Countering Antibiotic Resistance

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Before the availability of antibiotics, infection was a key cause of illness and treatments were mostly ineffective, leading to a high mortality rate from this cause.

The first breakthrough in the medical treatment of infection came when Alexander Fleming discovered penicillin, the first antibiotic, in 1928. This was followed by the development of a host of widely diverse chemical molecules with antibiotic activity, and these have been used extensively to bring infections under control.

Today, the treatment of infection relies heavily on antibiotic use. However, there are rising concerns as more and more strains of bacteria develop resistance to even the most powerful of antibiotics.

A rapid change in antibiotic prescribing practice and usage, along with the development of novel antibacterial treatment strategies are required to reverse this worrying trend.

The Value of Antibiotics

The human body has a highly effective immune system that detects harmful invading bacteria and destroys them before they can multiply and cause symptoms. Left unchecked, bacteria can develop vast colonies and cause serious damage throughout the body. Even when symptoms occur, the immune system will usually fight off the infection and the body will recover from the attack.

However, in some cases the extent of the bacterial infection can overwhelm the immune system, and this is where antibiotics play a crucial role. They help in weakening or killing the invading bacteria, reducing the harm they can inflict on the body.

Some cases in which antibiotic use is vital include a state of immunocompromise, or when there is increased susceptibility to infection, such as in the presence of severe burns or serious wounds.

During invasive medical procedures when there is a high risk of infection, antibiotics are given prophylactically to help reduce the chances of infectious complications.

The most common source of infection associated with healthcare1, as well as the costliest, is surgical site infection, which could result in extremely dangerous complications following surgery. This is particularly the case when medical devices are implanted, since these could enhance the chances of biofilm development, which jeopardizes the outcome of the procedure2.

Available reports in scientific literature show that if the use of prophylactic antibiotics that are routinely used before orthopedic procedures were to become just 30% less effective, this could lead to an increase in infections by 120,000 per year, and result in 6,300 more deaths as a result of infection every year, in the US alone3.

Antibiotics are therefore essential for the success of modern medicine, which involves more and more extensive interventions. Without antibiotics even simple wounds and infections could become life-threatening and cancer chemotherapy, organ transplantations and common surgeries, like cesarean section, would be hazardous.

Antibiotic Resistance – A Growing Threat

Unfortunately, such a worrying scenario is not just a distant worry. Growing evidence indicates that the heavy dependence on, and widespread misuse of antibiotics is reducing their efficacy. This is mainly a result of the development of antibiotic resistance, which occurs when bacteria evolve to protect themselves from the effects of an antibiotic.

New resistance mechanisms are developing all the time, threatening our ability to treat common infectious diseases, such as pneumonia, septicemia, tuberculosis and gonorrhea4.

When infections are caused in humans or in animals by bacteria that are resistant to antibiotics, they are difficult to treat and lead to higher costs of medical care, the duration of hospitalization and the mortality rates.

Across all parts of the world, the antibiotic resistance levels have reached alarming heights. The World Health Organization (WHO) recently published its report on antimicrobial resistance, showing that common organisms such as E. coli, K. pneumoniae and S. aureus, were now resistant to common antibiotics in over 50% of cases, and concluded that in the 21st century it is quite likely that people may die of a minor injury5.

Another recent study on the effectiveness of using antibiotics for prophylaxis revealed that almost 50% of post-operative infections and more than 25% of post-chemotherapy infections were due to bacteria that were not susceptible to the prophylactic antibiotics routinely administered in the USA3.

Additionally, there is increasing concern that antibiotic resistance will reverse the significant progress made towards eliminating tuberculosis (TB). One in five cases of the disease are now resistant to at least one major anti-TB drug6. Mortality rates amongst patients with drug-resistant TB is as high as 60%.

Antibiotic resistance is putting the achievements of modern medicine at risk and increasing health care costs. Approximately two million people are infected by antibiotic-resistant bacteria annually, and it is estimated that, unless immediate action is taken, by 2050 ten million people will die per year from bacterial infections7.

Fighting the Threat

The main reasons for the acceleration of antibiotic resistance are antibiotic misuse and overuse, as well as improper control and prevention of infection. Both healthcare professionals and the general population need to develop a sense of urgency in limiting the emergence of further strains of antibiotic-resistant bacteria8.

Healthcare professionals must reserve the use of antibiotics strictly for situations that truly necessitate them, and patients must ensure they use antibiotics as prescribed and finish the entire course of treatment.

Additionally, behavioral changes to minimize the spread of infection and the need for antibiotics must be adopted. These include vaccination, good hand hygiene and food handling practices. Without such changes globally, antibiotic resistance will threaten, and potentially reverse, medical progress.

As well as limiting the development of antibiotic resistance, there is continuing research being carried out to identify novel antibacterial strategies to limit dependence on available antibiotics and reduce our vulnerability to the effects of increasing antibiotic resistance.

Research on Antibacterial Therapy

Now that bacteria are becoming resistant to the most powerful therapies, synthetic antibiotics are becoming an area of great interest. A host of scientific researchers are now focusing on the development of new ways to fight microbial infection.

Synthetic versions of biological compounds with antibacterial action, such as antimicrobial peptides, and pyridines, that can be easily mass produced are under investigation9,10. Additionally, novel strategies using a range of other compounds that have been shown to have antibacterial activity, including silver and zinc nanoparticles, are being explored11,12.

This work is being supported by the development of new tools that help speed up the development and testing of new antimicrobial compounds under a varied set of conditions to help determine their effectiveness and validity.

Among these, microplate readers are in the forefront, as they are important tools for research on the development and prevalence of antibiotic resistance, as well as in the assessment of novel antibacterial compounds.

Microplate Readers – Essential for Antibacterial Research

Microplate readers allow conventional light-based assays to be conducted in 96-well (or higher) format. As a result, operational time is minimized and costs are reduced. The most abundant task for microplate readers in studying antibiotics is the monitoring of growth by measuring optical density at 600 nm.

Rather than drawing samples every 30 minutes and measuring each condition individually, the microplate experiment automatically acquires data of 96 samples at each chosen interval.

Once started, manual intervention is not required. Though being the most popular application, multi-mode microplate readers by BMG LABTECH read a huge variety of assays, based on fluorescence, luminescence, fluorescence polarization, time-resolved fluorescence and FRET, absorbance and AlphaScreen®. The high versatility provides the solution to address each question arising in antibiotic resistance research.

For example, a recent study by Salem et al.11-12 featured a microplate reader from BMG Labtech; the study explored the effects of silver and zinc oxide nanoparticles and their potential for combatting E. coli and cholera. The SPECTROstarNano microplate reader was used in the study to assess the quantity of silver and zinc oxide nanoparticles as they were produced.

Cell growth was tracked during exposure to differing levels of each nanoparticle. Absorbance spectra were used to characterize the nanoparticles and subsequently the SPECTROstarNano measured the antibacterial activity of nanoparticles in a biofilm assay.

The investigation showed that silver and zinc oxide nanoparticles can be used to tackle bacterial biofilm formation and is an attractive method to help treat drinking water before it is consumed11-12.

Another study employed the multiplexing capabilities of the CLARIOstar multi-mode reader to study translation influenced by a regulatory RNA and normalized it to bacterial growth. A fluorescent beta-galactosidase assay was used to measure gene expression, growth by absorbance at 600 nm13.

BMG LABTECH is proud to provide devices specifically meeting the requirements of antibiotics resistance research and thus helping to combat the emerging threat.

References

  1. Perencevich EN, et al. Health and economic impact of surgical site infections diagnosed after hospital discharge. Emerg Infect Dis. 2003;9:196–203.
  2. Sherry L, et al. Biofilms formed by Candida albicans bloodstream isolates display phenotypic and transcriptional heterogeneity that are associated with resistance and pathogenicity. BMC Microbiology2014;14:182.
  3. Teillant A, et al. Potential burden of antibiotic resistance on surgery and cancer chemotherapy antibiotic prophylaxis in the USA: a literature review and modelling study. Lancet Infect Dis. 2015; 15(12):1429-37.
  4. Tadros M, et al. Epidemiology and outcome of pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) in Canadian hospitals. PLoS One 2013;8:e75171.
  5. World Health Organisation. Antimicrobial Resistance Global Report on Surveillance 2014.
  6. Dheda K, et al. The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis. The Lancet Respiratory Medicine Commission 2017;5(4):291‑360.
  7. de Kraker MEA, et al. Will 10 Million People Die a Year due to Antimicrobial Resistance by 2050? PLoS Med 2016;13(11):e1002184.
  8. WHO Antibiotic Resistance Fact Sheet 2018. Available at http://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance
  9. Azmi F, et al. Towards the Development of Synthetic Antibiotics: Designs Inspired by Natural Antimicrobial Peptides. Current Medicinal Chemistry 2016;23(41): 4610‑4624.
  10. Saloman L. New Synthetic Antibiotics May Combat MRSA and Other Superbugs. Contagion Live March 29, 2018.
  11. Salem W, et al. Antibacterial activity of silver and zinc nanoparticles against Vibrio cholerae and enterotoxic Escherichia coli. Int. J Med Microbiol. 2015;305(1):85‑95
  12. Salem W, Schild S. Detection of plant-synthesized nanoparticles and their antibacterial capacity. BMG LabTech Application note 303. Available at https://www.bmglabtech.com/detection-of-plant-synthesized-nanoparticles-and-their-antibacterial-capacity
  13. Rochat T, et al. The conserved regulatory RNA RsaE down-regulates the arginine degradation pathway in Staphylococcus aureus. Nucleic Acids Res. 2018 Sep 28;46(17):8803-8816. doi: 10.1093/nar/gky584.

About BMG Labtech

BMG LABTECH has been committed to producing microplate readers for more than twenty years. By focusing on the needs of the scientific community, the company’s innovative microplate readers have earned the company the reputation of being a technology leader in the field.

BMG LABTECH has developed a wide range of dedicated and multi-mode microplate readers for life sciences applications and high-throughput screening.

All BMG LABTECH microplate readers are "Made in Germany" and are conceived, developed, assembled, and tested entirely at our headquarters in Germany.

Since our establishment in Offenburg, Germany in 1989, BMG LABTECH has expanded to offer a worldwide sales and support network with offices in the USA, UK, Australia, Japan and France. Our subsidiaries, regional offices and distributors are committed to bringing you innovative microplate reader technology with the quality and reliability you expect from a German company.

Our staff includes engineers and scientists from the fields of biology, biochemistry, analytical chemistry, and physics.


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Last updated: Mar 28, 2019 at 5:29 AM

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