Antimicrobial drugs

According to the spectrum of activity, antimicrobial drugs are divided into: antibacterial, antifungal and antiprotozoal. In addition, all antimicrobial agents are divided into drugs of a narrow and wide spectrum of action.

Drugs with a narrow spectrum of action mainly on gram-positive microorganisms include, for example, natural penicillins, macrolides, lincomycin, fusidin, oxacillin, vancomycin, cephalosporins of the first generation. The drugs with a narrow spectrum of action mainly on gram-negative rods include polymyxins and monobactams. Broad-spectrum drugs include tetracyclines, levomycetin, aminoglycosides, most semi-synthetic penicillins, cephalosporins starting from the 2nd generation, carbopenems, fluoroquinolones. The antifungal drugs nystatin and levorin have a narrow spectrum (only against candida), and clotrimazole, miconazole, amphotericin B have a wide spectrum.

According to the type of interaction with the microbial cell, antimicrobials are divided into:

• bactericidal-irreversibly disrupt the functions of the microbial cell or its integrity, causing the immediate death of the microorganism, are used in severe infections and in weakened patients
• bacteriostatic-reversibly block cell replication or division, are used for non-severe infections in untreated patients.

According to acid resistance, antimicrobials are classified into:

• acid-resistant – can be used orally, for example, phenoxymethylpenicillin
• acid-resistant – intended only for parenteral use, for example, benzylpenicillin.

Currently, the following main groups of antimicrobial drugs are used for systemic use.

Antimicrobial drugs: Lactam antibiotics

Lactam antibiotics (table 1) are the least toxic of all antimicrobial drugs, since, disrupting the synthesis of the bacterial cell wall, they do not have a target in the human body. Their use in the presence of sensitivity to pathogens is preferable. Carbapenems have the widest spectrum of action among lactam antibiotics, they are used as reserve drugs-only for infections resistant to penicillins and cephalosporins, as well as for hospital and polymicrobial infections.

Antibiotics of other groups have different mechanisms of action. Bacteriostatic drugs violate the stages of protein synthesis on ribosomes, bactericidal drugs violate either the integrity of the cytoplasmic membrane, or the process of DNA and RNA synthesis. In any case, they have a target in the human body, therefore, compared to lactam preparations, they are more toxic, and should be used only if it is impossible to use the latter.

Synthetic antibacterial drugs also have different mechanisms of action: inhibition of DNA gyrase, violation of the inclusion of PABA in DGFK, etc. They are also recommended for use if it is impossible to use lactam antibiotics.

Side effects of antimicrobial drugs, their prevention and treatment

Antimicrobials have a number of different side effects, some of which can lead to serious complications and even death.

Allergic reactions

Allergic reactions can occur when using any antimicrobial drug. Allergic dermatitis, bronchospasm, rhinitis, arthritis, Quincke’s edema, anaphylactic shock, vasculitis, nephritis, lupus-like syndrome may develop. They are most often observed with the use of penicillins and sulfonamides. Some patients develop a cross-allergy to penicillins and cephalosporins. Allergies to vancomycin and sulfonamides are often noted. Very rarely, allergic reactions are given by aminoglycosides and levomycetin.

Prevention is facilitated by a thorough collection of an allergic history. If the patient cannot indicate which antibacterial drugs he has had allergic reactions to, it is necessary to perform tests before the introduction of antibiotics. The development of an allergy, regardless of the severity of the reaction, requires the immediate withdrawal of the drug that caused it. Subsequently, the introduction of even antibiotics similar in chemical structure (for example, cephalosporins in case of allergy to penicillin) is allowed only in cases of extreme necessity. Treatment of the infection should be continued with drugs of other groups. In severe allergic reactions, intravenous administration of prednisone and sympathomimetics, infusion therapy is required. In mild cases, antihistamines are prescribed.

Superinfection, including dysbiosis

The probability of dysbiosis depends on the breadth of the spectrum of action of the drug. The most frequently occurring candidomycosis develops with the use of narrow – spectrum drugs after a week, with the use of broad-spectrum drugs-already from one tablet. However, cephalosporins relatively rarely give a fungal superinfection. Lincomycin is on the 1st place in terms of the frequency and severity of the caused dysbiosis. Violations of the flora when using it can take the character of pseudomembranous colitis – a severe intestinal disease caused by clostridium, accompanied by diarrhea, dehydration, electrolyte disorders, and in some cases complicated by perforation of the colon. Glycopeptides can also cause pseudomembranous colitis. Tetracyclines, fluoroquinolones, and levomycetin often cause dysbiosis.

Dysbiosis requires the withdrawal of the drug used and long-term treatment with eubiotics after preliminary antimicrobial therapy, which is carried out according to the results of the sensitivity of the microorganism that caused the inflammatory process in the intestine. Antibiotics used for the treatment of dysbiosis should not affect the normal intestinal autoflora – bifido and lactobacilli. However, metronidazole or, alternatively, vancomycin is used in the treatment of pseudomembranous colitis. Correction of water-electrolyte disorders is also necessary.

Table 1

Drug group		Name	Characteristics of the drug
Penicillins	Natural penicillins	sodium and potassium salts of benzylpenicillin	administered only parenterally, effective for 3-4 hours			they are highly effective in their spectrum of action, but this spectrum is narrow, in addition, the drugs are unstable to lactamases
		bicillin 1,3,5	administered only parenterally, effective from 7 to 30 days
		phenoxymethylpenicillin	drug for oral administration
	Anti-staphylococcal	oxacillin, methicillin, cloxacillin, dicloxacillin	have less antimicrobial activity than natural penicillins, but are resistant to lactamases of staphylococci, can be used per os
	Amino-penicillins	ampicillin, amoxicillin, bacampicillin	broad-spectrum drugs, can be used per os, but unstable to beta-lactamases
	Combined bathrooms	Ampiox-ampicillin + oxacillin	a broad-spectrum drug resistant to beta-lactamases can be used per os
	Antisine-purulent	carbenicillin, ticarcillin, azlocillin, piperacillin, meslocillin	have a wide spectrum of action, act on strains of Pseudomonas aeruginosa that do not produce beta-lactamases, during treatment, the rapid development of resistance to them of bacteria is possible
	Protected from lactamases – preparations with clavulanic acid, tazobactam, sulbactam	amoxiclav, tazocin, thimentin, cyazine, unazin	the drugs are a combination of broad-spectrum penicillins and beta-lactamase inhibitors, therefore they act on bacterial strains that produce beta-lactamases
Cephalosporins	1st generation	cefazolin	antistaphylococcal drug for parenteral ed.		are not resistant to lactamases, they have a narrow spectrum of action		with each generation of cephalosporins, their spectrum expands and their toxicity decreases, cephalosporins are well transferred and occupy the first place in terms of frequency of use in hospitals
		cephalexin and cefaclor	apply per os
	2 generations	cefaclor, cefuraxime	apply per os		resistant to lactam, the spectrum includes both gram-positive and gram-negative bacteria
		cefamandol, cefoxitin, cefuroxime, cefotetan, cefmetazole	apply parenterally only
	3 generations	ceftizoxime, cefotaxime, ceftriaxone, ceftazidime, cefoperazone, cefmenoxime	only for parenteral use, with anti-inflammatory activity		resistant to lactamases of gram-positive bactenia, not effective in staphylococcal infections
		cefixime, ceftibutene, cefpodoxime, cefetamet	used per os, have anti-anaerobic activity
	4 generations	cefipim, cefpiron	the widest range of actions, applied parenterally
Cephalosporins with beta-lactamase inhibitors		sulperazone	Has a spectrum of action of cefoperazone, but it also acts on lactamase-producing strains
Carbapenems	imipenem and its combination with cilostatin, which prevents destruction in the kidneys, – thienam	Is more active to gram-positive microorganisms		they have the widest spectrum of action of lactam antibiotics, including anaerobes and blue-purulent bacillus, and are resistant to all lactamases, they practically do not develop resistance to them, they can be used in almost any pathogens, excluding methicillin-resistant strains of staphylococcus, and in the form of monotherapy even in severe infections, they have an aftereffect
	meropenem	Is more active against gram-negative microorganisms
	ertapenem
Mono-bactams	aztreonam	a drug of a narrow spectrum, acts only on gram-negative rods, but is very effective and resistant to all lactamases