ANTIBIOTICS
chemicals produced by microorganisms that can inhibit the growth and cause the death of bacteria and other microbes. The antimicrobial effect of antibiotics is selective: they act more strongly on some organisms, less on others, or have no effect at all. Antibiotics also have a selective effect on animal cells, as a result of which they differ in the degree of toxicity and effect on blood and other biological fluids. Some antibiotics are of significant interest for chemotherapy and can be used to treat various microbial infections in humans and animals.
HISTORICAL SKETCH
IN folk medicine Lichen extracts have long been used to treat wounds and treat tuberculosis. Later, extracts of the bacteria Pseudomonas aeruginosa began to be included in ointments for treating superficial wounds, although no one knew why they helped, and the phenomenon of antibiosis was unknown. However, some of the first microbiological scientists were able to discover and describe antibiosis (inhibition of the growth of others by some organisms). The fact is that antagonistic relationships between different microorganisms appear when they grow in a mixed culture. Before the development of pure culture methods, different bacteria and molds were grown together, i.e. in optimal conditions for the manifestation of antibiosis. Louis Pasteur described the antibiosis between soil bacteria and pathogenic bacteria - the causative agents of anthrax - back in 1877. He even suggested that antibiosis could become the basis of treatment methods. The first antibiotics were isolated even before their ability to inhibit the growth of microorganisms became known. Thus, in 1860, the blue pigment pyocyanin, produced by small mobile rod-shaped bacteria of the genus Pseudomonas, was obtained in crystalline form, but its antibiotic properties were discovered only many years later. In 1896, another chemical of this kind, called mycophenolic acid, was crystallized from a mold culture. It gradually became clear that antibiosis is of a chemical nature and is caused by the production of specific chemical compounds. In 1929, Alexander Fleming, observing the antagonism of Penicillium notatum and staphylococcus in a mixed culture, discovered penicillin and suggested the possibility of its use in medicinal purposes. The antagonistic relationship between plant pathogenic microbes and non-pathogenic soil microorganisms identified in mixed crops interested plant pathologists, and they tried to use this phenomenon to combat plant diseases. It was known that there was a certain fungus present in the soil that reduced damping off of sprouts; In 1936, an antibiotic called gliotoxin was isolated from a culture of this fungus. This discovery confirmed the importance of antibiotics as a means of disease prevention. Among the first researchers who began a targeted search for antibiotics was R. Dubos. The experiments he and his collaborators conducted led to the discovery of antibiotics produced by certain soil bacteria, their isolation in pure form and use in clinical practice. In 1939, Dubos received tyrothricin, an antibiotic complex consisting of gramicidin and tyrocidin; this was an incentive for other scientists who discovered antibiotics that were even more clinically important. In 1942, H. Flory and his colleagues at Oxford University re-examined penicillin and proved the possibility of its clinical use as a non-toxic treatment for many acute infections. Then these substances began to be called antibiotics. Z. Waksman and his students at Rutgers University, USA, studied actinomycetes (such as Streptomyces) and in 1944 discovered streptomycin, an effective treatment for tuberculosis and other diseases. After 1940, many clinically important antibiotics were obtained, including bacitrapin, chloramphenicol (levomitsetin), chlortetracycline, oxytetracycline, amphotericin B, cycloserin, erythromycin, griseofulvin, kanamycin, neomycin, nystatin, vanimikin, viomitsin, cephalospilinin, Ampylsiline, Ampylsiline, Amplines , carbenicillin, aminoglycosides, streptomycin, gentamicin. Currently, more and more new antibiotics are being discovered. In the mid-1980s, antibiotics were prescribed more frequently in the United States than any other drug except sedatives and tranquilizers.
OBTAINING ANTIBIOTICS
Not all microorganisms have the ability to produce antibiotics, but only some strains of certain species. Thus, penicillin is produced by some strains of Penicillium notatum and P. chrysogenum, and streptomycin is produced by a certain strain of Streptomyces griseus, while other strains of the same species either do not produce antibiotics at all or produce different ones. There are also differences between antibiotic-producing strains, and these differences can be quantitative or qualitative. One strain, for example, gives the maximum yield of a given antibiotic when the culture grows on the surface of the medium and is in stationary conditions, while another only when its culture is immersed in the medium and is constantly shaken. Some microorganisms secrete not one, but several antibiotics. Thus, Pseudomonas aeruginosa produces pyocyanase, pyocyanin, piolipoic acid and other pyo-compounds; Bacillus brevis produces gramicidin and tyrocidin (a mixture known as tyrothricin); P. notatum - penicillin and penatine; Aspergillus flavus - penicillin and aspergillic acid; Aspergillus fumigatus - fumigatin, spinolosin, fumigacin (gelvolic acid) and gliotoxin; Streptomyces griseus - streptomycin, mannosidostreptomycin, cycloheximide and streptocin; Streptomyces rimosus - oxytetracycline and rimocidin; Streptomyces aureofaciens - chlortetracycline and tetracycline. The same antibiotic can be produced by different types of microorganisms. Thus, gliotoxin is produced by Gliocladium and Trichoderma species, as well as Aspergillus fumigatus, etc. Different microorganisms or their strains can produce different chemical forms of the same antibiotic, for example, different penicillins or different forms of streptomycin. IN last years A huge number of antibiotics produced by various organisms have been isolated and described. Both spore-forming and non-spore-forming bacteria, as well as more than half of the fungal genera studied on this subject, have the ability to produce antibiotics.
Non-spore-forming bacteria. From a group of bacteria formerly called Bacillus pyocyaneus and later known as Pseudomonas aeruginosa, pyocyanin and pyocyanase were isolated. Other non-spore-forming bacteria also produce antibiotics, which vary greatly in chemical structure and antibacterial properties. An example is the colicins produced by various strains of Escherichia coli.
Spore-forming bacteria. Many species of spore-forming bacteria produce various antibiotics. Thus, strains of Bacillus subtilis produce bacitracin, subtilin, etc.; B. brevis - tyrothricin, B. polimixa (B. aerosporus) - polymyxin (aerosporin). Various, still insufficiently studied compounds have been isolated from B. mycoides, B. mesentericus and B. simplex: bacillin, costatin, etc. Many of them inhibit the growth of fungi.
Actinomycetes. Apart from penicillin, the most important antibiotics used as chemotherapeutic agents were derived from actinomycetes (fungus-like bacteria). To date, more than 200 such compounds have been isolated or described. Some of them are widely used in the treatment of infectious diseases in humans and animals. Such antibiotics include streptomycin, tetracyclines, erythromycin, novobiocin, neomycin, etc. Some of them have a primarily antibacterial effect, others have an antifungal effect, and still others are active against some large viruses.
Fungi. In medicine, fungi are microorganisms belonging to the fungi kingdom. These are one of the most important producers of antibiotics. They produce cephalosporin, griseofulvin, mycophenolic acid, penicillic acid, gliotoxin, clavacin, aspergillic acid and many other compounds.
Other organisms.
Seaweed. Many algae are capable of producing substances that have antibiotic properties, but so far none of them have found clinical use.
Lichens. Antibiotics produced by lichens include lichenin and usnic acid.
Higher plants. Higher green plants also form antibacterial substances, similar in their properties to true antibiotics. These include phytoncides - allicin, tomatine, etc.
Animals. Among animal products with antibacterial properties, lysozyme occupies an important place. Many protozoa, insect larvae, and some other animals can digest living bacteria and fungi, but the extent to which this ability is related to the production of substances with antibiotic properties has not yet been determined.
CHEMICAL NATURE
Several classification systems for antibiotics have been developed, based on different criteria: origin, antimicrobial properties, toxicity to animals, solubility or chemical nature. The last approach to classification seems to be the most logical. Antibiotics can, for example, be divided into lipoids, pigments, polypeptides, sulfur-containing compounds, quinones, ketones, lactones, nucleosides and glycosides. Some antibiotics have been synthesized (pyocyanin, cycloserine and, most importantly, penicillin). However, all penicillin G (benzylpenicillin) used in medicine before 1962 was of biological origin. The combination of biological and chemical synthesis made it possible to create a large family of new penicillins, many of which have found use as drugs.
MECHANISM OF ACTION
Antibiotics are considered primarily bacteriostatic agents, i.e. growth inhibitors, although some of them have a pronounced bactericidal or even bacteriolytic effect. Many antibiotics, such as actinomycin, are highly toxic to animal tissues and are used only as antitumor drugs; others, in particular penicillins, are completely non-toxic or (like streptomycin) have only mild toxicity. Broad-spectrum antibiotics (for example, tetracyclines) disrupt the normal intestinal microbial flora and can cause gastrointestinal disorders or promote secondary infections. Some are insoluble in water and therefore are used only for the treatment of superficial or local infectious processes. Some (for example, tyrothricin) have a hemolytic effect, i.e. destroy red blood cells; others (for example, imipimen), on the contrary, are inactivated by the body's cells. (The enzyme that inactivates imipimen is now known; administering imipimen together with an inhibitor of this enzyme allows the antibiotic to maintain high activity across the entire spectrum of action.) Since antibiotics have selective antibacterial activity, none of them can be used as a general disinfectant against any bacteria . Penicillin and erythromycin are active mainly against coccal forms and various gram-positive bacteria, and streptomycin is active against tubercle bacilli. Penicillin and streptomycin have a relatively weak effect on fungal flora and viruses, although the former has some activity against large viruses, such as psittacosis virus, and the latter against some rickettsia and tropical inguinal granuloma pathogens. However, a number of antibiotics, primarily tetracyclines, act on many gram-positive and gram-negative bacteria, as well as rickettsia and large viruses. Some antibiotics have high antifungal activity, while others have antitumor activity.
Place of action. Antibiotics differ from each other not only in their chemical structure, but also in the place of action on the microbial cell. The action of antibiotics used in low concentrations is usually aimed at the specific characteristics of the life of pathogenic microorganisms. The cell walls of bacteria and molds are very different from the cell walls of animal cells, and many non-toxic antibiotics block the formation of cell walls. This is how penicillin, bacitracin, cycloserine and cephalosporins, used in the clinic for bacterial infections, work, as well as griseofulvin, which is used for skin fungal diseases. A particularly important role in the life of a bacterial cell is played by its plasma membrane, located under the cell wall. It regulates passage into the cell nutrients and the yield of excretory products; many enzymatic processes take place in it. The antibiotic polymyxin binds to the cell membrane of many gram-negative bacteria and disrupts its function. Tyrocidin has the chemical properties of a detergent and destroys the membrane. Streptomycin also affects it: the newly synthesized membrane turns out to be defective, and the cell loses vital components. Nystatin, by binding to the cell membranes of various yeasts and molds, leads to the loss of an essential element by their cells - potassium. Protein synthesis occurs in all living cells. Chloramphenicol specifically blocks this process in many bacteria. Tetracyclines also block protein synthesis, but an equally important aspect of their effect is the formation of complexes with metals and the effect on the binding of calcium, magnesium and manganese in the cell. Erythromycin also affects protein synthesis. The study of the mechanisms of action of various antibiotics has provided a lot of useful information about the biochemical processes occurring in the cells of microorganisms. Even those antibiotics that are not used for medicinal purposes can be used as an important tool for biochemical research. The basic mechanism by which penicillin kills bacteria (including cultured bacteria, which is used to determine the sensitivity of bacteria to the antibiotic) is now well understood. Penicillin acts on the bacterial cell wall; its most important component is peptidoglycans - complex structures in which sugars similar to glucose are linked to each other by cross-peptide bridges formed by amino acids. Normally, peptidoglycans give bacterial walls mechanical strength and stability. Penicillin changes their biosynthesis so much that the cell wall loses the necessary strength. As a result, the contents of the bacterial cell leak out and the cell dies. Since mammalian cells have a completely different membrane that does not contain peptidoglycans, penicillin has virtually no effect on them. Thus, penicillin is, as a rule, absolutely harmless to humans, except for rare side effects, such as severe allergic reactions.
Antibiotic resistance. Many bacteria, with prolonged contact with antibiotics, are able to adapt to their action; this leads to the emergence of resistant strains of such bacteria. Thus, cultures of Staphylococcus aureus, initially sensitive to penicillin, can become resistant to it. Other strains of S. aureus produce the enzyme penicillinase, which breaks down penicillin, and therefore can cause severe infections even in individuals receiving this antibiotic. The tuberculosis bacillus, Mycobacterium tuberculosis, being initially sensitive to streptomycin, in some cases adapts to it. Some strains of microorganisms become resistant to several antibiotics. In recent years, many doctors have expressed concerns that the widespread enthusiasm for antibiotics is sharply reducing their effectiveness in treating gonorrhea, typhoid fever, pneumococcal pneumonia, tuberculosis, meningitis and other serious diseases.
CLINICAL APPLICATION
Antibiotics have revolutionized medical practice. Among the many antibiotics widely used as chemotherapeutic agents, the largest quantities penicillins, cephalosporins, streptomycin and other aminoglycosides, chloramphenicol, tetracyclines and erythromycin are used. Besides, important have bacitracin, polymyxin, neomycin, nystatin and griseofulvin. IN certain cases Other antibiotics are also used. Penicillin is widely used in the treatment of staphylococcal infections - osteomyelitis, infectious arthritis, pneumonia, bronchitis, empyema, endocarditis, furunculosis, laryngotracheitis, mastitis, meningitis, inflammation of the middle ear, peritonitis, infected wounds and burns, septicemia, sinusitis, tonsillitis and many other diseases. It is successfully used for various infections caused by hemolytic and anaerobic streptococci, pneumococci, gonococci, meningococci, anaerobic clostridia (causative agents of gas gangrene), diphtheria bacilli, anthrax pathogens, spirochetes and many other bacteria. However, for mixed infections caused by gram-negative bacteria, as well as for malaria, tuberculosis, viral infections, fungal and some other diseases, penicillin is ineffective. The toxic effect of penicillin manifests itself mainly in the form of allergic reactions (even to minimal doses) and convulsive seizures (when very large doses are administered).

Cephalosporins are close in chemical structure to penicillin, but are highly resistant to the action of destructive enzymes (beta-lactamases), which are produced by a number of bacteria to protect against penicillin. Therefore, cephalosporins are highly active against coliform bacteria (Gram-negative rod-shaped bacteria such as Escherichia coli), which normally inhabit the large intestine, and are moderately active against the very dangerous Pseudomonas aeruginosa, which causes severe skin lesions. Currently, a large number of cephalosporins have been obtained, among them are cephalothin, cefazolin, cephalexin, cefamandole, defoxitin and ceftriaxone used in the clinic. These compounds are of particular value in cases of severe nosocomial infections, when the likelihood of infection with resistant strains is high, as well as in cases of proven resistance of the pathogen to older and less effective antibiotics. Streptomycin is used for many infections. It is an effective treatment for meningitis, endocarditis, laryngotracheitis, as well as diseases of the urinary tract and lungs caused by the Pfeiffer bacillus (Hemophilus influenzae). Meningitis, pneumonia and urinary tract infections can also be treated with streptomycin if the cause of these diseases is strains of Escherichia coli, Proteus vulgaris, Klebsiella pneumoniae (Friedlander's bacillus), Aerobacter aerogenes and Pseudomonas that are sensitive to it. It is effective against meningitis caused by Salmonella strains sensitive to this antibiotic, and against tularemia. In addition, streptomycin is used for peritonitis, liver abscesses, biliary tract infections and empyema caused by microorganisms sensitive to it, tuberculosis, chronic pulmonary infections caused predominantly by gram-negative bacteria, and endocarditis caused by penicillin-resistant but streptomycin-sensitive bacteria. At the same time, streptomycin has some toxicity and can cause dizziness, deafness and other undesirable effects. In addition, infectious agents quickly become resistant to this antibiotic. Side effects It can largely be eliminated by reducing the dose and administering streptomycin more rarely, and pathogen resistance (in particular in the treatment of tuberculosis) can be eliminated by using it together with other substances, for example para-aminosalicylic acid and isonicotinic acid hydrazide.
Other aminoglycosides. In addition to streptomycin, a number of other aminoglycosides (gentamicin, tobramycin, kanamycin) are used in medicine. As their generic name suggests, they all contain amino sugars linked by a glycosidic bond. Antibiotics of this group, like streptomycin, have severe toxicity, especially in relation to the auditory and vestibular (determining a sense of balance) systems, but often also in relation to the kidneys. These antibiotics are mainly affected by aerobic gram-negative flora, while most gram-positive bacteria are highly resistant to them.
Chloramphenicol and tetracyclines. Judging by the cross-resistance of various bacteria and the spectrum of antimicrobial action, these antibiotics, especially tetracyclines, have similar biological properties. They are effective when taken orally and are widely used for numerous infectious diseases caused by bacteria and some major viruses. Such diseases include typhoid fever, various forms of typhus, spotted fever, gonococcal infections, syphilis, brucellosis, urinary tract infections, lymphogranuloma venereum and many others. These antibiotics are also effective for most diseases for which penicillin is indicated and are often prescribed for penicillin-resistant infections and in cases where oral therapy is preferred.
Erythromycin and novobiocin. Erythromycin and other antibiotics (for example, carbomycin, oleandomycin), which have a special (macrolide) chemical structure, as well as novobiocin, are characterized by a wide spectrum of action - approximately the same as that of penicillin, but also covering some gram-negative bacteria. Their advantages include the possibility of oral administration and low toxicity; they cause gastrointestinal disorders relatively rarely.
Other antibiotics. Other clinically important antibiotics include tyrothricin, polymyxin (aerosporin), and bacitracin. Being relatively toxic, they are used mainly externally and orally. For fungal infections, nystatin, amphotericin B and griseofulvin are mainly used.
Other applications. Antibiotics are widely used in veterinary practice to combat a number of plant diseases (pears, beans and peppers) and to purify viral preparations. Farmers add antibiotics to feed to speed up the growth of poultry, pigs and cows. This practice is controversial: many scientists believe that it contributes to the spread of pathogens that are resistant to antibiotics, thereby threatening human health. Some microorganisms produce substances that inhibit the reproduction of viruses or destroy them; in particular, these substances are active against bacteriophages and viruses that cause diseases of plants and animals. Other microbial waste products similar to antibiotics destroy or prevent the proliferation of tumor cells, in some cases acting as true antibiotics. Some compounds, in particular actinomycin, azaserine, sarcomycin and mitomycin, have specific antitumor activity and are used in the treatment of human cancer.

PRODUCTION OF ANTIBIOTICS (THE EXAMPLE OF TERRAMYCIN)
1. Spores of carefully selected, highly productive strains of mold fungi are germinated in a flask. 2. Since the amount of mold grown in the flask is small, it continues to be grown in a larger container - a small fermenter. 3. Meanwhile, a large fermenter is filled with a sterile nutrient medium containing in the required ratio the substances necessary for mold growth. 4. Since mold requires oxygen to grow, sterile air is passed through the fermenter. 5. The contents of the small fermenter are transferred to the production fermenter. Any other additives are pre-sterilized to avoid microbial contamination that could reduce the yield of the antibiotic. 6. When the antibiotic output reaches its maximum, the contents of the fermenter are fed to a rotating filter, where the mold is filtered out. 7. The filtrate containing terramycin enters a container where chemical reagents are added that precipitate the antibiotic. 8. The mixture is then filtered under pressure, separating the partially purified precipitated antibiotic from the impurities remaining in the solution. 9. The Terramycin precipitate is further processed to remove remaining impurities. 10. The purified crystalline antibiotic is centrifuged and dried. 11. Now it can be packaged and used.

Modern encyclopedia

- (from anti... and Greek bios life) organic substances formed by microorganisms and having the ability to kill microbes (or prevent their growth). Antibiotics are also called antibacterial substances extracted from plant and... ... Big Encyclopedic Dictionary

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- (from anti... and Greek bios life), specific. chemical substances formed by microorganisms and capable of exerting selective influence in small quantities. toxic effect on other microorganisms and on malignant cells. tumors. A. in a broad sense also includes... ... Biological encyclopedic dictionary

Specific chem. substances produced by microorganisms that can, in small quantities, have a selective toxic effect on other microorganisms and on the cells of malignant tumors. In a broad sense, A. also includes antimicrobial... ... Dictionary of microbiology

Antibiotics- (Latin anti against + Greek bios life) substances of natural or semi-synthetic origin that suppress the growth of living cells, most often prokaryotes or protozoa (including bacteria, viruses, etc.)...

Antibiotics are a group of medicines that are used to destroy and suppress the proliferation of pathogens, including bacteria. These drugs are ineffective against viral infections, particularly the common cold. Many antibiotics are derived from living pathogens, although last decades Pharmaceutical companies have synthesized new drugs.

Antibiotics first found widespread use during World War II. Since the 40s of the 20th century, with their help it has been possible to save the lives of millions of people, to win a convincing victory in the fight against childhood infectious diseases, sexually transmitted diseases, inflammatory diseases of the pelvic organs and other life-threatening conditions. We are talking about bacterial meningitis (infectious inflammation of the membrane of the brain and spinal cord), as well as endocarditis (infectious inflammation of the endocardium - the inner lining of the heart, which lines its cavities and forms the valve leaflets).

However, due to the recent resurgence of such serious infectious diseases as, in particular, tuberculosis, doubts have arisen about the validity of triumphal declarations about the final and irreversible victory over all infections. According to doctors, the current spread of untreatable diseases is due to the emergence of resistant strains of microorganisms that are no longer affected by existing antibiotics. From the point of view of many experts, this is largely due to the massive and not always justified prescription of antibiotics by doctors and the uncontrolled use of these drugs by patients.

Since the mid-90s of the 20th century, more and more data have confirmed that new strains of Streptococcus pneumonia have appeared, resistant to all groups of antibiotics, which can be considered a paradox. Estimated World Organization healthcare, pathogens of almost all infectious diseases slowly but steadily develop resistance (immunity) to existing drugs. Experts from this organization warn that there is reason to fear that previously curable diseases - from tonsillitis to tuberculosis, malaria and gonorrhea - will become untreatable, even in developed countries. It is possible that the decrease in the prevalence of pathogens and diseases caused by them in the past was explained by natural fluctuations in the evolution of infectious agents, that is, by something that happened more than once throughout the history of medical science even before the discovery of penicillin.

However, this does not mean that antibiotics are inferior to diseases. It’s just that medications need to be used carefully and wisely - only to combat bacterial and certain fungal infections and only in the most exceptional cases for preventive purposes. Parents must ensure that the prescribed regimen and duration of treatment are followed even after the initial symptoms have disappeared.

Women should remember that taking antibiotics worsens fungal infections because it disrupts the natural balance of microflora in the body. If signs of candidiasis appear during antibiotic therapy, the patient should consult a doctor.

S. Aizenshtat

Antibiotics are substances of natural or artificial origin that reduce the number of pathogenic microorganisms or destroy them altogether.

Useful features and side effects of antibiotics

Antibiotics were first extracted from mold and only began to be widely used during World War II. Many infectious diseases that were previously incurable have become amenable to drug therapy. Epidemics of plague, typhoid, tuberculosis (consumption) claimed the lives of thousands of people in entire cities. And sexually transmitted diseases such as syphilis tormented people for years, leading to rotting of soft and hard tissues and ultimately to death. The use of antibiotics has reduced the number of child deaths, because the child’s body does not yet have a strong enough immune system to fight serious infectious pathogens. Also, such drugs have reduced the mortality rate of livestock and poultry.

Penicillin could provoke a large number of side effects:

• disappearance of beneficial microflora of the body, which can lead to dysbiosis of the intestines, mucous membranes, and skin;
• damage by fungal flora of the stomach, mucous membranes and skin;
• harmful effects on the fetus in pregnant women;
• detection in breast milk during lactation;
• allergic reactions.

Therefore, when taking antibiotics, it is also necessary to take antifungal, antihistamines, and medications containing beneficial microflora.

Modern antimicrobial drugs

New generation antibiotics are less toxic and have a specific selective spectrum of action. For example, they can act only in the intestines, without being absorbed. These properties help to use antibacterial drugs for pregnant and breastfeeding women, for infants and children early age. Also, the current pharmaceutical industry allows the production of antibacterial substances, similar to antibiotics, chemically, which makes these drugs widely available in price and quantity. However, modern pathogenic microorganisms are capable of mutating and becoming accustomed to antibiotics, which is why they produce increasingly stronger and modernized drugs.

Antibiotics are special substances of organic or inorganic origin that have a distinctive characteristic - they are capable of destroying any living cells nearby. From Latin, "antibiotic" literally means "against life." The first antibiotic in history was penicillin, produced by the mold penicillium. Antibiotics are capable of destroying not only harmful bacteria (prokaryotes) or microorganisms (protozoa), but also cells and bacteria that are important to the body, which is the main disadvantage of these drugs. They are taken when a creature’s body contains a huge number of pathogenic bacteria that urgently need to be suppressed. Antibiotics are taken only as a last resort, because after treatment with them, a person needs to restore the intestinal microflora that was destroyed by the drug.