1. Toxic effects on the macroorganism
The toxicity of antimicrobial agents is due to the similarity of their targets with cellular structures of the macroorganism or specific features of organ blood supply. The risk of developing complications depends on the properties of the drug itself, dosage, route of administration, and the patient's condition. Most frequently, toxicity manifests during prolonged administration due to the accumulation effect (cumulation). Special risk groups include children, pregnant women, and patients with hepatic and renal pathologies.
Main types of organotoxicity:
- Neurotoxicity and ototoxicity: the use of glycopeptides and aminoglycosides can lead to damage to the auditory nerve, up to the development of complete deafness.
- Nephrotoxicity: renal damage is caused by polyenes, polypeptides, aminoglycosides, macrolides, glycopeptides, and sulfonamides.
- General toxic effect: specific to antifungal agents (polyenes, imidazoles).
- Hematotoxicity: suppression of hematopoiesis is characteristic of tetracyclines and sulfonamides. Chloramphenicol (levomycetin) is distinguished separately — its composition contains a nitrobenzene group, which is a direct suppressor of bone marrow function.
Teratogenic and embryotoxic effects: Drugs can severely interfere with the development of the fetus and children. Aminoglycosides and tetracyclines disrupt osteogenesis and chondrogenesis (bone and cartilage development). Tetracyclines also cause permanent brownish discoloration of enamel due to impaired tooth formation. Quinolones specifically damage developing cartilage and connective tissue.
Gray baby syndrome: This is a specific toxicity in newborns caused by chloramphenicol. Infants have not yet fully formed liver enzymes (a deficiency of glucuronyl transferase is observed). As a result, the drug is not metabolized into glucuronides, but accumulates in toxic concentrations. The clinical picture includes a gray skin color, hepatomegaly, vomiting, cardiac pain, and sharp generalized weakness. Prevention of any toxic complications requires strict avoidance of contraindicated agents and careful monitoring of hepatic and renal functions.
2. Dysbiosis and negative impact on the immune system
Dysbiosis (dysbacteriosis) is a direct consequence of the destruction of normal symbiote microflora. Most commonly, it occurs upon the prescription of broad-spectrum agents.
The pathogenesis of dysbiosis leads to impaired gastrointestinal functions, the development of severe avitaminoses, and the emergence of a secondary infection (superinfection). The vacated ecological niche is occupied by resistant opportunistic flora. This is how endogenous infections arise, such as candidiasis or pseudomembranous colitis, the causative agent of which is C. difficile. To prevent dysbiosis, it is recommended to use narrow-spectrum agents, combine antibiotics with antifungal agents (e.g., nystatin), and prescribe vitamin therapy and probiotics.
Negative impact on the immune system: Antibiotics are capable of exerting an immunosuppressive effect, leading to secondary immunodeficiencies and a decrease in overall immune responsiveness. However, the main immunological complication is allergic reactions. The causes of sensitization can be the drug itself, its degradation products, or haptens — complexes of the drug with serum proteins. The frequency of allergic reactions reaches 10%.
- Mild and moderate forms: pruritus, rash, urticaria, angioedema.
- Severe forms: anaphylactic shock (rarely encountered) and delayed-type hypersensitivity.
Drugs with the highest allergenic potential include beta-lactams (especially penicillins), rifamycins, and sulfonamides. The main preventive measure is a thorough allergy history taking.
3. Endotoxic shock, drug interactions, and effects on microbes
Therapeutic endotoxic shock: This is a specific complication that occurs during the treatment of infections caused by Gram-negative bacteria. Under the action of an effective antibiotic, massive death and destruction of bacterial cells occur. A gigantic amount of endotoxin is released into the bloodstream all at once. Clinically, this manifests as a temporary but sharp deterioration in the patient's condition.
Drug interactions: Chemotherapeutic agents actively influence the pharmacokinetics of other medications, causing their potentiation or inactivation. For example, erythromycin stimulates the production of liver enzymes, leading to an undesirably accelerated metabolism and elimination of other drugs taken by the patient.
Alteration of the properties of microorganisms themselves: The adverse impact of chemotherapeutic agents is not limited to the destruction of the pathogen. Bacteria adapt, leading to the formation of atypical forms.
- Formation of L-forms — bacteria that have completely lost their cell wall.
- Appearance of persistent forms and alteration of initial biological properties.
The clinical significance of these transformations is colossal: the atypical behavior of the pathogen greatly complicates the laboratory diagnosis of infections. In addition, in the process of evolution of microbial responses, antibiotic dependence (rarely encountered) and antibiotic resistance (very frequently encountered) can form.
To memorize the groups of antibiotics with the highest risk of allergic reactions, use the abbreviation PRS: Penicillins (beta-lactams), Rifamycins, Sulfonamides.
Class and exam questions
Why might a patient's condition sharply worsen during the treatment of Gram-negative infections?
This is a manifestation of therapeutic endotoxic shock. The antibiotic causes massive death of Gram-negative bacteria, their cells are destroyed, and a large amount of endotoxin is released into the blood all at once, causing a temporary deterioration in condition.
What is the cause of gray baby syndrome?
The syndrome is caused by the drug chloramphenicol (levomycetin). In newborns, there is a deficiency of the enzyme glucuronyl transferase, due to which the drug is not metabolized by the liver and accumulates in the body to toxic concentrations.
How do antibiotics interfere with the laboratory diagnosis of infections?
Under the influence of chemotherapeutic agents, bacteria can lose their cell wall (L-forms), transition into a persistent state, and alter their biological properties. This complicates their detection and identification by standard laboratory methods.
What causes the development of pseudomembranous colitis against the background of chemotherapy?
This is the result of profound dysbiosis. The administration of broad-spectrum antibiotics destroys the normal intestinal microflora, which allows opportunistic microorganisms, specifically C. difficile, to multiply unhindered.
What else to study on this topic
- Molecular mechanisms of antibiotic resistance formation in bacteria
- Properties and clinical significance of microbial L-forms
- Pathogenesis and diagnosis of pseudomembranous colitis
- Specifics of probiotic use for the correction of dysbiosis
- Principles of rational antimicrobial chemotherapy
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