Empirical therapy for what. Empirical therapy for inflammatory lesions of the skin of large folds. Types of antimicrobial therapy and selection criteria for AMP

If an early etiological diagnosis of pneumonia is impossible (in half of the cases, using the most complex techniques, it is not possible to identify the causative pathogen), then carry out empiric therapy for pneumonia... A broad spectrum antibiotic (preferably macrolides) is prescribed, acting on both extracellular and intracellular pathogens. The daily dose of the antibiotic depends on the degree of intoxication.

Based on the data of the anamnesis, the clinical picture (taking into account the risk factors for the development of complications) and the chest X-ray, they decide on need for hospitalization and conducting empirical treatment. Beta-lactam antibiotics are usually prescribed for outpatients, as pneumonia is most often caused by pneumococcus. If pneumonia is not severe and is atypical (intracellular pathogen), then young patients and previously healthy ones are given macrolides.

Depending on the severity of the pneumonia treatment is carried out differentially and in stages... So, in mild cases, the antibiotic is prescribed orally (or intramuscularly), with moderate pneumonia - parenterally. In severe cases, treatment is carried out in 2 stages: first, bactericidal antibiotics are administered intravenously (for example, cephalosporins), and then bacteriostatic antibiotics (tetracyclines, erythromycin) are prescribed in the aftercare phase. The following stepwise monotherapy with antibiotics is also used: a gradual transition (3 days after receiving the effect) from injections to oral administration of an antibiotic. According to this scheme, amoxiclav, clindamycin, ciprofloxacin and erythromycin can be prescribed.

If the patient does not tolerate antibiotics and sulfonamides, then the treatment is focused on physiotherapy and NSAIDs... In the presence of risk factors in patients with outpatient pneumonia, it is preferable for them to prescribe combined drugs (with a lactamase inhibitor) - amoxiclav, unazine or 2nd generation cephalosporin.

Inadequate doses of antibiotics, non-observance of the intervals between their introduction contributes to the emergence of resistant strains of the pathogen and the patient's allergization. The use of small, subtherapeutic doses of antibiotics (especially expensive, imported ones for the purpose of a falsely understood "economy") or non-observance of the intervals between antibiotic administration in outpatient settings lead to ineffective treatment, patient allergization, selection of resistant forms of microbes.

In the treatment of patients with pneumonia use etiotropic drugs (antibiotics, and if they are intolerant - sulfonamides), pathogenetic and symptomatic agents (NSAIDs, mucolytics and expectorants, physiotherapeutic treatment), if necessary, carry out infusion and detoxification therapy.

Antibiotic treatment for pneumonia not always effective, since it is often carried out not etiotropically, "blindly", using subtherapeutic or excessively large doses. Physiotherapeutic treatment and NSAIDs are not prescribed in a timely manner. If the recovery is delayed, then this may be due to various reasons (Table 9).

If the patient's condition improved during treatment (body temperature returned to normal, intoxication and leukocytosis decreased, cough and chest pain disappeared), but at the same time a moderate increase in ESR and a slight infiltration on radiographs persist, then the antibiotic should be canceled and physiotherapeutic treatment should be continued, so how is it no longer sick, but feeling healthy convalescent... All this common evolution of pneumonia, and the preservation of weak infiltration is not the basis for judging the ineffectiveness of the antibiotic with positive clinical results. Any antibiotic, as already noted, acts only on the pathogen, but does not directly affect the morphology of inflammation (resolution of infiltration in the lung) and nonspecific indicators of inflammation - increased ESR, detection of C-reactive protein.

In general, antibiotic therapy for pneumonia uncomplicated if the pathogen is identified(see Table 10). In this case, an appropriate antibiotic is prescribed, to which the microbe is sensitive in vitro. But treatment is complicated if there is no bacteriological analysis or it cannot be carried out, or sputum analysis does not allow identifying the causative agent of pneumonia. Therefore, in half of cases, pneumonia is treated empirically.

Usually reassessment of the effectiveness of the initially used antibiotic can be done only after analysis (after 2-3 days) of its clinical effectiveness. So, if at the beginning of the treatment of pneumonia (while its causative agent is unknown), a combination of antibiotics is often used (to expand their spectrum of action), then the spectrum of action of antibiotics should be narrowed, especially if they are toxic. If there are complications of pneumonia (for example, empyema), then antibiotics are given in a more aggressive mode. If an adequate response to treatment with narrow-spectrum antibiotics (benzylpenicillin) is obtained, then the treatment should not be changed.

In dermatovenerology, syndromes similar in localization and clinical manifestations often cause difficulties in differential diagnosis. The subject of this study is the symptom complex of lesions of large skin folds, which includes: itching of varying intensity, hyperemia, infiltration, swelling, peeling, cracks, erosion and some other manifestations, the specificity of which will allow an experienced specialist to identify them as a specific disease. Despite the availability of research on the etiology of such lesions, the clinical picture of the lesions has similar symptoms in various diseases, which makes possible diagnostic errors, including due to the ambiguity in determining the primary or secondary nature of the changes detected. The article discusses the aspects of the use of the syndromic approach and empirical therapy of a group of diseases with skin lesions of large folds, the clinical picture of which creates difficulties for visual differential diagnosis. The possibilities of using fixed topical combinations of glucocorticosteroid, antibiotic, and antimycotic for such an approach to treatment have been evaluated. The research data are presented and conclusions are drawn about the possibility of using Triderm for empirical therapy of the syndrome of lesions of large skin folds.

Keywords: empirical therapy, syndromic hike, large skin folds, skin fold diseases, Triderm.

For citation: Ustinov M.V. Empirical therapy of inflammatory lesions of the skin of large folds // BC. 2016. No. 14. P. 945–948.

For citation: Ustinov MVMV .. Empirical therapy of inflammatory lesions of the skin of large folds // BC. 2016. No. 14. S. 945-948

Empirical therapy of inflammatory lesion of large skin folds
Ustinov M.V.

Central Military Clinical Hospital named after P.V. Mandryka, Moscow

Dermatologic syndromes with similar localization and clinical manifestations, often cause difficulties in differential diagnosis. The present study addresses the problem of lesion of large skin folds, that comprises: itching of varying intensity, hyperemia, infiltration, edema, peeling, cracks, erosion, and other symptoms. Doctor with good experience can establish the diagnosis on the basis of their specificity. Clinical picture of lesions is quite similar in various diseases, that leads to diagnostic errors. Primary or secondary nature of detectable changes are not always obvious. The paper discusses aspects of application of the syndromic approach and empirical treatment of diseases with damage of large skin folds, creating difficulties for visual differential diagnosis. Fixed combinations of topical glucocorticosteroids, antibiotics and antimycotics are reviewed. Study results are presented as well as conclusions about the possibility of Triderm application for empirical therapy of syndrome with large skin folds lesion.

Key words: empirical therapy, syndromic approach, large skin folds, diseases of skin folds, Triderm.

For citation: Ustinov M.V. Empirical therapy of inflammatory lesion of large skin folds // RMJ. 2016. No. 14. P. 945-948.

The article is devoted to the empirical therapy of inflammatory lesions of the skin of large folds.

Empirical therapy is the method most often used in relation to bacterial lesions when the etiological agent is unknown, its species identification is difficult or lengthy, and the start of treatment cannot be delayed, often for health reasons. However, in a broad sense, empiric therapy can be more than just antibacterial. In various branches of medicine, there are diseases that are extremely similar not only in symptoms, but also in approaches to therapy, while being separate nosological units. Empiric therapy usually precedes etiotropic (if possible), consists of etiological agents of an overlapping spectrum of action, and often contains pathogenetic and / or symptomatic components. Often, therapy, begun as an empirical one, leads to recovery and even complicates the final diagnosis.
Orientation to certain symptom complexes - syndromes - led to the emergence of the so-called syndromic approach in therapy, which is, in fact, a kind of empirical therapy. The syndrome is a group of subjective and objective symptoms, i.e., patient complaints and symptoms that the doctor observes when examining the patient. The syndromic approach provides for the treatment of one symptom complex of different diseases with a drug with the maximum therapeutic breadth for this group of diseases. Usually, a syndromic approach is not used, and sometimes it is unacceptable if there is a laboratory-instrumental or other quick way of establishing an etiological diagnosis. But even WHO experts in cases where etiological diagnosis is not possible at a specific point in time, it is allowed to use a syndromic approach to treatment, in particular, the syndromic approach to the treatment of sexually transmitted infections is widely known in flowcharts. Moreover, there are additional arguments in favor of this approach:
the urgency of treatment, since medical care can be provided in medical institutions of the primary level; therefore, patients can begin treatment at their first visit to a health facility;
wider accessibility of treatment due to the possibility of providing it in more institutions.
There are situations when the syndromic approach is especially in demand, for example: when specialized medical care is not available, while on vacation, in emergencies or a military situation, etc.
In dermatovenerology, syndromes similar in localization and clinical manifestations often cause difficulties in differential diagnosis. The subject of this study is the symptom complex of lesions of large skin folds, which includes: itching of varying intensity, hyperemia, infiltration, swelling, peeling, cracks, erosion and some other disorders, the specificity of which will allow an experienced specialist to identify them as a specific disease. Lesions of large folds of the skin are not uncommon and show a certain seasonality, more often occurring in the warm season. Despite the availability of research on the etiology of such lesions, the clinical picture of the lesions has similar symptoms for various diseases, which makes diagnostic errors possible, including due to the ambiguity in determining the primary or secondary nature of the detected changes.
Large folds of skin traditionally include: armpits, elbow folds, inguinal areas (inguinal-femoral, inguinal-scrotal in men), intergluteal, femoral-scrotal in men, femoral-gluteal, perineum proper, popliteal and folds under the mammary glands in women ... In addition, obese people have large folds of skin formed by folds of subcutaneous fat outside the indicated anatomical areas, while excess body weight itself also serves as a risk factor for skin diseases in large folds.
The syndrome can have an inflammatory, fungal or bacterial etiology, chronic dermatosis, friction, or irritation. The most common lesions (classification according to ICD-10):
1) infections of the skin and subcutaneous tissue: erythrasma, bacterial intertrigo;
2) other bacterial diseases: actinomycosis, nocardiosis;
3) mycoses: dermatophytosis of large folds, candidiasis of large folds, malasseziosis;
4) dermatitis and eczema: erythematous diaper rash, iritant dermatitis, infectious dermatitis, atopic dermatitis, less often - seborrheic dermatitis (in the folds of the skin behind the ears);
5) papulosquamous disorders: inverse psoriasis;
6) bullous disorders: familial benign chronic pemphigus (Haley-Haley disease);
7) diseases of the skin appendages: inverse acne, hydradenitis.
Other diseases can be diagnosed in the skin folds: vitiligo, skin tumors, cutaneous hemoblastosis, etc. But they, like the listed bacterial diseases and diseases of the skin appendages, do not satisfy the isolation criterion by the similarity of clinical symptoms and a syndromic approach cannot be applied to them suggested below.
Anatomical and physiological features of the skin of large folds make it more sensitive to external influences, and also create conditions for the formation of a special microbiocenosis on the surface. As can be seen on the map of human skin microflora (Fig. 1), the flora of large folds is normally more diverse than on smooth skin, and often includes opportunistic strains of bacteria and fungi in the form of a carrier. Pathogenic strains of microorganisms often transiently join the predominant resident species of bacteria and fungi (Fig. 2).

As a result, in practice, we often see that inflammatory non-infectious dermatoses in large folds are susceptible to secondary infection, and dermatoses with infectious etiology often lead to a pronounced focal inflammatory reaction. In addition, inflammatory and infectious processes in the folds of the skin are in dynamic interaction, supporting each other and forming a vicious circle in the pathogenesis of diseases.
The main and additional scenarios are considered, according to which this interaction mainly takes place, namely:
a) main scenarios:
secondary infection complicates the course of the existing primary non-infectious dermatosis,
primary flaccid skin infection causes an inadequate and incomplete immune response, manifested by sensitization, and clinically - by eczematization;
b) additional scenarios:
infection can be a trigger factor for chronic immune dermatosis,
on the primary flaccid long-existing skin infection with a flaccid inflammatory response, a more aggressive infection is superimposed, provoking a pronounced inflammatory reaction, eczematization.
The described scenarios are the classic concept of a group of dermatoses of combined etiology, which allows us to classify most diseases with the syndrome of large folds in it. As you know, with dermatoses of combined etiology, the maximum therapeutic breadth will be possessed by a complex of drugs or a complex drug aimed at the main general etiopathogenetic mechanisms at the same time. To avoid drug interactions and side effects in empiric treatment of skin lesions, only topical treatment should be prescribed. Given the range of possible diseases in large folds of the skin, in the syndromic approach of empirical therapy, preference is given to combinations of drugs with the following effects:
anti-inflammatory;
antiallergic;
antipruritic;
antiproliferative;
decongestant;
membrane stabilizing;
antibacterial;
antifungal.
These effects are achieved only by using topical glucocorticosteroids in combination with local forms of antibiotics and antimycotics. The applied value of the syndromic approach of empirical therapy is that the mechanisms of diseases are distinguished (in our case, with a single localization) and a drug is prescribed taking into account the spectrum of possible final diagnoses. Preference should be given to fixed officinal topical three-component combinations, each of which should be received by the patient in a single package - this significantly increases compliance and, accordingly, the final effectiveness of therapy.
A topical drug to increase adherence to the prescribed treatment must meet the following criteria:
powerful, fairly quick therapeutic effect;
prolonged action (frequency of application - no more than 2 times a day);
good cosmetic tolerance;
minimal risk of developing systemic adverse reactions.
Satisfying all of the above and, as a result, the most demanded from the very moment of its appearance on the market, and therefore the most studied, remains the topical original combination, including: glucocorticosteroid betamethasone dipropionate, antibiotic gentamicin and antimycotic clotrimazole (Triderm®, Bayer). The popularity of this topical agent is so great that its name has become a household name for a large direction of external combined agents that contain a corticosteroid and antimicrobial components. It has become the benchmark for evaluating other three-component drugs. With strict adherence to the instructions for use, the drug is not only very effective, but also safe. Dermatologists often use this combination for trial or initial treatment, when difficulties arise with the differential diagnosis of inflammatory and infected dermatoses, regardless of localization, which, in fact, is empirical therapy. But it is precisely the lesions of large skin folds, in our opinion, one of those localizations where this tactic can really be justified.
In order to demonstrate the possibility of empirical therapy within a short period of time at an outpatient appointment, 20 patients with lesions of large skin folds were selected in a row, meeting the following criteria:
acute onset of the disease or exacerbation of the disease against the background of complete remission;
the presence of subjective syndromes: local itching, pain, burning, discomfort, affecting the quality of life of patients;
clinical manifestations in the form of: hyperemia, infiltration, edema, peeling, cracks, erosion;
age over 2 years;
no previous therapy since the onset of an acute illness and at least 1 month. with exacerbation of chronic;
strict fulfillment of appointments.
This sample cannot be called refined; in the process of recruiting patients with lesions of folds, 2 patients identified during the study period did not meet its criteria. The age in the sample ranged from 18 to 64 years old. The distribution of patients by sex and preferential localization of lesions is shown in Table 1.

Despite the anamnestically and clinically obvious diagnoses in some patients, none of them was given additional medications and systemic therapy was completely ruled out. Patients were recommended a rational hygienic regimen and skin care of the affected areas, monotherapy of one of the forms of the drug (cream or ointment, depending on the prevailing symptoms) of the original fixed combination of betamethasone dipropionate, gentamicin and clotrimazole, applied 2 times a day until the clinical picture is completely resolved, plus 1 –3 days, but not more than 14 days.
Not taking into account the incoming preliminary diagnoses, as a result of treatment, 18 out of 20 patients achieved remission within the specified timeframe, and 2 - a significant improvement. The average time to achieve remission is 8-10 days, the relief of subjective symptoms is 1-3 days from the start of treatment. A high adherence of patients to therapy was stated, which is explained by a pronounced effect already at its start. The tolerability of the original fixed combination of betamethasone dipropionate, gentamicin and clotrimazole both in the form of an ointment and in the form of a cream did not cause any comments in patients, no undesirable effects were noted.
The results obtained allow us to conclude that in the treatment of dermatoses of combined etiology localized in large folds of the skin, Triderm cream / ointment is an effective drug for empirical therapy. Long-term positive experience of use, high degree of safety, good cosmetic and organoleptic properties, trust in the manufacturer increase compliance, which is necessary to obtain a stable effect and achieve stable remission in diseases with different etiopathogenetic mechanisms, but similar clinical symptoms and localization. With this demonstration, we do not call for the widespread introduction of the syndromic approach and empirical therapy using three-component topical drugs into the practice of dermatovenerologists, but at the same time, every specialist should know about the existence of such a possibility in case of skin lesions of large folds (and not only).

Literature

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4. Kotrekhova L. P. Diagnostics and rational therapy of dermatoses of combined etiology // Consilium medicum (supplement "Dermatology"). 2010. No. 4. P. 6–11.
5. Belousova T.A., Goryachkina M.V. Algorithm for external therapy of dermatoses of combined etiology // Bulletin of Dermatol. 2011. No. 5. P. 138–144.
6. Ustinov M.V. The choice of a topical drug for the treatment of combined dermatoses of predominantly fungal etiology // Advances in medical mycology. T. XIV: mater. III Int. mycological forum. Moscow: National Academy of Mycology, 2015.
7. Dikovitskaya NG, Korsunskaya IM, Dordzhieva OV, Nevozinskaya Z. Therapy of secondary skin infections in chronic dermatoses // Effective pharmacotherapy. Dermatology. 2014. No. 2. P. 10-11.
8. Kolyadenko V.G., Chernyshov P.V. Combined preparations of the betamethasone group in the treatment of allergic dermatoses // Ukrainian Journal of Dermatology, Venereology, Cosmetology. 2007. No. 1. P. 31–34.
9. Tamrazova O.B., Molochkov A.V. Combined topical corticosteroids in pediatric practice: indications for use and errors of external therapy // Consilium medicum (supplement "Dermatology"). 2013. No. 4.

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MINISTRY OF AGRICULTURE

Ivanovo Academy named after academician D.K. Belyaeva

on virology and biotechnology

Empirical and etiotropic antibiotic prescription

Completed:

Kolchanov Nikolay Alexandrovich

Ivanovo, 2015

Antibiotics (from other Greek? NfYa - against + vYapt - life) are substances of natural or semi-synthetic origin that suppress the growth of living cells, most often prokaryotic or protozoa. Some antibiotics have a strong suppressive effect on the growth and reproduction of bacteria and at the same time relatively little or no damage to the cells of the macroorganism, and therefore are used as medicines. Some antibiotics are used as cytostatic drugs in the treatment of cancer. Antibiotics usually do not affect viruses and are therefore not useful in treating diseases caused by viruses (eg, influenza, hepatitis A, B, C, chickenpox, herpes, rubella, measles). However, a number of antibiotics, primarily tetracyclines, also act on large viruses. Currently, in clinical practice, there are three principles of prescribing antibacterial drugs:

1. Etiotropic therapy;

2. Empirical therapy;

3. Preventive use of AMP.

Etiotropic therapy is the targeted use of antimicrobial drugs based on the isolation of the causative agent from the focus of infection and the determination of its sensitivity to antibiotics. Obtaining correct data is possible only if all stages of bacteriological research are correctly performed: from taking clinical material, transporting it to a bacteriological laboratory, identifying the pathogen to determining its sensitivity to antibiotics and interpreting the results obtained.

The second reason for the need to determine the sensitivity of microorganisms to antibacterial drugs is to obtain epidemiological / epizootic data on the structure and resistance of infectious agents. In practice, these data are used for the empirical prescription of antibiotics, as well as for the formation of hospital records. Empiric therapy is the use of antimicrobial drugs until knowledge of the pathogen and its susceptibility to these drugs is obtained. Empirical prescription of antibiotics is based on knowledge of the natural susceptibility of bacteria, epidemiological data on the resistance of microorganisms in the region or hospital, as well as the results of controlled clinical trials. The undoubted advantage of empirical antibiotic prescription is the possibility of rapid initiation of therapy. In addition, this approach eliminates the cost of additional research. However, with the ineffectiveness of the antibiotic therapy, infections, when it is difficult to assume the pathogen and its sensitivity to antibiotics, they seek to carry out etiotropic therapy. Most often at the outpatient stage of medical care, due to the lack of bacteriological laboratories, empirical antibiotic therapy is used, which requires a doctor to take a whole range of measures, and each of his decisions determines the effectiveness of the prescribed treatment.

There are classical principles of rational empirical antibiotic therapy:

1. The pathogen must be sensitive to the antibiotic;

2. The antibiotic must create therapeutic concentrations at the site of infection;

3. It is impossible to combine bactericidal and bacteriostatic antibiotics;

4. Do not share antibiotics with similar side effects.

The algorithm for prescribing antibiotics is a series of steps that allow you to choose one or two of the thousands of registered antimicrobial agents that meet the criteria for effectiveness:

The first step is to compile a list of the most likely pathogens.

At this stage, only a hypothesis is put forward which bacteria could cause the disease in a particular patient. General requirements for an "ideal" pathogen identification method are speed and ease of use, high sensitivity and specificity, and low cost. However, it has not yet been possible to develop a method that meets all these conditions. Currently, Gram stain, developed at the end of the 19th century, to a greater extent meets the above requirements, and is widely used as a quick method for preliminary identification of bacteria and some fungi. Gram staining allows you to determine the tinctorial properties of microorganisms (i.e., the ability to perceive the dye) and determine their morphology (shape).

The second step is to compile a list of antibiotics that are active against the pathogens suspected at the first stage. For this, microorganisms are selected from the generated resistance passport in accordance with the pathology that most fully satisfy the characteristics presented in the first step.

The third step - for antibiotics active against probable pathogens, the ability to create therapeutic concentrations at the site of infection is assessed. Localization of infection is an extremely important point in deciding not only on the choice of a specific AMP. To ensure the effectiveness of therapy, the concentration of AMP in the focus of infection must reach an adequate level (in most cases, at least equal to the MIC (minimum inhibitory concentration) in relation to the pathogen). Antibiotic concentrations that are several times higher than the MIC, as a rule, provide a higher clinical efficacy, but they are often difficult to achieve in a number of foci. At the same time, the impossibility of creating concentrations equal to the minimum inhibitory concentration does not always lead to clinical ineffectiveness, since subinhibitory AMP concentrations can cause morphological changes, resistance to opsonization of microorganisms, and also lead to increased phagocytosis and intracellular lysis of bacteria in polymorphonuclear leukocytes. Nevertheless, most specialists in the field of infectious pathology believe that optimal antimicrobial therapy should lead to the creation of AMP concentrations in the foci of infection, exceeding the MIC for the pathogen. For example, not all drugs penetrate into organs protected by histohematogenous barriers (brain, intraocular area, testes).

The fourth step is to take into account the factors associated with the patient - age, liver and kidney function, physiological state. The age of the patient, the type of animal is one of the essential factors when choosing an AMP. This, for example, causes in patients with a high concentration of gastric juice, in particular, an increase in their absorption of oral penicillins. Reduced kidney function is another example. As a result, doses of drugs, the main route of excretion of which is renal (aminoglycosides, etc.), should be subject to appropriate correction. In addition, a number of drugs are not approved for use in certain age groups (for example, tetracyclines in children under the age of 8, etc.). Genetic and metabolic traits can also have a significant impact on the use or toxicity of some AMPs. For example, the rate of conjugation and biological inactivation of isoniazid is genetically determined. The so-called "fast acetylators" are most common in the Asian population, the "slow" ones in the United States and Northern Europe.

Sulfonamides, chloramphenicol and some other drugs can cause hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency. The choice of drugs in pregnant and lactating animals also presents certain difficulties. It is believed that all AMPs are capable of crossing the placenta, but the degree of penetration among them varies considerably. As a result, the use of AMP in pregnant women provides their direct effect on the fetus. Despite the almost complete absence of clinically confirmed data on the teratogenic potential of antibiotics in humans, experience shows that most penicillins, cephalosporins, and erythromycin are safe for use in pregnant women. At the same time, for example, metronidazole had a teratogenic effect in rodents.

Almost all AMPs pass into breast milk. The amount of the drug that penetrates into milk depends on the degree of its ionization, molecular weight, solubility in water and lipids. In most cases, the concentration of AMP in breast milk is quite low. However, even low concentrations of certain drugs can lead to adverse effects on the baby. So, for example, even small concentrations of sulfonamides in milk can lead to an increase in the level of unbound bilirubin in the blood (displacing it from its association with albumin. The ability of the patient's liver and kidneys to metabolize and eliminate the used AMP is one of the most important factors in deciding on their appointment , especially if high serum or tissue concentrations of the drug are potentially toxic.In case of impaired renal function, most drugs require dose adjustments.For other drugs (eg erythromycin), dose adjustments are required for impaired liver function. Exceptions to the above rules are drugs that have a dual route of excretion (for example, cefoperazone), the dose adjustment of which is required only in case of combined impairment of liver and kidney function.

The fifth step is the choice of AMP based on the severity of the course of the infectious process. Antimicrobial agents can have a bactericidal or bacteriostatic effect in terms of the depth of their effect on a microorganism. The bactericidal effect leads to the death of the microorganism, for example, beta-lactam antibiotics, aminoglycosides act. The bacteriostatic effect is the temporary suppression of the growth and reproduction of microorganisms (tetracyclines, sulfonamides). The clinical effectiveness of bacteriostatic agents depends on active participation in the destruction of microorganisms by the host's own defense mechanisms.

Moreover, the bacteriostatic effect can be reversible: when the drug is canceled, microorganisms resume their growth, the infection again gives clinical manifestations. Therefore, bacteriostatic agents should be used longer to ensure a constant therapeutic level of drug concentration in the blood. Bacteriostatic drugs should not be combined with bactericidal drugs. This is due to the fact that bactericidal agents are effective against actively developing microorganisms, and the slowdown of their growth and reproduction by static agents creates the resistance of microorganisms to bactericidal agents. On the other hand, a combination of two bactericidal agents is generally very effective. Based on the foregoing, in severe infectious processes, preference is given to drugs that have a bactericidal mechanism of action and, accordingly, have a faster pharmacological effect. In milder forms, bacteriostatic AMPs can be used, for which the pharmacological effect will be delayed, which requires a later assessment of clinical efficacy and longer courses of pharmacotherapy.

Sixth step - from the list of antibiotics compiled in the second, third, fourth and fifth steps, select drugs that meet safety requirements. Undesirable adverse reactions (ADRs) develop on average in 5% of patients treated with antibiotics, which in some cases leads to lengthening of the treatment period, an increase in the cost of treatment, and even death. For example, the use of erythromycin in pregnant women in the third trimester causes pylorospasm to develop in a newborn baby, which further requires invasive methods of examination and correction of the emerging NRD. If NCDs develop when using a combination of AMPs, it is extremely difficult to determine which drug is causing them.

Seventh step - among the drugs that are suitable in terms of effectiveness and safety, preference is given to drugs with a narrower antimicrobial spectrum. This reduces the risk of pathogen resistance.

Eighth step - AMP with the most optimal route of administration is selected from the remaining antibiotics. Oral administration of the drug is acceptable for moderate infections. Parenteral administration is often necessary in acute infectious conditions requiring emergency therapy. The defeat of some organs requires special routes of administration, for example, into the spinal canal with meningitis. Accordingly, for the treatment of a particular infection, the doctor is faced with the task of determining the most optimal route of its administration for a particular patient. In the case of choosing a specific route of administration, the doctor must be sure that the AMP is taken in strict accordance with the prescriptions. So, for example, the absorption of some drugs (for example, ampicillin) is significantly reduced when taken with food, while for phenoxymethylpenicillin, such a dependence is not observed. In addition, the concomitant use of antacids or iron-containing drugs significantly reduces the absorption of fluoroquinolones and tetracyclines due to the formation of insoluble compounds - chelates. However, not all AMPs can be administered orally (eg, ceftriaxone). In addition, for the treatment of patients with severe infections, parenteral administration of drugs is more often used, which allows to achieve higher concentrations. So, cefotaxime sodium salt can be effectively used intramuscularly, since this route of administration achieves its therapeutic concentrations in the blood. In extremely rare cases, intrathecal or intraventricular administration of certain AMPs (for example, aminoglycosides, polymyxins), which poorly penetrate the blood-brain barrier, are possible in the treatment of meningitis caused by multi-resistant strains. At the same time, intramuscular and intravenous administration of antibiotics makes it possible to achieve therapeutic concentrations in the pleural, pericardial, peritoneal or synovial cavities. As a consequence, the administration of drugs directly to the above areas is not recommended.

The ninth step is the choice of AMPs, for which the possibility of using stepwise antibiotic therapy is permissible. The easiest way to achieve guaranteed administration of the desired antibiotic to a patient is parenteral administration by a conscientious doctor. It is better to use drugs that are effective when administered once or twice. However, the parenteral route of administration is more expensive than oral administration, is fraught with post-injection complications and is uncomfortable for patients. Such problems can be circumvented if oral antibiotics exist that meet the previous requirements. In this regard, the use of stepwise therapy is especially relevant - a two-stage application of anti-infectious drugs with a transition from parenteral to, as a rule, oral route of administration as soon as possible, taking into account the clinical condition of the patient. The main idea of stepwise therapy is to shorten the duration of parenteral administration of an anti-infectious drug, which can lead to a significant decrease in the cost of treatment, a reduction in the length of hospital stay, while maintaining a high clinical effectiveness of therapy. There are 4 options for step therapy:

I - option. Parenteral and oral administration of the same antibiotic, oral antibiotic has good bioavailability;

II - Parenteral and oral administration of the same antibiotic - oral drug has low bioavailability;

III - Different antibiotics are prescribed for parenteral and oral administration - oral antibiotic has good bioavailability;

IV - Different antibiotics are prescribed for parenteral and oral administration - oral drug has low bioavailability.

From a theoretical point of view, the first option is ideal. The second option of stepwise therapy is acceptable for infections of mild to moderate severity, when the pathogen is highly sensitive to the oral antibiotic used, and the patient does not have an immunodeficiency. In practice, the third option is most often used, since not all parenteral antibiotics are oral. It is justified to use at the second stage of stepwise therapy an oral antibiotic of at least the same class as the parenteral drug, since the use of an antibiotic of a different class may cause clinical ineffectiveness due to the resistance of the pathogen to it, an inequivalent dose or new adverse reactions. An important factor in stepwise therapy is the time of transfer of the patient to the oral route of administration of the antibiotic; the stage of infection can serve as a reference point. There are three stages of the infectious process in the treatment:

Stage I lasts 2-3 days and is characterized by an unstable clinical picture, the pathogen and its sensitivity to the antibiotic, as a rule, are not known, antibiotic therapy is empirical, most often a broad-spectrum drug is prescribed;

At stage II, the clinical picture is stabilized or improved, the pathogen and its sensitivity can be established, which makes it possible to correct the therapy;

At stage III, recovery occurs and antibiotic therapy can be completed.

There are clinical, microbiological and pharmacological criteria for transferring a patient to the second stage of stepwise therapy.

Choosing the optimal antibiotic for stepwise therapy is not an easy task. There are certain characteristics of the "ideal" oral antibiotic for the second stage of the gradual therapy:

The oral antibiotic is the same as the parenteral antibiotic;

Proven clinical efficacy in the treatment of this disease;

The presence of various oral forms (tablets, solutions, etc.);

High bioavailability;

Lack of drug interactions at the absorption level;

Good oral tolerance;

Long dosing interval;

Low cost.

When choosing an oral antibiotic, it is necessary to take into account its spectrum of activity, pharmacokinetic characteristics, interaction with other drugs, tolerance, as well as reliable data on its clinical efficacy in the treatment of a specific disease. One antibiotic is bioavailability.

Preference should be given to the drug with the highest bioavailability, it must be taken into account when determining the dose. When prescribing an antibiotic, the doctor must be sure that its concentration at the site of infection will exceed the minimum inhibitory concentration (MIC) for the pathogen. Along with this, pharmacodynamic parameters such as the time of concentration retention above the MIC, the area under the pharmacokinetic curve, the area under the pharmacokinetic curve above the MIC, and others should be taken into account. After choosing an oral antibiotic and transferring the patient to the second stage of stepwise therapy, it is necessary to continue dynamic monitoring of his clinical condition, antibiotic tolerance and adherence to the therapy. Step therapy provides clinical and economic benefits to both the patient and the hospital. The benefits for the patient are associated with a decrease in the number of injections, which makes the treatment more comfortable and reduces the risk of post-injection complications - phlebitis, post-injection abscesses, catheter-associated infections. Thus, stepwise therapy can be used in any medical institution, it does not entail additional investments and costs, but only requires a change in the usual approaches of doctors to the antibiotic therapy.

The tenth step is to choose the cheapest one from the remaining antibiotics. With the exception of benzylpenicillin, sulfonamides, and tetracyclines, AMPs are expensive drugs. As a consequence, the irrational use of combinations can lead to a significant and unjustified increase in the cost of patient therapy.

The eleventh step is to ensure that the correct drug is available. If the previous and subsequent steps relate to medical issues, then organizational problems often arise. Therefore, if the doctor does not make an effort to convince the people on whom the availability of the required drugs depends, then all the steps described earlier are unnecessary.

The twelfth step is to determine the effectiveness of antibiotic therapy. The main method for assessing the effectiveness of antimicrobial therapy in a particular patient is to monitor clinical symptoms and signs of the disease on the 3rd day (the “rule of the 3rd day”). Its essence is to assess whether the patient has positive dynamics on the second or third day. For example, you can evaluate how a temperature curve behaves. For some antibiotics (for example, aminoglycosides), it is recommended to monitor serum concentrations in order to prevent the development of toxic effects, especially in patients with impaired renal function.

The thirteenth step is the need for a combination antimicrobial therapy. Despite the fact that most infectious diseases can be successfully treated with one drug, there are certain indications for prescribing combination therapy.

When combining several AMPs, it is possible to obtain in vitro various effects in relation to a specific microorganism:

Additive (indifferent) effect;

Synergism;

Antagonism.

An additive effect is said if the activity of AMPs in combination is equivalent to their total activity. Potentiated synergism means that the activity of the drugs in combination is higher than their total activity. If two drugs are antagonists, then their activity in combination is lower than when used separately. Possible variants of the pharmacological effect with the combined use of antimicrobial drugs. Depending on the mechanism of action, all AMPs can be divided into three groups:

Group I - antibiotics that disrupt the synthesis of the microbial wall during mitosis. (Penicillins, cephalosporins, carbapenems (thienam, meropenem), monobactams (aztreonam), ristomycin, glycopeptide drugs (vancomycin, teicoplanin));

Group II - antibiotics that disrupt the function of the cytoplasmic membrane (Polymyxins, polyene drugs (nystatin, levorin, amphotericin B), aminoglycosides (kanamycin, gentamin, netilmicin), glycopeptides);

Group III - antibiotics that disrupt the synthesis of proteins and nucleic acids (chloramphenicol, tetracycline, lincosamides, macrolides, rifampicin, fuzidin, griseofulvin, aminoglycosides).

With the joint appointment of antibiotics from group I, synergism occurs by the type of summation (1 + 1 = 2).

Antibiotics of group I can be combined with drugs of group II, while their effects are potentiated (1 + 1 = 3), but they cannot be combined with drugs of group III, which disrupt the division of microbial cells. Group II antibiotics can be combined with each other and with Group I and III drugs. However, all these combinations are potentially toxic, and the summation of the therapeutic effect will cause the summation of the toxic effect. Group III antibiotics can be combined with each other if they affect different ribosome subunits, and the effects are summed up.

Ribosome subunits:

Levomycetin - 50 S subunit;

Lincomycin - 50 S subunit;

Erythromycin - 50 S subunit;

Azithromycin - 50 S subunit;

Roxithromycin - 50 S subunit;

Fusidin - 50 S subunit;

Gentamicin - 30 S subunit;

Tetracycline - 30 S subunit.

Otherwise, if two AMPs act on the same ribosome subunit, then there is indifference (1 + 1 = 1), or antagonism (1 + 1 = 0.75).

The fourteenth step is to continue therapy or, if necessary, adjust it. If positive dynamics are revealed at the previous step, then the treatment continues. If not, then the antibiotics should be changed.

Replacing one AMP with another is justified in the following cases:

If the treatment is ineffective;

With the development of adverse reactions that threaten the patient's health or life, which are caused by an antibiotic;

When using drugs that have restrictions on the duration of use, for example, with aminoglycosides.

In some cases, it is necessary to revise the entire tactics of managing patients, including clarifying the diagnosis. If you need to select a new drug, you should go back to step number one and re-list the microbes under suspicion. By this time, microbiological results may arrive in time. They will help if the laboratory has managed to identify pathogens and there is confidence in the quality of the analyzes. However, even a good laboratory is far from always able to isolate pathogens, and then the compilation of a list of probable pathogens is again speculative. Then all other steps are repeated, from the first to the twelfth. That is, the antibiotic selection algorithm works in a closed cycle, as long as there is a need to prescribe antimicrobial agents. I would like to remind you that the easiest thing when changing AMP is to change it, and the most difficult thing is to understand why the need to change AMP has arisen (significant interactions of AMP with other drugs, inadequate choice, low patient compliance, low concentrations in damaged organs, etc.).

Conclusion

On paper, the algorithm looks very cumbersome, but in fact, with a little practice, this whole chain of thoughts scrolls through the mind quickly and almost automatically. bacteria therapy antibiotic

Naturally, some of the steps in prescribing antibiotics do not occur in thought, but require real interaction between several people, for example, between a doctor and a host.

But a timely, correct treatment plan helps to reduce material costs and accelerate the patient's recovery with minimal side effects from the use of these drugs.

Posted on Allbest.ru

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Drugs	Selectable determinants of resistance	Drugs of the same class that overcome resistance, or alternative drugs
Natural penicillins	Staphylococcal beta-lactamase	Protected penicillins, cephalosporins, alternative drugs possible
Semisynthetic penicillins, 1st generation cephalosporins	Broad-spectrum beta-lactamases of gram (-) bacteria TEM-1,2, SHV-1	Generation II-IV cephalosporins, carbapenems, protected penicillins, alternative drugs possible
Cephalosporins II-III generation	Extended spectrum beta-lactamases of gram (-) bacteria TEM-3-29, SHV-2-5	Carbapenems, partially protected penicillins, alternative drugs possible
Aminoglycosides	Modifying enzymes with different substrate specificity	The use of other aminoglycosides is not predictable; alternative drugs are possible
Glycopeptides	Vancomycin-resistant enterococci	No, "new" quinolones, synercid, experimental drugs are possible

Drugs	Selectable microorganisms	Effective antibiotics
Beta-lactams	Methicillin-resistant staphylococci	Glycopeptides
Cephalosporins of I-III generations	Enterococci	Glycopeptides
Cephalosporins II-III generations	Gram (-) bacteria producing chromosomal class C beta-lactamases	IV generation cephalosporins, carbapenems, drugs of other classes
Fluoroquinolones	Gram (+) and (-) bacteria (topoisomerase mutations)	Drugs of other classes
Carbapenems	Naturally resistant bacteria (Stenotrophomonas, Flavobacterium, F. faecium)	Limited alternatives, sometimes co-trimoxazole

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