Antibiotic

An antibiotic (of the Greek anti : “against”, and bios : “the life”) is a Chemical substance which has a specific action with a destroying capacity on the Micro-organisme S. It is deprived of Toxicité for the others cells.

This substance can have a direct toxic action, i.e. Bactéricide; its effectiveness can be also limited to prevent the development of the micro-organisms (action Bactériostatique).

The “antibiotic” term is reserved for the action on the Bactérie S. For the other micro-organisms, we must employ the term of “Antifongique” to fight against the mushrooms, or of “Antiviral” to fight against the Virus.

General information

Description, specificity

An antibiotic substance is thus a Médicament which causes of " tuer" Bacterium S in a targeted way: in fact there exist two kinds of antibiotics of which one which stops the growth of the bacteria whereas the other is distinguished (Antiseptique) which destroys any germ and sometimes even the cell, in a not targeted way. Remark : a Antiseptique is a Disinfecting not introduced.

History and importance of the discovery

The first antibiotic, identified as of the end of the 19th century by Ernest Duchesne, was the Pénicilline. Its properties were redécouvertes by chance in 1928 by Sir Alexander Fleming which realized that some of its bacterial cultures in boxes of forgotten $petri had been contaminated by the experiments of its neighbor of straw mattress on a mushroom: the Penicillium notatum . But the importance of this discovery, its implications and its uses medical were included/understood and worked out only after its redécouverte, between the two Great Wars.

Foot-note: the antibiotics exist in fact in nature, used for example since of the millenia by certain species of ants, but we noted it only very recently.

The first antibiotic (of synthesis) opened a new way in the fight against many Maladie S which was regarded as incurable before. The antibiotics increased the life expectancy of those which have access of approximately 15 years there. Comparatively, a drug which would cure 100% of cancers would increase the life expectancy only by 5 years.

Increasing resistance of the bacteria

Nowadays, much of antibiotics are known, but their overconsumption involves resistances of certain bacteria to some of them, and even of the multirésistances (case of the Staphylocoque gilded), at the point to make again incurable the first diseases which we had treated successfully with antibiotics…

The most probable mechanism of this resistance is undoubtedly that the antibiotic used creates a pressure of selection, which supports the selection of natural changes (even rare), which confer on the bacterium a resistance to antibiotic in question and thus a selective advantage. Certain bacteria (bacteria known as qualified) are able to integrate exogenic DNA (present in the medium) and thus to potentially acquire genes of resistance to antibiotics of another bacterial species.

How to choose antibiotic to be used

The choice of the antibiotic depends on the responsible germ, of the localization of the infection and the ground (impaired renal function or hepatic, concept of allergy…). It can be directed by the Antibiogramme : the responsible germ is put in culture in a box of Gélose containing several antibiotic pastilles of which will inhibit the development of the micro-organism more or less, which makes it possible to compare the sensitivity of the bacteria with such or such antibiotic. Certain antibiotics are Bactéricide S , i.e., the bacteria kill. Others are only Bactériostatique S , i.e. preventing the development of the germ.

Families of antibiotics

See also: Family of antibiotic

There exists more 10  000 antibiotic molecules, but only one hundred, of which a quarter Penicillin S, are effective and usable. The majority of antibiotics are produced by Procaryote S, Champignon S, plants higher, animals or Lichen S.

Mode of action of antibiotics

Action on the bacterial Wall

These antibiotics operate extracellular targets and are active only on the germs in growth. The cells at rest are not disturbed by the action of these molecules.

The antibiotics block the synthesis of the wall, the cell lengthens without making wall (partition) and it explodes under the effect of the internal osmotic pressure. If one adds one stabilizing osmotic, one obtains a Protoplaste.

Examples:

Action on the membrane of the cells

  • the Polymyxine : it is about a Surfactant (detergent) which acts with the membrane lipids and which disorganizes the membrane phospholipidic double-layered . This destroyed the integrity of the membrane, the water-soluble elements leave the cell. This molecule is effective on the cells in growth and at rest.

Action on DNA

  • the Mitomycine is a molecule of which the structure is asymmetrical. It is fixed on the bits of the propeller of DNA and establishes a bridging between them. This prevents the Réplication of the DNA by blocking the progression of DNA polymerase.

  • the Actinomycine: the mechanism is identical to that of the mitomycine, but this molecule is symmetrical. While being fixed on the two bits of DNA this molecule blocks the progression of ARN polymerase.

  • the Sulfamidé S are analogues structural of biological molecules; they resemble molecules normally used by the cell. The cell will recognize them for what they are not and to integrate them in its metabolism, and, because they are similar molecules, the metabolic ways will be blocked. This causes an inhibition of the synthesis of the nucleic bases and the cell dies by deficiency in nucleic bases.

  • the Quinolone S and fluoroquinolones act on the topology of the DNA. These molecules inhibit the DNA gyrase which controls surenroulement DNA. The inhibition of the gyrase prevents the replication of the DNA and thus the growth of the bacteria.

Action on bacterial ribosome

Roughly half of antibiotics used into therapeutic (laying out of the BITTER ) have as a target the bacterial Ribosome, the cellular Organite which is responsible for the synthesis of proteins. These antibiotics are divided into several classes, of chemical nature and different mode of action. The majority interact with ribosomal ARN.

  • the Phénicol S (examples: Chloramphenicol, thiamphénicol) blocks the formation of the peptide Liaison. They are fixed on the large sub-unit of bacterial ribosome (50 Svedberg) but not on that of ribosomes eucaryotes.

  • the cycline S (examples: Tétracycline, doxycycline, auréomycine): while being fixed on the sub-unit (30 S), they block the elongation of the polypeptide chain.

  • macrolides and kétolides (examples: érythromycine, Azithromycine) acts on part 50 S of ribosome and blocks the elongation of the polypeptide chain.

  • the Puromycine MIME the end of a ARNt, takes its place in ribosome and blocks the elongation of the polypeptide chain.

Resistances to antibiotics

See also: Resistance to the antibiotics

Natural resistance

One can speak about natural resistance if all the stocks of the same species are resistant to an antibiotic. It is the expression of an innate property reflecting the prevention to reach the target or the absence of the target. Example: impermeability of the walls of the Gram- bacteria or their absence of wall.

Acquired resistance

Acquired resistance occurs when some normally sensitive stocks of the same species become resistant. This resistance perhaps acquired by mutagenèse: it is a chromosomal resistance.

The phenomenon of change is spontaneous with a frequency of appearance of 10-6 with 10-7. It is a rare event. The antibiotic is not the mutagen agent, it selects only the mutants become resistant. That can lead to resistance to a whole family of antibiotics.

The changes are independent, therefore the risks to have resistances by mutagenèse to several antibiotics are rare. A double resistance multiplies the probabilities of appearance of resistance to each molecule, i.e. 10-14.

Other types of resistance

The bacteria have the capacity to transfer genetic information. The majority of these cases of resistances meet at the hospital. It is exogenic genetic information which is recovered by the bacterium.

The first case of resistance was observed in 1951 on a Japanese patient. He suffered from a shigelle infection with (a Entérobactérie, i.e. a bacillus gram-, mobile). The shigelle one caused a dysentery which could be neat by sulphamides, but it had become resistant to these sulphamides. The researchers showed that this resistance was accompanied by resistances in vitro to others antibactériens.

They isolated in the digestive tract from other patients from the stocks from Escherichia coli (another enterobactery, very widespread in water, the ground, milk and the saddles) which had acquired a resistance to sulphamides by a horizontal transfer between the two species.

Mechanisms of genetic transfer of element

The bacteria can transfer from the variable components of their Génome: Plasmide S and Transposon S.

Often the bacteria gathered several genes of resistance on their plasmide and exchange it.

  • the vertical transfer is obvious between of the same bacteria species.
  • the horizontal transfer intervenes on the other hand in the exchanges between bacterium Gram-plus, Gram- or in direction Gram-plus towards Gram-. The reverse, Gram- towards Gram-plus, are not realizable because the genes of Gram- are not expressed at Gram-plus.

  • the transduction : the vector is a Bactériophage. While being retorted, the phage integrates part of the bacterial genome. By leaving the cell, it carries additional genes (bacterial) which could be transfectés in another bacterium. This system is effective, but the exchanges are limited in the face (the phage cannot transfer a long piece of bacterial DNA) to the close organizations phylogenetically for the recognition phage/bacterium.

  • the transformation : the bacterium acquires and incorporates naked exogenic DNA present in its environment. That can be DNA of a dead bacterium which, once collected, allows the expression of its genes by the new bacterium. It is a very rare event which exists in the Gram- bacteria.

  • the conjugation : the DNA is transferred from a bacterium donor to a receiving bacterium during a close cellular contact (Pilus). It is the mode of transmission of horizontal transfer.

Method of resistance in the bacterium

  • the jamming : the bacterium synthesizes proteins which can sequester antibiotic or to degrade it to make it inoffensive (hydrolases, transférases…). This jamming can be done outside (beta-lactamase on antibiotics of the family of penicillins) of the cell, like inside.

  • the camouflage : the bacterium can modify the target of antibiotic. This one is not any more recognized and becomes insensitive with antibiotic.

  • the shielding : the bacterium prevents the access of antibiotic to the intracellular targets, by:

    • modification of the membrane permeability;
    • installation of a system of expulsion of antibiotic. A membrane pump drives back the antibiotic which enters the cell.

  • the dodging : the bacterium substitutes another molecule for the target. The antibiotic, while being fixed on this lure, does not fulfill its role.

Current acquired resistances

  • the Pneumocoque ( Streptococcus pneumoniae ) developed a resistance by modification of a specific membrane protein where penicillins (the PLP) imposing of the higher antibiotic amounts are fixed (typically, the amoxicilline), even constraining to prescribe a cephalosporine of 3rd generation (often the ceftriaxone). Resistances in France are documented since 1978. In 2000, one counted approximately 50% of resistant stocks, in particular in the big cities.

  • the Staphilococcus S méti-resistant, particularly frightening, are insensitive with penicillins (at-them also by modification of their PLP), but also by production of beta-lactamase and a méticilinase. The staphilococcus méti-R infections are typically severe infections nosocomiales, persons in charge of a heavy mortality. The glycopeptides are a traditional therapeutic alternative.

The Overconsumption: public health problems

The specialists criticize in this context the Prescription sometimes too much with light (attends) certain antibiotics (Surprescription), including when they are ineffective (against the Virus for example).

The phenomenon would be also amplified by the use of too weak amounts (including in drugs on sale free) or over one too short duration (less than 8 days), or too long, as by the presence of antibiotics in the meats of industrial breeding (they are used massively to protect the breedings Porcin S from the diseases).

Resistances carry out sometimes the epidemiologist S to recommend a reasoned use of the antibiotics (a little with the manner of the international management concerted by WHO of the drugs antipaludéen S).

The antibiotics are without effect on the Virus; however, it happens that those are prescribed if the organization is weakened, to prevent that this one does not become vulnerable to bacteria. Unfortunately, still too many (in France) are the doctors who systematically prescribe antibiotics for viral affections, whereas they are not effective and that they do nothing but reinforce the resistance of the bacteria to antibiotics.

These resistances to antibiotics become extremely alarming, they are the object of regular warnings of the government agencies and international. For example:

  • more than one third of the affections to the Staphylocoque gilded is from now on impossible to treat with antibiotics, causing amputations and death. It is probable that the 3/4 of the 4.200 deaths for infections nosocomiales are the fact of bacteria multirésistantes to the antibiotics.
  • the resistance of the Pneumocoque to penicillin G passed to France, from 0,5% to 45% between 1984 and 2001. France - which is one of the countries the largest antibiotic consumers - account the greatest number of therapeutic failures against pneumococci completely resistant to penicillin.

AntibioQuizz

  • do the antibiotics destroy all the microbes?

the antibiotics are drugs able to inhibit or destroy certain bacteria. They are not of any utility on the other types of microbes like the parasites, the viruses or the mycoses (mushrooms). Moreover, they directly do not treat the symptoms of an infection (fever, pains…).

  • can one become resistant to antibiotics?

It is not the human body which becomes resistant to antibiotic but the bacteria themselves while becoming less sensitive to the drug or any more. It is about a natural phenomenon, related to the evolution of the species; in contact with antibiotics, the bacteria sensitive to managed antibiotic disappear, but of others manage to survive or adapt thanks to modifications of their genes. It is said whereas they developed resistances.

  • do the bacteria resistant to antibiotics become more numerous?

With each time antibiotics are used during a treatment, the risk of selection exists: the sensitive bacteria disappear, but of others can adapt and survive.
the hospitals, the old people's homes, the cribs and the schools also support the development of resistances, because, in these buildings, côtoient people often treated by antibiotics. This promiscuity supports the transmission of the new bacteria resistant of an individual to the others.

  • are the children more often carrying resistant bacteria than the adults?

According to a French study undertaken in 1999 on children, nearly 53% of the Pneumococcus S, persons in charge inter alia Otitis S, of Pneumonia S, Méningite S… were resistant to antibiotic of reference, the Pénicilline.
the same study undertaken on adults showed as only 40  % of these bacteria were resistant to this antibiotic.
This difference can be explained:
- by a greater antibiotic consumption by the children. In 2002, a study showed that the children of less than 3 years received four times more antibiotics than the remainder of the population;
- by the fact that the children are more often sick than the adults and moreover, receive antibiotics too easily, whereas many respiratory infections, colds and other otitises, is in fact due in 80  % of the cases to viruses, against which the antibiotics are completely ineffective. For example in the case of the Bronchiolite of the infant, best of the treatments consists of a kinesitherapy.

  • is the health of the children threatened by the resistant bacteria?

It becomes indeed increasingly difficult to look after Otite S or Méningite S, since the bacteria all are not destroyed by antibiotic not prescribed.
What pushes the doctors to give two different antibiotics that they think complementary, like taking the bacteria out of clipper, and moreover to increase the amounts.

  • the fact of taking in the future less useless antibiotics, will it make it possible to reduce the resistance of the bacteria?

It is difficult to answer this question today! Because it there yet have really in France, on the whole of the population, of significant change in the regulation of antibiotics, and there is not thus enough retreat.
Cependant, if one refers to some other countries, and an experiment test realized in the department of the the Alpes-Maritimes, it proves that a bond between less antibiotics and the development slower of the resistance of the bacteria, can be quickly observed indeed.
Before with the experiment, the doctors had observed, over one 4 years duration, an increase of 20% of the presence of Pneumocoque S resistant in the children. After an information campaign, to which they adhered, the antibiotic catch dropped by 10% and resistance did not increase any more, remainder on the same level of 64% of resistant bacteria.

Current events

  • the French Agence of public health of the health products made the decision to withdraw market, after the June 30th, 2003, fifteen drugs containing of antibiotics, supposed to relieve the colds, rhinopharyngites and sinusitises. These judged drugs “ nonuseful for the cure ” and like “ being able to support the appearance and the diffusion of bacterial resistances ”, for the majority, were proposed in nasal solutions, sprays or drops. It acts: of Cortifra , Framyxone , Frazoline , Isofra , Pivalone neomycine , Polydexa neosynephrine , the Rhine ATP , Rhinobiotal 1,25% , Rhinotrophyl , Rhinyl , Soframycine 1,25% , Soframycine 100 G , Soframycine hydrocortisone , Soframycine naphazoline .
    It was estimated that the recourse to the physiological Solution to wash the nose and to the Paracétamol or the aspirine to relieve the fever and the pain, could replace them advantageously.

  • the decision was taken recently (September 2005) by the Ministry for the Health of dérembourser of many drugs which contained antibiotics (among most known: Solutricine , Lysopaïne ), to avoid increasing these phenomena of resistance, extremely previous occupants.

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