empiric therapy. Empirical and etiotropic prescription of antibiotics

Antimicrobial therapy (AT) is a type of therapy that involves the use of antimicrobial drugs (AMP) - a group of drugs (PM), the action of which is selectively aimed at suppressing the vital activity of pathogens of infectious diseases, such as bacteria, fungi, protozoa, viruses. Selective action is understood as activity only against infectious agents while maintaining the viability of the host cells, and the effect is not on all, but on certain genera and types of microorganisms.

All AMPs, despite the differences in chemical structure and mechanism of action, are united by a number of specific properties: the target for their action is not in human tissues, but in the cell of a microorganism; the activity of this group of drugs is not constant, but decreases with time, which is due to the formation of drug resistance / resistance in microorganisms.

Progress in the field of clinical microbiology, which has significantly expanded the understanding of pathogens of infectious diseases, as well as the constant need for new classes of AMPs, due to the spread of antibiotic-resistant pathogens and growing requirements for the safety of pharmacotherapy, have turned AMPs into the most numerous group of drugs. Thus, more than 30 groups of AMPs are currently used in the Russian Federation, and the total number of drugs (excluding generics) exceeds 200.

AMPs, like other drugs, are divided into groups and classes (penicillins, cephalosporins, macrolides, etc.). Such a division is of great importance from the point of view of understanding the generality of the mechanisms of action, the spectrum of activity, pharmacokinetic features, and the nature of adverse reactions (ARs).

It should be noted that there may be significant differences in pharmacodynamics and pharmacokinetics between AMPs of the same generation or class that differ slightly in chemical structure. Therefore, it is wrong to consider them as interchangeable.

Types of antimicrobial therapy and criteria for selecting AMP

AT can be etiotropic and empirical. Etiotropic AT is the targeted use of AMPs that are active against an established infectious agent. This type of AT is the most rational, as it allows you to choose a drug (s) of a narrow spectrum with the most optimal ratio of efficacy / safety.

Empirical AT is the use of AMPs until information about the causative agent of the infectious process and its sensitivity to AMPs is obtained. It forms the basis of modern therapy of community-acquired infections. Empirical AT is carried out taking into account the most likely pathogens of this infection and their alleged sensitivity to available AMPs. In this case, if possible, local data on antibiotic resistance of potential pathogens should be taken into account. There are several general principles for prescribing systemic AMPs to ensure their most effective use in clinical practice:

• An accurate diagnosis, which allows you to determine, on the one hand, the localization of the infectious process, on the other hand, the alleged pathogen.
• The validity of the use of AMP. Some bacterial and many viral infections do not require specific treatment. At the same time, their use contributes to the selection of antibiotic-resistant strains of microorganisms and creates a potential risk of developing AR.
• Selection of the optimal AMP/combination of AMP taking into account the nature of the infection, its localization and severity of the course, as well as the individual characteristics of the patient and the pharmacological properties of drugs. It is known that most infectious diseases today can be successfully treated with one drug (monotherapy), however, in certain cases, two or more AMPs should be used simultaneously (combination therapy).

When combining several AMPs, it is possible to obtain in vitro various effects in relation to a certain microorganism: additive action, synergism, antagonism. There are several indications for the use of AMP combinations:

1. Prevention of the formation of resistance of microorganisms to AMP. Despite the fact that this indication is one of the most common in the appointment of combined AT, the advantages of this approach have been proven only in certain clinical situations - tuberculosis, invasive Pseudomonas aeruginosa. This same indication underlies the use of rifampicin in combination with other AMPs for the treatment of staphylococcal infections.
2. Treatment of infections of polymicrobial etiology. In a number of polymicrobial infections, the use of AMP monotherapy is sufficient. At the same time, in some cases (for example, with intra-abdominal infections caused by mixed aerobic and anaerobic microflora), it becomes necessary to use drug combinations. At the same time, it should be noted that there are alternatives to such an approach in the form of prescribing carbapenems, inhibitor-protected penicillins, or antianaerobic fluoroquinolones (moxifloxacin).
3. Empiric therapy in patients with neutropenia or infections of unknown etiology. If it is necessary to start therapy before obtaining the results of a microbiological study, it is advisable to prescribe a combination of AMPs, which makes it possible to cover the widest possible range of suspected pathogens. Subsequently, after receiving the results of the microbiological study, it is possible to transfer the patient to monotherapy.
4. Synergy. Use of AMP combinations with synergism in vitro for the treatment of infections caused by microorganisms with reduced susceptibility is an extremely attractive approach. However, under the conditions in vivo only in a limited number of infections, combined AT was more effective than monotherapy. One of the most significant examples is the treatment of enterococcal endocarditis. Treatment of this disease with penicillins in monotherapy leads to a high failure rate due to the fact that enterococci have a reduced natural sensitivity to this drug. The addition of gentamicin or streptomycin to penicillin leads to in vitro, And in vivo to synergism with the achievement of clinical efficacy similar to that of streptococcal endocarditis. Higher clinical efficacy of AMP combinations with synergism in vitro compared with monotherapy has been demonstrated in immunocompromised patients.

At the same time, it should be remembered that combined AT is usually a more expensive therapeutic alternative. In addition, the combined use of several AMPs increases the likelihood of developing an AR, and if they occur, it is extremely difficult to determine which specific drug is associated with an AR. It is necessary to avoid the use of unstudied combinations of AMPs, as they can weaken the effect of each other and worsen the patient's outcome.

• Choosing the optimal dosing regimen(single dose, frequency of use) and route of administration, indications for monitoring its concentration in blood serum.
• Determination of the duration of AT. With few exceptions, the optimal duration of AT remains not fully defined due to the lack of clinical studies aimed at studying this issue. The recommended duration of AT is based primarily on the analysis of clinical experience in managing patients with a particular infection and may depend on many factors - the causative agent, the location of the infection, the state of the immune system, the presence of significant comorbidities and complications. For patients with non-severe infections, the duration of taking AMPs usually does not exceed 7-14 days, studies are increasingly appearing in the literature indicating the possibility of even further reduction in the duration of AMP use in respiratory infections; and single-dose fosfamycin is a highly effective therapeutic alternative for acute uncomplicated cystitis. At the same time, patients with immunosuppression, some bacterial (osteomyelitis, endocarditis, chronic prostatitis) and viral infections (chronic hepatitis, HIV infection) require long courses of AT.

The most significant characteristics of AMP and factors on the part of the patient that determine the choice of AMP are presented in the table. Rational AT should provide the highest possible probability of clinical cure (tactical goal) and minimal risk of development and spread of antibiotic resistance (strategic goal). Since there are usually several therapeutic alternatives with similar microbiological and clinical characteristics on the market for the treatment of the same infection, the cost of therapy and convenience of use play an important role in the choice of AMP.

Table. Factors Significant in Choosing AMPs for Empirical Antibiotics

Age patient is one of the essential factors when choosing an AMP. So, in young children and elderly patients, there are some peculiarities in the etiology of infections, which in the first case is due to intrauterine infection and insufficient maturity of the immune system, in the second - the presence of chronic concomitant diseases and physiological weakening of anti-infective protection factors. The likelihood of infection of microorganisms with certain mechanisms of secondary resistance may also depend on age. Thus, a known risk factor for the detection of penicillin-resistant S. pneumoniae is under 2 and over 65 years of age.

With age, the pharmacokinetics of AMP may also change. Thus, the pH of gastric juice in children under the age of 3 years and in persons over 60 years of age is higher compared to other age groups. This causes, in particular, an increase in their absorption of oral penicillins. Another example is kidney function, which is reduced in neonates and elderly patients. As a result, the dose of AMPs, which are excreted mainly through the kidneys, must be adjusted in proportion to the degree of reduction in glomerular filtration. Newborns are also characterized by immaturity of the liver enzyme systems, a change in the distribution of AMP due to a larger volume of extracellular fluid, and a lower content of albumin in the blood plasma. Elderly people often receive other drugs due to the presence of chronic comorbidities, so they are more at risk of drug interactions, and AR on AMPs is recorded in them significantly more often. A number of AMPs (for example, fluoroquinolones) are not approved for use in children, others have age restrictions (in particular, tetracyclines are not used in children under the age of 8 years). When choosing AMP in both children and elderly patients, special attention should be paid to the convenience of the prescribed AT regimen. For children, when taken orally, the use of special children's dosage forms is relevant; in elderly patients, one should strive to prescribe AMP with 1-2 times a day, which increases compliance with the therapy.

Genetic and metabolic features. The presence of genetic and metabolic differences can also have a significant impact on the use or tolerability of some AMPs. For example, the rate of conjugation and biological inactivation of isoniazid is genetically determined. The so-called "fast acetylators" are most often found among the Asian population, "slow" - in the USA and Northern Europe. Sulfonamides, chloramphenicol, and some other drugs can cause hemolysis in individuals with glucose-6-phosphate dehydrogenase deficiency.

Analysis previous intake of AMP allows you to assess their tolerance, including the presence and nature of allergic reactions. In addition, the fact of a recent intake of AMPs (1-3 months before the development of this episode of infection) is significant in terms of assessing the structure of potential pathogens and their antibiotic resistance profile.

Location of infection plays a key role in choosing the regimen of empirical AT, as it determines the structure of pathogens and their sensitivity to AMP. Community-acquired infections develop in patients outside the hospital. Nosocomial infections include infections that develop in a patient at least 48 hours after hospitalization, provided that no signs of infection were observed upon admission to the hospital, and the patient was not in the incubation period of an infectious disease. This category also includes infections resulting from previous hospitalization (≤90 days) and infectious diseases in healthcare workers. Along with the traditional term "nosocomial infection", in recent years the term "infections associated with the provision of medical care" has been used, which more fully reflects the fact that infection is associated with the patient's stay in the hospital. This category, in particular, includes infections that develop in people in long-term institutions (nursing homes, disabled people, hospices, etc.). The structure of causative agents of community-acquired infections and their sensitivity profile to AMPs, as a rule, is easily predictable and does not require additional studies. The etiology of nosocomial infections depends on many factors - the profile of the hospital, the patient population, and the policy of using antibiotics. Nosocomial infections can be caused by the so-called "opportunistic" pathogens with relatively low virulence, which are widespread in the environment, resistant to many external factors and quickly acquire resistance to AMP.

The choice of AMPs for empirical therapy of nosocomial infections is not an easy task. It involves regular monitoring of the structure of pathogens and antibiotic resistance in a particular health facility and its structural subdivisions, which should include an assessment of the prevalence of strains of enterobacteria producing extended spectrum β-lactamase (ESBL), MRSA, the level of production of metallobetalactamases among P. aeruginosa And Acinetobacter spp., resistance of pathogens of nosocomial infections to fluoroquinolones, aminoglycosides and inhibitor-protected penicillins.

Localization of infection is an extremely important point not only when choosing a specific AMP, but also the route of its administration and dosing regimen. To ensure effective elimination of the pathogen, the concentration of AMP in the focus of infection should reach an adequate level (at least not lower than the MIC in relation to the pathogen). AMP concentrations several times higher than the MIC, as a rule, provide higher clinical efficacy, but may be difficult to achieve in some lesions. The greatest problem for achieving therapeutic concentrations and effective elimination of pathogens is infection in the so-called "barrier" organs (infections of the central nervous system, prostate, eyeball), loci with impaired blood supply (abscesses), in the presence of foreign bodies (shunts, artificial joint, etc.) Serum concentrations of AMP are most often used to predict clinical efficacy. However, their prognostic value in most cases (with the exception of bacteremia) is relative, since it can differ significantly from tissue concentrations of AMP.

Severity of infection plays a decisive role in determining the timing of the onset of AT and the route of administration of AMP. It is known that in patients with severe infections, it is advisable to prescribe antibiotics as early as possible from the moment of diagnosis, since this significantly improves the prognosis. Thus, the time interval for making a decision on the initiation of AT in sepsis should not exceed 60 minutes, in case of community-acquired pneumonia in hospitalized patients - 4 hours. The choice of the optimal route of administration of AMP is determined by the severity of the clinical manifestations of the infection and the possibility of oral administration of drugs, which, in turn, depend on the general condition of the patient and concomitant diseases. In patients with mild infections, AMPs are administered orally, with preference given to drugs with high and predictable bioavailability, which is independent of food intake and other drugs. In severe, especially life-threatening infections (sepsis, meningitis, etc.), AT should begin with intravenous administration of AMP. In the future, with clinical improvement, it is possible to transfer the patient to oral administration of the same or a similar AMP in the spectrum. This treatment regimen is known as "stepped" therapy, while being equally effective as parenteral administration, it provides significant cost savings and earlier discharge of the patient from the hospital. It should be noted that the treatment of patients in a hospital should not always begin with parenteral administration of AMPs; in individuals with a mild infection and a favorable premorbid background, ATs can be started immediately with oral dosage forms of drugs.

In extremely rare cases, intrathecal or intraventricular administration of some AMPs that poorly penetrate the blood-brain barrier is possible in the treatment of meningitis caused by multidrug-resistant strains of pathogens. At the same time, intravenous administration of AMPs makes it possible to achieve therapeutic concentrations in the pleural, pericardial, peritoneal, or synovial cavities, as a result of which their administration directly into the above areas is not recommended.

Liver and kidney function is one of the most important factors when deciding on the choice of AMP, especially if high serum or tissue concentrations of the drug are potentially toxic. Since most AMPs are partially or completely excreted through the kidneys, in the event of a violation of their function, many of them require a correction of the dosing regimen (dose and / or frequency of use). Based on the degree of influence of renal failure on AMP excretion, AMPs can be divided into 3 groups:

1. drugs that are used in the usual dose. These include, for example, most macrolides, ceftriaxone, cefoperazone, phenoxymethylpenicillin, clindamycin.
2. Drugs that are contraindicated in renal failure, as they are excreted in the urine in active form and are characterized by a particularly pronounced cumulation in case of impaired renal function. This group includes non-fluorinated quinolones, nitrofurantoin, sulfonamides, tetracycline.
3. Drugs, the dosage regimen of which varies depending on the degree of renal failure.

Inactivation of some AMPs (macrolides, lincosamides, tetracyclines, etc.) can be significantly slowed down in case of impaired liver function. It should be noted that in conditions of liver failure, when taking such AMPs, due to the increasing “load” on hepatocytes, in turn, the risk of developing hepatic coma increases. Therefore, in the presence of clinical and / or laboratory signs of liver failure, a correction of the dosing regimen is necessary, or a refusal to take AMPs that are intensively metabolized in the liver. There are no clear recommendations for adjusting the dose of AMP in liver failure; usually, in the case of severe liver disease, the daily dose is reduced by 50%.

Pregnancy and lactation. The choice of AMP in pregnant and lactating women also presents certain difficulties. It is believed that all AMPs are able to cross the placenta to some extent, and as a result, their administration to pregnant women can have a direct effect on the fetus. However, the degree of penetration of AMP and the "consequences" for the fetus can vary significantly. Currently, several classifications are used to determine the safety of AMP use in pregnant women. Risk categories developed by the FDA (U.S. Food and Drug Administration) have become widespread in the Russian Federation. In accordance with the criteria below, all AMPs are divided into 5 categories according to the risk of use in the fetus:

BUT- in controlled studies in pregnant women, there was no risk of adverse effects on the fetus. Harmful effect on the fetus is unlikely.

IN- studies in animals have not revealed a risk to the fetus; in studies in animals, data on undesirable effects on the fetus were obtained, however, these data were not confirmed in controlled studies in pregnant women.

FROM- studies in animals have shown adverse effects on the fetus, controlled studies in pregnant women have not been conducted, the potential benefits associated with the use of the drug in a pregnant woman may justify its use, despite the possible risk, or studies in animals and pregnant women have not been conducted.

D- there is evidence of the risk of an adverse effect of the drug on the human fetus, however, the potential benefit associated with the use of the drug in pregnant women may justify its use, despite the possible risk (a situation that threatens the woman's life, in which other drugs are ineffective or cannot be used).

X- Animal studies and clinical trials have revealed fetal developmental disorders and / or there is evidence of the risk of an adverse effect of the drug on the human fetus, obtained on the basis of experience with the use of the drug in humans; The risk associated with the use of drugs in a pregnant woman outweighs the potential benefit. This group of drugs is contraindicated in pregnant women and women of reproductive age who do not use adequate methods of contraception.

Despite the almost complete absence of clinically confirmed data on the teratogenic potential of AMP in humans, animal studies, as well as the analysis of practical experience in epidemiological studies, can be a source of information. So, today it is known that most penicillins and cephalosporins are safe for the fetus when used in pregnant women. At the same time, for example, metronidazole had a teratogenic effect in rodents, so it is not recommended to prescribe it to pregnant women in the first trimester.

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 for the child. For example, even low concentrations of sulfonamides in breast milk can lead to an increase in the level of unbound bilirubin in the blood (displacing it from its association with albumins) in premature newborns.

It should be emphasized that in the absence of reliable data on the safety of a particular AMP in pregnant and / or lactating women, it is better to refrain from using them. In addition, the appointment of any AMP in this category of patients should be carefully monitored due to the lack of drugs with proven safety for the fetus in controlled studies (category A).

Evaluation of the effectiveness of antimicrobial therapy

The main method for assessing the effectiveness of AT in a particular patient is monitoring the clinical symptoms and signs of the disease, as well as the results of paraclinical examination methods. For some AMPs (eg, aminoglycosides, vancomycin), their serum concentrations may be monitored to prevent the development of toxic effects, especially in patients with impaired renal function.

Another method for monitoring the effectiveness of therapy is the determination of serum bactericidal titer (used in patients with osteomyelitis, bacteremia and infective endocarditis). The principle of the method is based on the incubation of serial dilutions of the patient's serum with a bacterial suspension of the pathogen in order to determine the maximum dilution at which growth is suppressed or death of the microorganism isolated from the patient occurs. According to the results of a multicenter study, peak and residual titers of at least 1:64 and 1:32, respectively, are predictive indicators of the effectiveness of therapy for infective endocarditis. However, due to the relatively low standardization of the method, it is not widely used in clinical practice.

Efficacy of empirically prescribed AT is assessed within 48-72 hours from the start of treatment, with a sufficient clinical response, AT continues, in the absence of the desired effect, it is reviewed. A change in the AT regimen is carried out with documented clinical inefficiency, the development of adverse events that threaten the health or life of the patient caused by AMP, when using drugs that have limitations on the duration of use due to cumulative toxicity (for example, aminoglycosides, chloramphenicol).

The change of AMP in case of inefficiency should be approached intelligently, taking into account the characteristics of the clinical picture of the disease and the characteristics of the drug. AT failures can be due to many reasons. In this case, first of all, it is necessary to assess the correctness of the diagnosis, since many non-communicable diseases cause clinical symptoms similar to infections. The lack of effect from the ongoing AT may be due to the wrong choice of AMP, which was made without taking into account its natural activity and the level of antibiotic resistance of key pathogens, the late start of treatment, the use of low doses, an irrational route of administration, and the insufficient duration of the course of AT.

The effectiveness of AMP may decrease with the simultaneous appointment of other drugs that have antagonism or affect the metabolism and excretion of AMP. Even with proper sensitivity of the pathogen to AMP, unsatisfactory results of treatment are possible due to poor penetration of the drug into the focus of infection due to its physicochemical properties, insufficient blood supply, the formation of a biological barrier around the focus of infection, and the addition of superinfection.

It should be noted that fever, which is one of the key clinical manifestations of the infection, can also develop when taking AMPs. The use of etiotropic agents should be supplemented by adequate detoxification therapy, as well as the use of drugs or agents of pathogenetic therapy that improve the prognosis (vasopressors, oxygen therapy, dexamethasone, activated protein C, etc.). Equally important is the consideration of compliance with the therapy.

In dermatovenereology, 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 into the etiology of such lesions, the clinical picture of lesions has similar symptoms in various diseases, which makes diagnostic errors possible, including due to the ambiguity in determining the primary or secondary nature of the detected changes. The article discusses aspects of the application of the syndromic approach and empirical therapy for a group of diseases with lesions of the skin 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 this approach to treatment were evaluated. The data of the study 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 approach, 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 M.V.M.V.. Empirical therapy of inflammatory lesions of the skin of large folds // BC. 2016. No. 14. pp. 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, which 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. The clinical picture of lesions is quite similar in various diseases, which 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 quote: 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.

Empiric therapy is the method most often used for bacterial lesions when the etiological agent is unknown, its species identification is difficult or prolonged, and the start of treatment cannot be delayed, often for health reasons. However, in a broad sense, empirical therapy can be not only antibacterial. In various branches of medicine, there are diseases that are extremely similar not only in terms of symptoms, but also in terms of approaches to therapy, while being separate nosological units. Empiric therapy usually precedes etiotropic therapy (if possible), consists of etiological agents with an overlapping spectrum of action, and often contains pathogenic and/or symptomatic components. It is not uncommon for therapy begun as empiric to lead to recovery and even make it difficult to make a definitive diagnosis.
Orientation to certain symptom complexes - syndromes - has led to the emergence of the so-called syndromic approach to therapy, which in fact is a kind of empirical therapy. The syndrome is a group of subjective and objective symptoms, i.e., patient complaints and symptoms that a doctor observes when examining a patient. The syndromic approach involves the treatment of one symptom complex of various diseases with a drug with the maximum therapeutic breadth for this group of diseases. Usually, the syndromic approach is not used, and sometimes it is unacceptable if there is a laboratory-instrumental or other quick way to make an etiological diagnosis. But even WHO experts in cases where etiological diagnosis is not possible at a particular point in time, the use of a syndromic approach to treatment is allowed, in particular, the syndromic approach to the treatment of sexually transmitted infections is widely known by flowcharts. Moreover, there are additional arguments in favor of this approach:
urgency of treatment, since medical care can be provided in primary care facilities; therefore, patients can start treatment at their first visit to a health facility;
Wider access to treatment by being able to provide it in more facilities.
There are situations when the syndromic approach is especially in demand, for example: when specialized medical care is unavailable, while on vacation, in emergency situations or in a military situation, etc.
In dermatovenereology, syndromes similar in localization and clinical manifestations often cause difficulties in differential diagnosis. The subject of this study is the symptom complex of damage to 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 skin folds are not uncommon and show a certain seasonality, occurring more often in the warm season. Despite the availability of research into the etiology of such lesions, the clinical picture of 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 skin folds traditionally include: armpits, elbow folds, inguinal regions (inguinal-femoral, inguinal-scrotal in men), intergluteal, femoral-scrotal in men, femoral-buttock, perineum itself, popliteal and folds under the mammary glands in women . In addition, obese people have large skin folds formed by folds of subcutaneous adipose tissue outside these anatomical zones, while excess body weight itself also serves as a risk factor for skin diseases in large folds.
The syndrome may have an inflammatory, fungal or bacterial etiology, be a consequence of 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, irritant 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 (Hailey-Hailey disease);
7) diseases of the skin appendages: inverse acne, hidradenitis.
Other diseases can be diagnosed in skin folds: vitiligo, skin tumors, skin hemoblastoses, etc. But they, like the listed bacterial diseases and diseases of the skin appendages, do not satisfy the criterion for selection by the similarity of clinical symptoms and the syndromic approach cannot be applied to them. proposed below.
The 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 as carriers. Pathogenic microbial strains 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 subject to secondary infection, and dermatoses with an infectious etiology often lead to a pronounced focal inflammatory reaction. In addition, inflammatory and infectious processes in skin folds 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 occurs, namely:
a) main scenarios:
secondary infection complicates the course of an existing primary non-infectious dermatosis,
initially sluggish infection of the skin causes an inadequate and incomplete immune response, manifested by sensitization, and clinically - eczematization;
b) additional scenarios:
infection may be a trigger factor for chronic immune dermatosis,
a primary sluggish long-term skin infection with a sluggish inflammatory response is superimposed by a more aggressive infection that provokes a pronounced inflammatory reaction, eczematization.
The described scenarios are a classic representation of the group of dermatoses of combined etiology, which makes it possible to attribute to it the majority of diseases with the syndrome of lesions of large folds. As is known, in dermatoses of combined etiology, a complex of drugs or a complex drug aimed at the main general etiopathogenetic mechanisms at the same time will have the maximum therapeutic breadth. Empiric treatment of skin lesions should only be treated with topical treatments to avoid drug interactions and side effects. Given the range of possible diseases in large skin folds, in the syndromic approach of empirical therapy, combinations of drugs with the following effects are preferred:
anti-inflammatory;
antiallergic;
antipruritic;
antiproliferative;
decongestant;
membrane stabilizing;
antibacterial;
antifungal.
These effects are achieved only by the use of topical glucocorticosteroids in combination with local forms of antibiotics and antimycotics. The applied significance of the syndromic approach of empirical therapy lies in the fact that the mechanisms of diseases are distinguished (in our case, with a single localization) and the drug is prescribed taking into account the range of possible final diagnoses. Preference should be given to fixed official topical three-component combinations, each of which the patient must receive in the form of 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, fast enough therapeutic effect;
prolonged action (frequency of application - no more than 2 times a day);
good cosmetic tolerance;
minimal risk of systemic adverse reactions.
Satisfying all of the above and, as a result, the most in demand from the very moment it appeared 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 area of ​​external combined agents that contain corticosteroid and antimicrobial components. The drug has become a benchmark in the evaluation of 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 there are difficulties with the differential diagnosis of inflammatory and infected dermatoses, regardless of localization, which, in fact, is empirical therapy. But it is 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 empiric therapy for a short period of time, 20 consecutive patients with lesions of large skin folds were selected on an outpatient basis, 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, swelling, peeling, cracks, erosion;
age over 2 years;
lack of previous therapy since the onset of acute illness and at least 1 month. with exacerbation of chronic;
strict adherence to orders.
This sample cannot be called refined; in the process of recruiting patients with fold lesions, 2 patients identified during the study period did not meet its criteria. Age in the sample ranged from 18 to 64 years. The distribution of patients by sex and predominant localization of lesions is presented in Table 1.

Despite the anamnestic and clinically obvious diagnoses in some patients, none of them received additional drug prescriptions and systemic therapy was completely excluded. Patients were recommended a rational hygienic regimen and skin care of the affected areas, monotherapy of one of the drug forms (cream or ointment, depending on the prevailing symptoms) of the original fixed combination of betamethasone dipropionate, gentamicin and clotrimazole with application 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 time frame, and 2 had a significant improvement. The average time to achieve remission is 8-10 days, 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. 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 obtained results allow us to conclude that in the treatment of dermatoses of combined etiology, localized in large skin folds, 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 sustainable 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 a syndromic approach and empirical therapy using three-component topical preparations into the practice of dermatovenereologists, but at the same time, every specialist should be aware of the existence of such a possibility in case of damage to the skin of large folds (and not only).

Literature

1. Gladko V.V., Shegay M.M. Syndromic approach in the treatment of patients with sexually transmitted infections (a manual for physicians). M.: GIUV MO RF, 2005. 32 p. .
2. Bijal Trivedi. Microbiome: The surface brigade // Nature 492. 2012. S60–S61.
3. Rudaev V.I., Kuprienko O.A., Microbial landscape of burn wounds: principles of treatment and prevention of purulent-septic complications in burn patients at the stages of care // Presentation. Slide number 4. 2015. .
4. Kotrekhova L.P. Diagnosis and rational therapy of dermatoses of combined etiology // Consilium medicum (application "Dermatology"). 2010. No. 4. S. 6–11.
5. Belousova T.A., Goryachkina M.V. Algorithm for external therapy of dermatoses of combined etiology. Vestnik dermatol. 2011. No. 5. S. 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 Intern. mycological forum. M.: National Academy of Mycology, 2015 .
7. Dikovitskaya N.G., Korsunskaya I.M., Dordzhieva O.V., Nevozinskaya Z. Therapy of secondary skin infections in chronic dermatoses // Effective pharmacotherapy. Dermatology. 2014. No. 2. S. 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. S. 31–34.
9. Tamrazova O.B., Molochkov A.V. Combined topical corticosteroids in pediatric practice: indications for use and errors in external therapy // Consilium medicum (Dermatology appendix). 2013. No. 4.

In some cases, already during the microscopy of the test sample (within 1-2 hours after taking the material), the laboratory assistant manages to make an assumption about the identification of the pathogen. These data provide significant assistance in choosing the optimal antimicrobial agent, since bacteriological research, which makes it possible to isolate the pathogen from a specific biological substrate, requires much more time (from 2 days or more); in addition, a certain amount of time is needed to determine the sensitivity of the isolated microbe to antibacterial agents. However, the appointment of antibacterial drugs is most often urgent, so the doctor has to choose an antibacterial agent, as a rule, without waiting for the results of a bacteriological study. In this case, the doctor, when choosing an antimicrobial drug, should focus on the most likely etiology of the suspected disease. Thus, community-acquired pneumonia is most often caused by pneumococcus.

Therefore, drugs effective against Streptococcus pneumoniae - penicillins, macrolides, etc. - can be used as empirical antibiotic therapy. In meningococcal infection, the drug of choice is penicillin; in acute infections of the kidneys and urinary tract, it is most advisable to choose cephalosporins of II-III generations, inhibitor-protected penicillins or fluoroquinolones, since the most commonly isolated pathogen in this pathology is E. coli (the previously used ampicillin has lost its effectiveness due to the emergence of a large number of strains of E, coli resistant to ampicillin).

In severe course of the disease, if its etiology is unclear, and it can be caused by various pathogens (pneumonia, sepsis, etc.), it is necessary to prescribe emergency antibiotic therapy using several antimicrobial agents. In the future, after the isolation of the pathogen, you can switch to monoetiotropic therapy. Combined etiotropic therapy is also used in the association of two or more pathogens, in the presence of weakly sensitive strains of microorganisms, when antibiotics are combined based on a synergistic effect and an increase in the bactericidal effect. Changing the antibacterial drug due to its inefficiency is possible no earlier than 2-3 full days of treatment, since the effectiveness of the ongoing antimicrobial therapy cannot be judged earlier than these dates.

When choosing an antimicrobial agent, it is necessary to take into account the localization of the pathological process. In the event that the inflammatory focus is located behind the biological barrier (BBB, blood-ophthalmic barrier, etc.), it is necessary that the drug penetrates the biological barrier well, creating the necessary concentration in the lesion. For example, the use of chloramphenicol or co-trimoxazole, even in the usual daily dose, allows you to create a therapeutic concentration of an antimicrobial agent in the CSF. In order to achieve the desired concentration of penicillins, fluoroquinolones, third-generation cephalosporins or meropenem, it is necessary to use the maximum dosages of these drugs; macrolides, amioglycosides, first-generation cephalosporins, and lincosamides penetrate poorly through the BBB even in the presence of inflammation in the meninges.

Therefore, despite the sensitivity of some pathogens of purulent meningitis to these antibiotics, their use for the treatment of purulent meningitis is impractical. For bronchitis, it is better to prescribe drugs that penetrate the sputum well (for example, amoxicillin creates much higher and more stable concentrations in the sputum than ampicillin, and amioglycosides do not penetrate the sputum well enough).

Empirical involves the introduction of antibiotics with clear signs of infection even before the identification of the pathogen. It is based on the sensitivity of the probable pathogen that caused the infectious process. Valuable information is provided by a bacterioscopic study of biological material obtained from infectious foci during their sanitation with mandatory Gram staining. The results of this study can be obtained as early as 30 minutes after the sampling of the material and based on them, empirical therapy can be prescribed. As an empirical therapy, as a rule, broad-spectrum antibiotics are prescribed.

Precision Therapy

Precise therapy is directed to one or more microorganism whose role in patients is determined (isolation of the pathogen from the blood and confirmation by means of an isolated pathogen agglutination test). The most specific and least toxic drug is selected. Positive results of blood cultures were obtained by us in about 30% of cases, which corresponds to the data available in the literature.

However, in recent years there has been a sharp decrease in the frequency of positive culture results (20.1%), which is explained by the possibly powerful antibacterial therapy that was carried out by patients before admission to our hospital. In this regard, we are conducting a thorough analysis of the results of blood culture in patients admitted to the antiseptic center. Crops are performed on the first day of the patient's stay in the hospital. Isolation and identification of microorganisms is carried out by the Bactek-Phoenix system. The start of precision therapy was possible no earlier than 72 hours later. Even 5-7 years ago, Gram+ flora prevailed (73.6%), the sensitivity of which to thienam was 98.8%, to cephalothin - 96%, to netromycin - 79.7%. gram - flora was 26.4%, and it was sensitive almost only to tienam. . Out of 209 blood cultures during 2006, a positive result was obtained in 42 cases, which is 20.1%. Gram-positive microorganisms (59%), such as representatives of the genus Staphylococcus: St. aureus, St. haemolyticus, St. hominis, St. epidermidis. The percentage of gram-negative organisms was 31% and they were represented by the Enterobacteriaceae family, the genera Escherichia (E. Coli), Proteus, Morganella, as well as Pseudomonas aeruginosa Gram-positive microorganisms represented by the genus Staphylococcus were affected by vancomycin, linezolid and rifampicin in 100%, in % - macrolides. Gram-negative bacteria were most effectively affected by carbapenems, the latest aminoglycosides, fluoroquinolones, monobactams, III generation cephalosporins, and protected penicillins. The data obtained allow optimizing antibiotic therapy.

Another important point is that endotoxin is released when microorganisms die under the action of antibiotics. Moreover, the degree of release of endotoxin is not the same. Toxin formation increases in the following order: thienams - aminoglycosides - fluoroquinolones - cephalosporins (most of all). Based on this, when prescribing an antibiotic to a septic patient, one should take into account the degree of endotoxicosis he has, as well as its possible aggravation as a result of the action of this drug.

Basically, we adhered to empirical antibiotic therapy, using broad-spectrum antibiotics, taking into account their effect on toxin formation.

DETOXICATION THERAPY. In severe patients with severe endotoxemia, we consider it mandatory to use extracorporeal detoxification methods (plasmapheresis, hemoperfusion, hemodiafiltration). The choice of method and frequency of extracorporeal detoxification depended on the severity of the condition and the nature of the development of multiple organ dysfunction. The most productive way to interrupt the cytokine cascade is plasmapheresis. In our clinic, continuous plasmapheresis is performed using the apparatus of the Fresenius company or plasma filtration using plasma filters of the same company. With severe fermentemia and proteolysis (peritonitis, pancreatitis, etc.), multiple blood perfusion through Ovosorb becomes the method of choice. Multiple organ dysfunction with impaired renal function requires the use of hemodiafiltration using increased permeability membranes. Extracorporeal detoxification almost always led to an improvement in the general condition of patients and significantly influenced the outcome of the disease. Early use of extracorporeal detoxification significantly enhances drug therapy and, above all, antibacterial therapy, as it changes the degree of blocking of all life support systems by toxins.

The use of TNF inhibitors and non-steroidal anti-inflammatory drugs, in our opinion, did not affect the course of sepsis and outcome.

IMMUNOTHERAPY. In the last ten years, dosed cytokine therapy with roncoleukin (recombinant human interleukin-2) has been used in our clinic. The use of IL-2 to correct immunosuppression in severe and generalized forms of surgical infection was first proposed and patented in 1989 in Germany. In Russia, a preparation of recombinant IL-2 appeared in 1995. This is practically a fundamentally new direction - cytokine immunocorrection in sepsis. This direction is currently being actively developed in Russia and Belarus.

As a result of the inclusion of roncoleukin in the complex therapy of sepsis in patients, body temperature decreases for 2-3 days, tachycardia decreases, the general condition improves, appetite appears and sleep normalizes. From the side of purulent wounds, their speedy cleansing and the formation of granulations occur.

As a result, it should be noted that the use of the drug leads to a decrease in the integral indicator of the severity of the condition according to APACHE II and a decrease in mortality.

However, along with the advantages of the drug, one should point out the reactions and complications that arose in patients receiving the drug. The most frequent of them was fever, observed by us on the first administration of Roncoleukin in 85% of patients. Repeated injections of the drug caused this reaction in almost 100% of patients.

It is known that pyrogenic peptides contained in poorly purified protein preparations cause fever. Fever increases the level of corticosteroids in the blood, i.e. immunosuppressive hormones. Perhaps, by preventing the development of this complication, it would be possible to increase the anti-lethal effect of Roncoleukin. This method has been developed in our clinic and is patented. For about 25 years, in the complex therapy of sepsis, we have been using methods of extracorporeal detoxification, such as plasmapheresis and hemosorption. The anticytokine orientation of plasmapheresis is especially high, the use of which in recent years has limited the widespread spread of AIDS.

Sepsis is a systemic disease with multiple defects in homeostasis and, above all, in the humoral link of its regulation. Here, the relationship between the hormonal and immune systems comes to the fore, which, in the aspect of sepsis, are not actually analyzed in the literature and are not taken into account in clinical practice, which, of course, reduces the effectiveness of treatment. Traditional intensive therapy for sepsis (radical sanitation of foci, antibiotics, extracorporeal detoxification, immunoreplacement therapy) does not eliminate the initial immunodeficiency and does not reduce mortality. Moreover, according to the data available in the literature, these measures can even aggravate it.

Extracorporeal detoxification methods cause a particularly severe adrenal stress response.

Why this happens can be shown by the example of hemosorption. Hemosorption (HS), which makes it possible to eliminate from the blood substances with a molecular mass of 500 to 5000 daltons, the so-called medium molecules, including peptides, the accumulation of which is associated with the development of endotoxicosis and immunosuppression, is today one of the methods in the complex scheme of intensive treatment of sepsis. Nevertheless, GS not only does not compensate for the insufficiency of T and B-links of immunity that occurs during sepsis, but causes a certain tendency to deepen it, as a result of stimulation of steroidogenesis. The activation of the adrenal glands is fixed already after the first procedure and persists throughout the entire period of extracorporeal detoxification, forming a state of stable hypercortisolism.

Elimination of glucocorticosteroids from the blood during GS leads to supercompensation of losses due to the disinhibition of the pituitary gland (elimination of negative feedback) and the development of a normal stress reaction.

It is known that corticosteroids inhibit the migration of stem and B cells from the bone marrow, the cooperation of T and B cells, and cause transient lymphopenia. Under stress, not only the spectrum of lymphocytes changes, but also the total mass of lymphoid tissue in the body (thymus atrophy, spleen involution, etc.), which is the morphological basis for the development of immunodeficiency.

Thus, the problem of immunocorrection in sepsis is largely a problem of stress optimization, which in practical terms is associated with the solution of the following issues: 1. Decreased steroid biosynthesis 2. Decreased steroid reception 3. Activation of steroid catabolism; 4. Removal of the immunosuppressive effect of steroids. Based on the concept of vitamin-hormonal relationships and the available data that: 1. Vitamin B 1 is an anti-stress, activates the insular apparatus of the pancreas, normalizes carbohydrate metabolism 2. Vitamin B 6 blocks steroid receptors, and, consequently, the biological effect of hormones; 3. Vitamin B 12 activates steroid catabolism and is a metabolic antagonist of steroid hormones, normalizes protein and fat metabolism; 4. T-activin has a reciprocal immunomodulatory effect in relation to glucocorticosteroids - it was assumed that this combination (B 1 + B 6 + B 12 + T-activin) can give an anti-stress immunocorrective effect in sepsis.

Clinical trials have confirmed this assumption. Studies were carried out on patients with sepsis, in the treatment of which detoxification hemosorption was widely used. The use of antistress agents here is regulated by the fact that the pathology itself (sepsis) and treatment (powerful antibiotic therapy, surgical debridement of foci, the use of various types of extracorporeal detoxification) are large, and in combination, possibly, an excessive stress load on the adrenal glands (activation of steroidogenesis), which in turn, the immunosuppression already present in sepsis. The reasons for the decrease in the functional activity of lymphocytes under stress are: transient lymphopenia, which causes depletion of the intravascular pool of lymphocytes due to selective immigration of recirculating cells, as well as direct inhibition of the proliferation of individual subpopulations of lymphocytes by glucocorticosteroids.

The use of a complex of vitamins of group B with an immunomodulator causes a pronounced anti-stress effect (decrease in the functional response of the adrenal glands) and elimination of the initial immunodeficiency (a significant increase in the content of immunocompetent cells in the blood). A clear mirror image of the shifts indicates their mutual conditioning. It is well known that the biological effect of thymus hormones is sharply enhanced against the background of hypocorticism, and often even a short-term decrease in the level of glucocorticosteroids in the blood is often enough to create conditions that provide a long-term stimulating effect of thymosin to the cellular immunity system. Our data show that immunomodulation and leveling of hormone-mediated immunosuppression caused by a complex of vitamins of group B and T-activin or roncoleukin can significantly reduce the mortality rate in patients under conditions of intensive complex treatment of sepsis. In this regard, I would like to draw attention to the following problem. Since 1986, admission to the intensive care unit of the Grodno regional hospital of septic patients has been steadily increasing. If 20 years ago this figure was 4-5 patients per year, now 3 times more patients are admitted per month, i.e. on the face of the growth of immunodeficiency in the population.

The reason for such a significant increase in the number of septic patients may be not only the radiation exposure of the hematopoietic tissue as a result of the accident at the Chernobyl nuclear power plant, but also the stress load on the lymphoid tissue. The positive experience of using a complex of B vitamins in combination with immunomodulators in sepsis indicates not only ways to correct stress-induced immunodeficiency, but also ways to prevent it.

The described approach to the treatment of sepsis and the widespread use of extracorporeal detoxification methods have made it possible to reduce mortality from 36 to 18-22% and keep it at this level for many years.

Analysis of the results of sepsis treatment allows us to conclude that the treatment of this severe pathology should be complex. At the very beginning of the disease, the elimination of the primary focus of infection and antibiotic therapy using broad-spectrum antibiotics is of fundamental importance. In our conditions, a favorable impression is made by tienam monotherapy in the first 4-5 days. In the future, the need for immunocorrection, as well as intensive treatment aimed at restoring disturbed homeostasis of the body, comes to the fore. Summarizing the above, it should be noted that a complex of vitamins (B 1 + B 6 + B 12) in combination with drug or non-drug immunostimulating therapy, in our opinion, is the basic prescription for the treatment of septic patients. With the development of septic shock and ARDS in the clinic, methods of treatment using extracorporeal magnetic blood processing have been developed and patented in the EAPO.

The essence of the methods of treatment is described in other sections (treatment of septic shock and ARDS).

The complexity of the problem under consideration is determined by its multifactorial nature and the lack of knowledge of the pathophysiological processes that develop in sepsis.

Empirical therapy is carried out until the result of a microbiological study from a purulent focus is obtained and plays one of the main roles in complex therapy in patients with purulent-necrotic foot lesions in diabetes mellitus.

Adequate empiric therapy is based on the following principles:

The antimicrobial spectrum of the drug should cover all potential pathogens in this pathology;

The antibiotic therapy regimen takes into account current trends in antibiotic resistance and the likelihood of the presence of multidrug-resistant pathogens;

The regimen of antibiotic therapy should not contribute to the selection of resistant strains of pathogens.

As drugs of choice, it is advisable to use fluoroquinolones of III-IV generations (levofloxacin, moxifloxacin), cephalosporins of III-IV generation (cefotaxime, ceftazidime, cefoperazone, cefetim), glycopeptides (vancomycin), inhibitor-protected penicillins (co-amoxil). A number of empirical therapy drugs that do not have a spectrum of action on the anaerobic microflora are prescribed in combination with metronidazole. In especially severe cases (with a septic condition), it is considered justified to prescribe a group of carbapenems (imipenem, meropenem) as empirical therapy. The drugs of these groups are characterized by low toxicity, good tolerance by patients, long-term preservation of high concentrations in the blood and tissues of the purulent focus, which makes it possible to prevent the development of resistance of microorganisms to them. Of the combinations of antibacterial drugs, the following are mainly used: levofloxacin + metronidazole; levofloxacin + lincomycin (clindamycin); III-IV generation cephalosporins (cefotaxime, ceftazidime, cefepime) + amikacin (gentamicin) + metronidazole. The scheme for choosing antibacterial drugs is shown in fig. one.

After receiving the results of a bacteriological study, a correction of antibiotic therapy is carried out, taking into account the isolated microorganisms and their sensitivity to antimicrobial drugs. Thus, timely and adequate empirical antibiotic therapy allows stopping the progression of the purulent-necrotic process on the affected foot, giving time, especially in the neuroischemic form of foot damage, to restore disturbed macro- and microhemodynamics in the lower limb and perform adequate surgical treatment of the purulent focus, and when neuropathic form of the lesion after early surgical debridement of the purulent focus to prevent the spread of infection and thereby avoid repeated surgical interventions, and preserve the supporting function of the foot.