Astonishing facts
about the resistance of bacteria to antibiotics.

1) Resistance is an old phenomenon

It is a natural phenomenon that has been around since the birth of antibiotics. All bacteria is capable of synthesising enzymes it can direct against agents trying to destroy it.

2) Resistance mechanisms

Bacteria are made up of chromosomes and plasmids: Plasmids are DNA that forms a crown shape around the cell. This DNA does not form part of the chromosomal constitution of the cell but stands ready to be diffused.
Bacteria gains resistance either chromosomally through the cell or extra-chromosomally using the plasmid as a support.
- Chromosomally:This is through a mutation of the genome, the aim being to give it a different status. This slow and rare phenomenon is sporadic and can only be detected by taking an antibiotic (AB).
It occurs in a hereditary, vertical mode, completely altering the structure of the bacteria.
- Extra-chromosomally: This is linked essentially to plasmid activity.
Bacterial resistance is linked to the synthesis and release of proteins intended to contaminate surrounding bacteria.
This resistance does not show up when ABs are taken; this is a de facto propagation, based on a mass effect and occurs on a horizontal mode.

3) The biochemistry of resistance

- A reduction in the membrane permeability of bacteria: change in structure.
- A change in the antibiotics' target: The AB no longer recognises the bacteria.
- The production of enzymes harmful to antibiotics: beta-lactamines and carbapenemases.

4) Selection and diffusion of resistant bacteria

Antibiotics do not cause resistance but, because of the pressure they exert on selection, they facilitate the emergence of resistant strains which, within a biotope, will be favoured over more sensitive strains.
- If the resistance originates from a mutation, the biotope will be colonised by a strain, often monoresistant and usually more fragile than wild strains. This will only show up in the presence of ABs. Indeed, once the selection pressure lessens, by stopping taking antibiotics, the mutated strain is de-selected and the biotope is once again colonised by sensitive wild strains. The effect does not last.

- If the resistance is down to an extra-chromosomal mechanism then the opposite occurs.
For example: antibiotics used by farmers and vets (for the treatment of bacterial diseases in plants, fruit, cattle and sheep etc.) the antibiotic residue present in the surroundings prompt the selection of the most resistant, extra- chromosomal bacteria.

In human medicine, all use of antibiotics, however successful, fosters a selection of resistant strains. The greater (or more anarchic) the use of antibiotics, the more often we will note the appearance of resistant bacteria. This defines "multi-resistance".
So where are antibiotics most used?
The answer is in hospitals or other care centres; places where the antibiotics used are latest generation.

- Speed of resistance: What makes this even more rapid is that the bacterial inoculation of resistant strains is already pre-selected by the confinement and the premises. In fact, it is exponential.

 

Multi-resistance and public health

We are in the habit of talking of multi-resistance, or multi-drug resistance, when faced with bacteria which, having built up natural or acquired resistance, are no longer sensitive to a small number of antibiotics commonly used as a treatment or a bacteria sensitive to less than three groups of antibiotics. So multi-resistance can be acquired or natural.
This term is generally employed for bacteria that create a problem when it comes to therapeutic resources.
The role played by exposure to antibiotics in the growth of multi-resistance in bacteria has been widely reported.
Currently, the emergence and spread among human populations of bacteria that have slowly acquired resistance to antibiotics has become a worrying public health problem.

 

From the individual to the collective

Antibiotics administered to an individual with the aim of treating that individual effectively have an impact on the collective because of the anti-bacterial activity they provoke in ecosystems. So the evolution of acquired bacterial resistance to antibiotics is now materialising in high levels of multi-resistance in some species of bacteria which were "originally" sensitive, species often present in hospital-acquired infections (nosocomial infections) such as Staphylococcus aureus and also species of bacteria responsible for community infections such as Streptococcus pneumoniae. The progression of this multi-resistance combined with the lack of any real perspective of discovering new antibiotics in the next few years could lead to an increase in the lethality of some bacterial infections and therefore represents a real threat for the future. 10,000 die of this in France each year, far more than are killed in road traffic accidents.
This report explains the problem clearly:
http://www.assemblee-nationale.fr/12/rap-off/i3188.asp
Consequently, controlling bacterial resistance to antibiotics would seem to be a major public health issue and crucial to preventing a health crisis.

The three factors involved in the emergence and diffusion of bacterial resistance to antibiotics are:
- The exposure of the public to antibiotics
- The failure to sterilise medical equipment used in handling excreta
- The transmission between individuals of resistant strains, depending on the premises and their origins.

So it would be advisable to tackle all three factors:
- Adopting best practices in prescribing antibiotics
- Using appropriate medical equipment and making single use compulsory
- Fighting cross-transmissions.
The use of innovative technology and the improvement in health care, such as the optimisation of the performance of medical equipment and the implementation of single usage are major issues for today because tomorrow it will be too late.
The current battle against the propagation of these kinds of infections has only been relatively successful as far as certain multi-resistant bacterial pathogens such as Staphylococcus aureus and pneumococcus are concerned.

The list of the most virulent and the most worrying, highly pathogenic and multi-resistant to AB bacteria in the communal environment are:

Clostridium difficile
Enterococcus
Pseudomonas aeruginosa
Acinetobacter
Klebsiella spp
E-coli: multi-resistant of the "type CTX-M extended spectrum beta-lactamases" type
Staphylococcus aureus and streptococcus pneumoniae

 

In conclusion:

The three unquestionable imperatives

- To fight against excessive use of antibiotics: target their usage better.
- To render obligatory the systematic use of single-use medical equipment.
- To systematically contain a patient's excreta as near to the patient as possible: Avoid local dissemination and propagation.

 

To find out more :

Documents available on line
General information:
Epidemiological data on the main multi-resistant bacteria in France and Europe:
- National data on the surveillance of multi-resistant bacteria RAISIN (Alert and Intervention Network and Surveillance of Nosocomial Infections): http://www.invs.sante.fr/raisin/
- European Antimicrobial Resistance Surveillance System: http://www.rivm.nl/earss/result/
The role of antibiotics in the emergence of resistance. NosoBase website (Nosothème n° 8 – March 2009)
http://nosobase.chu-lyon.fr/Nosotheme/antibiotique/Nosotheme8.pdf
Articles and works
Acar et coll. Résistance aux antibiotiques : une perspective aux antibiotiques : une perspective écologique à un
vieux problème. Bull Soc Fr Microbiol 2009.
Biochimie de la résistance (P Plésiat) in Antibiogramme Ed Eska, 2Ième édition 2006.
Génétique de la résistance (I Podglalen) in Antibiogramme Ed Eska, 2Ième édition 2006.
Mechanisms of resistance to antibacterial agents. In the Manual of Clinical Microbiology Vol 1 9th Ed 2007.
Martinez JL. The role of natural environments in the evolution of resistance traits in pathogenic bacteria. Proc Biol
Sci. 2009; 276(1667): 2521-2530.
Fajardo A, Linares JF, Martínez JL. Towards an ecological approach to antibiotics and antibiotic resistance genes.
Clin Microbiol Infect 2009; 15 (Suppl 1): 14-16.
Bruce J, MacKenzie FM, Cookson B, Mollison J, Van der Meer JW, Krcmery V, Gould IM. ARPAC Steering Group.
Antibiotic stewardship and consumption: findings from a pan-European hospital study. J Antimicrob Chemother.
2009; 64(4): 853-860.
Baquero F. Environmental stress and evolvability in microbial systems. Clin Microbiol Infect 2009; 15 (Suppl 1): 5-
10.
Martínez JL, Baquero F, Andersson DI. Predicting antibiotic resistance. Nat Rev Microbiol 2007; 5(12): 958-65.
Review.