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Antibiotics: take only when needed!

Antibiotics are life-saving drugs, but their incorrect use can generate bacterial resistance mechanisms, rendering them ineffective. Some considerations on the use of antibiotics and the main therapies available.

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For the first time, American doctors have recorded a case of urinary infection resistant to all antibiotics. The case was published in the American Society for Microbiology's journal Antimicrobial Agents and Chemotherapy. The bacterial infection is caused by a species of Escherichia coli, isolated in the urine of a Pennsylvania woman. The report does not disclose the condition of the carrier woman, but explains that experts from the centers for disease control and prevention are investigating how the patient would have contracted the infection, including the possibility of hospitalization.

In the US, resistance of bacteria to antibiotics causes 2 million cases of disease and 23,000 deaths a year, according to estimates. Scientists underlined the strong concern for this type of resistant bacteria that could represent a serious danger in the near future to fight even routine infections.

In November 2015, the concern of scientists worldwide was triggered when some Chinese and British researchers found bacteria of the strain resistant to the latest generation antibiotic drug colistin in pigs and some people in China. The lethal strain of Escherichia coli was subsequently identified in other parts of Europe.

The discovery also in the USA is showing us that the way to use antibiotics may have come almost to an end, a situation in which doctors may no longer have effective drugs to offer to patients in intensive wards or with simple urinary infections.

According to the Istituto Superiore di Sanità, even in Italy there are already patients infected with bacteria that resist the action of antibiotics, even if of a different species from the one that affected the Pennsylvania woman.

For the treatment of these resistant infections, non-traditional antibiotics are used, often fallen into disuse, or toxic to the body, or combinations of several drugs, but mortality is still very high and the 50% of people infected with multi-resistant bacteria risks dying.

Resistors

Resistance of bacteria to the toxic effects of antibiotics develops quite easily both in the laboratory and in clinical practice. A genetic mutation leading to lower susceptibility can also enable some bacteria to survive the antibiotic's selective attack. When the origin of this resistance was studied, it was almost always found that the cause was to be found in a biochemical alteration of the bacterial colony that made the molecular target of the drug less sensitive. All this is fixed by the bacterial genome and passed on to the next generation by binary fission.

The use of inadequate antibiotics in therapy to eliminate all the pathogenic colony favors the spread of resistance factors. To counter this phenomenon it is necessary to control the use of antibiotics by promoting the use of the appropriate drug, in the correct dosage, for the correct duration of therapy. In addition, the 8-10 % of patients in hospital undergo infections contracted during hospitalization, and very often these are multidrug-resistant infections to antibiotics. It is therefore essential to control infections in hospitals through measures adopted by healthcare personnel, such as frequent hand washing and changing of the gown, which comes into contact with infected subjects.

What worries the experts most, and ultimately the sufferer, is that innovative therapeutic options are in short supply. There are 37 new antibiotics in development by pharmaceutical companies, some of which are expected to be effective against pathogens classified as urgent threats by health authorities, but almost certainly, only 1 in 5 molecules will be able to receive agency approval governmental in the United States and Europe.

Deepening: antibiotics

Antibiotics are valuable life-saving drugs, among the most prescribed drugs today.

The goal of antibiotic therapy is to inhibit the growth and survival of microorganisms without causing excessive toxicity in the host organism.

The whole environment in which we live and our body itself as a whole is rich in a characteristic bacterial flora that generally does not cause disease until we engage in incorrect behaviors that cause the abnormal growth of these microbes in parts of the body. which they should normally be absent. To avoid this, the first protection consists of public hygiene measures, correct individual habits, the integrity of the skin and mucous membranes and a properly functioning immune system. All parts of the body that come into contact with the environment promote the life of microbes. On the contrary, all our fluids, organs and internal body structures are, as a rule, sterile, and the presence of bacteria in them is a first evidence of infection.

The history of man before the discovery of bacteria and their role in infectious diseases, and then the discovery of antibiotics, is punctuated by the recurring appearance of devastating pandemics, such as the waves of bubonic plague that have drastically reduced the population of ' Europe in the Middle Ages. In times of war, infections caused far more damage than armies did.

The first effective drugs, sulfonamides, date back to the mid-1930s. In 1929 Alexander Fleming first observed that a bacterial colony contaminated with mold Penicillum notatum developed a zone of bacterial lysis around it. The first clinical treatment with crude penicillin, which began in February 1941, led to an explosion of research, often crowned with success. In rapid succession, drugs such as thyrotricin (1939),streptomycin (1943), chloramphenicol (1947), chlortetracycline (1948), neomycin (1949), erythromycin (1952) and many others. These drugs have had a major impact on medical and pharmaceutical practice, and particularly on people who had firsthand experience of how life-threatening was before the introduction of antibiotics.

General information on the main classes of antibiotics

Sulfonamides

Sulfonamides are the first antibiotic drugs to enter therapy. They are drugs with bacteriostatic action, that is, they do not cause the death of the bacterium, but facilitate the defensive function of the immune system, preventing the colony from expanding in the body.

The mechanism of action of these drugs is the inhibition of the enzyme dihydropteroate synthetase, which leads to the formation of folic acid, essential for the synthesis of the nitrogenous bases that make up the bacterial DNA.

Sulfonamides are selective towards bacteria since the eukaryotic cells of our body do not synthesize folic acid, but extract it as such from the foods ingested with the diet.

Sulfonamides are currently little used drugs in antibiotic therapy; the main ones include thesulfamethoxazole, the sulfadoxine used in combination with other drugs such as biguanides in malaria prophylaxis; theresilver sulfadiazine it is found in ointments for topical use against skin infections, while for the treatment of ulcerative colitis and Crohn's disease it is administered salazosulfapyridine, which in the digestive system turns into acid para amino-salicylic (anti-inflammatory) e sulfapyridine (bacteriostatic).

Quinolones

The first quinolone to be released in 1965 was nalidixic acid. They followed later oxolinic acid, cinoxacin, enoxacin, however, drugs with a low spectrum of action, used to a limited extent for the treatment of urinary tract infections.

Later they entered therapy there norfloxacin, ofloxacin and ciprofloxacin, with a broad spectrum of action and used not only for the treatment of urinary infections, but also against prostatitis, upper respiratory tract and bone infections, septicemia, staphylococcal endocarditis, meningitis, sexually transmitted diseases and chronic ear infections.

These drugs block bacterial DNA synthesis by inhibiting the enzyme DNA-gyrase and causing the selective death of the microorganism, since in humans, the enzyme that gives the biological form of DNA, is the topoisomerase II, which does not bind quinolones.

Nitrofurans and nitroimidazoles

THE nitrofurans they are drugs that date back to the 1940s; they are concentrated in the urine, and are used against urinary tract infections.

THE nitroimidzoles they are newer and the most important drugs are metronidazole is romidazole.

The metronidazole it has been used for the treatment of vaginal amoeba infections, it has also proved effective in trichomoniasis and giardiasis. The metronidazole it has also found use in the parenteral treatment of Clostridium difficile infections, an opportunistic pathogen that occasionally develops as a consequence of broad-spectrum antibiotic therapy, and often endangers the life of the patient who is affected. These drugs selectively kill the pathogenic bacterium by damaging the DNA and blocking the action of repair enzymes.

Beta-lactam antibiotics

They are the most used, widespread and studied antibiotics. Both the penicillins that thecephalosporins, but also other less used drugs such as monobactams is carbapenems.

The name "lactams" derives from the cyclic amide and its analogues which form a cyclic ring with four atoms called lactone, a chemical functionality essential for the antibacterial action of these chemicals.

The mechanism of action of beta-lactams consists in the inhibition of the bacterial enzyme transpeptidase, an essential enzyme for guaranteeing the integrity of the bacterial membrane, a structure of fundamental importance for the survival of the microorganism. The transpeptidase block causes membrane lysis and violent death of the pathogen due to the leakage of the intracellular contents.

The spectrum of action of these drugs varies greatly depending on the chemical functions present within the structural formula of the drug. However, there are still very effective and powerful drugs that have made it possible to revolutionize antibiotic therapy. However, incorrect use and abuse of these drugs have resulted in the spread of bacteria resistant to even the most potent beta-lactams. The main reason for resistance is the presence of bacterial enzymes called beta-lactamases, proteins with different functions able to bind the lactone ring of the antibiotic and inactivate the drug. For this reason, some penicillins are administered in combination with other drugs called beta-lactamase inhibitors, such as clavulanic acid or sulbactam (Clavulin¬ģ¬†or Augmentin¬ģ¬†are combinations of amoxicillin with clavulanic acid).

Among the best known penicillins in therapy: ampicillin, amoxicillin, bacampicin, benzylpenicillin, carbenicillin, methicillin, oxacillin, sulbactam, clavulanic acid. The most common cephalosporins are: cefaclor, cefazolin, cefixime, cefmetazone, cefoperazone, cefoxitin, ceftibuten, ceftriaxone, cefuroxime, cefalexime.

Penicillins are allergenic drugs: 6-8% of the US population is allergic to these drugs; the main symptoms are manifested by skin rashes, itching, cardiovascular collapse. In the worst cases, the allergic reaction caused by penicillins can be lethal.

Allergies to cephalosporins are less common and symptoms less severe, however they should be administered with caution in patients allergic to penicillins.

Phosphomycin

Extremely effective drug against gram- and lower urinary tract infections. It can resolve an infection in a few days with a single dose. Its mechanism of action consists in inhibiting the synthesis of peptidoglycan precursors, which contributes to the formation of the bacterial wall. The effectiveness of fosfomycin is jeopardized by the bacterial resistance created by the disproportionate use of this precious drug.

The¬†Monuril¬ģ¬†is the most used medical specialty based on fosfomycin for the treatment of urinary infections.

Antibiotics that inhibit protein synthesis

Some families of antibiotics exert lethal effects on bacteria by inhibiting the synthesis of proteins mediated by bacterial ribosomes, different in structure from those of the cells of our organism. In fact, at therapeutic doses these drugs do not interfere with the functions of our cells, therefore the selective toxicity of these drugs is evident.

Interaction with bacterial protein biosynthesis prevents repair, cell growth and reproduction. Drugs with this mechanism of action are aminoglycosides, macrolides and tetracyclines.

Aminoglycosides: they are antibiotics with a complex molecular structure, similar to polysaccharides. Chemically they are very soluble in water, therefore intestinal absorption is almost nil, therefore the route of administration by injection is that of choice. They are broad spectrum antibiotics, but unfortunately toxic to both the liver and the kidneys.

Numerous efforts have been made by the pharmaceutical industry to remedy this problem, but with poor results.

Aminoglycosides are used intravenously in the treatment of central nervous system infections, bacterial meningitis or particularly persistent bacterial infections, or topically for skin and dermal infections.

Among the most used aminoglycosides: amikacin, gentamicin, kanamycin, neomycin, tobramycin.

Macrolides: antibiotics with a macrocyclic structure. They are drugs with a restricted spectrum of action to gram + bacteria; they cause few and rare side effects, and their use is safe, for this reason they are administered in pediatrics against modest Staphylococcal and Streptococcal infections of the lower and upper airways.

Among the best known: azithromycin, clarithromycin and erythromycin.

Tetracyclines: drugs chemically characterized by the cyclic system of naphthalene (4 rings with six atoms fused in a linear fashion), partially reduced and with numerous substituents.

They exhibit a very broad antibiotic activity; they are almost never the first choice drugs because of the bacterial resistance, which is established quickly, and because of the annoying side effects, such asyellowing of the teeth which lead to having to resort to remedies, including home remedies, such as for example teeth whitening strips.

They are generally used for the treatment of sexually transmitted diseases and zoonoses transmitted by ticks and lice. They are also used for the prophylaxis of malaria, traveler's diarrhea and many other less common ailments.

Among the best known drugs: tetracycline, sancycline, minocycline, doxycycline

Second choice or specific antibiotics

This category of antibiotics includes antibiotics with different structures, whose toxicity or very limited activity makes them very specific drugs for some types of therapy.

Chloramphenicol: it was the first broad-spectrum antibiotic used in the US in 1947, and for a long time it was widely used. However, it can cause serious blood dyscrasias, which have drastically reduced its use. The low cost and effectiveness mean that it is still widely used in developing countries. Its mechanism of action consists in the inhibition of bacterial protein synthesis. It is very effective in the treatment of typhoid fever, Haemophilus infections (meningitis), meningococcal and pneumococcal meningitis and rickettsiae infections.

Vancomycin: produced by fermentation from Amycolatopsis orientalis (a kind of bacterium), and is the only glycopeptide antibiotic to have entered clinical use. It is particularly effective against gram + bacteria, such as staphylococci. It is used against mutidrug-resistant bacteria such as penicillin-resistant Staphylococcus aureus and against Clostridium difficile when the patient's life is at risk. Intravenous administration can cause renal toxicity and acoustic nerve damage. The release of histamine caused by the drug can cause intense skin rashes.

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