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Treatment

Comprehensive treatment of IE should be etiotropic, pathogenetic and symptomatic. Treatment includes: the appointment of 2 or 3 AB synergistic action, taking into account the sensitivity of the selected microorganism, the use of hyperimmune plasma and glucocorticoids, correction of heart failure, symptomatic treatment and extracorporeal hemocorrection, which reduces the resistance of pathogenic bacteria to AB.

In each case, the treatment is individual, taking into account the general condition of the patient, the type of pathogen, the phase of development and the course of the disease, the volume of therapeutic measures at the previous stages. The basis for conservative treatment of IE is ABT. Before the onset of AB, the outcome of IE depended on the development of the infectious process. Currently, the relief of the infectious process is possible in 50-70% of cases, since the valves are only partially supplied with blood and AB do not penetrate into the MV. The effectiveness of ABT is monitored based on the results of multiple bacteriological blood tests, positive only in 35-45% of cases.

For an effective ABT, the necessary conditions are:

Early initiation of treatment (delay with the appointment of AB from 2 to 8 weeks from the onset of the disease reduces survival by half).

The use of maximum daily doses of bactericidal AB with a parenteral route of administration.

Performing ABT for at least 4-6 at early and 8-10 weeks with treatment started late.

The use of AB, taking into account the sensitivity of bacteria to them.

Determination of the in vitro sensitivity of pathogenic bacteria to AB, identification of their minimum inhibitory concentration (MIC).

Empirical ABT with 1st-3rd generation cephalosporins with aminoglycosides with negative blood culture results.

Correction of dose and intervals of AB administration depending on the state of renal excretory function.

AB replacement in case of resistance of bacteria within 3-5 days.

The average duration of treatment with streptococcal IE is 4 weeks, with staphylococcal and gram-negative IE - 6-8 weeks until a pronounced clinical effect is obtained.

The choice of AB depends on the selected microorganism. For the treatment of streptococcal IE, penicillin (30-40 million units / day), gentamicin (2-2.5 mg / kg / day), vancomycin (40 mg / kg / day or more) are initially used. Nonhemolytic streptococci in 50% of cases are resistant to penicillins and aminoglycosides. However, the use of combinations of these ABs allows overcoming the secondary resistance of bacteria. When isolating streptococcus with a MIC of 5 μg / ml or less, vancomycin (1000 mg, 2 times / day intravenously) is used. In case of detection of penicillin-sensitive strains of streptococcus, a combination of semisynthetic penicillins (oxacillin 2-3 g or more, 4-6 times / day; ampicillin 500 mg, 4-6 times / day) with gentamicin (60-80 mg, 2-3 once / day intravenously). For allergies and (or) the development of secondary resistance to penicillin, use vancomycin (500 mg, 4 times / day intramuscularly). In the absence of a positive effect from the indicated ABs, 3-5-generation CSs (cephalotin, cefazolin, cefotaxime, ceftriaxone), imipenem (500-750 mg, 2 times / day intramuscularly) are used for 3-5 days. In the absence of the ABT effect for 4 weeks, the development of septic complications, decompensation of HF, surgical treatment is indicated.

Staphylococci are the most common pathogens of IE of the current course. Staphylococcus aureus and coagulase-negative staphylococci in most cases are resistant to penicillin, but are sensitive to penicillin-resistant semi-synthetic penicillins. When epidermal and golden staphylococci resistant to semisynthetic penicillins are isolated, vancomycin (500 mg, 4 times / day; 1000 mg, 2 times / day, IV or IM) is used as monotherapy or in combination with aminoglycosides (gentamicin 60 -80 mg, 2-3 times / day; amikacin 5 mg / kg, every 8 hours). The use of vancomycin (500 mg after 6 hours, IM or IV) with gentamicin (60-80 mg, 2-3 times / day) has a pronounced clinical effect due to the synergistic effect. In patients with IE caused by a methicillin-resistant Staphylococcus aureus strain, vancomycin is used in the treatment (1000 mg after 12 hours, iv).

Enterococcal IE develops after operations on the stomach and intestines, urinary organs, prolonged catheterization of the bladder, etc. In 45% of cases, enterococci are determined to be resistant to cephalosporins, semisynthetic penicillins, and macrolides. Most strains of enterococci (E. Faecalis, E. Faecium) retain isolated sensitivity to gentamicin, vancomycin. Therefore, ABT begins with the intravenous administration of a combination of ampicillin (up to 20 g / day) with gentamicin (240 mg / day). In the absence of the effect of using AB for 3-5 days and (or) an allergy to penicillin, intravenous administration of vancomycin (0.5 g, 4 times / day) with gentamicin (80 mg, 3 times / day) is carried out for 4 -5 weeks. In case of resistance to gentamicin (MPC more than 2000 μg / ml), ABT is unpromising, surgical treatment is indicated.

When conducting antibiotic therapy of IE caused by gram-negative bacteria, it is effective to use 1st-3rd generation CS (cephalotin, cefazolin, cefotaxime 8 g / day; ceftriaxone 6 g / day) with gentamicin (5-6 mg / kg / day) within 6-8 weeks. Fungal endocarditis is often caused by fungi of the genus Candida and Aspergillus. For its treatment, amphotericin B (1 or more mg / kg / day) is used in combination with flucytosine (150 mg / kg / day) or fluconazole (200-400 mg / kg / day). Fungal endocarditis does not respond well to ABT; in most cases, surgical treatment is required.

To obtain the results of bacteriological blood tests and (or) with negative results of the study, an empirical ABT is performed. Its content and duration is determined by the variant of the clinical course, the severity of fever and the nature of the complications. The effectiveness of treatment is established by clinical and laboratory signs of activity of the infectious process. The choice of AB is carried out on the basis of the analysis of the structure of positive blood culture of modern IE and possible entry gates of infection. The duration of an empirical ABT is from 4 to 8 weeks. Achieving a pronounced clinical effect is a determining time factor for ABT.

With OIE with a sudden increase in body temperature from 39.5 ° C to 41.5 ° C, tremendous chills, irregular fever, arthromyalgia, profuse sweat, increased heart rate to 136, significant weight loss, hepatosplenomegaly, frequent development of septic and embolic complications, Empirical ABT begins with the use of a combination of 2-3 ABs from the 1st-3rd generation CA group (cephalotin, cefazolin, cefotaxime - 6-8 g / day; ceftriaxone - 4 g / day) and (or) AB reserve (imipenem - 4 g / day, carbapenem - 3 g / day, vancomycin - 2-4 g / day, ciprofloxacin - up to 4-5 g / day). Treatment lasts 6-8 weeks until a pronounced clinical effect.

In the case of PIE with an increase in body temperature from 38 ° C to 40 ° C, hyperthermic fever, severe sweating, chills, arthromyalgia, splenomegaly, frequent development of immunocomplex lesions of organs, empirical ABT begins with 2 synergistic antibiotics: ampicillin (12- 16 g / day) with gentamicin (2-2.5 mg / kg / day) or vancomycin (2-4 g / day) with gentamicin (2-2.5 mg / kg / day) for 4-6 weeks. In the absence of a clinical effect within 3-5 days, two to three drugs from the 1st-3rd generation CA group are prescribed (cephalotin, cefazolin, cefotaxime - 6-8 g / day; ceftriaxone - 4 g / day) and one AB reserve (imipenem - 4 g / day, carbapenem - 3 g / day, vancomycin - 2-4 g / day). Treatment lasts 6-8 weeks.

Treatment of patients with ZIE, in the clinical picture of which there is subfebrile fever, chills, an increase in heart rate to 110-115, begins with the use of 2 ABs: ampicillin (12-14 g / day) or benzylpenicillin (18-20 million units / day) s gentamicin (1-2 mg / kg / day) for 4 weeks. In the absence of a clinical effect, CS is prescribed for 3-5 days (ceftriaxone - 2-4 g / day, cefotaxime - 4-6 g / day) for a period of 4-6 weeks.

It is rational to conduct empirical ABT on the 1st-3rd generation CS and reserve AB. This approach allows us to overcome the resistance of bacteria to AB and achieve in 85-90% of cases of clinical and bacteriological remission of the disease. The content of empirical ABT algorithms is determined by the variant of the course of IE and the resistance of bacteria to AB. With OIE with severe infectious-toxic syndrome, frequent development of septic and embolic complications, it is effective to use a combination of 2-3 ABs from the CA group of the 1-3rd generation and 1st AB reserve (imipenem, carbapenem, vancomycin, ciprofloxacin). In patients with PIE with a mild infection-toxic syndrome and immunocomplex organ damage, the use of 2 synergistic antibiotics is effective (ampicillin with gentamicin, vancomycin with gentamicin). In the absence of a clinical effect within 3-5 days, the ABT regimen of acute IE is used for 4-6 weeks. Empirical ABT of protracted IE begins with the use of a combination of ampicillin with gentamicin (penicillin with gentamicin). In the absence of effect for 3-5 days, CS (ceftriaxone, cefotaxime) is used for 4 weeks.

With adequate ABT, the clinical effect occurs after 3-6 days. The criteria for the effectiveness of ABT are: improvement in the general condition of patients in the first 48-72 hours of treatment, the appearance of appetite, a decrease in asthenia, the disappearance of chills, sweating and fever. At the end of the first week, body temperature, chills, petechiae, embolic manifestations disappear or significantly decrease, hemoglobin decrease stops, ESR slows down, sterile blood culture is determined. At the end of the 2-3rd week, the leukocyte blood count normalizes, ESR slows down significantly, the size of the liver and spleen decreases, indicators of acute phase reactions normalize, and manifestations of urinary syndrome decrease. At the end of the 4-6th week, ESR reaches 10-20 mm / h, proteinogram, blood normalization occurs, the size of the liver and spleen returns to normal, vasculitis and feasibility study disappear.
In the absence of these signs, dose adjustment or replacement of AB is performed.

The effectiveness of ABT depends on the age of the patient, the duration of the disease, the magnitude, location and mobility of MV, changes in the immune system, and the type of bacteria. Mortality from IE caused by staphylococcus remains high and amounts to 60-90%. The reason is the development of resistance to AB. Distinguish between primary and secondary resistance. With primary resistance, the use of AB does not cause remission of the disease (Pseudomonas aeruginosa, gram-negative bacteria). Secondary resistance is more common, in which there is an initial positive effect from ABT.

The formation of secondary resistance of bacteria is associated with untimely treatment, the specific composition of microflora (Staphylococcus aureus, gram-negative bacteria, fungi), changes in immunity (deficiency of the T-system of immunity, phagocytosis) in the elderly and drug addicts, patients with chronic hemodialysis. Secondary resistance can be dealt with as a result of timely replacement or increase in doses of AB, the simultaneous use of 2-3 AB, the use of extracorporeal hemocorrection, immunomodulating therapy, the use of small doses of HA (15-20 mg of prednisolone) for 7-10 days.

In patients with IE, significant changes in the immune system occur. To correct changes in immunity and detoxification, therapeutic plasmapheresis, xenosplenoperfusion, intravascular laser blood irradiation, ultraviolet blood irradiation are used. These methods of extracorporeal hemocorrection have a pronounced immunomodulating effect, reduce endogenous intoxication in the septic phase of IE.

The main indication for PF in patients with IE is increasing endogenous intoxication. To release toxic substances from the blood depot, small doses of reopoliglyukin, trental and droperidol are administered intravenously before the PF. As a result of elimination of bacterial toxins, endogenous intoxication decreases, the general condition of patients improves, and central hemodynamics are normalized.

Plasmapheresis is used to remove excess CEC and immunoglobulins from the blood, which reduces the likelihood of development and progression of immunopathological complications in PIE. The clinical efficacy of PF was registered in 90% of patients: hectic fever of the body decreases to subfebrile, the general condition of the patients improves, the blood coagulation system normalizes, the inflammation indicators decrease, and anemia is corrected. Removing 75-100% of the blood plasma volume and replacing it with an equivalent volume of albumin, protein, plasma substitutes has a beneficial effect on hemorheological parameters and contributes to the correction of DIC. Plasmapheresis is an important additional treatment method, however, without effective ABT, it does not lead to recovery of patients with IE.

After two or three sessions of CPSS, through intoxication of freshly prepared and washed xenose-spleen, intoxication decreases and the general condition of patients with IE improves. However, the method has a drawback: the blockade of the xenospleen microcirculatory bed develops when blood passes through it, its functional activity and therapeutic effect decrease. To eliminate this drawback, autoplasma obtained during PF is used.

An important method of extracorporeal hemocorrection is VLOK. Its main mechanisms of therapeutic action include: immunocorrective, antianemic and antitoxic. Under the action of VLOK, the state of aggregation of blood and the electrical stability of the myocardium are normalized, the contractility of the left ventricle increases. The number and activity of immunocompetent cells, factors of nonspecific immunity and immunoglobulins increase, phagocytosis is stimulated, and bactericidal activity of blood increases. There is a stimulation of erythropoiesis, an improvement in the oxygen-transport function of red blood cells, and stabilization of cell membranes. The intensity of the processes of lipid peroxidation and activation of the antioxidant system is reduced, the concentration of medium-weight molecules is reduced, and tissue metabolism is normalized. The hypocoagulation and disaggregation effect is manifested by stimulation of fibrinolysis and an increase in the concentration of natural blood anticoagulants. The immunomodulating effect of VLOK is caused by the normalization of subpopulations of T-lymphocytes and a decrease in the electrostatic charge of the cytoplasmic membrane of these cells.

The clinical effectiveness of VLOK is due to the immunoregulatory effect. Conducting 2-3 sessions of VLOK in patients with IE changes the expression of the differentiating receptors of CD3, CD5 and CD8 receptors of lymphocytes, reduces the expression of lymphocyte activation markers CD25 and DR antigen, increases the production of Niterleukin-1 and tumor necrosis factor. The mechanism of action of ultraviolet radiation is due to the stimulation of immunity and the effect on bacteria, the removal of medium molecular proteins from the body, the reduction of arterial hypoxemia, the improvement of the oxygen transport function of red blood cells, and the activation of redox processes. Ultraviolet irradiation of autologous blood activates erythro- and leukopoiesis, has a regulatory effect on the calicreinkinin system, and increases the nonspecific resistance of the body.

In the clinical picture of PIE, autoimmune complications come to the fore. In this situation, the question arises about the use of HA. The use of HA allows maintaining the stability of myocardial cell membranes, preventing nonspecific damage to cells by endotoxins and proteolytic enzymes, blocking the permeability of lysosomes and the release of acid hydrolases, and providing a suppressive effect on each stage of the immune response. The use of HA at the stage of preoperative preparation contributes to the achievement of good results in the surgical treatment of patients with OIE. At the same time, the uncontrolled use of HA in PIE activates the infectious process (9.5%), increases the number of deaths and feasibility studies by 1.5-2 times, causes the progression of heart failure; reduces the activity of neutrophils, monocytes and the phagocytic activity of leukocytes; suppresses cellular immunological reactions. The use of small doses of prednisolone in 120 patients with PIE with myocarditis, glomerulonephritis, severe urinary and nephrotoxic syndrome caused a severe course of the disease in 31.1% of cases.

Small doses of prednisone (20-30 mg / day) are used in patients with PIE with the development of polyserositis, glomerulonephritis, myocarditis and hemorrhagic vasculitis. Some authors have observed a positive effect of using HA in PIE with high titers of rheumatoid factor (<1/320) and cryoglobulinemia. Rapid regression of immunopathological manifestations occurred in cases where ABT did not stop the manifestations of immunopathological reactions.

The use of HA is advisable for infectious toxic shock, in the immuno-inflammatory phase of IE with severe immunocomplex complications (myocarditis, DG with severe urinary or nephrotic syndrome, polyserositis, vasculitis, hepatitis, etc.) and an increase in the concentration of CIC and immunoglobulins M, A in the blood, development secondary resistance of bacteria to AB. However, in foreign manuals, the use of HA in the treatment of the disease is not mentioned.

При ИЭ происходит активация тромбоцитов, развивается ДВС-синдром (73,4%) и выраженные нарушения микроциркуляции, увеличивается активность фактора Виллебранда (63,7%). Эти патологические процессы наиболее выражены при ОИЭ. Поэтому нормализация показателей свёртывающей системы крови является обязательным лечебным мероприятием. Управляемая гипокоагуляция осуществляется внутривенным введением дезагрегантов (трентала по 300-600 мг/сут). При развитии ТЭО и значительном снижении концентрации антитромбина III вводят 20 000-30 000 ЕД гепарина в сутки, свежезамороженную плазму. Для улучшения микроциркуляции необходимо применять антиагреганты в течение 4-х недель.

При ОИЭ повышается активность системы протеолиза. Поддержанию воспалительного процесса способствует активация кининовой системы. Для блокады высвобождения протеаз и кининов применяют контрикал (до 1000 ЕД/кг/сут). При развитии ДВС-синдрома суточная доза препарата может увеличена до 300 000-500 000 ЕД. Ингибиторы протеолитических ферментов вводят ежедневно и отменяют после ликвидации синдрома интоксикации, нормализации температуры тела.

Анализ причин неудовлетворительных результатов лечения ИЭ выявил, что наибольшее влияние на исход заболевания оказывают: время установления диагноза (более 8-ми недель) и назначение антибактериальной терапии (более 4-х недель), полиорганная недостаточность, СН III-IV ФК, множественные очаги лёгочной деструкции, билатеральное поражение сердца, множественные, крупные и высокоподвижные МВ, видовой состав микрофлоры (золотистый стафилококк, грибы, грамотрицательная бактерии, кишечная палочка), быстрое (в течение 2-3-х недель) разрушение клапанов сердца.

Успешное лечение ИЭ невозможно без своевременной операции, которую необходимо выполнять в ранние сроки или по завершении 4-6-ти недельного курса АБТ. Хирургическое лечение заключается в удалении поражённого клапана и имплантации искусственного. Количество больных, нуждающихся в оперативном лечении, зависит от своевременной диагностики, эффективности АБТ, осложнений, вида возбудителя. При стрептококковом ИЭ протезирование клапанов сердца выполняется у 17% больных, при стафилококковом - у 51,7-70%.

Показаниями к хирургическому лечению ИЭ являются: прогрессирующая СН (60-81%), высокая активность инфекционного процесса, некупируемая АБТ (10-19%); грибковый эндокардит (75-86%), ИЭ протеза клапана (11-26%), множественные ТЭО или высокий риск рецидивов эмболий (3,4-14%), быстрое разрушение АК (88-91%).
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Treatment

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