Bacterial Skin Infections

Problem of Choosing the Optimal Antibiotic

Pyoderma-pustular skin diseases, caused mainly by strepto-staphylococci, are the most common infectious diseases in the practice of a dermatologist. In the structure of infectious diseases in economically developed countries, patients with pyoderma make up 30-40%, and the disease is often the cause of temporary disability. In countries with cold climates, the peak of morbidity falls on the autumn–winter period. In hot countries with humid climates pyoderma occur year-round, ranking second in frequency after skin mycosis.

Any infection develops as a result of the interaction between macro– and microorganisms under certain environmental conditions. Thus, the pathogenesis of pyoderma should be considered from the standpoint of the interaction of 3 “M” (Micro, Macro, Medium). The main pathogens of pustular infections of the skin are gram-positive cocci: in 80-90% of cases of Staphylococcus (Staphylococcus aureus, Staphylococcus epidermidis); in 10-15% of Streptococcus (Streptococcus pyogenes). Recently, in crops from the foci of purulent skin lesions, both pathogens are detected simultaneously. In a small percentage of cases in the development of purulent inflammation in the skin involved gram-negative microorganisms: Pseudomonas aeruginosa and E. coli, vulgar Proteus and other microbes. Coccal flora is constantly in some areas of the skin (hair follicles, sebaceous and sweat glands, skin folds, around the natural holes). In most cases, pyoderma develops due to the transformation of saprophytic cocci into pathogenic, and therefore most cases of pyoderma are non-contagious. Pathogenic staphylococci secrete a number of pathogenic toxins and enzymes that delaminate the layers of the epidermis and cause coagulation, hemolysis and necrotization of all skin layers.

The skin has a natural resistance to pyogenic cocci, which is due to the integrity of the stratum corneum, acidic environment on the surface of the skin, constant peeling of the upper layers of the epidermis, which protects it from the penetration of pathogenic microbes. Under unfavorable environmental influences in the form of high or low temperature, high humidity, leading to maceration of the skin, increased pollution, microtraumatization (injections, cuts, scuffs), dryness and thinning of the stratum corneum, the natural resistance of the skin and the development of pyodermic process.

The state of the macroorganism and the presence of concomitant pathology plays an important role in the occurrence of pyoderma.

• Diseases of the Central and autonomic nervous system; mental or physical strain;
• “Debilitating diseases” – alcoholism, malnutrition, vitamin deficiency;
• Endocrinopathy (obesity, diabetes) contribute to the reduction of mechanisms of anti-infectious protection of the body.

Chronic infectious diseases of various organs and tissues, such as periodontal disease, caries, gingivitis, tonsillitis, pharyngitis, infections of the urogenital tract, which reduce the overall and local antibacterial resistance of the body, are of great importance in the development of pustular skin diseases.

Particular importance in the development of bacterial infections of the skin is given to the state of specific mechanisms of immunological reactivity, and above all – to the violation of the t–cell system of immunity. Conditions of congenital or acquired immunodeficiency (HIV infection, taking glucocorticosteroids, cytostatics and immunosuppressants) play an important role in the development of pyoderma. Of great importance is the inhibition of the phagocytic activity of leukocytes. Defects of cellular antibacterial protection in the form of violation of chemotactic activity of neutrophils (syndrome IgE-hypergammaglobulinemia) and intracellular lysis (chronic granulomatous disease), contribute to the long-term flow of bacterial processes in the skin and frequent recurrence.

Currently, there is no generally recognized classification of pyoderma. In practical terms, the most acceptable is the classification, which is based on two principles: the nature of the pathogen and the depth of skin lesions. In addition, pustular skin diseases are divided into primary (arising on unchanged skin) and secondary, developing as complications against the background of existing dermatosis, more often itchy (scabies, eczema, atopic dermatitis). The duration of the course distinguish between acute and chronic pyoderma. Staphylococcal pyoderma is usually associated with skin appendages (hair follicles, apocrine glands). There is a formation of a deep pustule, in the center of which a cavity is formed, filled with purulent exudate. On the periphery is the area of erythematous-edematous inflammatory skin. The suppuration process ends with the formation of a scar. Streptococcal pyoderma often develop on the smooth skin around the natural openings (mouth, nose) and starts with education phlyctenas – superficial-bladder with a flabby fold the tire inside of which contains serous–purulent contents. The thin walls of the flickens are quickly opened, and the contents pour out on the surface of the skin, shrinking into honey–yellow layered crust. The process is prone to spread to the periphery as a result of auto-induction. Stafilodermia most men suffer, streptodermii women and children.

Therapy of patients with bacterial infections of the skin should be comprehensive (etiotropic and pathogenetic) and be carried out after a thorough anamnestic, clinical and laboratory examination of the patient. It is necessary to identify and treat comorbidities, examination for foci of focal infection, and in the case of a long – lasting process-immunostatus studies. The main etiotropic drugs prescribed to patients with staphyloderma are antibiotics. In acute surface processes (impetigo, paronychia, folliculitis) treatment may be limited to local means. Depending on the clinical situation, ointments and creams with antibiotics are used in combination with aniline dyes, disinfectant antiseptic solutions. Indications for systemic antibiotic therapy are deep forms of pyoderma: boils, especially with localization on the face and neck, carbuncle, hidradenitis, erysipelas, cellulite. These forms of bacterial infections of the skin have a long, often chronic recurrent course and are often accompanied by symptoms of General intoxication in the form of fever, headache, weakness, as well as the development of regional complications (lymphadenitis, lymphangitis). As an etiotropic, antibiotics are used in the treatment of bacterial dermatosis – Lyme disease. They are the drugs of choice in the treatment of acne vulgaris.

Assessing more than half a century of experience in the use of antibiotics in clinical practice, we can say with confidence that they have made a real revolution in the treatment of infectious diseases. Academician I. A. Kassirskiy wrote: “Before the advent of antibiotics, the doctor’s role in many diseases has often been reduced to the contemplation of death.” It is known that the Russian composer of the XIX century. Scriabin died of sepsis caused by a complicated course of boils on his face. The use of antibiotics has had a serious evolutionary change not only in the clinical course of infections, but also dramatically transformed the epidemiological process and the ecology of microbial flora. With the advent of antibiotics, medical practice has been enriched with unique drugs that selectively inhibit the vital activity of microorganisms while maintaining the viability of host cells. With the advent of antibiotics came a new era in medicine. For this reason it is possible to claim that antibiotics are unsurpassed etiotropic means, preparations of the first line in treatment of infectious diseases, including skin. The first antibiotic (penicillin purified) was obtained independently from other two scientists – Alexander Fleming in 1940, the Term “antibiotic” was suggested in 1942 Z. A. Waxman after the discovery of penicillin to denote substances produced by microorganisms and have antimicrobial properties. Antibiotics are the largest group of medicines. Currently uses 30 different groups of antibiotics, and the number of drugs (excluding generics) is approaching 200.

Traditionally, antibacterial drugs are divided into natural (actually antibiotics, for example, penicillin), semi-synthetic (products of modification of natural molecules, for example, amoxicillin) and synthetic (for example, sulfanilamides, nitrofurans). Currently, this division has lost relevance, as a number of natural antibiotics are obtained by synthesis (chloramphenicol), and some drugs, called antibiotics (fluoroquinolones), de facto are synthetic compounds. Antibiotics should be distinguished from antiseptics, which act on microorganisms indiscriminately and are used for their destruction in living tissues, and disinfectants intended for the indiscriminate destruction of microorganisms outside the living organism (care items, surfaces, etc.).

All antibiotics, despite the differences in the chemical structure and mechanism of action, combines a number of unique qualities. First, the uniqueness of antibiotics lies in the fact that, unlike most medicines, their target receptor is not in human tissues, but in the cell of the microorganism. Secondly, the activity of antibiotics is not constant, but decreases with time, due to the formation of drug resistance (resistance). Antibiotic resistance is an inevitable biological phenomenon, and it is almost impossible to prevent it. Third, antibiotic-resistant microorganisms are dangerous not only for the patient in whom they were isolated, but also for many other people separated by time and space. Currently, the reduction of antibiotic resistance of microbial agents and increase the effectiveness of antibiotic therapy can be achieved through the introduction of new antibiotics in medical practice and adherence to the principles of rational antibiotic therapy.

The most common mistakes in the use of antibiotics are the following:

• 1. The purpose of the drug, which does not have high activity to the microbial agent, without taking into account the sensitivity of the microorganism to it.
• 2. Treatment is carried out or too short course, or Vice versa too long.
• 3. The daily dose is incorrectly chosen, the frequency of reception is not observed.
• 4. The possibility of side effects in the presence of concomitant pathology in the patient is not taken into account.
• 5. Pharmacokinetics of the drug does not provide its sufficient concentration in the focus of inflammation to suppress the infection.

As the analysis of modern literature and own clinical experience shows, today the following groups of antibiotics are most often used in the treatment of bacterial infections of the skin.

B-lactams:

• a) natural penicillin, its Durant forms and semisynthetic penicillins;
• b) cephalosporins (1-4 generations).

2. Macrolides.
3. Tetracyclines.
4. Fluoroquinolones.

Tetracyclines, aminoglycosides are now used much less frequently. This is due to the large number of resistant strains of microorganisms to these antibiotics, which implies their low therapeutic activity, as well as the presence of severe side effects. B–lactams are used much less frequently than before due to the pronounced resistance of peococci to these antibiotics and the high frequency of allergic reactions. Fluoroquinolones are prescribed mainly in the treatment of sexually transmitted diseases. due to the high sensitivity of urogenital infections to them, and in pyoderma, they are used only in case of ineffectiveness of other groups of antibiotics.

Modern medical practice imposes certain requirements to the choice of antibiotic. First of all, the drug should have a wide range of antimicrobial action and minimal antibiotic resistance to microbial agents, not have severe side effects, be convenient to use for the patient (oral form, convenient dosing regimen) and affordable. In addition, it is very important that the antibiotic has no clinically significant interactions with other drugs. To date, these requirements are fully consistent with antibiotics – macrolides. Macrolides have been widely used in clinical practice for more than 50 years. The first natural antibiotic of this group – erythromycin (metabolite Strepomyceus erytheus) was obtained in 1952. The antibacterial effect of macrolides is based on the violation of the synthesis of ribosomal proteins of the antibacterial cell and thereby inhibiting the process of reproduction of the pathogen. They mainly have a bacteriostatic effect, which makes it advisable to prescribe them in the acute phase of inflammation. Macrolides are “tissue antibiotics“, i.e., when distributed in the body, they accumulate mainly not in the bloodstream, but in those organs and tissues where there is inflammation, thereby creating high concentrations of the drug. However, widespread (and often – unreasonable) use quickly led to the emergence of a high percentage of erythromycin-resistant strains of pathogens, especially staphylococci. Interest in macrolides has re-emerged in the early 80–ies of XX century, after the emergence of new generations of antibiotics of this group, in particular, azalidov. “New” macrolides have proven to be highly effective and at the same time the safest antibiotics with a minimum number of contraindications to the appointment. Modern macrolides show the most effective against such pathogens as S. pyogenus, S. aureus, S. pneumoniae, some gram-negative microorganisms (gonococcus), as well as intracellular pathogens (in particular, chlamydia trachomatis, Ureaplasma urealiticum), which causes a high demand for them in the dermatology-venereal practice. In dermatology, primarily macrolides are the basic therapy of staphylococcal and streptococcal lesions of the skin and soft tissues (boils, impetigo, cellulite). This is due to the fact that, along with antimicrobial action, these antibiotics have moderate anti-inflammatory activity. By activating the cells of the macrophage series, they are able to penetrate them and the migration of phagocytic cells in the focus of inflammation to come there with them. The uniqueness of these drugs lies in the fact that they have a pronounced postantibiotic effect, that is, they retain high concentrations in the focus of inflammation within a few days after withdrawa. Classification macrolides, and the basic scheme of their destination when intermech presented.

The ideal approach to choosing an antibiotic before the treatment of pyoderma is to carry out the sowing of pus with the determination of the sensitivity of the pathogen to certain drugs. However, this is not always feasible, especially with the threat or development of complications of infection. In this regard, quite often there is a question of empirical choice of antibacterial agent, which would be the most effective in this case and meet the modern requirements of rational therapy. As the analysis of modern literature and own clinical experience shows, in infectious diseases of the skin and soft tissues, the second generation macrolides are most effective, primarily 15– and 16– member (azithromycin, josamycin, roxithromycin). According to a study by the European society for antimicrobial therapy (ESOC), carried out in 2001-2002 in most European countries, these macrolides are second in terms of consumption among antibiotics used in outpatient practice, second only to penicillins. Azithromycin is one of the” top five ” most actively sold in the world of antibacterial drugs. Consumption of azithromycin (Chemomycin) reaches colossal proportions and continues to increase steadily. In 1999, azithromycin was the most prescribed macrolide in the world (drug monitoring AIS, 1999), and its sales in 2002 exceeded $ 1 billion. Already Accumulated 10 years of positive experience in the use of azithromycin (Chemomycin) in the domestic dermatological practice indicates its truly worldwide recognition. The basis for such popularity and demand of the drug was the proven clinical efficacy of azithromycin, its optimal pharmacokinetic properties, convenient dosing regimen and good tolerability.

The basic properties of azithromycin (Hemomitsin):

* High activity against major infectious diseases of the skin and subcutaneous tissue (Ntks. aureus, Str. pyogenes, Str. viridans, Streptococcus groups CF and G burgdorferi sense B. N. gonorrhoeae) and atypical intracellular parasites (chlamydia).

* High concentration of the drug in the affected area is 10-100 times higher than the concentration in the bloodstream. This allows you to actively influence the pathogenic focus, thereby providing a rapid clinical effect and early recovery.

* The presence of postantibiotic effect (i.e. the preservation of high bactericidal concentrations of the drug in the lesion within 5-7 days after its cancellation). This made it possible to develop short courses of treatment.

* Lack of clinically significant interaction with other drugs. Hemomitsin unlike the majority of macrolides, does not bind with the enzyme complex of cytochrome P450, resulting in not showing reaction drug interactions with drugs metabolized this way. This property is important, because in real clinical practice, most patients who have pustular skin diseases, have background or concomitant diseases, for which receive appropriate treatment.

* Convenient dosing regimen (1 time per day), a short course of application (not exceeding 3-5 days) ensures the compliance of treatment and improves the quality of life of the patient.

* Good portability and proven safety.

* The possibility of appointment of pregnant, nursing, children.

* Pharmacoeconomics.

As shown in a number of studies, the clinical efficacy of Azithromycin and other macrolides of the last generation is higher than that of tetracyclines and b–lactam antibiotics. This is due to the fact that the resistance of microorganisms sensitive to them does not exceed 2-10%. At the same time, the frequency of adverse reactions, as a rule, do not require discontinuation of the drug, does not exceed 5%. Comparative clinical and microbiological study of the effectiveness of deep staphyloderma 5 day course of azithromycin and 10 day administration of cephalexin showed higher therapeutic activity of macrolide. Eradication of the pathogen in the application of azithromycin was observed in 94%, in cephalexin in 90% of cases, clinical cure-in 56% and 53% of cases, respectively.

Thus, Azithromycin (Hemomitsin) has a broad spectrum of antimicrobial activity, high bacteriostatic activity against susceptible to infections, high bioavailability with selective effect in the inflammation, low-toxic, has low side effects and convenient regimen. Therefore, the drug meets the modern requirements of rational antibiotic therapy and can be recommended for effective treatment of pustular diseases of the skin and subcutaneous tissue.