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Antibiotic Resistance 窶・Factsheet!

Background


For this edition of MICKS I have decided to look at an important issue 窶・antibiotic resistance. I have taken a different approach for this edition and decided to write fact sheet, noting key points which are concise in order to provide an overview of this subject which has significant infection control implications.

What are antibiotics?

  • They are antimicrobial agents produced by microorganisms that kill or inhibit other microorganisms. Antibiotics are low molecular-weight molecules produced as secondary metabolites, mainly by microorganisms that live in the soil. Most of these microorganisms form some type of a spore or other dormant cell. Among the molds, the notable antibiotic producers are Penicillium and Cephalosporium , which are the main source of the beta-lactam antibiotics (penicillin and its relatives). With regard to bacteria, the Actinomycetes, notably Streptomyces species, produce a variety of types of antibiotics including the aminoglycosides (e.g. streptomycin), macrolides (e.g. erythromycin), and the tetracyclines. Endospore-forming Bacillus species produce polypeptide antibiotics such as polymyxin and bacitracin.
  • They are used to treat, and sometimes to prevent, infection.
  • They are different from most disinfectants, which also kill bacteria, because they do not harm the person taking them. This is called ‘selective toxicity’
  • When organisms are exposed to an antibiotic various things can happen: they can be killed or; they can be weakened or disabled thus making them easier for the animal's own natural defences to kill or; they can remain unaffected.
  • Antibacterial agents which are of synthetic origin are also used in clinical practice to treat bacterial or viral diseases.


ツWhat is antibiotic resistance?

  • Antibiotic resistance is commonly used to describe the situation when the concentrations of antibiotic needed to kill the bacteria cannot be achieved at the site of the infection.
  • Not all microorganisms are susceptible to all antibiotics. Microorganisms which are not killed or inhibited by an antibiotic are called "antibiotic resistant". They continue to grow and multiply in the presence of that antibiotic. Organisms which are resistant to several antibiotics are called "multiresistant".
  • Therefore, resistance is the ability of a organism to survive in the presence of concentrations of a an antibiotic which are normally lethal to organisms of that species.
  • There are several ways in which bacteria can be resistant. Some destroy the antibiotic, for example by producing enzymes against it; some prevent the antibiotic getting into their cells; others get the antibiotic out of their cells before it can harm them.
  • If a bacteria is resistant to one antibiotic does not mean that it is resistant to all antibiotics. However, some bacteria can be resistant to more than one antibiotic and these are called multi-resistant. It is these bacteria that cause the most concern.


ツHow does antibiotic resistance develop?

  • Bacteria that are resistant to antibiotics have antibiotic resistance genes. Different bacterial genes confer resistance to different antibiotics.
  • Some bacteria are naturally resistant; new resistances also arise spontaneously by chance mutations and these resistant strains then multiply.
  • 窶「 Some resistances can be passed from one bacterium to another, spreading resistance between species. Parts of DNA (called plasmids) carry the resistance genes from one bacterium to another.
  • When an antibiotic is given, it kills the sensitive bacteria, but any resistant ones can survive and multiply a concept known as selective evolution. The more antibiotics are used (in animals and agriculture as well as in man) the greater will be the "selective pressure", therefore favouring resistant strains. This is an example of Charles Darwin's Theory of evolution, operating the "survival of the fittest".
  • Antibiotics don’t ‘cause’ resistance; rather, they create an environment which favours the growth of resistant variants which already exist in nature or arise by chance.


The Basis of Bacterial Resistance to Antibiotics

    1. Inherent (Natural) Resistance : Bacteria may be inherently resistant to an antibiotic. For example, a streptomycete has some gene that is responsible for resistance to its own antibiotic; or a Gram-negative bacterium has an outer membrane that establishes a permeability barrier against the antibiotic; or an organism lacks a transport system for the antibiotic; or it lacks the target or reaction that is hit by the antibiotic.
    2. Acquired Resistance: Bacteria can develop resistance to antibiotics, e.g. bacterial populations previously sensitive to antibiotics become resistant. This type of resistance results from changes in the bacterial genome. Acquired resistance is driven by two genetic processes in bacteria:
      • mutation and selection sometimes referred to as vertical evolution. Vertical evolution is driven by principles of natural selection: a spontaneous mutation in the bacterial chromosome will impart resistance to a bacterium. Consequently, in the selective environment of the antibiotic, the non mutant bacteria are killed and the resistant mutant one is able to grow and flourish in the presence of the antibiotic.
      • exchange of genes between strains and species, sometimes called horizontal evolution. Horizontal evolution is the acquisition of genes for resistance from another organism. More likely to occur is that bacteria which have developed genetic resistance through the process of mutation and selection, are then able to ‘donate’ these resistant genes to other bacteria through one of several processes for genetic exchange that exist in bacteria.
      • Bacteria are able to exchange genes in nature by three processes:
          1. Conjugation which involves cell-to-cell contact and so bacterial DNA crosses a sex pilus, a hairlike structure on the surface of bacteria, from donor bacteria to recipient bacteria.
          2. Transduction, a specific virus which has the ability to transfer the genes between mating bacteria.
          3. Transformation - DNA is acquired directly from the extracellular environment, having been released from another cell. Genetic recombination can then follow, leading to the emergence of a new genotype (recombinant). It is common for DNA to be transferred as plasmids between mating bacteria.


ツHow has antibiotic resistance spread?

  • Once resistance has been established, it can evolve rapidly because bacteria multiply quickly. Resistant variants can swiftly over-run a bacterial population.
  • The resistant bacteria then spread through direct contact with a person or animal with that infection in the same way that other bacteria spread. The combined effects of fast growth rates, high concentrations of cells, genetic processes of mutation and selection, and the ability to exchange genes, all account for the extraordinary rates of adaptation and evolution that can be observed in the bacteria. For these reasons bacterial resistance to the antibiotic environment seems to take place very rapidly in evolutionary time, thus having major clinical effects and implications.
  • Resistance is a particular problem in hospitals, particularly in critical care areas or amongst vulnerable patients e.g. the very young and older people.
  • Antibiotic resistance is more common in some countries than others (usually those where use of antibiotics is less strictly controlled). Increased international travel means that individuals infected with resistant microbes in one country can spread them to another country very quickly.
  • It is thought that the widespread use of antibiotics in animals has led to resistant strains of some bacteria being transmitted to humans through food.


What is the impact of antibiotic resistance?

  • Prolonged hospitalization
  • Increased need of isolation precautions
  • Increased cost
  • This can result in a longer illness and sometimes higher mortality

Preventing and Controlling antibiotic resistance.

  • Antibiotic resistance is to some extent inevitable because we cannot stop using antibiotics. However, we can do a lot to slow down its prevalence and contain its spread. Therefore, all antibiotics should be used carefully and health practitioners should adhere to an Antibiotic Policy.
  • Infection control practices to miminise the transmission of resistant organisms such as: hand hygiene, standard and transmission based precautions, surveillance, environmental disinfection, in some situations screening for resistant organisms.
  • Educating health practitioners and patients to discourage inappropriate prescriptions for antibiotics.
  • Advising patients, if they are prescribed antibiotics, to complete the course.
  • Reducing the use of antibiotics in farm animals, especially where these are used just to enhance their growth.
  • International co-operation is needed to minimise the future emergence and spread of antibiotic resistance.


Jg/2009

University of Wales
Dr. John Gammon
Profile


Dr Gammon is recognised as an international authority on infection prevention and control. Currently, he is a Non -Executive Director of Carmarthenshire NHS Hospital Trust and Deputy Head of the School of Health Science, at Swansea University, Wales, UK. He has practiced as an infection control practitioner for many years and been instrumental in Wales in establishing infection control services. Furthermore he has lead on the establishment infection control courses, and national guidance on hospital and community infection prevention strategies. He has been central to the development of, evidence based, international guidance on patient isolation. His research interests include patient isolation, standard precautions and hand decontamination. He has published a number of research papers and continues to advise the Welsh Government on infection control practice and strategy. He acts as key advisor to a number of commercial companies involved in infection control. His focus of academic interest for the last few years has been the education and professional development of practitioners and specifically infection control practitioners. This has included e-learning course as well as Masters programmes in infection control.