A modern look at the recommendations for antibiotic prophylaxis of infectious endocarditis

Despite the fact that the pathogenesis of all types of infectious endocarditis (IE), including acute and subacute infectious endocarditis (OIE), has been studied in detail, many doctors are unclear the use of antibiotics for the prevention of EI. Very often the fundamentals of primary antibiotic prophylaxis are overlooked, despite the fact that recommendations for its implementation have been developed over the past 45 years. The first of these were proposed in 1955 to prevent rheumatic fever. Then there were many protocols for antibiotic prophylaxis of EI, including well-known European consensus recommendations, medical letters, and finally the guidelines from the American Hospital Association (ANA). The manuals have been constantly revised and improved to make them more suitable for routine use. For example, in these recommendations, the ANA (1997), which is a revised version of 1990, rejected the parenteral route of administration of antibiotics, except for high-risk patients who will undergo treatment or diagnostic procedures on the genitourinary or gastrointestinal tract [1].

The vast majority of infectious endocarditis develops a second time as a result of bacteremia which occurs spontaneously during daily activity (brushing, intestinal motility, etc.). However, any manipulation that violates the integrity of the mucous membranes colonized by microorganisms can lead to bacteremia. Dental procedures, mini-abortions and tonsillectomy, among other routine medical procedures, can cause bacteremia. Thus, antibiotic prophylaxis is mandatory for a number of diagnostic procedures, but unfortunately, many doctors do not understand its importance or have no motivation for its implementation. In 1992, a study was carried out with Israeli dentists, showing that only 58% used an antibiotic prophylaxis acceptable for infectious endocarditis [2]. In addition, only 50% of those who knew which antibiotics to use had to have a correct idea of their appointment regime. About 29% knew which diseases of the cardiovascular system belong to the high-risk category of AE and therefore require prophylaxis (Table 1). At the same time, 64% of doctors were aware of the need for antibiotic prophylaxis for certain dental procedures (Table 2).

Experimental models of infectious endocarditis have provided a clearer picture of the effects of antibiotics. Their main preventive effect has been shown to suppress bacterial growth on valve thrombi, which helps the immune system to perform its protective function. Antimicrobials prescribed within 2 hours of the procedure, along with bacteremia, can successfully prevent the development of an infection. This is also indicated by the fact that the addition of penicillinase to the experiment after the initial infection of the thrombus blocks the prophylactic effect of ampicillin [3]. In the treatment of infectious endocarditis, the appointment of antibiotics makes it possible to sterilize the vegetation in more than 90% of cases with PIE and in 70% with OIE. Nevertheless, in 15 to 25% of patients, in the end, surgical correction of the damaged heart valves is necessary. These figures are significantly higher (70%) with IE in patients with artificial heart valves. In addition, it is necessary to remember the threat of an increased EI caused by antibiotic-resistant and methicillin-resistant S. aureus (MRSA) enterococci. Obviously, it is much easier to prevent the development of an endocardial infection than to cope with the early and late complications of infectious endocarditis.

Awareness of the benefits of antibiotic prophylaxis is extremely important, especially in connection with an increase in the frequency of OIE [4]. With this type of AE, patients who do not have previous heart disease often suffer, therefore they often do not receive antibiotic prophylaxis. Currently, only 15-25% of AE cases occur a second time after invasive procedures. Only 50% of these patients have a history of changes in the heart valves, which could serve as the basis for the appointment of antibiotics for prophylactic purposes. So, if modern recommendations are followed, only 10% of EIs can be avoided.

The agents responsible for infectious endocarditis can vary widely, depending on the type of AE. In general, the most common pathogen is Staphylococcus aureus. In 50% of cases, ART is caused by green streptococci; moreover, they occupy a prominent place among the pathogens IE which arise after manipulations in the oral cavity, the respiratory tract or the esophagus. The drug of choice for prevention in these cases is amoxicillin. It is preferred over phenoxymethylpenicillin, given the better absorption in the stomach and intestines. In accordance with ANA guidelines (1990), the recommended dose of amoxicillin for oral administration was 3 g 1 hour before the invasive procedure and 1.5 g 6 hours after the first dose. Later, the regimen was simplified to a single dose of 2 g of antibiotic 1 hour before handling. Although this dose provides sufficient serum concentration to prevent infection, the extent of absorption of amoxicillin can vary widely among patients. In this regard, it seems appropriate to return to the previous recommendations.

5-10% of the population shows signs of mitral valve prolapse (MVP) - a condition that is sometimes the basis of prophylactic antibiotic administration. Despite the fact that, in general, patients with MVP are not at high risk, IE develops in them 5 to 10 times more often than in the general population. Patients with regurgitated MVP [5] require antibiotic prophylaxis. In 3% of patients with regurgitation and / or thickening of the anterior mitral valve, infectious endocarditis eventually develops.

Intensive care units use various monitoring and therapeutic devices (catheters, endotracheal tubes, catheters for parenteral nutrition), which violate the integrity of natural protective barriers and can lead to blood poisoning. For example, with catheters, bacteremia is observed in 4 to 14% of cases [6], which corresponds to 120,000 cases of hospital bacteremia per year. Central catheters cause 30 to 90% of blood infections in intensive care units. The risk of developing an infection is greatly increased when using these devices for more than 4 consecutive days. Up to 45% of all bacteremia associated with the catheter is seen in patients with artificial heart valves, 15% of whom are infected when bacteria enter the bloodstream.

Since when using clindamycin, pseudomembranous colitis often develops (up to 10% of patients), it is advisable to limit its use for prophylactic purposes. The new macrolides, azithromycin and clarithromycin, are more expensive antibiotics than erythromycin and do not have tolerance benefits in many patients. The advantage of macrolides is the low incidence of severe allergic reactions. This is particularly important in cases where the degree of risk of developing infectious endocarditis is not entirely clear. According to a study, in patients with MVP, intravenous administration of penicillin has shown one case of fatal anaphylactic reaction for 2 to 3 cases of AE avoided [7]. This probably served as the basis for proposing erythromycin as the antibiotic of choice for the prevention of EI in patients with MVP [8].

In patients with artificial heart valves, antimicrobials are taken orally to prevent EI. However, given the disastrous consequences of the development of AE on artificial valves, it is necessary to consider the administration of antibiotics intravenously to obtain more predictable concentrations. As alternative modes, new macrolides and modern fluoroquinolones (for example, levofloxacin and trovafloxacin *) can be used. However, despite their stable absorption in the gastrointestinal tract, their effectiveness in antibiotic prophylaxis remains to be proven.

Typically, invasive vascular procedures (for example, stent replacement) do not require antibiotics. The manipulations or surgical interventions, carried out under the conditions of a good preparation of the skin, do not require the prophylactic prescription of antibiotics. In addition, there is very limited evidence to support the effectiveness of antibiotic prophylaxis in oral surgery. According to one study, the effectiveness of prevention reached 91% [9], while in two other studies the effect was minimal [10] or completely absent [11]. In order to reliably prove the effectiveness of antibiotic prophylaxis, in most cases an extremely large number of patients must be included in the study. Consequently, such work is easier to perform in patients belonging to the high-risk group [12].

It is important to note that none of the prophylactic regimens of antibiotics proposed are active against S. epidermidis, which is one of the main agents responsible for infectious endocarditis in patients with artificial heart valves [13] and which almost always occurs during implantation. valve. Apparently even the AEs that developed a year after the operation are due to the delayed clinical manifestation of the infection, which started in the operating room.

However, special attention should be paid to patients receiving antibiotics to prevent other infections, such as penicillin for the prevention of rheumatic fever. About 15% of green streptococci living in the oral cavity in these patients have intermediate resistance or resistance to penicillin. At the same time, an increase in the dose of penicillin for the prevention of EI during invasive procedures is not necessary. The sensitivity of the microflora in the oral cavity will return to normal 9 to 14 days after the penicillin is canceled, although stopping antibiotic prophylaxis for such a period may be unacceptable to many patients. It should be remembered that penicillin-resistant green streptococcus strains are not much more sensitive to cephalosporins, so clindamycin, erythromycin, or clarithromycin can be used. In addition, given the risk of developing pseudomembranous colitis when using clindamycin, it should not be considered as an antibiotic suitable for antibiotic prophylaxis [14].

The factors inherent in the success of conducting antibiotic prophylaxis are educational programs for patients and increase their compliance. The ineffectiveness of prevention is associated with the lack of necessary knowledge in patients [15]. According to one study, 78% of patients received the necessary instructions, but only 20% of them were able to reproduce this or that information on the characteristics of prevention [16]. These figures indicate that there is a need to broaden non-pharmacological approaches to the prevention of infectious endocarditis. For example, the main way to reduce the incidence of nosocomial bacteremia is to follow the strictest sterility rules during installation and to take care of the intravascular catheters. Compliance with these measures can contribute to a significant reduction in nosocomial infections of the blood circulation and, consequently, nosocomial IE. A certain effect has been observed when using catheters impregnated with various antiseptic substances [17]. A simple rinse of the mouth with an antiseptic before removing the tooth can also significantly reduce the risk of bacteremia.

Given the constant improvement of established standards and the introduction of new preventive measures, constantly updating the guidelines on antibiotic prophylaxis is a difficult task. Therefore, practical experience is often the basis on which decisions are made. The choice of prophylactic antibiotic depends on the patient's characteristics, including the presence of complicated allergic history, kidney function, and age. Each patient must be considered in a global manner, and not only from the point of view of his cardiac pathology. And, despite the presence of new classes of antibiotics that can be used for prevention, in the face of growing resistance, we must first of all limit the use of these very promising drugs to keep them in our arsenal.