Bacterial agents as etiological factors of infective endocarditis

Objective. To analyse bacterial agents as etiological factors of infective endocarditis in patients with mitral valve disease. Materials and methods. The study included 287 patients who underwent mitral valve surgery, 205 men and 82 women. The mean age of the patients in this sample was (50.1 ± 2.9) years, and they had a history of informative endocarditis with mitral valve involvement. All patients underwent surgical treatment – mitral valve repair (experimental group)/prosthetics (control group). The data of primary medical records (medical histories, primary medical records), results of histological and bacteriological studies and instrumental examination were analysed. Results. In 49.1% of patients, the etiological factors of infective endocarditis were bronchopulmonary (16.4%), urological (12.2%), general surgical (6.6%) diseases, and in 20.6% – hospital–acquired infection. In 30.3% of patients, the cause of infective endocarditis was not identified. The most common microflora was identified: Staphylococcus spp. (19.2%); Enterococcus spp. (15.0%); Streptococcus spp. (3.5%). In detailing the identification of the pathogen during the histological examination of intraoperative material, the most common bacterial agents were found to be etiological factors of infective endocarditis. Enterococcus, Staphylococcus and Staphylococcus epidermidis. The most common microflora in the study group: Enterococcus – 15.4%, Staphylococcus – 9.5%, Staphylococcus epidermidis – 9.5% and Staphylococcus aureus – 7.4% in the control group: Enterococcus – 23.2%, Staphylococcus – 10.6%, Staphylococcus epidermidis – 6.7% and Streptococcus – 4.7% (p (cid:116) 0.05). Histological examination of mitral valve vegetations revealed the most common bacterial agents: Staphylococcus aureus (3.6%), Staphylococcus epidermidis (5.1%) and Enterococcus faecalis (10.7%). Histological examination of the mitral valve revealed differences in predisposition factors for the development of infective endocarditis.

Infective endocarditis (IE) is a worldwide occurrence and is defined as an infection of the endocardial surface of a native valve, artificial heart valve, or implantable cardiac device such as a permanent pacemaker or defibrillator [1].
IE occurs due to the development of bacteremia and direct penetration of the pathogen into the heart.Many scientists consider IE to be a specific form of sepsis, as evidenced by its old Latin name, sepsis lenta (prolonged septic endocarditis).According to academicians G. V. Knyshov and V. M. Kovalenko, IE is a disease of septic genesis with predominant damage to the valvular or parietal endocardium, characterised by the rapid development of valvular insufficiency, systemic embolic complications, and immunopathological symptoms caused by pathogenic or opportunistic microflora [2].
The term "valve endocarditis" refers to a heart infection that involves the valve leaflets, endocardial surface, tendon chords, congenital defects and anastomotic sites.Prosthetic valve endocarditis is defined as an infection that affects artificial valves, conduits, catheters, ancillary devices, pacemak-ers, defibrillators, or other artificial intracardiac structures [3].
It is also necessary to note the definition of the term "microbiome" -it is a general term that describes trillions of different bacteria, fungi, parasites and viruses that live on and inside our bodies.The main microbiomes of the human body are the gut, mouth and skin [4].The microbiome plays a key role in the emergence of many complications of IE, including the rate of growth of resistance to antimicrobial agents and the "weapon" of probiotics and postbiotics against the patient, as well as the ability of infecting microbes to cause sterile inflammatory processes, reactions that mimic the original valve infection [4].Today, antibiotic therapy has made great strides, but despite progress in the development of antibiotic classes, it is still not possible to solve the medical problem associated with timely and adequate therapeutic treatment before mitral valve surgery (MVS) and to prevent the development of complications.Therefore, the mortality and complication rates after MV surgery in the setting of IE do not decrease [1].The latter is difficult to diagnose The Ukrainian Journal of Clinical Surgery in time, so the disease often requires concomitant medical and surgical treatment.IE is characterised by high mortality rates, despite important medical and surgical advances over the past decade [5,6].Half of hospitalised patients die from complications of IE [7,8].Early detection of the infectious etiological agent of IE makes it possible to optimise antibiotic treatment of patients.Thus, haemoculture remains the "gold standard" in the diagnosis of IE [1,9].
When the etiological agents involved are difficult to culture, data on the etiology of IE can be obtained by serological tests and by polymerase chain reaction "gene amplification" of infectious agents such as Coxiella burnetii or Bartonella henselae [9].
Antibiotic treatment at the current level gives good results, and there are many regimens depending on the etiology of IE and the type of affected heart valve (natural or prosthetic).In some patients, antibacterial treatment regimens are adjusted due to the impossibility of using a particular antibiotic due to allergic reactions or pathology associated with renal failure.The benefit-risk ratio of surgical interventions is the result of a treatment plan drawn up by a cardiologist, an infectious disease specialist, and a cardiovascular surgeon [9].A multidisciplinary approach is aimed at confirming the diagnosis and developing optimised diagnostic and therapeutic algorithms [10].Early diagnosis of IE, as well as the establishment of the correct treatment based on an interdisciplinary approach, increase the chances of a favourable development of the disease for almost all categories of patients with IE.This proves the relevance of further research on bacterial agents as etiological factors of IE and determines its purpose.
The aim of the study was to analyse bacterial agents as etiological factors of IE in patients with MC lesions.

Materials and methods
The study included 287 patients with MC lesions in the setting of IE: 205 men and 82 women aged 17 to 76 years.The average age of patients was (50.1 ± 2.9) years.
Participants of the study underwent surgical interventions for the lesions of the MC in the setting of surgical treatment of IE at the Amosov National Institute of Cardiovascular Surgery of the National Academy of Medical Sciences of Ukraine.
Depending on the surgical intervention performed on the MC, the patients were divided into two groups: the experimental group -137 patients who underwent organpreserving surgery on the MC -its plasticity, and the control group -150 patients who underwent MC prosthetics.
The material for the study and analysis was the data from the primary medical records (medical histories, primary medical records), the results of bacteriological and histological examinations and instrumental examinations provided for by the standards of inpatient care.
The study was conducted in compliance with the principles of bioethics, and the materials used in the study may be published.All patients who participated in the study signed an informed voluntary consent.
Statistical analysis was performed using the 2 test with the Yates correction.Statistically significant differences between the study groups were determined at a significance level of <0.05.
Patients underwent a bacteriological examination to identify the causative agent of IE in the preoperative period (see Figure ).
The analysis of the spectrum of bacterial agents as pathogens of IE showed that the most commonly detected in patients was the growth of Staphylococcus spp.
The next step in our study was to detail the secondary microbiological criterion, at the first stage of which the pathogen was identified by bacteriological examination of intraoperative patient material and the following distribution of bacterial agents was established: Staphylococcus spp. was detected in 34 (11.8%)patients, Streptococcus spp. in 4 (1.4%),Enterococcus spp. in 29 (10.1%), and micrococci in 2 (0.7%).
The second stage of detailing the secondary microbiological criterion was the identification of the pathogen in the histological examination of the intraoperative material: fungal microflora was detected in 28 (9.8%) patients.
For a thorough analysis of the data obtained on the origin of bacterial agents as etiological factors of IE, the distribution of their frequency in the study groups was studied depend-Ідентифікація бактеріальних агентів до виконання оперативного втручання на МК.

The Ukrainian Journal of Clinical Surgery
ing on the type of surgical intervention on the MC (Table 1).
According to Table 1, it is obvious that in half of the patients of each group, no pathogen was detected, while in the remaining patients, gram-positive microflora prevailed.In the group of patients who underwent MC prosthetics (experimental), there was no fungal microflora and mixed forms of microorganisms.Among the patients who underwent MC prosthetics (control group), fungi were detected in 1 patient, and mixed forms of microorganisms -in 1 patient.
For an in-depth study of the bacterial agents that were the primary cause of IE, they were analysed according to the bacteriological examination of the intraoperative material of each patient (Table 2).
As a result of this analysis, the three most common bacterial agents as etiological factors of IE were identified, namely: Enterococcus, Staphylococcus and Staphylococcus epidermidis.Regarding the differences between the study groups identified during the analysis of the microflora of intraoperative material, it was found that the most common microflora in the study group were Enterococcus (15,4%), Staphylococcus (9.5%), Staphylococcus epidermidis (9.5%) and Staphylococ-cus aureus (7.4%), and in the control group -Enterococcus (23.2%),Staphylococcus (10.6%),Staphylococcus epidermidis (6.7%) and Streptococcus (4.7%).Statistical analysis of the data showed that the established frequency of infectious agents was not characterised by statistical significance (p 0.05).
To determine the microflora found directly on the affected MC, the next step in our study was to analyse the presence of MC vegetations and the microflora present on them, as detected by histological examination (Table 3).
The data in Table 3 show that all the studied patients had MK vegetations, and their frequency in both groups was similar (p 0.05), and massive vegetations with a threat of detachment prevailed in both groups (p 0.05).
To clarify the characteristics of infectious agents in the study groups, we analysed the data of histological examination of the MC vegetations (Table 4).
This analysis showed that the most common bacterial agents had similar frequency rates in both study groups, which did not differ statistically significantly (p 0.05).The most common bacterial agents identified during the histological examination of intraoperative material -MC vege-UJCS.2024 May/June; 91(3) The Ukrainian Journal of Clinical Surgery tations were Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecalis.
We also performed an additional histological examination of the MC itself for the presence of fungal mycelium (Table 5).Fungal mycelium was identified in 13.9% of patients in the study group and 11.3% of patients in the control group (p 0.05).
Also, the histological examination of MCs revealed the etiological basis for the development of IE (Table 6).As a result of histological examination of intraoperative material -MC, the most common predisposing factors for the development of IE were identified, namely: primary IE, congenital heart disease and degenerative changes in MC.Some peculiarities in these predisposition factors for the development of IE between the studied groups were also found.It was found that primary IE of MV was statistically significantly more common in the group of patients who underwent MV repair -56.2%than in the group of patients after MV prosthetics -38.7% (p = 0.004, 2 = 8.15).There was also a tendency to a statistically significant difference (p = 0.07) between the incidence of The Ukrainian Journal of Clinical Surgery congenital heart disease as a factor of predisposition to the development of IE -this indicator was significantly higher in the control group.

Discussion
As a result of the scientific search, the causes of IE were identified.Thus, in 49.1% of the sample patients, the etiological factors were bronchopulmonary (16.4%), urological (12.2%), general surgical (6.6%) diseases, in 6.3% of patients injection drug addiction was noted, in 3.5% -COVID-19, in 2.4%cooling, in 1.7% -dental problems.In 20.6% of patients, a hospital-acquired infection was detected, and in 30.3% of patients, the cause of the infection was not identified.
As a result of studying bacterial agents as causes of IE, it was found that the most common was Staphylococcus spp.19.0%, the second place was taken by Enterococcus spp.15.0%, the third -Streptococcus spp.3.5%, in 1.4% of patients the growth of gram-negative microorganisms was observed, in 0.8% of patients micrococci were detected, and in 60.3% of patients the pathogen was not identified.In detailing the identification of the pathogen by histological examination of the intraoperative material, it was determined that in almost half of the patients the pathogen was not identified, in the rest the gram-positive microflora prevailed, in patients who underwent MC plastic surgery, there was no fungal microflora and mixed forms of microorganisms, and after MC prosthetics they were found only rarely.The data obtained coincide with and complement the findings of studies by foreign authors on the detection and identification of infectious agents and predisposing factors for the development of UI [1,4,9].
The bacteriological examination of intraoperative material revealed the most common bacterial agents as etiological factors of IE: Enterococcus, Staphylococcus and Staphylococcus epidermidis.Differences in the frequency of bacterial microflora between the study groups were found.Thus, in the experimental group, the most common microflora were Enterococcus -15.4%, Staphylococcus -9.5%, Staphylococcus epidermidis -9,5% and Staphylococcus aureus -7.4%, and in the control group it was Enterococcus -23.2%, Staphylococcus -10.6%, Staphylococcus epidermidis -6.7% and Streptococcus -4.7% (p 0.05).The frequency of bacterial agents found during the histological examination of intraoperative material -MC vegetations was determined: Staphylococcus aureus -3.7%, Staphylococcus epidermidis -5.2% and Enterococcus faecalis -10.7%.The obtained rates of bacterial agents as the primary cause of UI coincide with the results published in leading professional journals [4].
As a result of histological examination of intraoperative material -MV, it was found that primary IE of MV was statistically significantly more common in patients who underwent MV repair -56.2% than in patients after MV prosthetics -38.7% (p = 0.004, 2 = 8.15).There was also a tendency for a statistically significant (p = 0.07) difference between the incidence of internal heart disease: this rate was significantly higher in the control group (28.0%) than in the study group (18.2%).

Conclusions
1.As a result of studying bacterial agents as etiological factors in the development of UTI, the most common patho- The Ukrainian Journal of Clinical Surgery gens were identified: Staphylococcus spp.19.0%, Enterococcus spp.15.0%, Streptococcus spp.3.5%.
2. The predominance of gram-positive microflora was determined by histological examination of the intraoperative material.In patients who underwent MC arthroplasty, there was no fungal microflora and mixed forms of microorganisms, and after MC prosthetics they were found only rarely.
4. It was found that primary IE of MC was statistically significantly more common in the study group (56.2%) than in the control group (38.7%) (p = 0.004, 2 = 8.15).
Funding.This study is a fragment of the applied research work "Development of tactics and strategy for the treatment of COVID-19 complications in cardiac surgery patients with acquired heart disease" (years of implementation -2022 -2024, state registration number 0121U111834).
Authors' contribution.Soltani S.E.-collection and processing of material, writing the text, preparation of the article for publication; Krikunov O.A. -concept, conclusions.
Conflict of interest.The authors who participated in this study have declared that they have no conflicts of interest regarding this manuscript.
Consent for publication.All authors have read and approved the final version of the manuscript.All authors have agreed to the publication of this manuscript.