Array to analyze bacillus strains used in the cleaning products and on different isolates from the various hospital settings included in the study. The main finding was that the probiotic-based cleaning procedure is more effective in lowering the number of HAI-related microorganisms on surfaces, when compared to conventional cleaning products.

Caselli, E. et al. (2016) Impact of a probiotic-based cleaning intervention on the microbiota ecosystem of the hospital surfaces: focus on the resistome remodulation. PLoS One. 11, 2. (link)

As a follow-up to the Vandini et al. (2014) study, this study assessed the impact of the bacillus-based cleaner on the drug-resistance features of the healthcare pathogens population. Whether cleanser-derived bacilii were able to infect hospitalized patients was also investigated. The Antibiotic Resistance Genes Microbial DNA qPCR Array was used to identify antibiotic resistance genes on all collected environmental samples, on the bacillus strains originally present in the cleaning products and on the bacillus isolates collected from the hospital surfaces. The results of the study suggest that the probiotic-based cleaning procedure is active in controlling surface microbial contamination as well as lowering drug-resistant species. The cleaning intervention may have relevant cleaning and therapeutic implications for the management of HAIs.

Han, X-M. et al. (2015) Impacts of reclaimed water irrigation on soil antibiotic resistome in urban parks of Victoria, Australia. Environmental Pollution. 211. (link)

Runoff from wastewater treatment plants contains a significant amount of antibiotics and bacteria with antibiotic resistance genes. The aim of this study was to determine the impact of reclaimed water irrigation on the patterns of antibiotic resistance genes and the soil bacteria community. The researchers used the Antibiotic Resistance Genes Microbial DNA qPCR Array to identify antibiotic resistance genes in 12 urban parks with and without reclaimed water irrigation. The main findings of this study suggested that irrigation of urban parks with reclaimed water could have an effect on the abundance, diversity and composition of a wide variety of soil antibiotic resistance genes of clinical relevance.

Agga, G.E. et al. (2015) Antimicrobial-resistant bacterial populations and antimicrobial resistance genes obtained from environments impacted by livestock and municipal waste. PLoS One. 10, 7. (link)

The objective of this study was to compare antimicrobial-resistant bacteria and antimicrobial resistance genes from environments associated with municipal sewage treatment plant runoff, cattle feedlot runoff ponds, swine waste lagoons and environments with minimal direct fecal impact such as an urban lake. Liquid and solid samples were collected from each environment and tested for the presence of antimicrobial-resistant gram-negative (Escherichia coli and Salmonella enterica) and gram-positive (enterococci) bacteria. The samples were also tested for antibiotic resistance genes using the Antibiotic Resistance Genes Microbial DNA qPCR Array. This study concluded that antimicrobial-resistant bacteria and antimicrobial resistance genes exist in cattle, human and swine waste streams, but a higher diversity of antimicrobial resistance genes are present in treated human waste discharged from municipal wastewater treatment plants than in livestock environments.

 

Do you want to learn more about antibiotic resistance genes and hospital-acquired pathogens? Attend our new webinar on August 15, 1:00 – 2:00 pm EDT. Register now!

 

References

  1. 1. McGann, P. et al. (2016) Escherichia coli Harboring mcr-1 and blaCTX-M on a Novel IncF Plasmid: First report of mcr-1 in the USA. Antimicrob. Agents Chemother. 60, 6. Link
  2. 2. Liu, Y-Y. et al. (2015) Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infec Dis. 16, 2. Link
  3. 3. Hasman, H. et al. (2015) Detection of mcr-1 encoding plasmid-mediated colistin-resistant Escherichia coli isolates from human bloodstream infection and imported chicken meat, Denmark 2015. Euro Surveill. 20, 49. Link
  4. 4. Perrin-Guyomard, A, et al. (2016) Prevalence of mcr-1 in commensal Escherichia coli from French livestock, 2007 to 2014. Euro Surveill. 21, 6. Link
Miranda Hanson-Baseler

Dr. Miranda Hanson-Baseler is a Senior Global Market Manager in Demand Generation. She joined QIAGEN in early 2015 as a technical and marketing writer for life sciences. Miranda received her Ph.D. in Immunology and Microbial Pathogenesis from West Virginia University in 2009. Prior to entering the biotech industry, she worked as a post-doctoral fellow in the Cancer and Inflammation Program at the National Cancer Institute, where she studied the immune mechanisms of a localized therapeutic for inflammatory bowel disease.

Jihad Eltaher

Actually it’s not a comment it’s question: Why is some times there are some persons show high resistance to the antibiotics while others are susceptible for the same one or with low resistance, in another words: is there any researches or studies revealed that some genes in some persons responsible to growing resistance or it’s an issue regarding to the drug only

Reply
Christine Davis

Hi Jihad,

Thanks for commenting! The antibiotic resistance is within the bacteria itself, not the person. What makes an individual susceptible to developing an antibiotic-resistant bacteria is the state of their immune system. For example, an individual on chemotherapy who is immune-compromised has a higher chance of developing antibiotic-resistant bacteria. Plus, these individuals are more likely to be in a hospital setting which is filled with such bacteria, where chances of contracting such infections are higher.

If you want to learn more, we have a webinar today on antibiotic resistance genes and hospital-acquired infections. We will have a Q&A session at the end of the presentation to address any questions you might have as well. You can register here: Profiling Hospital-Acquired Pathogens and Antibiotic Resistance Genes.

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