Complications of antibiotic therapy, their prevention. Complications of antibiotic therapy: classification, diagnostic signs, treatment and consequences Treatment of complications of antibiotic therapy

Like any medicine, almost every group of antimicrobial chemotherapy drugs can have side effects, both on the macroorganism and on microbes, and on other drugs.

Complications from the macroorganism

The most common complications of antimicrobial chemotherapy are:

Toxic effect of drugs. As a rule, the development of this complication depends on the properties of the drug itself, its dose, route of administration, and the patient’s condition and appears only with prolonged and systematic use of antimicrobial chemotherapy drugs, when conditions are created for their accumulation in the body. Such complications occur especially often when the target of the drug is processes or structures that are similar in composition or structure to similar structures of the cells of the macroorganism. Children, pregnant women, as well as patients with impaired liver and kidney function are especially susceptible to the toxic effects of antimicrobial drugs.

Side toxic effects can manifest themselves as neurotoxic (for example, glycopeptides and aminoglycosides have an ototoxic effect, up to complete hearing loss due to their effect on the auditory nerve); nephrotoxic (polyenes, polypeptides, aminoglycosides, macrolides, glycopeptides, sulfonamides); general toxic (antifungal drugs - polyenes, imidazoles); inhibition of hematopoiesis (tetracyclines, sulfonamides, chloramphenicol/chloramphenicol, which contains nitrobenzene - a suppressor of bone marrow function); teratogenic [aminoglycosides, tetracyclines disrupt the development of bones, cartilage in the fetus and children, the formation of tooth enamel (brown coloration of teeth), chloramphenicol/chloramphenicol is toxic to newborns whose liver enzymes are not fully formed (“gray baby syndrome”), quinolones - act on developing cartilage and connective tissue].

Warning complications consists of avoiding medications that are contraindicated for the patient, monitoring the state of the liver, kidneys, etc.

Dysbiosis (dysbacteriosis). Antimicrobial chemotherapy drugs, especially broad-spectrum ones, can affect not only infectious agents, but also sensitive microorganisms of normal microflora. As a result, dysbiosis is formed, therefore the functions of the gastrointestinal tract are disrupted, vitamin deficiency occurs and a secondary infection can develop (including endogenous, for example candidiasis, pseudomembranous colitis). Warning consequences of this kind of complications consists in prescribing, if possible, narrow-spectrum drugs, combining treatment of the underlying disease with antifungal therapy (for example, prescribing nystatin), vitamin therapy, the use of eubiotics, etc.

Negative effects on the immune system. This group of complications includes, first of all, allergic reactions. The reasons for the development of hypersensitivity may be the drug itself, its breakdown products, as well as the complex of the drug with whey proteins. The occurrence of this kind of complications depends on the properties of the drug itself, the method and frequency of its administration, and the patient’s individual sensitivity to the drug. Allergic reactions develop in approximately 10% of cases and manifest themselves in the form of rash, itching, urticaria, and Quincke's edema. Such a severe form of allergy as anaphylactic shock is relatively rare. This complication is often caused by beta-lactams (penicillins) and rifampicins. Sulfonamides may cause delayed-type hypersensitivity. Warning complications consists of carefully collecting an allergic history and prescribing medications in accordance with the patient’s individual sensitivity. In addition, antibiotics have some immunosuppressive effects and can contribute to the development of secondary immunodeficiency and weakening of the immune system.

Endotoxic shock (therapeutic). This is a phenomenon that occurs when treating infections caused by gram-negative bacteria. The administration of antibiotics causes cell death and destruction, and the release of large quantities of endotoxin. This is a natural phenomenon, which is accompanied by a temporary deterioration in the patient’s clinical condition.

Interaction with other drugs. Antibiotics can help potentiate the action or inactivate other drugs (for example, erythromycin stimulates the production of liver enzymes, which begin to rapidly metabolize drugs for various purposes).

Side effects on microorganisms.

The use of antimicrobial chemotherapy drugs not only has a direct inhibitory or destructive effect on microbes, but can also lead to the formation of atypical forms of microbes (for example, the formation of L-forms of bacteria or changes in other properties of microbes, which significantly complicates the diagnosis of infectious diseases) and persistent forms of microbes. The widespread use of antimicrobial drugs also leads to the formation of antibiotic dependence (rarely) and drug resistance - antibiotic resistance (quite often). Principles of rational antibiotic therapy.

Prevention of the development of complications consists, first of all, in compliance principles of rational antibiotic therapy(antimicrobial chemotherapy):

Microbiological principle. Before prescribing the drug, the causative agent of the infection should be identified and its individual sensitivity to antimicrobial chemotherapeutic drugs should be determined. Based on the results of the antibiogram, the patient is prescribed a narrow-spectrum drug that has the most pronounced activity against a specific pathogen, at a dose 2-3 times higher than the minimum inhibitory concentration. If the causative agent is still unknown, then drugs of a wider spectrum are usually prescribed, active against all possible microbes that most often cause this pathology. Correction of treatment is carried out taking into account the results of bacteriological examination and determination of the individual sensitivity of a particular pathogen (usually after 2-3 days). You need to start treating the infection as early as possible (firstly, at the beginning of the disease there are fewer microbes in the body, and secondly, the drugs have a more active effect on growing and multiplying microbes).

Pharmacological principle. The characteristics of the drug are taken into account - its pharmacokinetics and pharmacodynamics, distribution in the body, frequency of administration, the possibility of combining drugs, etc. Doses of drugs must be sufficient to ensure microbostatic or microbicidal concentrations in biological fluids and tissues.

It is necessary to understand the optimal duration of treatment, since clinical improvement is not a reason to discontinue the drug, because pathogens may persist in the body and there may be a relapse of the disease. The optimal routes of drug administration are also taken into account, since many antibiotics are poorly absorbed from the gastrointestinal tract or do not penetrate the blood-brain barrier. When prescribing a drug, they take into account how safe it will be for a given patient, which depends on the individual characteristics of the patient’s condition (severity of infection, immune status, gender, pregnancy, age, state of liver and kidney function, concomitant diseases, etc.) In severe cases For life-threatening infections, timely antibiotic therapy is of particular importance.

Such patients are prescribed combinations of two or three drugs to ensure the widest possible spectrum of action. When prescribing a combination of several drugs, you should know how effective the combination of these drugs will be against the pathogen and how safe for the patient it will be, i.e., so that there is no antagonism of the drugs in relation to antibacterial activity and there is no summation of their toxic effects.

Epidemiological principle. The choice of drug, especially for an inpatient, should take into account the resistance status of microbial strains circulating in a given department, hospital, and even region. It should be remembered that antibiotic resistance can not only be acquired, but also lost, while the natural sensitivity of the microorganism to the drug is restored. Only natural stability does not change.

41.Pharmaceutical principle.

It is necessary to take into account the expiration date and follow the rules for storing the drug, since if these rules are violated, the antibiotic can not only lose its activity, but also become toxic due to degradation. The cost of the drug is also important.

Allergy tests, their essence, application. Allergy tests

- biological reactions for diagnosing a number of diseases, based on increased sensitivity of the body caused by an allergen. For many infectious diseases Due to the activation of cellular immunity, the body develops increased sensitivity to pathogens and their metabolic products. This is the basis for allergy tests used to diagnose bacterial, viral, protozoal infections, mycoses and helminthiasis. Allergy tests are specific, but they are often positive in those who have recovered from the disease and those who have been vaccinated. All allergy tests are divided into two groups - samples

in vivoDue to the activation of cellular immunity, the body develops increased sensitivity to pathogens and their metabolic products. This is the basis for allergy tests used to diagnose bacterial, viral, protozoal infections, mycoses and helminthiasis. Allergy tests are specific, but they are often positive in those who have recovered from the disease and those who have been vaccinated. ) And

It is necessary to take into account the expiration date and follow the rules for storing the drug, since if these rules are violated, the antibiotic can not only lose its activity, but also become toxic due to degradation.in vitro. are based on identifying sensitization outside the patient’s body. They are used when, for one reason or another, skin tests cannot be performed, or in cases where skin reactions give unclear results.

For carrying out allergy tests they use allergens - diagnostic drugs designed to identify specific sensitization of the body. Infectious allergens used in the diagnosis of infectious diseases are purified filtrates of broth cultures, less often suspensions of killed microorganisms or antigens isolated from them.

Skin tests.Infectious allergens administered, as a rule, intradermally or cutaneously, by rubbing into scarified areas of the skin. With the intradermal method, 0.1 ml of allergen is injected into the middle third of the anterior surface of the forearm with a special thin needle. After 28 - 48 hours, the results of the HRT reaction are assessed, determining the size of the papule at the injection site.

Non-infectious allergens(plant pollen, household dust, food products, medications and chemicals) are injected into the skin by injection (prick test), cutaneously by scarification and rubbing, or intradermal injection of a diluted allergen solution. ICN is used as a negative control, and a histamine solution is used as a positive control. The results are taken into account within 20 minutes (GNT) according to the size of the papules (sometimes up to 20 mm in diameter), the presence of swelling and itching. Intradermal tests are performed in case of a negative or questionable result of the prick test. Compared to the latter, the dose of the allergen is reduced by 100-5000 times.

Skin tests for the presence of HRT are widely used to detect infection of people with mycobacterium tuberculosis (Mantoux test), pathogens of brucellosis (Burnet test), leprosy (Mitsuda reaction), tularemia, glanders, actinomycosis, dermatomycosis, toxoplasmosis, some helminthiasis, etc.

Samplesin vitro. . These research methods are safe for the patient, quite sensitive, and allow one to quantitatively assess the level of allergization in the body.

Tests have now been developed to determine sensitization based on reactions T- and B-lymphocytes, tissue basophils, identifying common specific IgE in blood serum, etc. These include reactions of inhibition of leukocyte migration and blast transformation of lymphocytes, specific rosette formation, Shelley’s basophil test, degranulation reaction of tissue basophils, as well as allergosorbent methods (determination of specific IgE in blood serum).

Leukocyte migration inhibition reaction (LMIR). RTML is based on the suppression of the migration of monocytes and other leukocytes under the influence of mediators produced by sensitized lymphocytes in the presence of a specific allergen.

Lymphocyte blast transformation reaction (LBT). This reaction is based on the ability of normal peripheral blood lymphocytes to enter into mitosis and transform into blast forms when they are cultured in vitro. Under the influence specific factors - allergens and nonspecific stimulants of mitogenesis - mitogens (phytohemagglutinin, concanavalin A, lipopolysaccharides and other substances).

Specific rosette reaction. Rosettes are characteristic formations that arise in vitro. as a result of the adhesion of red blood cells to the surface of immunocompetent cells. Rosette formation can occur spontaneously, since human T lymphocytes contain receptors for sheep red blood cells. Spontaneous rosette formation in healthy people is 52 - 53% and serves as an indicator of the functional state of T-lymphocytes. This phenomenon is also reproduced if erythrocytes are used, on which the corresponding allergens are fixed.

Degranulation reaction of tissue basophils. The technique is based on the fact that under the influence of an allergen, degranulation of rat tissue basophils, previously sensitized with cytophilic AT from the patient’s blood serum, occurs.

Shelley's basophil test. It is known that human or rabbit basophilic granulocytes also degranulate in the presence of the patient's serum and the allergen to which the patient is sensitive.

Determination of antibody classIgE in vitro. Laboratory diagnosis of diseases based on HNT is based on the determination of allergen-specific IgEanti-IgE. When using a radioactive label, the method is called a radioallergosorbent test (PACT), but more often an enzyme or fluorescent substance (FAST) is used as a label. Analysis time - 6 - 7 hours. The principle of the method: a known allergen fixed on a solid base is incubated with the patient’s blood serum; specific in serum IgEanti-IgE bind to the allergen and thus remain fixed to the base and can enter into a specific interaction with added labeled anti-IgE.

ANTIBIOTICS AND THEIR PREVENTION

I.Side effects associated with the direct effect of antibiotics on the body are specific to each group of antibiotics.

1. Neurotoxic effect - irritation of the membranes of the brain, convulsions. It is observed with endolumbar administration or with intravenous administration of large doses of penicillins and aminoglycosides.

2. Ototoxic effect. Develops when the VIII pair of cranial nerves is damaged. Vestibular disorders (dizziness, unsteadiness of gait) and hearing loss occur. Possible when using aminoglycosides (for parenteral use).

3.Polyneuritis – occurs with parenteral administration of aminoglycosides and polymyxins.

4. Hepatotoxicity – liver damage by any route of administration, more often by parenteral routes. Possible when using macrolides and tetracyclines.

5. Inhibition of hematopoiesis (anemia, leukopenia). They occur with any route of administration of drugs from the chloramphenicol group.

6.Nephrotoxicity – toxic effect on the kidneys. Possible with the use of aminoglycosides and polymyxins.

7.Dyspepsia (epigastric pain, nausea, vomiting, diarrhea). They arise due to the very bitter taste of antibiotics and the irritating effect on the mucous membranes of the digestive tract when almost all antibiotics (except polymyxin) are administered orally.

8.Irritation of mucous membranes (stomatitis, proctitis, glossitis). Observed when ingesting macrolides, aminoglycosides, tetracyclines, chloramphenicol.

9.Teratogenic effect – possible with the use of tetracyclines and chloramphenicol.

10.Red neck and red face syndrome - caused by glycopeptides.

11. Pseudomembranous colitis - caused by lincosamides.

12. Hypovitaminosis of vitamin K, which provokes bleeding - possible when taking cephalosporins.

13. Convulsive reactions, taste disturbances are possible when using carbapenems.

14. Thrombocytopenia, increased prothrombin time - possible with the use of monobactams.

II.Allergic reactions(urticaria, contact dermatitis, angioedema, anaphylactic shock) are manifestations of the body’s increased sensitivity to antibiotics (sensitization). Allergic reactions are common to all antibiotics except polymyxin. Sensitization occurs to a certain group of chemically related antibiotics. More often occurs with drugs of the penicillin and tetracycline groups. If an allergic reaction occurs, stop treatment with this drug and replace it with an antibiotic of another group. For mild allergic reactions, antihistamines (diphenhydramine, diazolin) and calcium supplements are used. For reactions of moderate severity, additional glucocorticoids are added. In case of anaphylactic shock, adrenaline is administered parenterally, glucocorticoids, antihistamines and calcium preparations are administered intravenously, oxygen inhalation and warming the patient’s body, artificial respiration. In severe cases, penicillinase is administered (for allergies caused by beta-lactam antibiotics).

III.Side effects associated with chemotherapy– develop due to the influence of these substances on the microflora. This is dysbacteriosis (superinfection) - disruption and death of saprophytic (natural, normal) intestinal microflora. At the same time, putrefactive and pathogenic microflora predominate in the large intestine, and there is not enough beneficial microflora - bifidobacteria and lactobacilli. Conditions are created for the development of other species that are insensitive to this antibiotic (yeast-like fungi, staphylococci, Proteus, Pseudomonas aeruginosa). Most often, superinfection occurs due to the action of broad-spectrum antibiotics, although it is caused by every single antibiotic.

The essence of dysbiosis is expressed in the fact that a person has nothing to digest food with, i.e. break down proteins, fats, carbohydrates. And therefore, no matter how much he eats, the food does not go to waste. Moreover, in time (necessarily within 24-32 hours!) Unremoved, practically undigested foods rot in our body, making our breath and all secretions, including sweat, smelly. Dysbacteriosis causes chronic constipation and diarrhea, flatulence and gastritis, duodenal ulcers. It is the root cause of serious diseases: eczema, bronchial asthma, diabetes, intoxication, liver cirrhosis, vitamin deficiencies, allergies, immunodeficiency, poor absorption of minerals and, as a result, osteochondrosis and rickets. Drug treatment of these diseases is ineffective due to the fact that the cause of their occurrence – dysbacteriosis – has not been eliminated.

PREVENTION AND TREATMENT OF SIDE EFFECTS

ANTIBIOTICS

1.Eubiotics:

a) prebiotics – create conditions for the development of natural bacteria (hilak, duphalac, duspatalin);

b) probiotics – contain the necessary bifidobacteria and lactobacilli (lactobacterin, colibacterin, bifiform, bificol, bifidumbacterin, bactisubtil, linex).

2. Antifungal antibiotics - nystatin, levorin.

3.B vitamins.

The use of antibiotics (AB), like other medications, is associated with the risk of developing side effects. Side effects of AB can be varied: overdose, specific side effects, intolerance, secondary drug effect, drug interactions, idiosyncrasy, psychogenic reactions, teratogenic and carcinogenic effects, allergic and pseudoallergic reactions.

Most of them are caused by doctor errors: inattention to these direct toxic side effects, ignoring concomitant pathologies, incorrect combination of drugs, etc.

Allergies. They occur when using all groups of drugs, but are most typical for β-lactams. Cross-allergic reactions with some antibiotics (for example, β-lactams) are pronounced, but their theoretical probability is not an absolute contraindication to the use of a subsequent group of β-lactams.

Complications of chemotherapy

• Bacteriolysis reaction– essentially an infectious-toxic shock in response to the release of endotoxin during the massive destruction of microbes after giving a loading dose of a bactericidal AB. It is most significant when using antibiotics that cause rapid lysis and filamentation of bacteria (penicillins, cephalosporins, quinolones); is practically absent in carbapenems (spheroplast transformation of bacteria), monobactams, aminoglycosides and polymyxins (the prototype of endotoxin-binding ABs).
• Dysbiosis– inhibition of normal biocenosis with the development of superinfections, often UPM flora: staphylococcal enterocolitis, candidiasis, pseudomembranous colitis (PMC) caused by Cl. difficile, etc.
• Suppression of various links by some batteries immunity, naturally developed by the body in response to infection.

Direct specific effect on the body

Toxicity, as a rule, is dose-dependent, manifests itself during long courses and disappears after drug discontinuation. However, there are irreversible (eg, aminoglycoside-induced ototoxicity) and non-dependent (aplastic anemia with chloramphenicol) effects.

Due to the serious impact on the growing organism, a number of ABs are not recommended for use in children– tetracyclines (impair the growth of bones and teeth), chloramphenicol (myelotoxic effect, “gray collapse” in newborns), fluoroquinolones (suspected impaired growth of bones and cartilage tissue), sulfonamides (myelotoxic effect, displacement of bilirubin from albumin).

Many drugs in high concentrations, which are created on the surface of the brain or spinal cord, have a toxic effect on the central nervous system. For example, penicillins can cause epileptic seizures and encephalopathy. There are reports that paresthesia, sciatica and transverse myelitis have occurred with endolumbar administration of a number of drugs. There are also cases of arachnoiditis after repeated intrathecal administration of antibiotics.

Characteristics of complications of antibacterial therapy based on different groups of antibacterial drugs

Characteristics of complications of antibacterial therapy based on different groups of antibacterial drugs are presented in Table. 2.

Possible side effects of antibiotics

Some side effects of different groups of ABs

Antibiotics are very popular drugs today. Self-prescription of antibiotics by patients occurs on the advice of friends or previous treatment experience. Sometimes a doctor prescribes an antibiotic due to fear of complications and related problems. As a result, the drug is prescribed when it is possible to do without this “heavy artillery”.

In this article we will look at the complications that antibiotic treatment causes.

The most common side effect of antibiotics is allergic reactions - hypersensitivity reactions. This is an immunological response to antibiotics or their metabolites - substances formed during the biochemical transformations of antibiotics in the body. This response results in clinically significant adverse events.

There are several types of allergic reactions that develop under the influence of antibiotics.

1. Anaphylaxis - develops within 5-30 minutes after administration of antibiotics. Dangerous for life. Most often develops from penicillins. Previously, in hospitals, tests were required before administering these antibiotics. Now in many cases this practice is omitted.

Symptoms: bronchospasm, laryngeal edema - i.e. suffocation; decreased blood pressure, arrhythmia, urticaria, etc.

First of all, to stop anaphylaxis, adrenaline hydrochloride is administered intramuscularly.

1. Serum-like syndrome develops most often with beta-lactam antibiotics, as well as streptomycin. The syndrome usually manifests itself on the 7th-21st day from the start of antibiotic use or after a few hours if the antibiotic was used previously.

Symptoms: fever, malaise, pain in bones and joints, urticaria and swollen lymph nodes, damage to internal organs.

Serum-like syndrome resolves after discontinuation of the antibiotic.

1. Drug fever is a type of allergic reaction to beta-lactam antibiotics, streptomycin. Develops 6-8 days from the start of antibiotic treatment. After discontinuation of the drug, symptoms disappear after 2-3 days.

Clinic: temperature 39-40 degrees, bradycardia (decreased heart rate, a clear symptom), increased level of leukocytes in the blood, itchy rashes on the skin.

1. Mucocutaneous syndromes

They are characterized by rashes of various types on the skin, mucous membranes, and damage to internal organs. Symptoms disappear after discontinuation of the antibiotic and allergy therapy. Dangerous manifestations of this type of complications from antibiotic therapy include Steven-Johnson and Lyell syndrome, which can even lead to the death of the patient.

1. Skin manifestations

If we consider exclusively skin complications after taking antibiotics, they may not seem so formidable at first glance. However, the familiar urticaria, which is a skin manifestation of allergy, can develop into Quincke's edema and anaphylactic shock. Therefore, you should also take skin manifestations seriously and ask your doctor to change the drug that caused the hives. Also in this category is contact dermatitis after using topical antibiotic ointments.

Skin manifestations of complications resolve on their own after discontinuation of the antibiotic. For severe dermatitis, use ointments with synthetic glucocorticoids (hormonal) - Sinaflan, Celestoderm, Lorinden.

1. Photosensitivity reactions

They appear as solar dermatitis on exposed skin. Most often, these reactions are caused by tetracyclines (primarily doxycycline) and fluoroquinolones.

Most often, allergic reactions develop with beta-lactam antibiotics (penicillins, cephalosporins, carbapenems, monobactams). When prescribing an antibiotic, you can always ask the doctor which pharmacological group this drug belongs to and in case of a tendency to allergies or chronic allergic diseases (atopy, bronchial asthma), inform the doctor about this and express your concerns.

Without exception, all antibiotics cause dysbacteriosis, as well as a decrease in immunity.

In addition, many of these drugs disrupt hematopoietic function, have a nephrotoxic effect (toxic effects on the kidneys, caused by cephalosporins, aminoglycosides), neurotoxic effects (on the brain), hepatotoxic effects (caused by tetracyclines). Many antibiotics disrupt the intrauterine development of a child when used by pregnant women. Aminoglycosides affect hearing.

A huge problem after the use of antibiotics is the development of bacterial resistance to this drug. The instructions already contain warnings about which strains this drug does not work on and in which regions antibiotic resistance has developed. For this reason, instructions increasingly take on the appearance of sheets, and antibiotics cease to work. This global problem is growing more and more every year. Doctors predict the development of complete antibiotic resistance in bacteria in just 15-20 years. This means that mortality from bacterial infections in the absence of new drugs will become widespread.

That is why doctors are currently calling for a complete abandonment of antibiotics in unjustified cases. After all, the reason why bacterial resistance is increasingly increasing is unjustified and incorrect use. Patients prescribe antibiotics to themselves, do not complete the full course, and as a result, the bacteria mutate and the next time they cannot be treated with the drug used.

Be healthy without antibiotics!

Antibiotic therapy has firmly taken one of the leading places in the complex treatment of diseases, the main etiological factor of which is pathogenic microorganisms. Thanks to antibiotics, humanity has received a formidable weapon against many previously dangerous infectious diseases. Over the past 30 years, a large number of antibiotics with different spectrums of action have been synthesized and found clinical use.
If at the beginning of the era of antibiotic use there was almost no mention of the possibility of complications of antibiotic therapy, now the negative properties of antibiotics are known even to non-specialists. A significant number of special works have been devoted to the side effects of these drugs and various complications of antibiotic therapy, which indicates the seriousness and relevance of this problem.
Knowledge of possible adverse reactions during antibiotic therapy is important not only at the stage of prescribing antibiotics by a doctor, but also at the stage of direct implementation of prescriptions. The latter, as is known, is the responsibility of nursing staff.
However, before moving on to an analysis of the main forms of complications of antibiotic therapy, we should briefly touch on the issue of drug resistance, which is important when choosing a drug, its dose, method of administration, and duration of treatment.
It is necessary to strictly distinguish between forms of drug resistance. An example of primary drug resistance is that when treating peritonitis or sepsis caused by Escherichia coli, the use of penicillin will be of no use. Secondary drug resistance occurs as a result of unsystematic treatment, the prescription of small doses of the drug, long-term treatment with one type of antibiotic, or from frequent “encounters” of the microorganism with a certain antibiotic in many patients. To combat drug resistance, it is necessary to clearly know the specificity of the drug for a given type of microorganism, prescribe antibiotics in sufficiently high doses with an optimal rhythm of administration to maintain high concentrations of the drug in the blood. In addition, one type of antibiotic should not be used for more than 5-7 days. The combined use of antibiotics that affect different aspects of the microorganism's metabolism is advisable.
The method of administering antibiotics is of great importance in carrying out effective antibacterial therapy. The most common is oral administration of drugs. Currently, a large number of antibiotics have been created for oral administration, the intake of which provides sufficient therapeutic concentrations in the blood. It should be noted that oral use of antibiotics is most justified for various intestinal infections. However, the availability of these drugs to the population and ease of use often lead to their irrational use, which plays a large role in the development of secondary drug resistance.

Various parenteral methods of administering antibiotics are widely used in medical practice. The most common and recognized is their intramuscular administration. To maintain high concentrations of the drug in the blood in order to make it more effective in certain types of pathology, intravenous or intra-arterial administration of antibiotics is used. Intracavitary antibiotic therapy (administration of drugs into the abdominal, pleural cavities, joint cavities, etc.) has also been proven effective for diseases such as purulent pleurisy, peritonitis, and purulent arthritis. The search for new ways to administer antibiotics continues. An example is the work studying the endolymphatic method of administering antibiotics. This method makes it possible to create and maintain a high concentration of antibiotics with a single daily administration in the lymph nodes of the abdominal and pleural cavities, into which, as is known, there is an outflow of lymph containing pathogenic bacteria during inflammatory processes in these cavities. This technique has proven effective in the treatment of suppurative processes in the pleura, inflammatory infiltrates of the abdominal cavity, inflammatory diseases of the female genital area, and peritonitis.

Complications of antibacterial therapy are very diverse and range from mild discomfort to severe and even fatal outcomes.
Allergic reactions to antibiotics most often occur in sensitized people and, to a lesser extent, in people with congenital intolerance to a particular drug (idiosyncrasy). Allergic reactions usually occur with repeated administration of the drug. Antibiotic doses can be very small (hundredths and thousandths of a gram). Sensitization (increased sensitivity) to a drug can persist for a long time, and can also be caused by drugs that are similar in structure (cross-sensitization). According to various authors, sensitization to antibiotics develops in approximately 10% of patients undergoing antibiotic therapy. Severe allergic conditions occur much less frequently. Thus, according to WHO statistics, for every 70,000 cases of penicillin use, 1 case of anaphylactic shock occurs.
Anaphylactic shock is one of the most severe complications of antibacterial therapy in terms of course and prognosis. In almost 94% of cases, the cause of shock is sensitization to penicillin, but there are known cases of anaphylactic shock with the administration of streptomycin, chloramphenicol, tetracycline, etc. Cases of severe anaphylactic shock have been described that developed when using a penicillin aerosol, after injection with a syringe contaminated with penicillin, when contact with the skin of a small number of penicillin solutions. According to the Ministry of Health, allergic reactions complicated antibacterial therapy in 79.7% of cases, shock developed in 5.9% of patients, of which 1.4% died.
In addition to anaphylactic shock, there are other manifestations of allergies. These include skin reactions that occur immediately after administration of the drug or after a few days (blisters, erythema, urticaria, etc.). Sometimes allergic reactions occur with symptoms of swelling of the face (Quincke's edema), tongue, larynx, accompanied by conjunctivitis, joint pain, fever, an increase in the number of eosinophils in the blood, reactions from the lymph nodes and spleen; At the injection site, patients may develop tissue necrosis (Arthus phenomenon).
In conclusion of this section of the article, I would like to emphasize the importance of tests that determine hypersensitivity to antibiotics. Practice has shown the danger and unreliability of intradermal testing; In patients known to be sensitized to antibiotics, these tests turned out to be negative in 41% of cases; during the tests, allergic complications developed, including allergic shock. Taking this into account, it is recommended to completely abandon intradermal testing.
Unlike allergic reactions, toxic reactions are more specific to each group of antibiotics and are characterized by certain symptoms. Their occurrence is associated with the effect of antibiotics on a specific organ or organ system and depends on the properties of the drug or the action of its breakdown products in the body. Toxic reactions usually occur in cases where antibiotics are used in large doses and over a long period of time. The severity of toxic reactions directly depends on the duration of treatment and the total dose of the drug.
Sometimes the toxic effect of antibacterial therapy is associated with a disruption of the body's enzyme systems involved in the metabolism of the antibiotic, which leads to the accumulation of the antibiotic in the body (the effect of drug accumulation). Possible toxic effects of antibiotics on the nervous system (polyneuritis, paralysis when the drug enters the nerve trunk, neuritis of the auditory nerve up to complete deafness), on the blood, bone marrow (acute hemolysis, decrease in the number of granulocytes, bone marrow depletion), kidneys, liver (dystrophies of these organs with symptoms of dysfunction), local toxic effects (development of necrosis at the site of administration of the antibiotic in high concentrations).

Awareness of the toxic reactions of antibiotics allows you to anticipate possible complications in advance, and if they develop, change the tactics of antibacterial therapy in a timely manner.

Penicillin is the least toxic drug, but increasing its doses leads to some negative phenomena: the development of infiltrates, necrosis, pain, a burning sensation at the site of administration of the antibiotic in high concentrations (more than 500,000 BD in 1 ml).
A specific side effect of streptomycin and its analogues is their effect on the auditory and, to a lesser extent, the optic nerve. With an overdose (more than 1.5-2.0 g per day) of the drug or with prolonged use (more than 3 months), patients begin to complain of decreased hearing, vision, double vision, and impaired coordination. In severe cases, deafness develops. To a lesser extent, streptomycin affects the kidneys, worsening excretory function.
Tetracyclines (oxytetracycline, morphocycline, vibrimycin, metacycline, rhondomycin, oletethrin, tetraolean, sigmamycin) when taken orally have a pronounced local effect on the mucous membrane of the digestive tract, causing damage to the tongue, oral mucosa, and pharynx. Functional disorders also occur: loss of appetite, nausea, vomiting, flatulence, abdominal pain, diarrhea, constipation. The accumulation of tetracyclines in the liver lobules can lead to dysfunction of this organ with symptoms of hepatomegaly and jaundice; sometimes acute toxic liver dystrophy develops. It should be noted that tetracyclines accumulate well in tissues in which the process of calcification occurs - in bones and teeth. An overdose of these drugs can impair the growth and development of bones and teeth. In children treated with tetracycline, pigmentation of baby teeth is sometimes observed, caries occurs, the process of bone mineralization is disrupted and their growth is delayed. It is dangerous to use tetracyclines in pregnant women and newborns. Cases of hepatitis and acute toxic liver dystrophy with fatal outcomes have been described.
When using chloramphenicol (chloramphenicol), the development of bone marrow aplasia was noted. Treatment with chloramphenicol must be carried out under the supervision of a clinical blood test; If the number of reticulocytes decreases, you should stop taking the drug. It is not recommended to use chloramphenicol simultaneously with sulfonamides and amidopyrine, which also have a myelotoxic effect. The use of chloramphenicol is contraindicated in patients with any forms of anemia.
Antibiotics from the macrolide group include erythromycin and oleandomycin (tetraolean, oletethrin, and sigmamycin, a combination of oleandomycin and tetracycline, are widely used in clinical practice). Erythromycin is usually administered orally and produces toxic effects primarily in the gastrointestinal tract. According to some reports, approximately 73% of patients receiving this drug experienced nausea, vomiting, and diarrhea. With long-term use of large doses of erythromycin, liver function suffers, and cholestatic jaundice is sometimes observed. Unlike erythromycin, oleandomycin is practically devoid of any toxic properties.
The group of aminoglycosides is represented by neomycin, monomycin, kanamycin and gentamicin. The most toxic among them is neomycin, the least toxic is kanamycin. Complications when using these antibiotics are associated with their ototoxic, nephrotoxic and curare-like effects. Accumulating in the lymph that washes the elements of the inner ear, aminoglycosides cause irreversible changes in the auditory nerve, which entails decreased or complete hearing loss and vestibular disorders. Often, ototoxic complications occur immediately, without precursors, and, undoubtedly, their severity depends on single and total doses of the drug. The nephrotoxic effect of aminoglycosides is expressed in the appearance of protein and casts in the urine. These signs serve as a signal for complete and immediate discontinuation of the drug. The described toxic phenomena are so dangerous that the indications for the use of aminoglycosides are limited. The combined administration of aminoglycosides with streptomycin is strictly prohibited, since these drugs enhance the toxic properties of each other.
In recent years, new antibiotics have appeared - cephalosporins (ceporin, ceporex, kefzol, keflin, etc.). These antibiotics differ from others in their wide spectrum of action, the absence of allergic reactions and negligible toxicity. As for their nephrotoxic effect, unlike aminoglycosides, which have a direct toxic effect, cephalosporins cause only a secondary effect. It is associated with the accumulation of the drug in the kidneys with existing lesions of the excretory function of the kidneys (pyelonephritis, chronic renal failure, circulatory failure, etc.) The simultaneous use of cephalosporins with antibiotics that have a primary toxic effect on the kidneys is unacceptable.
A complication that can be caused by any group of antibiotics is dysbacteriosis. After all, antibiotics affect not only pathogenic microorganisms, but also a large number of saprophyte microbes that populate the skin and mucous membranes and have a positive effect on metabolic processes in the human body. Irrational use of antibiotics leads to disruption of the harmonious balance between the macroorganism and saprophytes, which entails the development of dysbacteriosis. It should be noted that dysbiosis can occur in severely weakened patients not treated with antibiotics. Dysbacteriosis has a one-time development, which is manifested in a change in the localization of microflora, its appearance in the biliary tract, in the gallbladder, etc. This indicates the destruction of the protective barriers of the macroorganism. In these cases, a second disease sometimes develops, that is, a superinfection occurs. Of particular interest are superinfections caused by yeast-like fungi (candidiasis) and antibiotic-resistant pathogenic staphylococci. Candidiasis of internal organs usually occurs in seriously ill patients and is dangerous in terms of the development of generalized fungal sepsis. Local candidiasis and superficial lesions of the mucous membranes do not pose a danger to the patient and cannot serve as a criterion for discontinuing antibiotics. Taking antifungal drugs such as nystatin, levorin, amphotericin B, including fermented milk products in the diet, and treatment with B vitamins help to eliminate local candidiasis in a timely manner.
Staphylococcal superinfections are characterized by the development of staphylococcal pneumonia and enteritis. The antibiotics of choice in these cases are semisynthetic penicillins and cephalosporins.

The teratogenic effect of antibiotics is associated with the penetration of the latter through the placental barrier. Cases of hearing damage in children born to mothers treated during pregnancy with streptocymin, hearing and kidney damage when using aminoglycoside antibiotics have been described. A slowdown in skeletal formation in the fetus has been noted in some cases when pregnant women took tetracycline. Due to the toxic effect of some antibiotics on the fetus, the use of chloramphenicol, tetracyclines, streptomycin, and aminoglycosides during pregnancy is contraindicated.
In conclusion, I would like to note that the success of antibiotic therapy is largely determined by the prevention or modern detection of certain complications during antibiotic treatment. The condition for this is knowledge of the main forms of these complications.