Catad_tema Children's infections - articles

Antibacterial therapy of respiratory diseases in the outpatient practice of a pediatrician

N.A. Korovina, A.L. Zaplatnikov, I.N. Zakharova

RATIONAL ETIOTROPIC THERAPY OF BACTERIAL INFECTIONS IN CHILDREN

Basic principles of rational antibacterial therapy

One of the main components of adequate etiopathogenetic treatment of bacterial infections, regardless of the severity and localization of the inflammatory process, is rational antibiotic therapy. The classic requirement for the choice of antibacterial therapy is the prescription of drugs in strict accordance with the antibiotic sensitivity of the pathogen. In addition, the ability of the antibacterial agent to penetrate into organs affected by infectious inflammation must be taken into account. This will allow us to assess the reality of creating effective therapeutic concentrations of the drug in the affected organs and tissues. Factors such as the epidemiological situation, the age of the child and his background pathology, as well as concomitant therapy, must be taken into account. Taking into account the age of the child, the diseases he suffers and the treatment carried out for this reason, will allow choosing from the entire arsenal of effective antibacterial agents those drugs whose use will not be accompanied by changes in pharmacokinetics and pharmacodynamics. This will help reduce the risk of developing side effects and unwanted effects of antibiotic therapy.

To choose the most effective drug from a large arsenal of modern antibacterial agents, it is necessary to take into account their degree of antimicrobial activity against specific pathogens. For objective comparative characterization of the antibacterial activity of various drugs in vitro, and, consequently, their supposed effectiveness against certain pathogens, standard methods are used. One of the main methods for microbiological testing of the sensitivity of pathogens to antibacterial agents is the determination of the minimum inhibitory concentration (MIC) of a pharmacological drug against a specific microorganism. Traditionally, the minimum inhibitory concentration of an antibacterial agent is determined, at which in vitro the growth of 90% of the strains of the identified pathogen is suppressed (MIC 90). MIC is the minimum inhibitory concentration at which 90% of pathogen strains are suppressed by an antimicrobial agent (in a microbiological study with a standard disk of this antimicrobial agent).

In subsequent sections of this manual, MIC 90 values ​​will be frequently encountered to characterize the antimicrobial activity of various antibacterial agents against specific pathogens. The authors consider it advisable to draw special attention of readers to the need for an independent comparative analysis of the values ​​of this indicator of various antibacterial drugs.

Rational antibacterial therapy is determined by a number of factors:

Nosological form of the infectious-inflammatory process;
- degree of sensitivity of the pathogen to antimicrobial agents;
- the degree of activity of the antimicrobial agent against a specific pathogen;
- the ability to achieve effective therapeutic concentrations of antimicrobial agents in damaged organs and tissues;
- knowledge of the characteristics of pharmacokinetics, pharmacodynamics and taking into account possible side effects of the selected drugs in children of different ages;
- the age of the child, his background pathology, as well as concomitant therapy.

Empirical choice of initial antibiotic therapy

Despite the fact that priority in the choice of antimicrobial therapy for infectious inflammation belongs to identifying the pathogen and determining its antibacterial sensitivity, outpatient doctors have to begin treatment of sick children more often without prospects for further verification of the etiological agent. The effectiveness of the choice of initial antibiotic therapy largely depends on the doctor’s knowledge of the epidemiological situation and likely potential pathogens that most often cause infectious processes of various localizations depending on the age of children. Knowledge and understanding of these points will improve the effectiveness of initial therapy. Empirical consideration of the above components will allow targeted antibacterial therapy to be carried out already at the first stage of treatment of a sick child (V.K. Tatochenko, 1996).

The choice of initial antibacterial therapy for infectious and inflammatory diseases in an outpatient setting is carried out empirically.

The empirical choice of initial antibacterial therapy is a choice that takes into account the antibacterial sensitivity of the suspected pathogens of a given nosological form of infection and world experience in the use of AB drugs for certain infectious and inflammatory diseases (N.V. Beloborodova, 1997).

The empirical choice of initial antibiotic therapy is not an intuitive choice, not at random. This is a choice based on convincing and reliable data on probable (potential) pathogens for various nosological forms of the infectious process in children of a certain age.

Thus, for the effective treatment of respiratory infectious diseases, the empirical choice of initial antibiotic therapy should take into account the location of the lesion, the likely pathogens and their potential sensitivity to antimicrobial agents. We will consider the etiological structure of acute respiratory diseases, the antibacterial sensitivity of pathogens of these infections and the tactics of empirical selection of etiotropic therapy in the following sections.

CLASSIFICATION OF CLINICAL FORMS OF ACUTE DISEASES OF THE RESPIRATORY TRACT IN CHILDREN

Timely diagnosis and rational therapy of various bronchopulmonary diseases requires the mandatory presence of a generally accepted classification, unified and very specific approaches to methodology and interpretation of the results of clinical and auxiliary research.

Conditional separation in the respiratory tract of the upper and lower sections is considered generally accepted (R.E. Berman et al., 1983; S.V. Rachinsky, V.K. Tatochenko, 1987). The pathological process during acute respiratory infection can involve both the upper and lower parts of the respiratory tract. At the same time, the degree of damaging effect of different parts of the respiratory tract, their clinical severity and significance differ significantly, which allows, with a certain degree of convention, to speak of predominant inflammation of the upper or lower respiratory tract.

Diseases of the upper respiratory tract include those nosological forms of respiratory pathology in which the localization of lesions is located above the larynx. Among the clinical forms of diseases of the upper respiratory tract, rhinitis, pharyngitis, nasopharyngitis, tonsillitis, sinusitis, laryngitis, and epiglotitis are distinguished. This group of diseases also includes acute otitis media. Among diseases of the lower respiratory tract, clinical forms such as tracheitis, tracheobronchitis, bronchitis and pneumonia are distinguished.

Agreed consensus provisions on the classification of the main clinical forms of bronchopulmonary diseases in children

In November 1995, at a joint meeting of a symposium of pediatric pulmonologists of Russia and the Problem Commission on Pediatric Pulmonology and Hereditary Lung Diseases of the Scientific Medical Council of the Ministry of Health of the Russian Federation, a new classification of nonspecific respiratory diseases was adopted, the main provisions of which are presented below.

Bronchitis (classification and diagnostic criteria)

Bronchitis is an inflammatory disease of the bronchi of various etiologies.

Criteria for diagnosing bronchitis: cough, dry and variable moist rales. An X-ray examination reveals the absence of infiltrative or focal changes in the lung tissue with possible 2-sided enhancement of the pulmonary pattern and the roots of the lung.

There are simple, obstructive and obliterating forms of acute bronchitis, recurrent (simple and obstructive) and chronic bronchitis.

Acute bronchitis (simple)- bronchitis occurring without signs of bronchial obstruction.

Acute obstructive bronchitis, bronchiolitis- acute bronchitis, occurring with signs of bronchial obstruction.

Diagnostic criteria: Obstructive bronchitis is characterized by the development of bronchial obstruction syndrome. Bronchiolitis is one of the clinical variants of acute obstructive bronchitis. Bronchiolitis is characterized by the development of more severe respiratory failure and an abundance of fine wheezing.

Acute obliterating bronchiolitis- a severe disease of viral or immunopathological origin, leading to obliteration of bronchioles and arterioles.

Recurrent bronchitis- bronchitis without obstruction, episodes of which are repeated 2-3 times over 1-2 years against the background of ARVI. Episodes of bronchitis are characterized by a duration of clinical symptoms of up to 2 weeks or more.

Recurrent obstructive bronchitis- obstructive bronchitis, episodes of which are repeated in young children against the background of ARVI. Unlike bronchial asthma, obstruction does not have a paroxysmal nature and is not associated with exposure to non-infectious allergens.

Chronic bronchitis- as an independent disease in children, it is rare; as a rule, it is a manifestation of other chronic diseases (cystic fibrosis, ciliary dyskinesia, and other chronic lung diseases).

Criteria for diagnosing chronic bronchitis- productive cough, variable moist rales in the lungs, heard for several months, 2-3 exacerbations per year with a total duration of the disease of at least 2 years.

Chronic bronchitis (with obliteration)- is the result of the consequences of acute obliterating bronchiolitis. McLeod syndrome (one-sided pulmonary “supertransparency”) is one of the variants of this disease.

Criteria for diagnosing chronic bronchitis (with obliteration)- respiratory failure of varying severity, persistent crepitus and fine bubbling moist rales in the lungs, increased transparency of the lung tissue during X-ray examination and a sharp decrease in pulmonary blood flow in the affected parts of the lungs during scintigraphic examination.

Pneumonia (classification and diagnostic criteria)

The uniform diagnostic criteria for pneumonia are the clinical picture and typical radiological signs. This approach to diagnosis was recognized by most researchers, supported by WHO specialists, and was adopted as the basis for the development of the X revision of the international classification of diseases and causes of death (ICD IX (1975) and X revisions (1992); WHO, 1990).

For morphological confirmation of the diagnosis of pneumonia, manifestations of acute infectious inflammation of the terminal respiratory sections of the lungs and the presence of exudate in the alveoli are mandatory.

Pneumonia is an acute infectious and inflammatory disease of the lungs with predominant damage to the respiratory sections and the obligatory presence of intra-alveolar exudation (ICD IX (1975) and X (1992)).

In clinical practice, for the diagnosis of pneumonia it is necessary to use the “gold standard” (S.V. Rachinsky, V.K. Tatochenko. 1987; WHO, 1990).

"Gold standard" for diagnosing pneumonia.

Pneumonia is an acute infectious and inflammatory disease of the lungs, diagnosed not only by the syndrome of respiratory distress and physical findings, but also by infiltrative, focal or segmental changes on an x-ray.

These diagnostic criteria make it possible to clearly distinguish pneumonia from many inflammatory diseases of the bronchopulmonary system, in which diffuse rather than focal or infiltrative changes in the lungs are detected on an x-ray (S.V. Rachinsky, V.K. Tatochenko, 1987).

Most researchers believe that the most optimal criterion for the classification of pneumonia should be the etiological principle of its construction. However, the lack of microbiological express diagnostics available for widespread practice does not allow a classification strictly based on the etiological factor. The results of multicenter epidemiological and microbiological studies to determine the etiology of respiratory infections made it possible to identify the most common pathogens of certain forms of pneumonia and the degree of their antibacterial resistance in various age and climatic geographic populations in children. This allows us to judge with a high degree of probability the most common potential pathogens, the degree of their antibiotic sensitivity, depending on the epidemiological characteristics and clinical variants of respiratory infections, including pneumonia. Thus, it was noted that the etiology of pneumonia depends on where and how the infection occurred, as well as on the age of the sick child. It is noted that under “home” (outpatient) conditions of infection, the most common etiological factors of pneumonia, depending on age, can be pneumococcus, Haemophilus influenzae, mycoplasma and moraxella. While in conditions of hospital (nosocomial) infection, the causative agents of pneumonia are often staphylococci and bacillary flora (Escherichia coli and Pseudomonas aeruginosa, Proteus, Klebsiella, etc.).

These factors are reflected in the new classification of pneumonia (Table 1).

Taking into account the presented epidemiological criteria for the classification of pneumonia, a doctor with a greater degree of confidence can empirically determine the range of the most likely causative agents of pneumonic infection. The latter allows you to rationally choose the initial etiotropic treatment and achieve a positive result of therapy, even in the absence of bacteriological control.

The pathogenesis and morphological picture of inflammation in focal, focal-confluent and segmental pneumonias are directly related to the primary infectious-inflammatory process in the bronchi. Therefore, focal, segmental and focal-confluent variants of inflammation of the lung tissue are classified as bronchopneumonia. These are the most common forms of pneumonia in childhood.

Lobar pneumonia is diagnosed in the presence of a typical clinical picture of pneumococcal pneumonia (acute onset with characteristic physical changes and cyclical course, rare tendency to destruction) and homogeneous lobar or sublobar infiltration on an x-ray. In young children, the typical clinical picture may be due to damage not to the entire lobe of the lung, but to only several segments (V.K. Tatochenko,

1987). Academician G.N. Speransky believed that the presence of a typical picture of lobar pneumonia in a young child is a reflection of the “degree of maturity of the response (resistance)” of his body. Currently, due to the widespread and timely use of antibacterial agents for respiratory infections, lobar pneumonia is a rare variant of infectious inflammation of the lung tissue (A.B. Kaukainen et al., 1990).

Table 1.
Classification of pneumonia (based on the results of a symposium of pediatric pulmonologists of Russia and a meeting of the Problem Commission on Pediatric Pulmonology and Hereditary Lung Diseases of the Scientific Medical Council of the Ministry of Health of the Russian Federation).

Depending on the conditions of infection: Community-acquired(“home”, outpatient). The most common pathogens: pneumococcus, Haemophilus influenzae, mycoplasma, moraxella. In-hospital(hospital, nosocomial). The most common pathogens: staphylococcus, Escherichia coli, Pseudomonas aeruginosa, Proteus, Serration, etc. Intrauterine.

Depending on the morphological changes: Bronchopneumonia: Focal; - segmental; - focal-confluent. Croupous. Interstitial.

Depending on the speed of resolution of the pneumonic process: Acute; Lingering.

IN depending on the nature of the flow: Uncomplicated; Complicated: pulmonary complications (pleurisy, destruction, abscess, pneumothorax, pyopneumothorax) extrapulmonary complications (infectious-toxic shock, disseminated intravascular coagulation syndrome, circulatory failure, adult-type respiratory distress).

Interstitial pneumonia is also a rare form of infectious-inflammatory lesion of the lungs. Interstitial pneumonia includes acute lesions of the lung tissue with predominant damage to the interstitium. As a rule, interstitial pneumonia is caused by pneumocysts, intracellular microorganisms and fungi.

Depending on the speed of resolution of the pneumonic process, acute and protracted course of pneumonia is distinguished. If the reverse development (resolution) of inflammatory changes in the lungs occurs within a period of up to 6 weeks, then the course of pneumonia is considered acute. Protracted pneumonia includes those forms in which the clinical and instrumental signs of the pneumonic process persist for 1.5 to 8 months from the onset of the disease.

ETIOLOGICAL STRUCTURE OF ACUTE INFECTIOUS DISEASES OF THE UPPER RESPIRATORY TRACT IN CHILDREN AND TACTICS FOR SELECTION OF RATIONAL ETIOTROPIC THERAPY

Etiological structure of acute infectious diseases of the upper respiratory tract in children

Among the etiological factors of acute infectious diseases of the upper respiratory tract, the leading place (in 95% of cases) is occupied by viruses (V.K. Tatochenko, 1987). At the same time, among acute respiratory viral infections (ARVI) in children, diseases of non-influenza etiology predominate (WHO, 1980). The most common cause of ARVI in children, especially young children, is respiratory syncytial virus (PC virus) (I Orstavik et al., 1984). Mycoplasma infection is associated with up to 6-10% of cases of acute respiratory diseases in children. The epidemic nature of respiratory mycoplasmosis has been noted with an interval of 4-8 years without a clearly defined seasonality and connection with climatogeographic zones (R.A. Broughton, 1986; G. Peter et al., 1994).

The tropism of viral pathogens to certain parts of the respiratory tract has been established. Thus, rhinoviruses and coronaviruses more often cause the “common cold” in the form of rhinitis and nasopharyngitis (V.K. Tatochenko, 1987; N.E. Kaue et al., 1971; J.P. Fox et al., 1975). Coxsackie viruses also more often cause acute diseases of the nasopharynx, while parainfluenza viruses are responsible for the development of stenosing laryngitis and tracheobronchitis, and the vast majority of cases of pharyngoconjunctivitis are caused by adenovirus infection (R.E. Berman, V.C. Vaughan, 1984).

It has been established that among acute respiratory infections, especially in children attending child care institutions, mixed viral-viral infections account for a high proportion - up to 7-35% (S.G. Cheshik et al., 1980). It should also be noted that among acute respiratory infections there are both isolated bacterial and mixed viral-bacterial lesions. The latter are associated with the activation of microbial autoflora due to disruption of the barrier function of the respiratory tract and a decrease in the body's defenses, as well as superinfection with bacterial agents. The addition of a bacterial infection leads to an increase in the severity of the disease and may be the main reason for the unfavorable outcome of the disease. At the same time, there are also primary bacterial lesions of the upper respiratory tract. Thus, acute pharyngitis, follicular and lacunar tonsillitis in more than 15% of cases are caused by isolated exposure to group A beta-hemolytic streptococcus. Acute purulent otitis media and sinusitis are mainly caused by pneumococcus, Haemophilus influenzae, Moraxella catarrhalis and pyogenic streptococcus (E.R. Wald, 1992; C. D. Bluestone et al., 1994). Bullous inflammation of the tympanic septum (myringitis) is associated with mycoplasma infection. The etiological role of Haemophilus influenzae (type B) in the development of acute epiglotitis has been proven. The presented data on the most common bacterial pathogens of acute respiratory infections of the upper respiratory tract are summarized and presented in table form (Table 2).

Tactics for choosing rational etiotropic therapy for acute infectious diseases of the upper respiratory tract in children

Unfortunately, to date there is no unified approach to the etiotropic treatment of respiratory viral infections in children. Drugs such as amantadine and rimantadine, successfully used in the treatment of influenza (especially effective against strain A 2) in adults, are officially approved in pediatric practice only for children over 7 years of age. The use of ribavirin, an effective viricidal drug against RS infection and influenza viruses, is possible only in a hospital setting with a specialized intensive care unit.

Since the late 70s of this century, leukocyte interferon for intranasal or inhalation use has been widely used for the prevention and treatment of initial manifestations of ARVI in children (A.B. Kornienko et al., 1980; L.V. Feklisova et al., 1982 and etc.). In recent years, recombinant interferon alpha-2b for rectal use (Viferon) has appeared on the domestic pharmaceutical market, which potentially expands therapeutic options in the treatment of ARVI in children.

Table 2.
The main bacterial pathogens of acute diseases of the upper respiratory tract in children.

Empirical choice of initial etiotropic therapy for acute bacterial diseases of the upper respiratory tract in children

Certain forms of respiratory infections (tonsillitis, pharyngitis, purulent sinusitis and otitis) or the development of bacterial complications of ARVI require mandatory and timely inclusion of antibacterial therapy in the complex of treatment measures. Timely and adequate etiotropic therapy for tonsillitis, pharyngitis and exacerbation of chronic tonsillitis in children with a hereditary predisposition to rheumatic diseases can reduce the risk of developing rheumatism (N.A. Belokon, 1987). A rational choice of initial antibiotic therapy for purulent sinusitis and otitis media allows one to prevent such serious complications as mastoiditis, bacteremia and meningitis (G.S. Giebink et al., 1991).

The basic principles of selection and tactics of initial antibiotic therapy in the treatment of bacterial infections of the upper respiratory tract in children are presented in Table 3.

It should be noted that the choice of initial etiotropic therapy may vary depending on epidemiological features, the nature of the pathogen, the clinical form of the disease and the background conditions of the child. Table 3 summarizes the generally accepted, consensual provisions on rational

Table 3.
Principles of selection and tactics of initial etiotropic therapy for mild and moderate clinical forms of bacterial infections of the upper respiratory tract in children

Clinical options	Main pathogens	Drugs of choice	Alternative drugs
Pharyngitis	Streptococcus pyogenes (p-hemolyt. Group A)
Angina	Streptococcus pyogenes (|3-hemolyt. Group A)	Natural Penicillin (Oral Forms)	If you are allergic to beta-l actinic antibiotics: macrolides or TMP/SM
Sinusitis	Streptococcus pneumoniae; Haemophilus Influenzae; Moraxella; catarrhalis.
Acute otitis media	Streptococcus pneumoniae; Haemophilus Influenzae; Moraxella catarrhalis.	“Protected” semi-synthetic penicillins (Oral forms) or cephalosporins 2P (Oral forms)	For allergies to beta-lactam ABs: TMP/SM or macrolides + sulfisoxazole

It should be noted that the choice of initial etiotropic therapy may vary depending on epidemiological features, the nature of the pathogen, the clinical form of the disease and the background conditions of the child. Table 3 summarizes the generally accepted, consensus statements on rational antibacterial therapy for upper respiratory tract infections. The column “drugs of choice” indicates antibacterial agents, the use of which is most rational for these clinical variants of respiratory infections. The column “alternative drugs” presents antibacterial agents that can be considered as “starter” for the specified nosological forms, if taking the “drugs of choice” is impossible for some reason (intolerance, allergy to medications of this group, unavailable in the pharmacy chain, etc. ).

Antibacterial therapy for tonsillitis and pharyngitis in children on an outpatient basis The empirical choice of initial etiotropic therapy for bacterial inflammation of the upper respiratory tract, as well as other infectious respiratory diseases in children, is based on reliable data from multicenter population studies to determine the main microbial pathogens and their resistance to antibacterial drugs.

Group A beta-hemolytic streptococcus, the main causative agent of sore throats and pharyngitis, continues to remain highly sensitive to natural beta-lactam antibiotics. This allows us to recommend natural penicillins as the drugs of choice for these diseases and for exacerbation of chronic tonsillitis. In this case, in mild and moderate cases, it is advisable to prescribe penicillins for oral administration. A contraindication to the prescription of penicillins is anamnestic evidence of allergic reactions to beta-lactam antibiotics (to all, not just penicillins). In this case, the drugs of choice are macrolides and biseptol (trimethoprim/sulfamethoxazole (TMP/SM)).

Table 4 presents the tactics of initial etiotropic therapy for mild and moderate forms of pharyngitis and tonsillitis in children. The main groups of drugs are indicated in large, underlined font. The international names of some of the most typical drugs from each group of antibacterial agents presented are also indicated. International names of active substances are presented in italics. Dosages and methods of administration are given below the international names of the drugs. In parentheses, under the name of the pharmacological group (in small italics), are the trade names of some of the most commonly used drugs.

Antibacterial therapy for sinusitis and acute otitis media in children.

The data on the development of antibiotic resistance of the main pathogens of purulent sinusitis and otitis media (pneumococcus, Haemophilus influenzae and Moraxella) look alarming (J.O. Klein., 1993; R. Cohen, 1997). Reports that appeared in the early 80s of this century about an increase in the frequency of isolation of penicillin-resistant strains of Streptococcus pneumoniae were subsequently confirmed by a decrease in the clinical effectiveness of traditionally used penicillins, macrolides and sulfonamides for pneumococcal infections (K.R. Klugman et al., 1986; Wust J . et al., 1987, etc.). The rate of increase in antibiotic resistance in the main causative agents of bacterial respiratory tract infections in children is especially alarming. Thus, over a 10-year period (from 1984 to 1994) in the Scandinavian countries, Great Britain, Spain, and France, an increase in the proportion of penicillin-resistant pneumococcal strains was noted from 1.5-3% to 32-55% (P. Geslin, 1995 ; R. Cohen, 1997). It has also been established that more than 90% of Moraxella strains and more than 20% of Haemophilus influenzae strains produce beta-lactamase (penicillinase). Table 5 presents summarized data on the frequency of isolation of beta-lactamase-producing strains among the main causative agents of bacterial infections of the upper respiratory tract in children.

Table 4.
Initial etiotropic therapy of mild and moderate forms of pharyngitis and tonsillitis in children (AB drugs for oral use)

Clinical options	Main pathogens	Drugs of choice	Alternative drugs
Pharyngitis	Streptococcus	Natural	Macrolides*.
Angina	pyogenes	penicillins	(erythromycin, macro-
	(P-hemolyt.	(V-penicillin,	pen, klacid, sumamed,
	Group A)	smallpox, cleacyl,	rulid).
		megacillin-oral,	Erythromycin**
		phenoxymethyl peni-	Daily dose: 30-50
		cillin)	mg/kg,
		Phenoxy methyl l peni-	Multiplicity - 4 rubles. per day
		cillin Daily	Course - 7-10 days.
		dose: up to 1 0 years - 50-	Midecamycin
		100 thousand units/kg,	Daily dose 30-50
		over 10 years old - 3	mg/kg, Multiplicity 2-3 r.
		million units per day.	per day. Course 7-10
		Frequency of reception	days or
		4-6 times a day for 1	TPM/SM (Biseptol).
		an hour before meals or 2 hours	Daily dose: 6-8
		hours after eating.	mg/kg by TMP.
		Course 5-10 days.	Multiplicity of reception - 2
			once a day. TO
			Course - 5-6 days

* drugs representing macrolides in the table are selected as the most characteristic for different chemical subgroups (14; 15; 16 members) of macrolide antibiotics;
** - erythromycin, due to the currently available “new” macrolide drugs, which are less likely to cause side effects, is not recommended for use in infants and preschool children.

The data presented in Tables 2 and 5 must be taken into account when initially choosing antibacterial therapy for acute otitis media and sinusitis. In this case, the choice should be made in favor of drugs with a wide spectrum of antibacterial action (the ability to suppress both gram-positive - pneumococcus and streptococcus pyogenes, and gram-negative pathogens - Haemophilus influenzae and Moraxella), and that are resistant to the effects of bacterial beta-pactamase. Therefore, it is considered justified to include semisynthetic penicillins, “protected” from the inhibitory effects of beta-lactamases and 2nd generation cephalosporins, as first-line drugs (drugs of choice) for the treatment of acute otitis media and sinusitis. At the same time, highly effective forms of antibacterial drugs for oral administration have recently appeared in the arsenal of practicing doctors. They should be given preference in the treatment of mild and moderate forms of sinusitis and acute otitis media on an outpatient basis.

Table 5.
Frequency of isolation of beta-lactamase-producing strains among the main causative agents of bacterial infections of the upper respiratory tract in children (%)*

* - filed by Red Book, 1994: J.P. Sanford, 1994; P. Geslin. 1995; R. Cohen. 1997.

Among the oral forms of “protected” semi-synthetic penicillins, it is more rational to use those combinations that include amoxicillin. Amoxicillin is an active metabolite of ampicillin with the same spectrum of antibacterial action, but is much more active than its predecessor - 5-7 times (Yu.B. Belousov, V.V. Omelyanovsky, 1996; J.O. Klein., 1993). The advantages of amoxicillin over ampicillin are summarized in Table 6.

Table 6.
Comparative characteristics of amoxicillin and ampicillin*

* - adapted from “Clinical pharmacology of respiratory diseases” (Yu.B. Belousov, V.V. Omelyanovsky, 1996).

The use of a combination of amoxicillin with substances that “protect” it from the inhibitory effect of bacterial beta-lactamases can significantly expand the spectrum of the antibacterial action of the drug. This is due to the fact that amoxicillin, “protected” from the effects of bacterial enzymes, retains bactericidal activity against penicillin-resistant strains. Considering the data on the frequency of detection of beta-lactamase-producing strains among the main pathogens of respiratory infections in children (Table 5), the practical significance of the use of “protected” penicillins becomes clear. Clavulanic acid and sulbactam are used to “protect” semisynthetic penicillins from the inhibitory effect of beta-l actamase. The most commonly used combination is amoxicillin with clavulanic acid (augmentin, amoxiclav, clavocin, moxiclav) and ampicillin with sulbactam (sulbacin, unazine). Less commonly used is a combination of two semi-synthetic penicillins, one of which is resistive to kbeta-lactamase (ampicillin + oxacillin (Ampiox) or amoxicillin + cloxacillin (Clonac-x)).

Oral forms of 2nd generation cephalosporins (CP-2p) can also be used as the drugs of choice. The latter have a bactericidal effect on the main pathogens of respiratory infections. Compared to 1st generation cephalosporins, they are significantly more active against pneumococci and Haemophilus influenzae, are more resistant to the effects of p-lactamase and have good bioavailability (Yu.B. Belousov, V.V. Omelyanovsky, 1996; S. V. Sidorenko, 1997). Among this group of antibacterial drugs, cefuroxime axetil (zinnate and analogues) and cefaclor (ceclor and its analogues) deserve attention. It is worth noting that cefuroxime, compared to cefaclor, has more pronounced activity against the main pathogens of infections of the upper respiratory tract, including penicillin- and ampicillin-resistant strains (J. Bauenrfiend, 1990). At the same time, when using cefaclor, adverse events in the form of dyspepsia are less common (W. Feldman et al., 1990). When using cefuroxime in the treatment of severe forms of the disease, you can use the so-called “stepped” (staged) therapy. Moreover, during the period of severe toxicosis, cefuroxime is prescribed parenterally (zinacef), and when the intensity of infectious and inflammatory manifestations decreases, therapy continues with the oral form of the drug (zinnat). It should be noted that although some authors recommend using cefuroxime as an alternative to penicillins if you are allergic to them (Yu.B. Belousov, V.V. Omelyanovsky, 1996), in some cases, the development of cross-allergy is still possible (J.P. Sanford , 1994).

In cases where the use of (5-lactam antibiotics as “drugs of choice” is contraindicated (intolerance, allergy to medications in this group, cross-allergy to beta-l acta derivatives, etc.) or is impossible for some other reason, starting Therapy for sinusitis and acute otitis media can begin with biseptol (TMP/SM) or, less rationally, with a combination of macrolides with sulfisoxazole (Table 3).

Table 7 presents data on the choice and characteristics of initial antibiotic therapy for mild and moderate forms of sinusitis and acute otitis media in children.

Table 7.
Tactics for choosing initial etiotropic therapy for mild and moderate forms of sinusitis and acute otitis media in children (oral forms of AB drugs)*

CLINICAL options	Main pathogens	Drugs of choice	Alternative drugs
Sinusitis	Streptococcus	Amoxicillin +	If you are allergic to
Spicy	pneumoniae-	clavulanic acid	beta-lactam
average	Haemophilus	Daily dose: (calculation according to	AB: TMP/SM
otitis	influenzae	amoxicillin): - up to 2	(Biseptol)
	Moraxella	years - 20 mg/kg, 2-5 years - 375	Daily dose
	catarralis	mg/day, 5-1 Oleg -750 mg/day,	6-8 mg/kg
		>10 years - 750 mg - 1 g / day.	TMP.
		Frequency of intake is 3 rubles. d.	Multiplicity
		Course 5-14 days or	taking 2 times a day
		Cefuroxime axetil	days
		Daily dose: up to 2 years -	Course 5-6 days
		250 mg/day, > 2 years - 500	or
		mg/kg. Multiplicity of reception 2	Macrolides +
		r. in the village Course 7 days or	Sulfixazole
		Cefaclor
		Daily dose: 20-40 mg/kg.
		Frequency rate: 2 rubles. V
		day. Course 7 days.

Treatment of mild and moderate forms of infectious diseases of the upper respiratory tract can be carried out on an outpatient basis. In this case, preference should be given to oral forms of antibacterial drugs. The latter is associated with high efficiency, good bioavailability and tolerability, rare development of undesirable effects and adequate compliance of modern antibacterial drugs. Children with severe clinical variants of respiratory infections should be treated in a hospital setting. The choice of etiotropic therapy is determined depending on the clinical and epidemiological features of the disease and with mandatory consideration of outpatient antibacterial treatment.

The principles and tactics of etiotropic therapy for bacterial infections of the upper respiratory tract in children outlined in this section and summarized in table form (Table 3) are generally accepted. At the same time, new and promising drugs are emerging, which are not yet widely known, for the treatment of bacterial infections of the respiratory tract. An example is the bacteriostatic antibiotic fusafungin, which in the form of a monodisperse non-hygroscopic aerosol form (bioparox) is successfully used for the local treatment of pharyngitis, exacerbation of chronic tonsillitis and rhinitis in children (G.L. Balyasinskaya, 1998).

ETIOLOGICAL STRUCTURE OF ACUTE INFECTIOUS DISEASES OF THE LOWER RESPIRATORY TRACT IN CHILDREN AND TACTICS FOR SELECTION OF RATIONAL ETIOTROPIC THERAPY

Etiology of “domestic” infectious diseases of the lower respiratory tract in children

Among diseases of the lower respiratory tract, clinical forms such as tracheitis, tracheobronchitis, bronchitis and pneumonia are distinguished.

The etiological factors of lower respiratory tract infections are often viral-viral and viral-bacterial associations, as well as fungal and intracellular pathogens. Viral infection is the most common cause of tracheitis, tracheobronchitis and bronchitis. While pneumonia is more typical of a mixed viral-bacterial infection. At the same time, the “triggering” role of viral agents in the pathogenesis of pneumonia is considered indisputable and has long been proven (Yu.F. Dombrovskaya, 1951; N.A. Maksimovich, 1959; M.E. Sukhareva, 1962, etc.). Activation of the bacterial flora and superinfection during ARVI are associated with disruption of the barrier function of the respiratory tract and a decrease in the body's resistance (S.G. Cheshik et al., 1980). Viral agents, violating the integrity and functional activity of the ciliary epithelium and alveolar barrier, lead to the “exposure” of receptors of the cells of the basal layer of mucous membranes and inhibition of local immunity factors of the respiratory tract (V.V. Botvinyeva, 1982; V.K. Tatochenko, 1987 and 1994) . At the same time, there is a decrease in functional activity and an imbalance of systemic immunity (inhibition of the T-cell link, disimmunoglobulinemia, high sensitization of leukocytes to bacterial and mycoplasma antigens, perversion of phagocytic functions, etc.) (O.I. Pikuza et al., 1980; L.V. Feklisova et al., 1982; V.P. Buiko, 1984; All this creates the preconditions for superinfection or activation of pneumotropic autoflora and the development of bacterial complications of the current acute respiratory viral infection. At the same time, tracheobronchitis and bronchitis, complicated by the addition of bacterial flora, clinically occur more severely and for a long time. Bacterial tracheobronchitis and bronchitis in outpatient settings are most often caused by pneumococci and other streptococci, as well as Haemophilus influenzae and Moraxella. In recent years, the importance of intracellular pathogens (chlamydia, mycoplasma, legionella) in the development of infections of the lower respiratory tract has increased (G.A. Samsygina et al., 1996).

Indications for X-ray examination of children suffering from acute respiratory diseases

The inclusion of mandatory x-ray confirmation of pneumonia in the “gold standard” of diagnosis makes it possible to diagnose the disease at the early stages of the pathological process and, by promptly prescribing targeted etiopathogenetic therapy, significantly improve its prognosis. If the development of pneumonia is suspected in children suffering from acute respiratory infections, an X-ray examination of the chest organs is indicated.

Indications for X-ray examination

An indication for prescribing an X-ray examination should be the presence of at least one of the following factors: a child with a cough and fever for 2-3 days;

Dyspnea;
- cyanosis;
- severe symptoms of intoxication;
- typical auscultatory or percussion changes (especially asymmetrical localization).

Antibacterial therapy of lower respiratory tract infections in children

In the vast majority of cases, acute bronchitis in children has a viral etiology. Therefore, as a rule, antibacterial therapy is not indicated for the treatment of uncomplicated forms of respiratory infections of the lower respiratory tract. Prophylactic administration of antibiotics for ARVI with symptoms of bronchitis does not reduce the duration of the disease and does not reduce the frequency of bacterial complications (R.E. Behrman, 1983). The use of only symptomatic drugs in the treatment of children with uncomplicated forms of acute bronchitis is accompanied by high therapeutic effectiveness (V.K. Tatochenko et al., 1984).

Antibacterial therapy for respiratory infections of the lower respiratory tract in children is indicated only if they simultaneously have foci of bacterial inflammation (purulent otitis, sinusitis, tonsillitis), severe symptoms of intoxication, prolonged - more than 2-3 days - febrile fever, as well as hematological changes (neutrophilic leukocytosis) that do not allow excluding the bacterial genesis of the disease. G.A. Samsygina (1997) believes that in young children antibacterial drugs should also be used in the complex treatment of obstructive syndrome. Strict adherence to the above indications will dramatically reduce the unjustified use of antibacterial agents for uncomplicated forms of acute bronchitis in children. The latter is very important, since one of the reasons for the increase in antibiotic resistance in bacteria is the widespread and uncontrolled use of antibiotics in acute respiratory infections. Thus, a strictly justified reduction in the use of antibacterial drugs in uncomplicated forms of acute bronchitis will reduce the frequency of development of antibiotic-resistant strains of the main pneumotropic pathogens.

In cases where there are indications for prescribing antibacterial therapy, the choice of starting drug should be made based on the expected etiology of the pathogen. Bacterial tracheobronchitis and bronchitis at home are most often caused by streptococci (mainly pneumococcus), Haemophilus influenzae and Moraxella. Considering the significant frequency of beta-lactamase-producing strains among these pathogens (Table 5), it is advisable to use “protected” penicillins, 2nd generation cephalosporins, TMP/SM as initial therapy.

One should also take into account the increasing role of intracellular pathogens (mycoplasma, chlamydia, etc.) in the etiology of infections of the lower respiratory tract. The lack of a therapeutic effect from the use of initial antibiotic therapy for 2-3 days may be due to atypical pathogens. In this case, macrolides should be considered the drugs of choice. When deciding to use macrolides in young children, preference is given to semi-synthetic 14-member (roxithromycin, clarithromycin, etc.), 15-member (azithromycin) and 16-member

In children aged from 3-6 months to 5 years of life, “domestic” pneumonia is most often caused by pneumococcus and Haemophilus influenzae. Whereas in children over 5 years of age, the main pathogens are pneumococcus, mycoplasma and, less commonly, Haemophilus influenzae (Table 9).

Recent years have been characterized by an increased role of intracellular pathogens in the development of ambulatory pneumonia. At the 7th European Congress of Clinical Microbiology and Infectious Diseases (1995), special attention was paid to the problem of mycoplasma pneumonia in children who became ill at home. In a prospective study of children with community-acquired pneumonia, it was found that the most common cause of infectious pneumonia in older schoolchildren, in addition to pneumococcus, is mycoplasma (up to 40%). Several studies presented at the congress focused on the occurrence of mycoplasma pneumonia in children under 5 years of age. This fact deserves close attention, since it was previously believed that mycoplasma is an extremely rare causative agent of pneumonia in children of early and preschool age (up to 2%) (N.M. Foy et al., 1979).

Changes in the etiological structure of pneumonia due to an increase in the proportion of intracellular pathogens (mycoplasma, chlamydia, etc.) require changes in the strategy and tactics of etiotropic therapy.

Tactics of antibacterial therapy for “domestic” pneumonia in children

Timely and targeted etiotropic treatment of pneumonia largely determines the prognosis of the disease. However, in an outpatient setting, bacteriological rapid diagnostics will obviously remain a problematic research method for many years to come. Therefore, the doctor, when empirically choosing initial antibacterial therapy, must take into account, depending on age and epidemiological situation, potential pathogens and their sensitivity to antimicrobial agents.

Table 9.
Etiological structure of extrapneumonia in children depending on age (generalized data)

Taking into account that the etiological structure of pneumonia in children of different ages has its own characteristics, it is advisable to consider the tactics of choosing initial antibiotic therapy separately for each age group.

The choice of initial antibiotic therapy for home pneumonia in children aged 6 months to 5 years

In newborns and children in the first six months of life, pneumonia is more common in premature infants, in children who have undergone intrapartum aspiration, asphyxia, tracheal intubation and mechanical ventilation and other pathological conditions of the neonatal period that required treatment with broad-spectrum antibiotics and prolonged stay in medical institutions. The latter determines the characteristics of infection in this category of children. In addition to infection by the flora of the birth canal, contamination with hospital strains of microorganisms, often polyresistant to antibacterial agents, is added. Features of the etiological structure of pneumonia in these children is the breadth of the spectrum of causally significant microbial pathogens (group B and D streptococci, staphylococci, bacillary flora, viruses, intracellular pathogens, etc.).

The development of pneumonia in children in the first weeks and months of life almost always requires observation and treatment in a hospital setting. Mandatory hospitalization of children in this age group with pneumonia is associated with the need for constant dynamic monitoring of their clinical condition. This is due to the high risk of rapid progression of pneumonia and the development of complications in children in the first months of life. The latter is associated with the characteristics of their infection, morphofunctional status and transient immaturity of organs and systems.

It should be emphasized once again that treatment of children with pneumonia in the first weeks and months of life should be carried out in a hospital setting. In this case, etiotropic therapy is carried out with broad-spectrum antibacterial drugs. The basic principles and features of the treatment of children with pneumonia in this age category, as well as the tactics for choosing the starting combination of antibacterial drugs, require special and separate analysis, which is not included in the scope of issues covered in this guide. For an in-depth and detailed study of this problem, you should refer to the monographs “Antibiotics and vitamins in the treatment of newborns” by N.P. Shabalov, I.V. Markova, 1993) and “Pneumonia in Children” (edited by Prof. Kaganov S.Yu. and Academician Veltishchev Yu.E., 1995).

“Domestic” pneumonia in children of early and preschool age is most often caused by pneumococcus and Haemophilus influenzae. Moreover, up to 1/3 of the strains of these pathogens produce (5-lactamases and, therefore, are resistant to natural and semi-synthetic penicillins. Therefore, suspecting pneumococcus or Haemophilus influenzae as etiological factors of pneumonia, it is advisable to prescribe those antibacterial drugs that are not destroyed (3 -lactamases (“protected” penicillins, second-generation cephalosporins, biseptol (TMP/SM)).

The main causative agents of “domestic” (community-acquired) pneumonia in children aged 6 months to 5 years: Streptococcus pneumoniae, Haemophilus influenzae.

It should also be noted that there is a tendency towards an increase in the etiological role of mycoplasma V development of domestic pneumonia in children aged 6 months to 5 years. Clinical differences in mycoplasma pneumonia are nonspecific. Mycoplasma genesis of pneumonia can be suspected through a comprehensive analysis of the clinical (persistent low-grade fever, persistent cough, absence of typical pneumonic equivalents during physical examination) and radiological (heterogeneous infiltration, usually 2-sided, asymmetrical, pronounced vascular-interstitial component) picture of the disease, as well as lack of therapeutic effect within 2-3 days from initial antibacterial therapy with beta-lactam antibiotics (penicillins or cephalosporins). In these clinical situations, it is advisable to switch to therapy with macrolides, which are highly active against intracellular pathogens, including mycoplasma.

Particular attention should be paid to the fact that the recent frequent, and not always justified, use of macrolides in the form of starting therapy is accompanied by the emergence of resistant strains of microorganisms. Thus, it was noted that penicillin-resistant strains of pneumococcus in 41% of cases are resistant to 14- and 15-membered macrolides (erythromycin, roxithromycin, clarithromycin, azithromycin) (J. Hofman et al., 1995). To a lesser extent, this applies to 16-membered macrolides (spiramycin, dzosamycin) (K. Klugman, W. Moser, 1996). At the same time, a decrease in the frequency of use of macrolides leads to the restoration of the sensitivity of pathogens to antibiotics of this group (L.S. Strachunsky, S.N. Kozlov, 1998). Obviously, taking into account the above data will reduce the uncontrolled prescription of macrolides. Moreover, in case of intolerance to 3-lactam antibiotics and the absence of data in favor of the mycoplasma genesis of the disease, biseptol (TMP/SM) should be considered the drug of choice for mild and moderate forms of domestic pneumonia.

Etiotropic treatment of children with mild and moderate clinical variants of pneumonia can be carried out with oral forms of antibacterial drugs. As a rule, with the right choice of drug, a positive clinical effect (normalization of body temperature, reduction of manifestations of intoxication, reverse development of physical symptoms) is observed within the same time frame as with parenteral administration of antibiotics (V.K. Tatochenko, 1994). Convincing data have been obtained on the possibility of widespread use of oral forms of antibiotics for the treatment of uncomplicated forms of pneumonia, not only of mycoplasma and chlamydial etiology, but also caused by other pneumotropic pathogens (A.M. Fedorov et al, 1991). For moderate forms of pneumonia with severe manifestations of intoxication and febrile fever, it is advisable carrying out “stepwise” (staged) etiotropic therapy (GA. Samsygina, 1998). In this case, the drugs of choice for parenteral administration are cefuroxime (zinacef) or a combination of ampicillin with sulbactam (unasin) After 2-3 days, with a decrease in the symptoms of intoxication. and relief of fever, a transition is made to oral forms of the corresponding drugs:

Zinacef (cefuroxime for parenteral administration) 60-100 mg/kg/day - in 3 intramuscular injections,
- zinnat (oral cefuroxime).

Children under 2 years old - 125 mg 2 times a day. Children over 2 years old - 250 mg 2 times a day. or

Unazine (ampicillin + sulbactam) for parenteral administration 150 mg/kg/day in 3 intramuscular injections,
- unasin (ampicillin + sulbactam) for oral administration. Children weighing less than 30 kg - 25-50 mg/kg/day in 2 divided doses. Children weighing more than 30 kg - 375-750 mg/day in 2 divided doses.

Table 10 presents the tactics for choosing empirical starting antibacterial therapy for “domestic” pneumonia in children aged 6 months to 5 years.

Treatment of mild and moderate forms of pneumonia in young children can be carried out on an outpatient basis only if it is possible to dynamically monitor the child’s condition (daily until body temperature normalizes and symptoms of intoxication are relieved), additional therapeutic and diagnostic measures are carried out, as required by the instructions for creation of a “hospital at home”. Social conditions and the general cultural and educational level of parents or relatives caring for the child must be taken into account. If it is impossible to create a “hospital at home”, or the low cultural level of the parents, as well as unfavorable social and living conditions, the child must be hospitalized.

Tactically correct, it should be considered mandatory to hospitalize a child with severe symptoms of infectious toxicosis and manifestations of pulmonary heart failure, regardless of age, form of respiratory disease and social and living conditions.

The choice of initial antibiotic therapy for “domestic” pneumonia in children over 5 years of age

Analysis of the results of numerous studies to clarify the etiology of acute infections of the lower respiratory tract (Table 9) allows us to conclude that in children over 5 years of age the main causative agents of pneumonia are pneumococcus, mycoplasma and Haemophilus influenzae.

Table 10.
Initial etiotropic therapy of mild and moderately severe forms of “domestic” neumonia in children aged 6 months to 5 years

The main causative agents of “domestic” (community-acquired) pneumonia in children over 5 years of age:

Streptococcus pneumoniae,
Mycoplasma pneumoniae
Haemophilus influenzae.

Expanding the range of potential pathogens of pneumotropic infection due to the greater etiological significance of mycoplasma in this age group requires the inclusion of macrolides in the initial antibacterial therapy as the drugs of choice (Table 11). At the same time, the appearance on the domestic pharmaceutical market of a macrolide drug with special pharmacokinetic properties (azithromycin) makes it possible to carry out antibacterial therapy for mild and moderate “domestic” pneumonia in a short (3-5-day) course ((L.S. Strachunsky et al., 1998; N. Principi et al., 1994; J. Harris et al., 1996). al., 1998). Discontinuation of azithromycin on days 3-5 from the start of therapy, when the physical manifestations of the disease still persist, should not mislead that etiotropic therapy for pneumonia has been discontinued. The pharmacokinetics of azithromycin are characterized by its ability to accumulate and persist for a long time in high concentrations. in tissues, providing a long-lasting antibacterial effect (J. Williams et al., 1993). Therefore, after discontinuation of the drug, even with a 3-day course of treatment, the antibacterial effect of azithromycin in tissues continues for another 5-7 days (G. Foulds et al., 1993).

Treatment of children with mild and moderate pneumonia, without significant manifestations of intoxication and febrile fever, is carried out with oral forms of antibacterial drugs. In cases where a moderate form of pneumonia is accompanied by severe symptoms of intoxication and febrile fever, it is advisable to begin therapy with parenteral administration of antibiotics (2nd generation cephalosporins (zinacef) or “protected” semi-synthetic penicillins (unasin)) followed by switching to oral administration. Thus, with the improvement of the child’s condition, a decrease in the manifestations of intoxication, and a tendency towards normalization of body temperature, a transition to therapy with oral forms of the appropriate antibiotics is carried out (zinacef is replaced by zinnat, and unasin for parenteral administration is replaced by unasin for oral administration).

Evaluation of the effectiveness and duration of antibacterial therapy for “domestic” pneumonia

The empirical choice of initial antibacterial therapy, unfortunately, does not always allow precise and targeted action on the etiologically significant microbial agent. It is very important to promptly assess whether the selected antibacterial agent has an inhibitory effect on the causative agent of pneumonia. The adequacy of the choice of initial antibacterial therapy is assessed primarily by the dynamics of the temperature reaction and the reduction in the manifestations of intoxication. Clinical criteria for the effectiveness of an antibacterial drug for pneumonia are a decrease in body temperature to normal or low-grade levels, improvement in well-being, appearance of appetite, decrease in respiratory rate and pulse during the first 24-48 hours of treatment (A.A. Arova, 1988). If fever and symptoms of intoxication persist during treatment with an antibacterial drug for 36-48 hours, one should conclude that there is no effect from the therapy and change the antibacterial drug to an alternative one (V.K. Tatochenko, 1987).

The vector of action of antibacterial agents is aimed at pathogens of the infectious process. Antibacterial agents do not have a direct effect on the processes of normalization of morpho-functional changes that have developed as a result of an infectious-inflammatory process in the lungs. Therefore, the duration of antibacterial therapy is determined by the timing of complete destruction of the pathogen or the degree of its suppression when the final elimination of the pathogen from the body is carried out by immunological mechanisms (V.K. Tatochenko, 1994). Complete elimination of the pathogen in uncomplicated pneumonia can be achieved by 7-10 days of using antibacterial agents. Therefore, in the uncomplicated course of typical pneumonia, the duration of antibacterial therapy can be limited to 7-10 days. For pneumonia of chlamydial origin, antibacterial therapy with macrolides should be carried out for at least 14 days (Red Book, 1994). In this case, as a rule, complete elimination of the pathogen occurs. The exception is azithromycin, the duration of treatment is 3-5 days.

ANTIBACTERIAL DRUGS USED FOR THE TREATMENT OF RESPIRATORY INFECTIONS IN CHILDREN IN AN OUTPATIENT CONDITION

Penicillins

Natural penicillins for oral use

Natural penicillins for oral use remain the drugs of choice in the treatment of upper respiratory tract infections such as tonsillitis, pharyngitis, and exacerbation of chronic tonsillitis. The narrowing of the range of clinical use of natural penicillins is associated with the wide distribution of penicillin-resistant strains among the main pneumotropic pathogens.

Table 12.
Natural penicillins for oral use (phenoxymethylpenicillin preparations are registered and approved for use in the Russian Federation)*

Trade name of the drug	Release form
Phenoxymethyl penicillin	table 0.25 granules for preparing a suspension (in 5 ml of the finished suspension - 125 mg of phenoxymethylpenicillin)
Ospen	table 0.25 (0.5) granules for preparing a suspension (in 5 ml of the finished suspension - 400,000 units of phenoxymethylpenicillin) syrup (in 5 ml of syrup - 400,000 (700,000) units of phenoxymethylpenicillin)
V-penicillin	table 0.25 (440000 units) tab. 0.5 (880000 units)
Vepicombin	table 300,000 (500,000 and 1,000,000) IU suspension (in 5 ml of suspension - 150,000 IU of phenoxymethylpenicillin) drops for oral administration (in 1 ml of drops - 500,000 IU of phenoxymethylpenicillin)
Cliacyl	table 1 200000 ME powder for making syrup (5 ml syrup - 300000 IU phenoxymethylpenicillin)
Megacillin yelled	table 600,000 (1,000,000) ME granulate for preparing a suspension (in 5 ml of suspension - 300,000 IU of phenoxymethylpenicillin)

* - State Register of Medicines, 1996; Register of Medicines of Russia 97/98,1997; Vidal,1998

The active substance of natural penicillins for oral use is phenoxymethium penicillin. Table 12 presents phenoxymethylpenicillin preparations registered and approved for use in the Russian Federation.

Doses and route of administration of phenoxymethylpenicillin: Daily dose: children under 10 years old - 50-100 thousand units/kg, children over 10 years old - 3 million units per day.

1 mg of the drug corresponds to 1600 units of phenoxymethylpenicillin. The frequency of administration is 4-6 times a day, 1 hour before or 2 hours after meals. Course duration is 5-10 days.

Adverse reactions. When using phenoxymethylpenicillin, allergic reactions are possible (urticaria, erythema, Quincke's edema, rhinitis, conjunctivitis, etc.). Stomatitis and pharyngitis may occur as a manifestation of an irritant effect on the mucous membranes of the oropharynx.

Contraindications. Hypersensitivity to penicillins.

Semi-synthetic broad-spectrum penicillins, resistant to penicillinase (“protected” aminopenicillins)

Among semisynthetic penicillins, which have a wide spectrum of antibacterial action, aminopenicillins are more often used in pediatric practice for the treatment of bacterial infections of the respiratory tract. At the same time, domestic pediatricians most widely use ampicillin. However, there is a more active form of ampicillin - amoxicillin. Amoxicillin is an active metabolite of ampicillin and has the same spectrum of antibacterial action. At the same time, amoxicillin is 5-7 times more active than ampicillin. In addition, amoxicillin is much better absorbed from the gastrointestinal tract. The degree of absorption of amoxicillin from the gastrointestinal tract does not depend on the intake and composition of food. Amoxicillin also produces higher concentrations in sputum.

A significant disadvantage of aminopenicillins is their sensitivity to the effects of bacterial beta-lactamases. Considering the significant increase in beta-lactamase-producing strains among pneumotropic pathogens (Table 5), it is advisable to use aminopenicillins in combination with substances that have an inhibitory effect on bacterial beta-lactamases. The most often used as “protection” for semisynthetic penicillins are clavulanic acid and sulbactam. Clavulanic acid and sulbactam irreversibly inhibit plasmid-encoded beta-lactamase (penicillinase) and thereby significantly increase the antibacterial activity and spectrum of action of aminopenicillins combined with them. At the same time, it should be remembered that the probability of induction of the synthesis of chromosomal beta-lactamase in bacteria under the influence of clavulanic acid has been established.

Most often in pediatric practice, combinations of amoxicillin with clavulanic acid and ampicillin with sulbactam (sultamicillin) are used in the treatment of respiratory infections (Table 13 and Table 14).

When using amoxicillin preparations potentiated with clavulanic acid, the dose calculation is based on amoxicillin.

Doses and method of administration of the combination of Amoxicillin + clavulanic acid.

Table 13.
Drugs combining amoxicillin and clavulanic acid, registered and approved for use in the Russian Federation*

* - State Register of Medicines, 1996; Register of Medicines of Russia 97/98, 1997; Vidal, 1998.
** - the content of amoxicillin is presented in finished dosage forms.

Table 14.
Preparations of sultamicillin* (ampicillin + sulbactam), registered and approved for use in the Russian Federation**

* - Sultamicillin is a registered international name for the combination of active substances - double ester of ampicillin and sulbactam.
** - State Register of Medicines, 1996; Register of Medicines of Russia 97/98. 1997: Vidal. 1998.

Daily dose (calculation based on amoxicillin):

Children under 2 years of age - 20 mg/kg,
- children aged 2-5 years - 375 mg/day,
- children aged 5-10 years - 750 mg/day,
- children over 10 years old - 750 mg - 1 g / day. Frequency of reception - 3 days. Course - 5-14 days.

Adverse reactions. When using a combination of amoxicillin and clavulanic acid, allergic reactions may develop. Rarely: dyspeptic symptoms, liver dysfunction (hepatitis, cholestatic jaundice), pseudomembranous colitis.

Contraindications. Hypersensitivity to penicillins, cephalosporins, clavulanic acid. Infectious mononucleosis.

Doses and method of administration of sultamicillin(combination of ampicillin with sulbactam):

Treatment with sultamicillin for moderate and severe forms of respiratory infections caused by bacterial pathogens can be carried out using a “step-by-step” method. Initially, during the period of pronounced manifestations of infectious toxicosis, parenteral administration of the drug is prescribed, and when the condition improves, they switch to oral administration. Daily dose for parenteral administration: 150 mg/kg/day of sultamicillin (corresponding to 100 mg/kg/day of ampicillin). The frequency of intramuscular administration is 3-4 times a day. Daily dose for oral administration:

Children weighing less than 30 kg - 25-50 mg/kg/day of sultamicillin,
- children weighing more than 30 kg - 375-750 mg/day of sultamicillin." Frequency of administration - 2 times a day. Course - 5-14 days.

Adverse reactions. When using a combination of ampicillin and sulbactam, allergic reactions, diarrhea, nausea, vomiting, epigastric pain, intestinal colic, drowsiness, malaise, headache, and rarely, enterocolitis and pseudomembranous colitis are possible.

Contraindications. Hypersensitivity to the components of the drug, intolerance to penicillins, cephalosporins. Infectious mononucleosis.

2nd generation cephalosporins

In recent years, in the treatment of respiratory infections in children, the choice of antibiotics from the group of cephalosporins has been in favor of 2nd generation drugs. This is due to the low activity of 1st generation cephalosporins (cephalexin, cefadroxil, cefradine) against Haemophilus influenzae and moraxella, as well as due to their destruction under the influence of most beta-lactamases. Unlike 1st generation cephalosporins, 2nd generation cephalosporins are highly active against Haemophilus influenzae and Moraxella. In addition, 2nd generation cephalosporins are more resistant to the action of beta-lactamases.

Oral forms of 2nd generation cephalosporins are most often used in outpatient settings. However, for moderate and severe forms of bacterial respiratory infections, it is possible to carry out “stepped” therapy with appropriate 2nd generation cephalosporin drugs.

When treating bacterial respiratory infections with severe manifestations of intoxication and febrile fever, “stepped” antibacterial therapy using 2nd generation cephalosporins is advisable. In this case, the drug of choice for parenteral administration is cefuroxime (zinacesr): zinacef (cefuroxime for parenteral administration) at a dose of 60-100 mg/kg/day - 3 IM injections.

After the child’s condition improves and the symptoms of intoxication decrease and the temperature reaction normalizes, antibacterial therapy continues with the use of the oral form of cefuroxime axetil (Zinnat).

Adverse reactions. When using cefaclor, allergic reactions, diarrhea, nausea, vomiting, dizziness, and headache are possible. When using cefuroxime, similar adverse reactions are observed, with gastrointestinal disorders being more common. In rare cases, pseudomembranous colitis develops. With long-term use in high doses, changes in the peripheral blood picture (leukopenia, neutropenia, thrombocytopenia, hemolytic anemia) are possible.

Sulfonamide drugs

Sulfonamide drugs (sulfonamides) are a group of chemotherapeutic agents with a broad antimicrobial spectrum of action. Sulfonamides are derivatives of sulfanilic acid amide.

Sulfanilic acid amide was synthesized by P. Gelrno in 1908. However, only in the early 30s of the 20th century was the high antibacterial effectiveness of its derivatives established and widespread use in medical practice began (F. Mietzsch, J. Klarer, 1932; G. Domagk, 1934; J. TrefoueletaL, 1935).

The mechanism of the antimicrobial action of sulfonamides

For normal life and reproduction of microorganisms, a certain level of nucleotide biosynthesis, controlled by growth factors, is required. Bacteria are not able to use exogenous growth factors (folic and dihydrofolic acids), because their shell is impermeable to these compounds. To synthesize their own growth factors, bacteria capture from the outside the precursor of folic acid - para-aminobenzoic acid (PABA). The latter is structurally close to sulfonamide drugs. Because of this similarity, microbial cells “erroneously” capture sulfonamides instead of PABA. Sulfonamide entering the bacteria competitively displaces PABA from the metabolic cycle and disrupts the formation of folic acid and its precursors. The latter leads to disruption of metabolic processes in the microbial cell and to the loss of its reproductive functions. Thus, sulfonamides have a bacteriostatic effect. The mechanism of the antimicrobial action of sulfonamide drugs is based on the blockade of folic acid synthesis in bacteria with subsequent disruption of the formation of nucleotides, suppression of the vital activity and reproduction of microorganisms.

Sulfonamides are rightfully considered the first modern chemotherapeutic antimicrobial agents. The use of sulfonamide drugs played a significant role in reducing the mortality and severity of various infectious diseases (R.J. Schnitzer, F. Hawking 1964). However, in recent decades, the indications for the use of sulfonamides in pediatric practice have sharply narrowed due to the widespread use of antibiotics. At the same time, the list of sulfonamide drugs recommended for use in children was significantly reduced (R.E. Behrman, 1983; G. Peter, 1991). Thus, in the treatment of infectious diseases of the respiratory system, at present, of all sulfonamide drugs, the use of only biseptol is considered justified (Belousov Yu.B., Omelyanovsky V.V., 1996).

Biseptol (TMP/SM) is a combined broad-spectrum antimicrobial drug. Biseptol contains: sulfonamide - sulfamethoxazole and diaminopyrimidine derivative - trimethoprim.

The history of the creation of the drug is associated with attempts to achieve a bactericidal effect when using therapeutic doses of sulfonamides. It turned out that the combination of sulfamethoxazole with trimethoprim in usual dosages leads not only to an increase in the bacteriostatic effect by almost 100 times, but also to the appearance of a bactericidal effect (R.M. Bushby, 1967 "And Ganczarski, 1972). Further studies showed that maximum antibacterial and therapeutic effectiveness was observed with a combination of trimethoprim and sulfamethoxazole in a ratio of 1:5. In this case, it was possible to achieve optimal synergy between the ingredients included in the drug.

Table 15.
2nd generation cephalosporins for oral use registered and approved for use in the Russian Federation*

* - State Register of Medicines, 1996.

The mechanism of antimicrobial action of biseptol

It turned out that the increase in antimicrobial activity and the development of a bactericidal effect when combining 2 bacteriostatic drugs (trimethoprim and sulfamethoxazole) is associated with a double blocking effect. Sulfamethoxazole, which is part of Biseptol, like all sulfonamides, competitively replaces PABA and prevents the formation of dihydrofolic acid. In turn, the second component of biseptol - trimethoprim - blocks the next stage of folic acid metabolism, disrupting the formation of tetrahydrofolic acid. Inhibition by biseptol of successive stages of the synthesis of growth factors in a microbial cell leads to pharmacological potentiation and the development of a bactericidal effect.

By blocking different stages of folic acid biosynthesis in the microbial cell, both components of the drug - trimethoprim and sulfamethoxazole - not only potentiate the bacteriostatic effects of each other, but lead to the appearance of the bactericidal effect of biseptol.

Antimicrobial spectrum of action of biseptol

Biseptol is a combined chemotherapeutic agent with a broad antimicrobial spectrum of action.

It should be noted that biseptol is active against many gram-positive and gram-negative microorganisms. Pathogens such as streptococci (including pneumococcus), Moracella, Haemophilus influenzae and staphylococci, which are the main etiological agents for bacterial respiratory infections, are highly sensitive to biseptol. Table 16 shows the antimicrobial spectrum of action of biseptol. Pseudomonas aeruginosa, treponema, mycoplasma, mycobacterium tuberculosis, viruses and fungi are resistant to Biseptol.

Biseptol is the drug of choice (“Drug of choice”) for pneumocystosis, nocardiosis, and coccidiosis. Biseptol is considered as an alternative first-line drug for intestinal scratch disease. Biseptol can also be used as an alternative or reserve drug for infectious diseases caused by streptococci, pneumococci, moraxella, Haemophilus influenzae, staphylococci, enterobacteria, toxoplasma (in combination with other chemotherapeutic drugs) and Brucella (in combination with rifampicin).

It should be noted that microorganisms may develop plasmid-associated resistance to Biseptol.

Pharmacokinetics of biseptol

After oral administration, Biseptol is quickly and well absorbed from the gastrointestinal tract. Bioavailability of the drug is 90-100%. The maximum concentration in blood plasma after oral administration is achieved within 2-4 hours, and a constant therapeutic concentration after a single dose is maintained for 6-12 hours (on average 7 hours). The components of biseptol (trimethoprim and sulfamethoxazole) bind to plasma proteins by 45% and 60%, respectively. Constant plasma concentrations of both components of Biseptol with a daily 2-fold dose are achieved within 3 days from the start of therapy. The half-life of Biseptol is 10-12 hours.

Sulfamethoxazole, which is part of Biseptol, is excreted from the body both in unchanged (active) form and in the form of hepato-biotransformation products. Sulfamethoxazole undergoes biotransformation in the liver by acetylation. Acetylated metabolites lose their antibacterial activity and are excreted from the body by glomerular filtration and are not capable of tubular reabsorption. Acetylated metabolites are poorly soluble in water, and in the acidic environment of the urine of the renal tubules they can even precipitate. In children, only 30-50% of the administered dose of sulfamethoxazole undergoes acetylation, while in adults it is 60-80%. It has been established that in children of the 1st year of life, the processes of acetylation of sulfamethoxazole are reduced and amount to 27%, and biotransformation also occurs due to glucuronidation. This creates the preconditions for increasing the concentration of active sulfamethoxazole not only in urine, but also in plasma, since its non-acetylated metabolites are able to be reabsorbed in the renal tubules. Consequently, in children of the first 12 months, the therapeutic effect of Biseptol can be achieved even at low doses. This is a fundamental position and must be taken into account when prescribing the drug to children 1 year of age. With age, the processes of hepatic acetylation of sulfamethoxazole are activated. Thus, in children aged 5 years, the amount of acetylated sulfamethoxazole is already 45%, and in children over 12 years old it approaches the values ​​of adults.

Table 16.
Antimicrobial spectrum of biseptol

Aerobic bacteria
cocci	sticks	cocci	Sticks
Staphylococcus spp. (including those producing penicillinase) Streptococcus spp. (including pneumococcus)	Corynebacterium diphteriae Nocardia asteroids Listeria monocytogenes	Neisseria Gonorrhoeae Moraxella catarrhalis	Escnerichia coli Shigella spp. Salmonella spp. Proteus spp. Enterobacter spp. Klebsiella spp. Yersinia spp. Vibriocholerae Haemophilus inf.
Anaerobic bacteria
Gram-positive microorganisms		Gram-negative microorganisms
cocci	sticks	cocci	Sticks
-	-	-	Bacteroides spp.
Protozoa
Toxoplasma gondii, Pneumocystis carinii, Isospora belli, Cyclospora

Trimethoprim is eliminated from the body through glomerular filtration. No more than 10-20% of the drug undergoes biotransformation, therefore 80-90% of trimethoprim is excreted in the urine in unchanged (active) form. In children of the first 3 months of life, the elimination of trimethoprim is reduced, because there is a functional immaturity of glomerular filtration - the main route of elimination of the drug from the body. This creates the preconditions for the occurrence of very high concentrations of trimethoprim in plasma. It should also be noted that although only 10-20% of trimethoprim is metabolized in the body, the resulting compounds (N-oxides) are highly histiotoxic.

Biseptol penetrates well into organs and tissues. When using conventional therapeutic doses of Biseptol, effective bactericidal concentrations of its components are achieved in blood plasma, lung tissue, sputum, cerebrospinal fluid of the inner ear, kidneys, and soft tissues. Biseptol penetrates the blood-brain barrier and also creates effective bactericidal concentrations in the cerebrospinal fluid.

Biseptol easily passes through the placental barrier. At the same time, plasma concentrations of the drug in the blood of the fetus may be close to those of a pregnant woman (V.A. Ritschel, 1987; R. Petel, P. Welling, 1980).

It should be remembered that the use of Biseptol by a lactating woman is accompanied by penetration of the drug into the mammary glands and its release into milk.

Side and undesirable effects when using Biseptol

The use of recommended doses and duration of therapy with Biseptol rarely leads to serious complications. In some cases, the use of Biseptol may be accompanied by the development of side effects. In young children, adverse events when using Biseptol may occur more often than in older age groups. This is due to the high and intense level of metabolic processes in children in the first years of life.

Table 17.
Daily therapeutic doses of Biseptol

The high need for folic acid in young children creates the preconditions for more frequent occurrence of undesirable effects when taking Biseptol. This is due to the fact that folic acid metabolism may be disrupted not only in bacteria, but also in the cells of the child’s body. The latter may be accompanied by clinical manifestations of vitamin B deficiency with the development of dyspeptic disorders and suppression of hematopoiesis (Table 17). It has been established that gastrointestinal dysfunction occurs in 9.2% of children who used Biseptol (C. Marchantetal., 1984; W. Feldman et al., 1990). Information on the incidence of platelet- and neutropenia (the vast majority of asymptomatic ones) is contradictory and, according to I.V. Markova and V.I. Kalinicheva (1987) from 16 to 50% of treated children. It was noted that attempts to use folic acid did not eliminate these side effects of biseptol (N.P. Shabalov, 1993). At the same time, the use of the active metabolite of folic acid - folinic acid (citrovorum factor) led to the relief of vitamin B deficiency. Currently, calcium folinate and leucovorin, the active principle of which is folinic acid, are registered and approved for use in the Russian Federation. In case of development of folic acid deficiency in the child's body, calcium folinate or leucovorin is prescribed, depending on age, 1-3 mg 1 time per 3 days per os, less often - parenterally.

Due to the biotransformation of sulfamethoxazole in the liver and subsequent elimination through the kidneys, crystals of its acetylated metabolites may form in the renal tubules. The latter disrupt the functioning of the tubular parts of the kidneys and, in severe cases, can lead to the development of interstitial nephritis. These side effects develop in cases where a rational drinking regimen is not observed and medications that acidify urine (ascorbic acid, calcium chloride, methenamine) are simultaneously used. Drinking plenty of alkaline water prevents these complications. Therefore, during therapy with Biseptol, the amount of fluid consumed by the child must be monitored.

In newborns, premature and morpho-functionally immature children in the first weeks and months of life with conjugation jaundice, the use of biseptol can lead to the displacement of bilirubin from compounds with plasma proteins and cause bilirubin encephalopathy. In this regard, biseptol is contraindicated for children of the first year of life with indirect hyperbilirubinemia (N.P. Shabalov, 1993).

The use of Biseptol in children of the first year of life can also occasionally be accompanied by the development of metabolic acidosis and hypoxia. This is due to the ability of sulfamethoxazole, which is part of Biseptol, to convert fetal hemoglobin into methemoglobin. It is believed that the simultaneous administration of vitamins C, E and glucose will prevent this complication.

Among the side effects of biseptol, photosensitivity, hypersensitivity and liver damage are also described.

It should be remembered that in children with impaired activity of erythrocyte enzymes (usually glucose-6-dehydrogenase deficiency), the use of biseptol can provoke a hemolytic crisis.

Interaction of Biseptol with other drugs

Using V In practical work when treating children with combinations of various pharmacological agents, the doctor must necessarily take into account possible interactions of drugs in the patient’s body. The latter can lead to both potentiation and weakening of the expected therapeutic effects, as well as contribute to increased toxic manifestations (L. Boreus, 1982).

Thus, it has been established that the antimicrobial activity of biseptol decreases with the simultaneous administration of drugs containing derivatives of para-aminobenzoic acid (novocaine, anesthesin, almagel-A). As a result of the structural identity between sulfamethoxazole and para-aminobenzoic acid included in these preparations, the accumulation of one of the active components of biseptol in the microbial cell is reduced. The latter leads to a sharp decrease in the bactericidal activity of the drug.

The antimicrobial activity of biseptol may also be reduced when administered simultaneously with barbiturates. This is due to the activation by barbiturates of liver enzyme systems involved in the biotransformation of sulfamethoxazole. As a result, the amount of unchanged (active) sulfonamide component biseptol is significantly reduced.

As noted above, the combined use of biseptol with drugs such as ascorbic acid, calcium chloride and methenamine promotes pronounced acidification of urine and, consequently, increased crystallization of acetylated metabolites of sulfamethoxazole.

The simultaneous use of biseptol with non-steroidal anti-inflammatory drugs and isoniazid leads to an increase in plasma concentrations of unchanged, active components of the drug (trimethoprim and sulfamethoxazole) and may enhance their toxic effects.

It should be remembered that the combined use of biseptol with diuretics increases the risk of developing thrombocytopenia.

It should be noted that Biseptol, in turn, can also enhance the undesirable effects of a number of drugs. So, with the simultaneous use of biseptol with diphenin, the risk of developing the toxic effects of the latter (nystagmus, ataxia, mental disorders) increases. The combined use of biseptol with indirect anticoagulants (phenyline) can lead to the development of hemorrhagic syndrome. When prescribing Biseptol to patients receiving antidiabetic drugs (sulfaurea derivatives - butamide, etc.), one should remember the possible potentiation of the hypoglycemic effect.

Thus, the simultaneous use of Biseptol and thiazide diuretics, oral antidiabetic agents, para-aminobenzoic acid derivatives, indirect anticoagulants, nonsteroidal anti-inflammatory drugs, and barbiturates is not recommended.

Dosage regimen and method of use of biseptol

Biseptol is not prescribed to premature babies, newborns and children under 3 months due to the risk of developing kernicterus.

Biseptol is administered orally 2 times a day (morning and evening) with an interval of 12 hours.

In patients with impaired renal function, in which endogenous creatinine clearance decreases to 30 ml/min and below, half the age-specific doses (1/2 the age-specific therapeutic dose) should be used.

The duration of biseptol therapy for acute infections is 5-7 days.

When using Biseptol, be sure to follow a rational drinking regimen. To do this, the volume of liquid consumed by the child must be monitored daily.

Macrolides

The uncontrolled use of macrolides in the form of routine therapy for various clinical variants of respiratory infections, including viral etiology (!), has led to the emergence of resistant strains of microorganisms. It has been established that penicillin-resistant pneumococcal strains in almost half of the cases (41%) are resistant to 14-member (erythromycin, roxithromycin, clarithromycin) and 15-member (azithromycin) macrolides (J. Hofman et al, 1995 ). At the same time, penicillin- and erythromycin-induced resistant pneumococci and pyogenic streptococci remain sensitive to 16-member macrolides (spiramycin, zosamycin) (K. Klugman, 1996).

In addition to the antibacterial effect, macrolides, by inhibiting the oxidative burst and influencing the production of cytokines, have an anti-inflammatory effect (C. Agen et al., 1993; A. Bryskier et al., 1995). The stimulating effect of macrolides on neutrophil phagocytosis and killing has been established (M.T. Labro et al., 1986; W. Horn et al., 1989). Macrolide antibiotics are also characterized by a pronounced anti-antibiotic effect (I. Odenholt-Toinqvist et al., 1995).

The appearance on the domestic pharmaceutical market of macrolides, which have better tolerability compared to erythromycin, allows their widespread use even in infants. The pharmacokinetic features of the “new” macrolides increase the compliance of the course (L.S. Strachunsky, S.N. Kozlov, 1998).

Table 18 presents the international names and trade names, doses and routes of administration of macrolides most commonly used in pediatrics.

When choosing a drug from the group of macrolides, especially in young children, preference is given to semi-synthetic 14-member (roxithromycin, clarithromycin, etc.), 15-member (azithromycin) and 16-member (midecamycin acetate, etc.). This is due to the fact that when using “new” macrolides, unwanted and side effects develop much less frequently. Most rarely, gastrointestinal disorders are observed with the use of 16-member macrolides (midecamycin acetate, etc.). This is related to that. that they, unlike other macrolides, do not have a motilinomimetic effect and do not cause hypermotility in the digestive tract (P. Peritietal., 1993). The nature of the interaction with drugs taken by the child simultaneously with macrolides must be taken into account (Table 19).

Table 18.
Macrolide antibiotics for oral use, registered and approved for use in the Russian Federation*

International and trade names	Release form, dose and method of administration
Erythromycin grunamycin, ilozon, ermiced, eric, erigexal, erythromycin, etomite)	table and capo. 0.1 (0.2; 0.25; 0.5), granulate for the preparation of suspension (in 5 ml of suspension - 0.125 (0.2; 1.83) erythromycin) suspension and syrup (in 5 ml - 0.1 25 (0.25) erythromycin), rectal suppositories (1 stick - 0.05 (0.1)) g erythromycin). Daily dose: 30-50 mg/kg. Frequency of intake - 4 days, between meals. Course - 5-14 days.
Clarithromycin (clacid, fromilid)	table 0.25 (0.5), dry solution for preparing a suspension (in 5 ml of suspension - 125 mg of clarithromycin). Daily dose: 7.5 mg/kg/day. Frequency of reception - 2 days. Course - 7-10 days.
^oxythromycin renicin, roxibid, eoximizan, rulide)	table 0.05 (0.1; 0.15; 0.3). Daily dose: 5-8 mg/kg/day. The frequency of administration is 2 times a day, before meals. Course - 7-10 days.
Azithromycin Azivok, Sumamed)	table and cape. 0.125 (0.25; 0.5), syrup (in 5 ml of syrup - 100 (200) mg of azithromycin). Daily dose (for children with BW>10 kg): Course - 5 days: or Course - 3 days: on day 1 - 10 mg/kg, on days 2-5 - 5 mg/kg, on days 2-3 - 10 mg /kg. Frequency of reception - 1 day.
Midecamycin (macropen)	table 0.4, dry solution for preparing a suspension (in 5 ml of suspension - 1 75 mg of midecamycin acetate). Daily dose: 30-50 mg/kg/day. Frequency of reception - 2 days. Course - 5-14 days.
Spiramycin (Rovamycin)	table 1.5 (3.0) million ME sachets with granulate for preparing a suspension (in 1 sachet - 0.375 (0.75; 1.5) million MEspiramycin). Daily dose: 1.5 million IU/10kg/day. Frequency of reception - 2-4 days. Course 5-14 days.
Josamycin (vilprafen)	table 0.5 suspension (in 5 ml of suspension - 150 (300) mg of josamycin). Daily dose: 30-50 mg/kg/day. Frequency of intake - 3 days, between meals. Course - 7-10 days.

* - State Register of Medicines, 1996: Register of Medicines of Russia 97/98, 1997; Vidal, 1998.

Table 19.
Drug interactions of macrolides (according to D.S. Strachunsky and S.N. Kozlov (1996), modified and supplemented)

Macrolides	Drugs	Result of interaction
Erythromycin Clarithromycin Midecamycin	Indirect anticoagulants (warfarin, etc.)	Increased hypoprothrombin
Erythromycin Clarithromycin Midecamycin Josamycin	Carbamezepine (t egr eto l, fi n l e p s i n	Increased toxicity of carbamezepine due to increased serum concentrations
Erythromycin Klar ig om icin Ro xitr om icin	Cardiac glyxides (digocoin)	Increased digoxin toxicity due to increased serum concentrations
Erythromycin Clarithromycin Josamycin	Other antihistamines (terfenadine, astemizole)
Erythromycin Kl ar game om icin Ro xitr om icin Josamycin	Theophylline	Increased theophylline toxicity due to increased serum concentrations
Erythromycin Roxithromycin	Benzodiazepines (triazolam, mi do zolam)	Increased sedative effect of benzodiazepines
Erythromycin	Valproic acid (Depakine, Convulex)	Increased sedative effect of valproate
Erythromycin	Methylprednisolone	Prolongation of the effect of methyl lprednisolone
Erythromycin Clarithromycin	Cisapride (coordinax, peristil)	High risk of developing ventricular arrhythmias
Erythromycin Kl ar games om its in	Dizopyramid (rhythm ilen, rigmodan)	Increased risk of disopyramide toxicity

Midecamycin does not affect the pharmacokinetics of theophylline.

Antacids, when used simultaneously with azithromycin, reduce its absorption from the gastrointestinal tract.

It should be noted that the simultaneous use of macrolides with ergot alkaloids or ergotamine-like vasoconstrictors promotes the development of ergotism with the development of a pronounced vasoconstrictor effect (up to the development of tissue necrosis of the extremities).

Adverse reactions. Macrolides are reliably considered one of the safest antibiotics. When using macrolides, serious adverse reactions are extremely rare. Among the undesirable manifestations, nausea, vomiting, abdominal pain are most often observed, and less often - diarrhea. With long-term use of “old” macrolides, the development of cholestatic hepatitis is possible.

Contraindications. Severe liver dysfunction. Increased individual sensitivity to macrolides. The simultaneous use of macrolides and ergot alkaloids, as well as ergotamine-like vasoconstrictors, is undesirable.

CONCLUSION

The problem of respiratory infections in children, despite significant progress in medical science in recent decades, continues to remain relevant.

The significant incidence of bacterial respiratory infections, as well as the high incidence of serious bacterial complications against the background of ARVI, require timely and justified inclusion of antibacterial drugs in therapy. However, despite the huge arsenal of highly active antibacterial agents, treatment of respiratory infections is not always successful. Late prescription, as well as a formulaic approach to the selection of antibacterial drugs, leads to an increase in the resistance of pneumotropic pathogens, which often causes the ineffectiveness of the etiotropic therapy. At the same time, a targeted and timely choice of initial etiotropic treatment, based on an empirical determination of the probable causative agent of a respiratory infectious disease, allows in practice, even without the possibility of bacteriological identification of the etiological factor, to achieve a clinical effect and a positive result of therapy in general.

The timeliness of prescription and the correct choice of antibacterial therapy, and therefore the effectiveness of treatment in general, are possible only if a number of factors are analyzed. The nosological form of the respiratory infection must be taken into account, since there is a certain connection between specific pneumotropic pathogens and the localization of damage to the respiratory tract. Based on epidemiological data, conclusions are drawn about the degree of sensitivity of probable pathogens to antimicrobial agents. Also, the choice of antibacterial drugs should be based on an analysis of the pharmacokinetic characteristics of the drug. This will determine the possibility of achieving an effective therapeutic concentration of the drug in damaged tissues and the likelihood of the risk of developing its side and undesirable effects. A rational choice of antibacterial therapy is possible only with mandatory consideration of the child’s age, his individual characteristics and background conditions.

Thus, the effectiveness of initial antibiotic therapy largely depends on the doctor taking into account the individual characteristics of the child, his age, the epidemiological situation and the nature of the infectious disease. Taking into account information about potential pathogens that most often cause infectious processes in a certain localization, as well as their sensitivity to antibacterial drugs, will make it possible to purposefully narrow the range of selected drugs. All this will make it possible to carry out rational etiotropic therapy in the early stages of the disease, reduce the risk of developing serious complications and increase the success of treatment of respiratory infections in general.

Rational choice of antibacterial drugs is a pressing problem in outpatient practice

In the second ten days of December, a regular meeting of the interregional school of family doctors, outpatient doctors and ambulance doctors was held in Vinnitsa. It was devoted to the problem of rational antibiotic therapy for diseases caused by opportunistic microorganisms in outpatient practice. Is this problem still relevant? Of course it is relevant.

Infectious diseases caused by opportunistic microorganisms are among the most common human diseases. Most of these infections occur in outpatient practice, i.e., they are classified as community-acquired. They are important not only in medical, but also in socio-economic aspects, as they are characterized by a high frequency in both children and adults, lead to disability, and are a common cause of hospitalization and the occurrence of chronic inflammatory diseases. In addition, the highest frequency of antibiotic prescriptions occurs in outpatient settings, and in this regard, it is necessary to consider their impact on the ecology and epidemiology of microbial resistance. Although specialists previously usually discussed the problems of resistance of microorganisms in the aspect of hospital infections, the trends of the 90s of the last century forced us to pay attention to the problem of resistance in the population as a result of the widespread, sometimes excessive, use of antibacterial drugs. An example is the global increase in the resistance of S. pneumoniae to penicillin and many antibiotics of other groups, pyogenic streptococcus to macrolides, Escherichia coli to ampicillin and co-trimoxazole, and gonococci to benzylpenicillin.

These trends force, on the one hand, to reconsider antibacterial treatment programs for community-acquired infections, and on the other, to try to globally limit the use of antibiotics, at least in situations where they are not vitally necessary or not indicated.

An important task is the rationalization of the choice of antibiotics for community-acquired infections, as it leads to a decrease in the frequency of prescribing these drugs, a more complete clinical and bacteriological cure of the patient and, ultimately, to limiting the growth of resistance in the population. Therefore, at present, recommendations for choosing the optimal antibacterial drug should be based not only on data on the clinical effectiveness of the antibiotic, but also take into account regional trends in antibiotic resistance, the ability of drugs to cause the selection of resistant strains, and pharmacodynamic aspects of treatment.

Head of the Department of Polyclinic Therapy and Family Medicine prof. V. M. Chernobrovy in his report dwelled in detail on the issues of classification of antibacterial drugs, as well as their rational use in gastroenterology and rheumatology.

A separate report was devoted to urinary tract infections. Urinary tract infections (UTIs) are common diseases in outpatient practice. The frequency of infections increases with age and in the presence of chronic diseases, such as diabetes mellitus, urolithiasis, prostate adenoma. At the same time, acute cystitis is predominantly observed in young women. In young and middle age, women get sick much more often than men, which is explained by the short urethra and the proximity of the urethra, vagina and rectum, which are highly colonized by various microorganisms. Most cases of urinary tract infections in women are an ascending infection, when microorganisms from the perianal area penetrate the urethra, bladder, and then through the ureters into the kidneys. In men, UTI infections are in most cases secondary, that is, they occur against the background of any structural changes in the genitourinary organs, most often the prostate gland.

Treatment of UTI infections, on the one hand, is simpler compared to infections of other localizations, since in this case an accurate etiological diagnosis is almost always possible and, in addition, the concentrations of antibacterial agents in the urine are tens of times higher than serum or concentrations in other tissues, which is an important condition for the eradication of pathogens. On the other hand, with complicated UTI infections there is always a cause (obstruction or other) supporting the infectious process, and in this case it is difficult, if not impossible, to achieve complete clinical or bacteriological cure.

More than 95% of urinary tract infections are caused by a single pathogen. According to the literature, most often (70-95% of cases) uncomplicated UTI infections are caused by Escherichia coli. Staphylococcus saprophyticus occurs in 5-20% of cases. Other enterobacteria are less commonly isolated: Proteus mirabilis, Klebsiella spp. or enterococci. As a result of a multicenter study conducted in Russia in 1998 (Moscow, Smolensk, St. Petersburg, Yekaterinburg, Novosibirsk), it was revealed that in 80% of UVP infections were caused by Escherichia coli, 8.2% Proteus spp., 3.7% Klebsiella spp., 2.2% Enterobacter spp., 0.7% Pseudomonas aeruginosa, 3% S. saprophyticus and 2.2% Enterococcus faecalis.

Based on the data presented, we can conclude that treatment of UTI infections in outpatient practice is possible on an empirical basis, based on data on the sensitivity of the main pathogen E. coli to antibacterial drugs. In routine outpatient practice, there is no need to conduct microbiological examination of urine for acute UTI infections, with the exception of special clinical situations (pregnant women, often recurrent infection).

First of all, it is necessary to highlight antibacterial agents, the use of which for UTI infections is inappropriate (Table 1).

Table 1

Reasons for the resistance of microorganisms that cause MPV infections to antibacterial drugs

Preparation	Reasons
Ampicillin, amoxicillin, ampiox	High level of resistance of uropathogenic E. coli strains to aminopenicillins
I generation cephalosporins - cefazolin, cephalexin, cefradine	Weak activity against gram-negative bacteria; high resistance of E. coli
Nitroxoline	Unproven clinical effectiveness; high level of pathogen resistance
Chloramphenicol	High toxicity
Sulfonamides, co-trimoxazole	Increased E. coli resistance; toxicity
Aminoglycosides	It is permissible to prescribe only in a hospital for nosocomial infections.

Table 2

Sensitivity of microorganisms to antibacterial drugs

Drugs	Level of sensitivity of microorganisms to antibacterial drugs (%)
	S. aureus	S. epidermidis	Strepto-coccus spp.	E.coli	Proteus spp.	K.pneumoni ae	P. aeruginosa
Ampicillin	mouth	21	18	23	mouth	mouth	mouth
Rifampicin	65	56	61	mouth	mouth	mouth	47
Furadonin	41	40	37	62	mouth	49	mouth
Furagin	24	21	27	2	mouth	39	mouth
Levomycetin	44	50	54	76	59	75	mouth
Ceftriaxone	75	87	92	88	74	82	91
Clarithromycin	65	78	86	mouth	Art.	48	49
Norfloxacin	79	82	76	96	95	92	86
Ofloxacin	83	94	74	100	98	97	89
Ciprofloxacin	82	92	74	100	98	87	92
Lomefloxacin	80	87	70	91	94	89	86

The choice of a rational antibiotic and the duration of therapy for various UTI infections is determined by the location and condition of the infection.

Acute cystitis is an acute uncomplicated infection of the urinary tract; it mainly affects young and middle-aged women. The etiology of the disease is dominated by Escherichia coli with a known level of sensitivity, therefore, in outpatient practice, microbiological diagnostics for acute cystitis is impractical, with the exception of pregnant women and recurrent infection.

The drugs of choice for acute cystitis may be fluoroquinolones or co-trimoxazole, for which the effectiveness of short courses (within 3 days) has been proven. Also, a reliable effect can be achieved by prescribing other antibiotics: amoxicillin/clavulanate, nitrofurans, non-fluorinated quinolones; in this case, the course of treatment should be 5 days.

If there are risk factors for recurrent infection (old age, pregnancy, diabetes, recurrent cystitis), a longer, 7-day course of antibiotic therapy is indicated. When prescribing therapy to pregnant women, it should be remembered that a number of antibiotics are contraindicated for them: fluoroquinolones, co-trimoxazole, tetracyclines.

Pyelonephritis can be an independent disease, but more often it complicates the course of various diseases (urolithiasis, prostate adenoma, diseases of the female genital organs, tumors of the genitourinary system, diabetes mellitus) or occurs as a postoperative complication.

Uncomplicated kidney infections occur in the absence of structural changes in patients without serious concomitant diseases; they are usually observed in outpatient practice.

Complicated infections occur in patients with various obstructive uropathy, against the background of bladder catheterization, as well as in patients with concomitant pathologies (diabetes mellitus, congestive heart failure, immunosuppressive therapy, etc.). In elderly patients, complicated infections are naturally observed.

A special place is occupied by senile pyelonephritis - the main problem of the geriatric nephrology clinic. Its frequency increases with each decade of an older person’s life, reaching 45% in men and 40% in women in the tenth decade.

Pyelonephritis is an infectious inflammatory disease of the kidneys affecting the pelvis and calyces, parenchyma and interstitial tissue. In the acute phase of the disease, bacteremia is usually observed. Clinical symptoms of sepsis can be observed in 30% of patients with pyelonephritis.

The main role in the treatment of pyelonephritis belongs to antibacterial agents. The choice of antibacterial drugs should be based on the spectrum of their antimicrobial activity and the level of sensitivity to them of the main pathogens of pyelonephritis. In this regard, the choice of antibacterial drugs for the treatment of pyelonephritis that occurs outside the hospital can be easily predicted taking into account data from regional pharmacoepidemiological studies. Table 2 presents the results of a study of the sensitivity of microorganisms isolated from patients with microbial inflammatory kidney diseases in the city of Vinnitsa to the most common antibacterial drugs.

An important issue is also the prevention of relapses and repeated infections. With frequent exacerbations of pyelonephritis, the generally accepted approach is to prescribe monthly preventive courses (1-2 weeks) of antibacterial drugs. However, the prophylactic use of antibacterial agents for pyelonephritis should be treated with extreme caution. Currently, there is no reliable data indicating the effectiveness and advisability of preventive courses of antibacterial drugs for pyelonephritis. In addition, it should be taken into account that the prophylactic use of antibiotics contributes to the selection of resistant strains of microorganisms. Moreover, the prophylactic prescription of antibiotics in elderly patients and patients with an indwelling urinary catheter should be considered unjustified, since the risk of treatment complications significantly exceeds the potential benefit.

Much more justified are non-drug measures to prevent exacerbations of pyelonephritis, which include an adequate drinking regimen 1.2-1.5 liters daily (cautiously in patients with impaired heart function), the use of herbal medicine. Regarding the latter, although there is no reliable evidence of its effectiveness, it helps improve urinary excretion and does not lead to the development of serious adverse events.

In conclusion, it should be noted that it is, of course, impossible to fully cover such a global problem as the problem of rational antibiotic therapy in one school meeting, but Vinnitsa doctors certainly succeeded in outlining the range of problems and outlining ways to solve them.

Irina Paliy

Advances in pharmaceutical science and industry have made it possible in recent years to introduce into clinical practice a large number of new antibacterial drugs of the main pharmacological groups with improved antimicrobial properties (Ill-GU generation cephalosporins, macrolides/azalides, III generation aminoglycosides, combinations of beta-lactams with beta-lactamase inhibitors) ; New classes of antimicrobial agents have also appeared - carbapenems, monobactams, fluoroquinolones. Currently, clinicians have a large number of different antibacterial agents at their disposal, so the most important task is to correctly select the optimal drug. Approaches to effective and safe antibiotic therapy should be based on taking into account many factors that are formulated in the basic principles of antibacterial therapy.

^ PRINCIPLES OF ANTIBACTERIAL THERAPY

Availability of indications for prescribing an antibacterial agent.

Establishing the reasons that impede effective antibacterial therapy.

Identification of microorganisms that cause an infectious disease, determination of the sensitivity of microbes to drugs.

Selection of optimal treatment regimens taking into account the localization of the infectious process (empirical therapy) or the type of pathogenic microorganism (targeted therapy).

The choice of antibacterial agent taking into account the characteristics of the disease, the patient (macroorganism) and the clinical pharmacology of the drugs.

Rational combination of antibacterial agents.

Determining the optimal route of drug administration.

Determining the adequate dose of the drug.

Implementation of adequate control during the treatment process.

Determination of the optimal duration of antibacterial therapy.

^

1. Indications for prescribing antibacterial agents

1.1. General and local symptoms of infections

The indication for the prescription of antibacterial agents is localized or generalized bacterial infection. The beneficial effect of chemotherapy on morbidity and mortality in infections and on the epidemiological process is an established fact.

A viral infection does not require antibiotic therapy. Signs of a bacterial infection are general or local symptoms.

1.1.1. Common symptoms of infection: acute onset, fever, chills, sweating, intoxication, weakness, intestinal dysfunction, myalgia, photophobia, lymphadenopathy, splenomegaly, leukocytosis, band shift in the leukocyte formula, lymphopenia, increased ESR.

All of these symptoms are not strictly specific to the infectious process and can be observed in other diseases of a non-infectious nature. Thus, fever (with or without chills) is characteristic of systemic vasculitis, systemic lupus erythematosus, lymphogranulomatosis, malignant tumors, or may be a consequence of drug therapy; lymphadenopathy can be observed in various hematological and oncological diseases.

At the same time, in some patients, for example, elderly and senile patients, an infection, even a severe one, can occur without fever and changes in the peripheral blood, but manifest itself with other symptoms (impaired function of the central nervous system, respiratory failure, progression of heart failure, anemia and etc.).

^ 1.1.2. Local symptoms of infection: pharyngitis/tonsillitis, cough, dysuria, arthralgia, diarrhea, etc.; in addition, localized tenderness, swelling and/or hyperemia may occur.
^

1.2. Diagnosis of the infectious process

Before prescribing antibacterial therapy, a thorough examination of the patient is required to determine the presence of a bacterial infection. Antibacterial agents should not be prescribed until the diagnosis has been clarified, except in emergency situations, when in severely ill patients antibacterial therapy can be prescribed only if a bacterial infection is suspected. Premature or unjustified prescription of antibacterial drugs is a wrong tactic, since these drugs are potentially dangerous, expensive and can contribute to the selection of resistant strains of microorganisms.

Antibacterial agents should not be prescribed for unremitting fever, except in difficult diagnostic cases.

Antibacterial agents should not be prescribed as antipyretic or diagnostic agents!
^

1.3. Prophylactic use of antibacterial agents

In some situations, antibacterial agents are prescribed in the absence of an infectious process, but in the presence of a high risk of its occurrence, i.e. prophylactically. Currently, the prophylactic use of antibacterial agents is limited to certain clinical situations:

Surgical interventions in patients with a high risk of developing infective endocarditis (congenital, acquired or operated heart defects, mitral valve prolapse with regurgitation, hypertrophic obstructive cardiomyopathy) or other infectious complications (primary and secondary immunodeficiency);

Surgical interventions in highly contaminated areas (colon, pelvis);

Prevention of sepsis in patients with agranulocytosis;

Prevention of relapses and repeated infections in patients with chronic pyelonsphritis;

Prevention of infection (mainly intestinal) in epidemiologically unfavorable regions.

^

2. Reasons preventing effective antibacterial

therapy

Sometimes antibacterial agents may not have a clinical effect, although the results of a bacteriological study showed good sensitivity of the isolated pathogenic microorganism to the selected drug. The reasons may be insufficient penetration of antibacterial agents into tissues and cells, a decrease in their activity in the presence of pus, a change in the pH of urine or other liquids. It has been established that the secretion of antibacterial agents into bile during bile duct obstruction is significantly reduced, which may cause the ineffectiveness of drugs before surgical restoration of the patency of the bile ducts. Drainage of abscesses, surgical treatment of wounds with the removal of all devitalized tissue, streaks, and pockets also help to enhance the antibacterial effect of drugs. With urinary tract obstruction (stones, tumor), the effect of antibacterial treatment is usually temporary and inconsistent; a stable effect can be expected after eliminating the causes that disrupt the passage of urine.
^

3. Identification of pathogens

3.1. Collection and transportation of biological material

For accurate etiological diagnosis of an infectious process, direct or indirect detection of a pathogenic microorganism in the tissues or cells of a sick person is necessary. For this purpose, depending on the nature and localization of the infectious process, biological material is collected: blood, urine, sputum, pus, tissue exudate, aspirate, wound discharge, cerebrospinal fluid, bile, feces. The technique for collecting and transporting biological material is presented in Appendix 1.

Material for bacteriological examination should be taken before antibacterial therapy is prescribed!

^ 3.2. Methods for identifying infectious agents

In practice, direct and indirect methods for identifying infectious agents are used.

Direct methods:

Direct microscopic examination of native preparations;

Microscopy of stained preparations;

Electron microscopy;

Cultural research - inoculation on artificial nutrient media, isolation and identification of pure culture.

^ Indirect methods:

Counter immunoelectrophoresis;

Radioimmunological research;

Enzyme immunoassay;

Chromatography;

Serological tests;

Skin tests.

In clinical practice, the most accessible and common methods are microscopy of stained preparations and cultural examination.

^ 3.3. Gram stain

It is an informative method for rapid indicative diagnosis of bacterial infections. Used in the study of almost all types of clinical materials (tissue exudates, aspirates, sputum, tissue fluids, including urine And cerebrospinal fluid). The Gram staining technique for smears is presented in Appendix 1.

The Gram staining method allows you to distinguish between gram-positive (colored, dark blue or purple) and gram-negative (uncolored, red, pink or pale yellow) microorganisms and clarify their morphological features - cocci (round), rods (oblong). In some cases, it is possible to more accurately identify microorganisms by the morphology and nature of the location of the colonies (staphylococci, streptococci, pneumococci, enterococci, gonococci, etc.). An approximate assessment of the pathogen can provide significant assistance in choosing initial antibacterial therapy (Table 6).

Table 6

Gram stain and drugs of choice

^ Identified microorganisms	1st line drugs
Gram-positive cocci:
staphylococci	Oxacillin or cephalosporins I order.
streptococci, pneumococci	Penicillin or macrolides
enterococci	Ampicillin or amoxicillin
Gram-negative cocci	Benzylpenicillin or co-trimoxazole
Gram-negative rods	Cephalosporins II-III generation; aminoglycosides; fluoroquinolones

^ 3.4. Cultural examination

The most accessible and accurate method of etiological diagnosis of an infectious process, which, however, requires a certain time (48 hours or more). Includes inoculation on artificial nutrient media, isolation and identification of a pure culture of microorganisms, determination of the sensitivity of microbes to antibacterial agents, determination of the minimum inhibitory concentration of the drug against the identified pathogen.

^ The diagnostic value of this method depends on many factors:

Correct collection of biological material;

Correct sample transportation;

Adequacy of cultural research methods (environment, conditions).

Rules for collecting and transporting various materials (blood, urine, sputum, cerebrospinal fluid, aspirate) are presented in Appendix 1.

Rational antibiotic therapy should be based on knowledge of the individual characteristics of the patient, the course of the disease, the nature of the pathogen and the properties of the drug. These include:

· chemotherapy prescribed strictly according to indications, i.e. only in cases where it is impossible to do without it;

· chemotherapy prescribed taking into account contraindications, for example, hypersensitivity or allergic reaction to drugs of a particular group. The choice of drug for chemotherapy can be made in various situations;

· for etiologically deciphered diseases, the choice of drug should be determined taking into account the sensitivity of the pathogen (antibioticogram) isolated from this particular patient as a result of bacteriological research;

· when isolating a pathogen without determining its sensitivity to chemotherapy, or during empirical initial chemotherapy of a disease with an unidentified but suspected pathogen, the choice of drug for chemotherapy should be based on antibiotic sensitivity indicators of the corresponding microorganisms - the most likely causative agents of a given nosological form of the disease, according to the literature, or when focusing on data on the regional sensitivity of certain infectious agents - pathogens;

· selection of the most active and least toxic drug for the macroorganism;

· timely initiation of treatment and carrying out courses of antibiotic therapy of the required duration until the therapeutic effect is stable;

· treatment should be carried out strictly according to the regimen recommended for the selected chemotherapy drug (method and frequency of administration of the drug, duration of treatment), as well as taking into account the coefficient of increasing drug concentration in order to create effective concentrations of the drug directly in organs and tissues (approximately 4 MIC - the minimum inhibitory concentration , determined, if possible, by the method of serial dilutions);

· the duration of taking chemotherapy drugs should be at least 4-5 days in order to prevent the development of pathogen resistance to this drug, as well as the formation of bacterial carriage;

· for dermatomycosis, candidiasis and vaginal trichomoniasis, in order to prevent relapses, treatment is continued for 2-4 weeks after the symptoms of the disease disappear;

· It is advisable to supplement chemotherapy with the use of agents that help increase the activity of the body’s defense mechanisms (the principle of immunochemotherapy);

· with empirical therapy, i.e. if the sensitivity of pathogens is unknown, it is advisable to combine drugs with a complementary spectrum of action - to expand the spectrum of action of fluoroquinolones on anaerobes and protozoa, in many cases their combination with metronidazole (Trichopolum), which has a bactericidal effect against these microorganisms, is recommended;

· Combinations of drugs with different mechanisms and spectrum of action are very effective in chemotherapy. For example, the drug Polygynax, which is a combination of neomycin, polymyxin and nystatin, is currently widely used in gynecological practice for the local treatment of vaginitis of unknown etiology;

· knowledge of the nature and frequency of side effects when prescribing antibiotics, especially in certain pathological conditions, for example, in cases of impaired renal excretory function;

· combining antibiotics with each other in order to enhance the antibacterial effect and prevent the formation of antibiotic resistance in microorganisms;

· gentle therapy using a minimum of antibiotics, while the clinical effect is achieved due to low and subinhibitory concentrations of antibiotics as a result of inhibition of adhesion and stimulation of phagocytosis;

· step therapy with a transition from parenteral to oral route of administration as soon as possible, determined by the clinical condition of the patient;

· use of an express method for determining the total microflora, which allows one to navigate the choice of “starting” antibiotic therapy.

However, when using drugs in combination, several factors must be taken into account:

· drug compatibility of chemotherapy drugs intended for joint use. For example, co-administration of tetracyclines with penicillins is contraindicated, since tetracyclines reduce the bactericidal effect of penicillins;

· the possibility that drugs containing the same substance as an active principle may have different trade names, since they are produced by different companies and may be generics (drugs produced under license from the original) of the same chemotherapy drug. For example, a combination drug of sulfonamides and trimethoprim, cotrimoxazole, is better known in the CIS countries as biseptol or bactrim, and one of the fluoroquinolones, ciprofloxacin, is known in the CIS and is widely used in practice as ciprobay, tsifran, quintor, neofloxacin;

· combined use of antibiotics increases the risk of developing an imbalance of normal microflora.

A prerequisite for successful treatment of any infectious disease is to establish the etiological factor and determine its antibiotic sensitivity. However, in the absence or remoteness of a bacteriological laboratory and for health reasons, depending on the clinical symptoms or the etiological factor that caused the disease, one of the broad-spectrum drugs (ampicillin, kanamycin, tetracycline, etc.) may be prescribed. After establishing an antibiogram, antibiotic therapy should be continued with the drug to which the pathogen is most sensitive.

During antibiotic therapy, the concentration of the drug achieved in the lesion must exceed the level of sensitivity of the pathogen to the antibiotic and provide the maximum bactericidal effect; only then can antibiotic therapy be considered effective and successful. The use of doses and methods that provide only subbacteriostatic concentrations of the antibiotic in the patient’s body should be avoided, as this can lead to the development of antibiotic resistance in microorganisms.

One of the proven methods for increasing the effectiveness of antibiotic therapy, preventing or slowing down the formation of resistance of pathogens to the action of these drugs is combination treatment with antibiotics. The basic principles of the combined use of antibiotics were formulated taking into account the properties of the pathogen, the mechanism and spectrum of action of antibiotics on the bacterial cell, the nature of the pathological process at the site of infection, the patient’s condition, etc. The main indications for combination antibiotic therapy include:

· severe infections requiring immediate initiation of treatment before a bacteriological diagnosis is established;

· mixed infection with the release of various microbial associations (peritonitis, pneumonia, etc.);

· preventing the development of toxic effects by achieving a quick and more complete effect with the simultaneous influence of two (or several) drugs in smaller doses than usual therapeutic ones;

· preventing or slowing down the development of pathogen resistance;

· the possibility of enhancing the antibacterial effect based on the synergistic effect of antibiotics;

· impact on insensitive pathogens.

Combination antibiotic therapy is especially indicated for mixed infections confirmed bacteriologically. It is also carried out in severe, life-threatening conditions immediately after taking material for bacteriological examination until an accurate diagnosis of the disease is established, as well as for preventive purposes.

It should be borne in mind that combination antibiotic therapy should be strictly justified and used only when it is not possible to achieve a good therapeutic effect when using one antibiotic in sufficient doses, with optimal methods of its administration and the required duration of treatment.

The prophylactic use of antibiotics is aimed, first of all, at preventing the development of infection in the patient’s body and is mainly used to prevent the generalization of infection in the patient, combat its latent course and the carriage of pathogens.

Antibiotic prophylaxis should always be etiotropic in nature. Its purpose is to prevent the development of a known or suspected pathogen in the body. They are prescribed strictly individually in accordance with the etiology of the process, according to vital indications, taking into account the effectiveness of the drug, as well as possible side effects and for certain indications. For example, in surgical practice, antibiotics are used during operations, diagnostic and therapeutic endoscopies (bronchi, urinary tract, etc.). The list of indications for pre- and postoperative use of antibiotics includes: heavily contaminated wounds, complicated bone fractures, burns, organ and tissue transplantation.

1. It is necessary to establish the etiological factor of the disease and determine its antibiogram.

2. Antibiotic therapy should be prescribed strictly according to indications, taking into account contraindications.

3. For the purpose of treatment, it is necessary to select the most effective and least toxic drug with further determination of optimal doses and methods of administration to create therapeutic concentrations in the lesion that exceed the MIC for a given pathogen by 2-3 times.

4. In the dynamics of treatment, it is necessary to conduct repeated bacteriological studies and determine antibiotic sensitivity in order to determine the effectiveness of the treatment.

5. Use a minimum of antibiotics for treatment, “gentle therapy”, while choosing the most active and least toxic drug.

6. In order to prevent the formation of antibiotic resistance, combination treatment with drugs should be carried out.

7. Based on the clinical condition of the patient, stepwise therapy should be carried out from parenteral to the oral route of administration.

8. Organize monitoring of the prevalence of resistant strains in a given medical institution, which will allow doctors to effectively carry out treatment.

Test tasks

1. What are antibiotics?

A) bacterial lipopolysaccharides;

B) cell metabolic products;

C) bacterial polyphosphates;

D) bacterial exotoxins;

E) microbial exoenzymes.

2. Which scientist coined the term “antibiotic”?

A) L. Tarasevich;

B) D. Ivanovsky;

C) A. Fleming;

D) Z. Vaksman;

E) A. Levenguk.

3. Choose a drug that has a bactericidal effect:

A) chloramphenicol;

B) cefazolin;

C) tetracycline;

D) erythromycin;

E) oleandomycin.

4. Select an antiherpetic drug:

A) tetracycline;

B) chloramphenicol;

C) cephalexin;

D) acyclovir;

E) erythromycin.

5. Who was the first to discover penicillin?

A) Z. Vaksman;

B) Z. Ermolyeva;

C) L. Tarasevich;

D) D. Ivanovsky;

E) A. Fleming.

6. Select an antibiotic that inhibits bacterial cell wall synthesis:

A) methicillin;

B) polymyxin M;

C) tetracycline;

D) rifampicin;

E) erythromycin.

7. Select a drug that disrupts the function of the cytoplasmic membrane in bacteria:

A) oxacillin;

B) polymyxin M;

C) streptomycin;

D) tetracycline;

E) rifampicin.

8. Select an antibiotic that inhibits protein synthesis at the ribosome level of the bacterial cell:

A) ampicillin;

B) vancomycin;

C) rifampicin;

D) cycloserine;

E) chloramphenicol.

9. Choose a herbal antibiotic:

A) neomycin;

B) ecmoline;

C) allicin;

D) lysozyme;

E) nystatin.

10. Which chemotherapy drug has an antiviral effect?

A) azidothymidine;

B) bismoverol;

C) erythromycin;

D) cycloserine;

E) primaquine.

11. Select an antibiotic to which mycoplasmas have primary (species) resistance.

A) erythromycin;

B) tetracycline;

C) kanamycin;

D) oxacillin;

E) chloramphenicol.

12. Acquired antibiotic resistance of microbes is associated with:

A) production of toxins by bacteria;

B) the action of viral enzymes;

C) the presence of R-plasmids in microbes;

D) weakening of the body’s reactivity;

E) the presence of microcapsules in microbes.

13. Select an antifungal drug:

A) amphotericin B;

B) streptomycin;

C) cephalexin;

D) erythromycin;

E) tetracycline.

14. What is the primary (natural) resistance of bacteria to

antibiotics?

A) with the presence of R-plasmids in the cytoplasm of bacteria;

B) with the presence of intracellular inclusions;

C) with proteins of the cytoplasmic membrane;

D) lacking a target for the action of antibiotics;

E) with the formation of a macrocapsule by bacteria.

15. Select an antibiotic synthesized by fungi:

A) griseofulvin;

B) chloramphenicol;

C) methicillin;

D) ampicillin;

E) gramicidin.

16. The bacteriostatic effect of antibiotics is:

A) impaired bacterial mobility;

B) increased enzyme synthesis;

C) strengthening the immune response;

D) violation of sporulation;

E) inhibition of bacterial growth.

17. Sensitivity to antibiotics is determined by:

A) aspiration method;

B) in the neutralization reaction;

C) paper disk method;

D) hanging drop method;

E) in the hemagglutination reaction.

18. Select an antibiotic that bacteria synthesize:

A) cephalexin;

B) erythromycin;

C) ampicillin;

D) polymyxin M;

E) griseofulvin.

19. Select a drug to treat malaria:

A) rimantadine;

B) chloroquine;

C) ampicillin;

D) cycloserine;

E) chloramphenicol.

20. Choose a drug that primarily affects

gram-positive bacteria:

A) tetracycline;

B) polymyxin M;

C) streptomycin;

D) neomycin;

E) cefazolin.

21. Select beta-lactam antibiotic:

A) ampicillin;

B) tetracycline;

C) erythromycin;

D) chloramphenicol;

E) rifampicin.

22. Choose an antibiotic that is bacteriostatic

action:

A) neomycin;

B) cefazolin;

C) erythromycin;

D) streptomycin;

E) nystatin.

23. Select an anti-tuberculosis drug:

A) tetracycline;

B) isoniazid;

C) nystatin;

D) fusidine;

E) ampicillin.

24. Select a drug to treat infections caused by

non-spore-forming anaerobes:

A) nystatin;

B) fusidine;

C) bioquinol;

D) chloroquine;

E) metronidazole.

25. Select a drug that is a β-lactamase inhibitor in

bacteria:

A) cycloserine;

B) chloramphenicol;

C) sulbactam;

D) erythromycin;

E) tetracycline.

26. Select the enzyme produced by bacteria for

enzymatic inactivation of antibiotics:

A) oxidoreductase;

B) transferase;

C) hyaluronidase;

D) beta-lactamase;

E) neuraminidase.

27. Choose a broad-spectrum drug:

A) tetracycline;

B) polymyxin M;

C) oxacillin;

D) cefazolin;

E) erythromycin.

28. Choose a drug that primarily affects

gram negative bacteria:

A) streptomycin;

B) oxacillin;

C) polymyxin M;

D) erythromycin;

E) cefazolin.

29. Select a drug for the treatment of amoebiasis:

A) erythromycin;

B) metronidazole;

C) rimantadine;

D) tetracycline;

E) rifampicin.

30. Select the diffusion method for determining the sensitivity of bacteria to antibiotics:

A) Grazia method;

B) Gram method;

C) Dick's method;

D) Gins method;
E) E-test method.

31. Select the accelerated method for determining sensitivity to

bacteria antibiotics:

A) Appelman's method;

B) disk method;

C) Kahn method;
D) Rogers method;

E) Price's method.

Answers to test tasks

1 B 7 B 13 A 19 B 25 C 31 D

2 D 8 E 14 D 20 E 26 D

3 V 9 C 15 A 21 A 27 A

4 D 10 A 16 E 22 C 28 C

5 E 11 D 17 C 23 B 29 B

6 A 12 C 18 D 24 E 30 E

List of used literature

1. Azizov I.S., Dyogtev A.Yu. Vancomycin-resistant Staphylococcus aureus // Medicine and ecology. - 2004. - No. 1.- P.41-43.

2. Akaeva F.S., Omarova S.M., Adieva A.A., Medzhidov M.M. Multiple antibiotic resistance of associative microflora in urogenital pathology // ZhMEI. - 2008. - No. 6. – pp. 85-87.

3. Baranov A.A., Maryandyshev A.O. Application of molecular biology methods for the study of Mycobacterium tuberculosis // Problems of tuberculosis and lung diseases. - 2008. - No. 4. - P. 3-7.

4. Bereznyakov I.G. Antibiotic resistance: causes, mechanisms, ways to overcome // Klin. antibiotic therapy. - 2001. - No. 4. – P. 18 - 22.

5. Biron M.G. Bulletin of the WHO program to combat tuberculosis in the Russian Federation. – Issue 4, July 2007. Information // Problems of tuberculosis and lung diseases. - 2008. - No. 3. - pp. 39-43.

6. Gorbunov V.A., Titov L.P., Ermakova T.S., Molochko V.A. Etiology of superficial mycoses and resistance of pathogens. // Materials of the 1st All-Russian Congress “Advances in Medical Mycology”. - 2003. - T.1. – pp. 12-13.

7. Dikiy I.L. and others. Microbiology: Guide to laboratory exercises. Study guide. - Kyiv: “Professional”. - 2004 - 594 p.

8. Dumpis U., Balode A., Eremin S.M. and others. Infection control and containment of antibiotic resistance // Epinort. - 2005. - No. 2. – pp. 45-47.

9. Ivanov D.V. Characteristics of resistance to beta-lactam antibiotics in nosocomial strains of Proteus mirabilis // JMEI. - 2008. - No. 6. - pp. 75-78.

10. Kozlov R.S., Krechikova O.I., Sivaya O.V. and others. Antimicrobial resistance of Streptococcus pneumoniae in Russia; results of a prospective multicenter study (phase A of the PeGAS-I project) // Klin. microbe. antimicrobial chemotherapy. – 2002. – T. 4. - No. 3. - pp. 267-277.

11. Krapivina I.V., Galeeva E.V., Veshutova N.S., Ivanov D.V., Sidorenko S.V. Antibiotic sensitivity and molecular mechanisms of resistance to beta-lactams in gram-negative microorganisms – causative agents of nosocomial infections // JMEI. – 2007. - No. 5. – P. 16-20.

12. Determination of the sensitivity of microorganisms to antibacterial drugs. MUK 4.2.1890-04 // KMAH. - 2004. – T.3. - No. 4. – pp. 306-359.

13. Pozdeev O.K. Medical microbiology / Ed. Pokrovsky V.I. – 2nd ed., revised – M.: “GEOTAR-MED”. - 2004. – 768 p.

14. Sidorenko S.V. Mechanisms of resistance of microorganisms // In the book: Practical Guide to Anti-Infective Chemotherapy / Ed. Strachunsky L.S., Belousova Yu.B., Kozlova. S.N. – M.: “Borges”. - 2002. – P. 21-31.

15. Sidorenko S.V., Berezin A.G., Ivanov D.V. Molecular mechanisms of resistance of gram-negative bacteria of the Enterobacteriaceae family to cephalosporin antibiotics // Antibiot. chemotherapy - 2004. - T. 49. - No. 3. – P. 6-15.

16. Sidorenko S.V., Rezvan S.P., Eremina L.V. et al. Etiology of severe hospital infections in intensive care units and antibiotic resistance among their pathogens // Antibiot. chemotherapy - 2005. - T. 50. - No. 2-3. – P. 33-41.

17. Skala L.Z., Lukin I.N., Nekhorosheva A.G. Organization of Microbiological Monitoring of the Microbial Landscape and the Level of Antibiotic Resistance in Medical Institutions // KMAH. - 2005. –T.7. - No. 2. – P.52.

18. Shaginyan I.A., Dmitrienko O.A. Molecular epidemiology of infections caused by methicillin-resistant staphylococci // JMEI. - 2003. - No. 3. - pp. 99-109.

19. Shub G.M., Khodakova N.G. Circulation of methicillin-resistant staphylococci in medical institutions of various profiles // JMEI. - 2008. - No. 1. - P. 66-68.

20. Hisanaga G.G., Laing T.L., De Corby N.M. et al. Antibiotic resistance in outpatient urinary isolates: final results from the North American Urinary Tract Infection Collaborative Alliance (NAUTICA) Int. J. Antimicrob. - 2005. – Vol. 26. - No. 5. – P. 380-388.

21. Horowitz J.B., Moehring H.B. How property rights and patents affect antibiotic resistance // Health Econ. - 2004. - Vol.13. - No. 6. – P. 575-583.

22. Horstkotte M.A., Knobloch J.K.-M., Rohde H. et all. Rapid Detection of Methicillin Resistance in Coagulase-Negative Stahpylococci with the VITEK 2 System // J. Clin. Microbiol. - 2002. Vol.40.- No. 9. - P. 3291-3295.

23. Li X.Z., Nikaido H. Efflux-mediated drug resistance in bacteria // Drugs. - 2004. – Vol.64. – P. 159-204.

24. Poole K. Efflux – mediated multiresistance in Gram-negative bacteria // Clin. Microbiol. Infect. - 2004. – Vol.10. – P. 12-26.

25. Vancomycin - resistant Staphylococcus aureus in the absence of vancomycin exposure. Whitener C.J., Park S.Y., Browne F.A. et al // Clin Infect Dis. - 2004.- Vol. 38. – P. 1049-1106.

Related information.

Principles of rational antibiotic therapy.

1. An antibacterial drug should be prescribed as soon as possible, from the moment the disease caused by a microbial pathogen is diagnosed.

2. The choice of drug is carried out in accordance with the type of pathogen. If an antimicrobial agent is prescribed empirically (before identification of the pathogen), then it is necessary to choose the drug that is most active against microorganisms that most often cause this type of disease. For example, the causative agents of erysipelas, scarlet fever, are always streptococci, lobar pneumonia - pneumococci, epidemic meningitis - meningococci. In cases where there are difficulties in identifying the suspected pathogen, a broad-spectrum drug is prescribed.

When a pathogen is identified, an antibacterial drug is selected in accordance with its properties (gram+, gram-, aerobic, anaerobic, intracellular pathogen) and sensitivity to known antibacterial drugs, taking into account their mechanisms of action and spectrum of antimicrobial action.

3. The choice of drug is influenced by factors related to the macroorganism and the disease itself. First of all, this is the localization of the infectious process. It is necessary to choose a drug that penetrates the organ or tissue where the pathological process is localized. The drug must create a minimum inhibitory concentration at the site of infection (bones, lungs, urinary tract, bile, skin and soft tissues, etc.)

If you have a urinary tract infection, consider the acidity of your urine. Depending on the effect of urine acidity on activity, the following antibiotics are distinguished:

1. Antimicrobial drugs effective against acidic urine (pH 5.0-6.5)

penicillins, tetracyclines, 8-hydroxyquinolones, quinolines, rifampicin, furadonin, furazolin

2. Antimicrobial drugs effective against alkaline urine reaction (pH 7.5-8.5): macrolides, lincomycin, aminoglycosides.

3. Antimicrobial drugs, the effectiveness of which does not depend on urine pH,

chloramphenicol, polymyxins, cephalosporins, ristomycin, vancomycin, furatsilin, furazolidone, cycloserine.

To acidify urine, ascorbic acid and calcium chloride are used, and for alkalization - soda drink, alkaline mineral water.

Secondly, comorbidities need to be taken into account. In particular, careful collection is required allergy history, especially for penicillins, cephalosporins, which often cause allergic reactions.

Kidney disease must be taken into account nephrotoxic– aminoglycosides, sulfonamides, polymyxins), liver diseases ( hepatotoxic– tetracyclines, rifampicin, chloramphenicol, erythromycin); blood diseases(inhibit hematopoiesis - chloramphenicol, amphotericin B, sulfonamides); central nervous system diseases(neurotoxic - aminoglycosides for hearing and vestibular apparatus, for the optic nerve - chloramphenicol, nalidixic acid); fluoroquinolones cause seizures); gastrointestinal diseases(the most dangerous are tetracyclines, ampicillins, macrolides; lincomycin, clindamycin cause pseudomembronous colitis).

4. It is necessary to take into account the physiological state (pregnancy, lactation).

During pregnancy absolutely contraindicated tetracyclines (impaired formation of bones and teeth in the fetus), aminoglycosides (oto- and nephrotoxicity), chloramphenicol (damage to the cardiovascular system - “gray baby” syndrome), sulfonamides (hyperbilirubinemia, methemoglobinemia), fluoroquinolones (impaired growth of cartilage tissue of joints), nitrofurans (methemoglobinemia).

During lactation contraindicated sulfonamides, tetracyclines, chloramphenicol, metronidazole, quinolones. Antibiotics, allowed during pregnancy: penicillins, cephalosporins, erythromycin

5. The patient's age should be taken into account.

In childhood contraindicated: tetracyclines up to 9 years, fluoroquinolones up to 15 years

6. Choice dosage of the drug, route of administration, depend on the severity of the condition, age, body weight (in children - calculation per kg of body weight, in the elderly and elderly - the dose is reduced by 25-30%), the pharmacokinetics of the drug itself (acid-sensitive ones are administered only parenterally), the localization of the process (for example, high doses ABs for meningitis are administered with the aim of creating a minimum inhibitory concentration in the cerebrospinal fluid, where ABs penetrate poorly), the functional state of the kidneys and liver.

Frequency of administration The drug depends on the half-life. It is necessary that the concentration of the drug in the blood does not decrease below the minimum inhibitory level, since during these intervals the growth and reproduction of bacteria will resume. Conditions are created for the development of resistant strains. So benzylpenicillin sodium salt should be administered 6-8 times a day.

7. The course of treatment for acute infection is 5-7 days. The effectiveness of prescribed antimicrobial therapy is determined on the 3rd day. If there is no positive dynamics of clinical signs of the disease after 72 hours, it is necessary to change the drug. If therapy is effective for an acute infection, but there is no full effect by the 7th day, then treatment can be continued with the same drug for up to 10 days. The course of treatment for chronic infection can be 14 days.

8. Combined antimicrobial therapy is prescribed:

1. for severe infections (peritonitis, sepsis, osteomyelitis, endocarditis, severe gynecological infections);

2. with a mixed flora (two or more pathogens are sown);

3. for diseases caused by a pathogen that quickly develops resistance to antimicrobial agents (tuberculosis, leprosy).

When choosing an AB for combination therapy, the following circumstances must be taken into account:

1. Synergism is observed when combining 2 drugs with the same type of action: bactericidal with bactericidal, bacteriostatic with bacteriostatic. When combining drugs with different types of action (bactericide with bacteriostatic), synergism is not observed, since bactericides act on “young” dividing forms, and bacteriostatics stop the growth and reproduction of microorganisms.

2. It is irrational to combine 2 drugs with unidirectional side effects. For example, two nephrotoxic drugs - aminoglycosides with sulfonamides, two hepatotoxic drugs - tetracyclines with rifampicin; chloramphenicol and sulfonamides that inhibit hematopoiesis

3. When choosing drugs for combination therapy, it is necessary that the spectrum of antimicrobial action expands, that is, one drug acts on gram (+) flora, and the other predominantly on gram (-). Thus, combinations of a broad-spectrum drug with a drug active against anaerobes (for example, cefuroxime + metronidazole).

9. It is necessary to rationally combine antimicrobial drugs with drugs from other pharmacotherapeutic groups. At the same time, rational combinations are those in which drugs can prevent or correct the adverse effects of antibiotics. Thus, the administration of vitamin B6 prevents the development of neuropathy caused by GINK-isoniazid derivatives; folic acid – development of B12-folate deficiency anemia caused by biseptol; probiotics prevent the development of dysbiosis with broad-spectrum antibiotics. Combinations of 2 drugs with unidirectional side effects are irrational. For example, when aminoglycosides are combined with loop diuretics (furosemide, uregit), the risk of oto- and nephrotoxicity increases sharply.

Combinations of ABs with drugs with immunostimulating effects in cases of decreased immunity are rational.