Role of risk factors in the development of nosocomial infections after cardiac surgery: a review

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INTRODUCTION

Nosocomial infections (NIs) are a global public health challenge, accounting for more than 140,000 deaths worldwide each year [1]. According to the World Health Organization (WHO), NIs affect approximately 15% of all hospitalized patients and are a frequent cause of mortality in both developed (7%) and developing (10%) countries [2]. These infections prolong hospital stay, contribute to the development of disability, and increase the economic burden on healthcare systems. The etiological agents of NIs include bacteria, viruses, and fungi. These agents may enter the patient’s body via exogenous routes (the hospital environment, healthcare personnel, other patients) or endogenous sources (pre-existing infectious foci within the patient). Multidrug resistance (MDR) of microorganisms substantially complicates the treatment of NIs and leads to prolonged courses of therapy.

The impact of NIs on outcomes after cardiac surgery remains controversial. According to the results of a multicenter study conducted in the Netherlands between 2015 and 2019, NIs did not have a significant effect on long-term outcomes in patients undergoing cardiothoracic surgery. Although NIs were associated with an increased risk of adverse outcomes and complications in the early postoperative period, propensity-adjusted analysis did not demonstrate a significant association with recovery or quality of life one year after surgery (p = 0.077). Control of risk factors and adequate preoperative preparation were shown to reduce the incidence of NIs following cardiac surgical procedures [3]. Other studies indicate that the risk of NIs after cardiac surgery ranges from 3% to 8.2% within 30–60 days, with associated mortality increasing 10–17-fold and overall, in-hospital mortality rising from 5.7% to 15.4% (p < 0.001) [1].

The prediction, prevention, and treatment of NIs following cardiac surgery are of considerable scientific interest, as their prevalence reaches 5%–7% of all patients undergoing such procedures. In cardiac surgery patients older than 60 years, the risk of infection from exogenous sources ranges from 5.9% to 20% [4]. Data regarding the risk of endogenous infection in this patient population are inconsistent and require further investigation [5]. Many studies have focused on identifying risk factors for NIs in cardiac surgery patients. A PubMed search using the query risk factor AND infection AND cardio surgery yields more than 7000 publications, nearly 2500 of which have been published within the past five years.

This review provides a comparative analysis and synthesis of published data between 2020 and 2025 addressing risk factors for NIs in cardiac surgery patients during the postoperative period.

DATA SEARCH METHODOLOGY

A scientific data search was conducted using publicly available databases, including PubMed, Embase.com, ResearchGate, eLibrary, and Google Scholar, covering the period from 2020 to 2025. The following keywords were used: факторы риска / risk factors, кардиохирургическое вмешательство / cardiac surgery, инфекционное осложнение / infectious complication, внутрибольничная инфекция / nosocomial infection, инфекции, связанные с оказанием медицинской помощи / healthcare-associated infections. Additionally, the search query risk factors AND cardiac surgery AND nosocomial infection NOT COVID-19 was applied to exclude studies related to COVID-19. Publications focusing on highly specific pathological conditions (e.g., poisoning, acute liver failure, pruritus, systemic diseases) were intentionally excluded, as these topics require separate consideration. Sources published in Russian and English that contained information on preoperative and perioperative risk factors for the development of NIs were considered. The analysis included clinical guidelines, review articles, case reports, retrospective and prospective studies, as well as publications reporting data on the incidence, etiology, and risk factors of NIs in patients after cardiac surgical procedures. The initial search identified 154 articles published between 2020 and 2025. After abstract screening, the following publications were excluded: studies on sepsis (20 articles); infectious and inflammatory complications in pediatric patients (18 articles); infectious complications in thoracic surgery (15 articles); articles focused on the epidemiology and microbiological characteristics of NIs pathogens from an infectious disease or microbiological perspective (33 articles); and articles addressing infections of implanted intracardiac devices in the late postoperative period (18 articles), as these publications either required separate consideration or did not meet the criteria for NIs (Fig. 1).

 

Fig. 1. Scientific data search algorithm for the analytical review. NIs, nosocomial infections.

 

DEFINITION AND CLASSIFICATION OF HOSPITAL-ACQUIRED INFECTIONS

According to para. 3395 of SanPiN 3.3686–21 Sanitary and Epidemiological Requirements for the Prevention of Infectious Diseases, NIs are defined as any infectious diseases (conditions) that develop in a healthcare facility in the absence of such conditions before seeking medical assistance, including during the incubation period, and manifest either during the hospital stay or after discharge within the incubation period. This definition also includes infectious diseases (conditions) developing in healthcare workers as a result of occupational exposure during their professional duties [6].

In the review, we focused on NIs occurring exclusively in patients of cardiac surgery departments during the postoperative period. According to the classification of the European Center for Disease Prevention and Control (ECDC), NIs include the following entities: bloodstream infections (BSI), sepsis, pneumonia, ventilator-associated pneumonia (VAP), which some authors consider a specific subtype of hospital-acquired pneumonia, and surgical site infections (SSI). In the Russian Federation, the most commonly distinguished infectious complications after cardiac surgery include SSIs, hospital-acquired pneumonia, urinary tract infections (UTIs), and sepsis [7, 8]. Infective endocarditis is a distinct nosological entity and a severe complication with high mortality, for example, after implantation of mechanical or biological heart valves. This condition requires separate consideration. BSIs are most often associated with the placement of central arterial and venous catheters. In Russian clinical practice, the term bacteremia is commonly used, although it is not synonymous with bloodstream infection. Some clinicians interpret the presence of pathogens in the blood as sepsis; however, BSI itself does not meet the criteria for either the quick Sequential Organ Failure Assessment (qSOFA) or the Systemic Inflammatory Response Syndrome (SIRS) [9]. According to published data, the incidence of NIs in cardiac surgery patients depends on sex, age, individual patient characteristics, and other factors, including the technical capabilities and experience of cardiac surgeons and anesthesiologists, duration of mechanical ventilation, length of preoperative hospital stay, and duration of postoperative intensive care unit stay [7]. In most studies included in this review, the odds ratio (probability) of developing an infectious complication after cardiac surgery was calculated based on retrospective analysis of medical records.

Reported results vary considerably across countries. For example, a retrospective cohort study conducted in Saudi Arabia in 2023 involving 364 patients who underwent cardiac surgery reported an overall NIs rate of 32.7%. Preoperatively, most patients exhibited cardiovascular risk factors, including diabetes mellitus (67%), arterial hypertension (63%), dyslipidemia (40%), smoking (22%), heart failure (11%), and chronic obstructive pulmonary disease (COPD) (1.6%) [10]. In the postoperative period, the incidence of hospital-acquired pneumonia was 6.6%, BSIs 1.4%, SSIs 20.7%, and UTIs 3.3%. Multivariate analysis demonstrated a significant association between postoperative infections and arterial hypertension, diabetes mellitus, prolonged preoperative activated partial thromboplastin time, and elevated glycated hemoglobin levels.

In contrast, a study conducted by Spanish investigators reported a twofold lower incidence of NIs, which developed in 124 of 800 patients (15.5%). Care settings had little influence on infection rates: NIs were identified in 54.8% of patients in the intensive care unit and in 40.3% of patients in general wards after intensive care unit. The most common infections were pneumonia, SSIs, and BSIs. Mortality attributable to infectious complications was 1.1% among all study participants and 13.7% among patients with NIs [4].

According to data from U.S. researchers, risk factors for SSIs include age, metabolic disorders, immunodeficiency of various etiologies, and chronic foci of infection. Perioperative risk factors include inappropriate antibiotic prophylaxis, breaches in aseptic and antiseptic technique, prolonged surgical duration (especially exceeding standard protocols), significant blood loss, transfusion of red blood cell concentrates and large volumes of plasma substitutes, the number and duration of surgical drains, prolonged mechanical ventilation, and associated tissue hypoxia [11].

Nevertheless, most investigators emphasize that assessment of NI risk should also take into account serum total protein and glucose levels, as well as the duration of preoperative hospitalization [10, 11]. Preoperative measures capable of reducing NI rates include hygienic showering, hair removal, and antiseptic preparation of the surgical field. Perioperative factors associated with a reduced risk of NIs include the use of sterile surgical attire and disposable equipment, together with strict control of environmental disinfection and instrument sterilization. Most preventive strategies are based on standard protocols for preoperative patient preparation, surgical site management, and adherence to sanitary and epidemiological regulations.

According to the scientific data, risk factors for SSIs, pneumonia, UTIs, and BSIs differ, and these will be discussed in detail below.

RISK FACTORS FOR THE DEVELOPMENT OF SURGICAL SITE INFECTIONS

SSIs include infections of the sternal wound and infections at the venous catheter insertion site. Sternal wound infections are classified as superficial and deep, the latter encompassing mediastinitis. The diagnosis of mediastinitis requires the detection of microorganisms in mediastinal tissues or fluids, or intraoperative identification of infection in the sternal wound in combination with characteristic clinical signs, including chest pain, fever, and purulent mediastinal discharge. Hospital mortality among patients with deep sternal infections is significantly higher than among patients without SSIs (6.9% vs. 2.8%, respectively; p = 0.0002) [11].

Despite the predominance of postoperative wounds with a low degree of contamination and the widespread use of antimicrobial prophylaxis (cephalosporins, β-lactam antibiotics, glycopeptides), the incidence of SSIs in cardiac surgery centers ranges from 0.9% to 20% [12]. According to 2022 data from the U.S., SSIs were diagnosed in 1.7% of cardiac surgery patients, with 67.3% of complications manifesting after hospital discharge [13]. In the Russian Federation, the mean incidence of SSIs is 1.84% (0%–4.5%) [8].

In a retrospective study of 1992 cardiac surgery patients, the impact of preoperative and perioperative risk factors for SSIs was evaluated. The investigators compared the prevalence of risk factors in patients with and without infectious complications. In the group with SSIs, the following risk factors were significantly more frequent: male sex (82.50% vs. 70.95% in patients without infection), obesity (43.3% vs. 30.3%), COPD (24.7% vs. 13.3%), use of bilateral internal mammary arteries during surgery (29.9% vs. 17.3%), and a crossed configuration of bilateral internal mammary artery grafting (55.2% vs. 34.1%). Male sex and COPD nearly doubled the risk of SSIs, whereas obesity increased the risk by 1.76-fold. Use of a single internal mammary artery increased the likelihood of complications by 1.67-fold, whereas bilateral use increased it by 3.27-fold. Each additional risk factor increased the risk of infectious complications by 1.31-fold [14]. Other significant risk factors include impairments of immune defense, particularly marked suppression of humoral and cell-mediated immunity. Timely SSIs risk assessment, early diagnosis, appropriately selected antibiotic therapy, aggressive surgical wound debridement, and the use of regional muscle flaps substantially improve treatment outcomes in patients with SSIs [12, 13].

RISK FACTORS FOR THE DEVELOPMENT OF HOSPITAL-ACQUIRED PNEUMONIA

Hospital-acquired pneumonia in cardiac surgery patients is reported with an incidence of up to 10% [15]. According to other studies, the incidence of this complication is 9.96%, with pneumonia developing in 87% of cases during the first postoperative week, on average on postoperative day 4 (2–5 days). Overall incidence rates range from 7% to 26%, whereas reported mortality varies from 20% to 70% [16]. Mortality among patients who develop pneumonia is remarkably higher than among patients undergoing cardiac surgery of comparable type and complexity without pneumonia (25.66% vs. 0.65%, respectively) [15]. In general surgical practice, the incidence of hospital-acquired pneumonia ranges from 5% to 40%, depending on clinical settings and diagnostic criteria [17].

VAP develops ≥48 hours after initiation of mechanical ventilation and represents a frequent complication in critically ill patients following tracheal intubation [18]. The risk of VAP increases with prolonged mechanical ventilation and extended stays in the intensive care unit (ICU), and it correlates with the likelihood of developing pneumonia and pleural empyema. The estimated mortality attributable to VAP is approximately 10%, with higher mortality observed among patients in surgical ICUs and those with moderate disease severity at admission [18]. Patients with postoperative pneumonia require longer ICU and hospital stays, and their mortality is markedly higher (25.66% vs. 0.65%). Multivariate analysis identified 13 independent risk factors for hospital-acquired pneumonia in cardiac surgery patients: age >60 years; hypertension; diabetes mellitus; smoking; COPD; body mass index (BMI) ≥24 kg/m²; renal insufficiency; previous cardiac surgery; chronic heart failure (CHF) class III–IV according to the New York Heart Association (NYHA) classification; preoperative anemia; hypoalbuminemia; and cardiopulmonary bypass duration >120 minutes [16].

VAP is an independent risk factor for increased mortality among hospitalized patients. The main mechanisms underlying postoperative acute lung injury following cardiac surgery include inflammatory responses, activation of the complement system, and ischemia–reperfusion lung injury [16]. Various humoral factors interact with leukocytes and platelets, leading to increased pulmonary vascular permeability and impaired postoperative lung function. Prolonged ICU stays exacerbate lung injury, resulting in longer durations of mechanical ventilation, reduced oxygenation indices, and an increased risk of pneumonia. Additional risk factors for VAP include heart failure, prolonged pulmonary congestion, hyperemia and edema of the bronchial mucosa, and reduced resistance to pathogens. Mechanical ventilation lasting more than 48 hours (p < 0.001) and reintubation (p = 0.009) significantly increase the risk of pneumonia. Furthermore, in cardiac surgery patients who received transfusions exceeding 800 mL of blood, the risk of pneumonia was also increased [16].

A meta-analysis including 5323 cases of postoperative pneumonia reported that blood products were administered in 83% of cases (4401 patients), and the mean duration of mechanical ventilation was 105 minutes (78–142 minutes). Study participants had diverse medical histories and comorbidities: 16% (876 patients) were classified as NYHA class III–IV; 29% (1548 patients) were smokers, and 22% (1174 patients) reported alcohol consumption. Previous cardiac surgery was noted in 7% (376 patients). Hypertension was present in 30% (1604 patients), diabetes mellitus in 8% (438 patients), COPD in 10% (557 patients), pulmonary hypertension in 26% (1390 patients), and renal insufficiency in 10% (524 patients). Rhythm disturbances manifesting as atrial fibrillation were present in 17% of patients (912 patients). Statistical analysis identified considerable independent risk factors for pneumonia, including congestive heart failure, preoperative pulmonary hypertension, elevated preoperative blood glucose levels, intraoperative red blood cell transfusion, and surgical re-exploration of the chest in the ICU [16].

NIs are frequently observed in patients receiving extracorporeal membrane oxygenation (ECMO) [17], including VAP (57.6%), BSIs (9.1%), and SSIs (9.1%) [18]. Due to the high incidence of complications, ECMO is considered a substantial risk factor for the development of VAP.

RISK FACTORS FOR THE DEVELOPMENT OF URINARY TRACT INFECTIONS

The use of urinary catheters and instrumental interventions involving the urinary tract in cardiac surgery frequently leads to UTIs [19]. The incidence of UTIs reaches up to 11 cases per 1000 patients [20]. Bladder catheterization inevitably causes epithelial injury, thereby increasing the risk of UTI development. When catheterization exceeds 48 hours, the likelihood of complications in cardiac surgery patients increases significantly (p < 0.0001). Chronic kidney disease (CKD) stage 3 or higher also increases the risk of UTIs (p < 0.0001). Female patients have a higher probability of urinary tract infection than male patients (p < 0.0001). An additional risk factor is hospitalization of cardiac surgery patients within the preceding 3 months (p = 0.0016). The presence of type 2 diabetes mellitus (T2DM) increases the risk of UTIs by 2.5-fold (p = 0.006), whereas overweight status doubles the risk (p = 0.02) [21]. T2DM is considered a modifiable risk factor for UTIs in surgical patients [22]. The association between BMI and T2DM, mediated by diabetic nephropathy and impaired renal filtration, contributes to the development of renal insufficiency. In addition, diabetic bladder neuropathy reduces the urge to void, leading to urinary stasis and glucosuria, which in turn creates a favorable environment for microbial growth and further increases the risk of UTIs [23].

RISK FACTORS FOR THE DEVELOPMENT OF BLOODSTREAM INFECTIONS

Bloodstream infections (BSIs) occur in approximately 15% of patients with NIs and in about 1% of all hospitalized patients. BSIs are defined by positive blood cultures in patients presenting with systemic signs of infection [24]. BSIs may be secondary, with an identifiable source of infection, or primary, when no definite source is established [25]. In infection surveillance, primary BSIs are classified as microbiologically confirmed infections, in contrast to sepsis, which is diagnosed based on clinical and laboratory criteria and may occur without identification of a causative pathogen. According to the current definition, sepsis is a dysregulated host immune response to infection leading to life-threatening acute organ dysfunction [26]. Thus, BSI may serve as an early indicator of subsequent sepsis development.

Approximately 30% of primary BSIs in cardiac and thoracic surgery patients are associated with the use of venous and arterial catheters (catheter-associated bloodstream infections, CABSI). These infections contribute to both local and systemic NIs [26]. The presence and number of intravascular catheters are considered independent risk factors that markedly increase the likelihood of NI by interacting with existing predisposing conditions. According to published data, microbial colonization occurs in approximately 24% of catheter placements [27].

BSIs account for approximately 2.6%–3.4% of all NIs, ranking fourth in prevalence, with an overall mortality rate of 33.3% [28]. Patients at increased risk of postoperative bacteremia include those with immunosuppression and nutritional deficiencies. Infectious complications in cardiac surgery patients with implanted devices (device-associated infections) are widely described in the scientific data and require separate analysis.

In 27.6% of BSI cases among cardiac surgery patients, a chronic infectious focus was identified, whereas in 16.4% of cases the infection developed as a result of CABSI. In 56% of cases, the source of infection could not be established. The incidence of bloodstream infection caused by Staphylococcus aureus in patients undergoing cardiac surgery was 0.57%, which is higher than that observed after orthopedic, neurological, and plastic surgical procedures [28]. Infection rates vary depending on the type of surgery: 2.6% after correction of congenital heart defects, 5.5% after valve replacement, 13.6% after coronary artery bypass grafting, and 16.8% after surgery for aortic aneurysm and dissection [22].

MAJOR PATHOGENS OF HOSPITAL-ACQUIRED INFECTIONS IN CARDIAC SURGERY PATIENTS

Postoperative NIs may be of monomicrobial or polymicrobial origin, with the latter accounting for more than 27% of cases [29]. Data on the etiology of NIs vary considerably, which is likely attributable to regional differences, the level of technical equipment of cardiac surgery centers, and adherence to methodological recommendations aimed at reducing the risk of NIs.

In a single-center study conducted at a cardiac surgery hospital in Saudi Arabia, Gram-negative bacteria were isolated in 42.4% of all NI cases, Gram-positive bacteria in 29%, and fungi in 28% [29]. In a multicenter study by Pérez-Granda et al. [4], which included 14 hospitals in Spain, a total of 193 pathogens were identified: Gram-negative bacilli (54.4%), Gram-positive cocci (30%), viruses (4.6%), and fungi (1.5%) [4]. Among Gram-negative bacteria, the most frequently isolated pathogens were Acinetobacter baumannii (8.8%), Pseudomonas aeruginosa (8.0%), Escherichia coli (5.6%), and Klebsiella pneumoniae (4.8%). Gram-positive cocci were predominantly represented by staphylococci. S. epidermidis was more commonly associated with surgical site infections, whereas S. aureus caused infections of the respiratory tract and surgical sites with approximately equal frequency [4]. Fungi of the genus Candida spp. were identified in two cases of catheter-associated infection, whereas Aspergillus spp. were detected in one case of invasive aspergillosis, reflecting postoperative immunosuppression. According to data from investigators in Shandong Province, China [28], Gram-negative bacteria were isolated in 78.36% of cases. Most frequently identified were Gram-negative A. baumannii (37.31%) and K. pneumoniae (14.18%). Gram-positive bacteria accounted for 14.93% of isolates, with S. epidermidis (6.72%), Enterococcus faecium (4.48%), and S. aureus (2.24%) being the most prevalent.

According to a review by [22], Gram-negative bacteria and S. aureus are considered the main causes of fatal outcomes in cardiac surgery patients with NIs, each being independently associated with 30-day mortality. In contrast, coagulase-negative staphylococci, despite their frequent isolation, were not associated with patient mortality. In a retrospective study conducted by Italian researchers [30], Pseudomonas spp. were the predominant pathogens, and isolation of P. aeruginosa was associated with a significantly increased mortality from NIs (p = 0.005) [30].

Patient prognosis deteriorates significantly in the presence of antimicrobial resistance among causative pathogens. An analysis of the prevalence of MDR among pathogens causing VAP in heart transplant recipients demonstrated MDR bacteria in 55.7% of cases (34 of 61) [31].

A multivariable logistic regression analysis of cardiac surgery procedures identified the following independent risk factors: preoperative creatinine clearance ≥86.6 mL/min; intraoperative cardiopulmonary bypass duration >150 minutes; postoperative acute kidney injury; and enteral (transnasal) tube feeding. Gram-negative bacteria predominated as causative agents (90.0%; n = 54), with antibiotic-resistant A. baumannii being the most frequently isolated pathogen (40.0%; n = 24) [32].

Persistence or carriage of opportunistic microorganisms substantially increases the risk of NIs, and the presence of multidrug-resistant strains within the gastrointestinal tract microbiome is also considered an independent risk factor. Key contributors to an increased risk of NI include S. aureus carriage, colonic dysbiosis [5], impairment of the mucosal barrier function, and replacement of the patient’s normal microbiota by hospital-acquired resistant strains.

Multidrug resistance reduces the effectiveness of standard perioperative antimicrobial prophylaxis and increases the likelihood of postoperative NIs. It is assumed that the high incidence of Gram-negative bacterial pneumonia in hospitalized patients is associated with factors facilitating the translocation of these microorganisms from the nasopharynx into the lower respiratory tract, as well as with hematogenous and lymphogenous dissemination. Although aerobic Gram-negative bacteria are rarely detected or are present in low quantities in pharyngeal cultures of healthy individuals, colonization markedly increases in patients with acidosis, alcoholism, azotemia, coma, diabetes mellitus, hypotension, leukocytosis, leukopenia, pulmonary diseases, and in those receiving antimicrobial therapy [33]. Analysis of antimicrobial resistance patterns plays a critical role in the multifactorial assessment of NI etiology and is essential for further prevention and treatment of these infections. According to a 2022 study by Stepin [34], the predominant pathogens in SSIs were staphylococci (19.5%). Among these, coagulase-negative staphylococci were the most frequent, identified in 15.9% of cases. Antimicrobial resistance was identified in 34% of all positive cultures. Methicillin-resistant S. epidermidis (MRSE) remained susceptible to ceftaroline, daptomycin, vancomycin, linezolid, and tigecycline. Extended-spectrum β-lactamase–producing organisms included E. coli and E. cloacae, which retained susceptibility to imipenem, tigecycline, ceftazidime/avibactam, and cefepime. The most common causative agents of postoperative pneumonia were A. baumannii and K. pneumoniae, followed by S. aureus and P. aeruginosa. A substantial number of fungal pathogens were also identified. Polymicrobial pneumonia (lung infection caused by two or more pathogens) developed in 34.34% of patients [34].

Antibiotic-associated diarrhea and intestinal dysfunction in cardiac surgery patients are often underestimated despite the high prevalence of this condition. Intestinal involvement with the development of intestinal failure, impaired absorptive function, and motility disorders worsens the patient’s clinical status, prolongs hospitalization, and increases the risk of systemic NI. Although diarrhea is not usually classified as a postoperative infectious complication, Clostridioides difficile–associated diarrhea (CDAD), which frequently develops during antibiotic therapy in cardiac surgery patients, may follow a severe course, including colitis with fatal outcomes [35]. The incidence and severity of nosocomial CDAD continue to increase worldwide. Identified risk factors include advanced age, female sex, use of broad-spectrum antibiotics, prolonged proton pump inhibitor therapy, chronic comorbid conditions, immunosuppressive states, and extended hospitalization. Patients undergoing surgical procedures have additional CDAD risk related to catheter use and intraoperative global hypoxia. Patients undergoing cardiac surgery, who had CDAD, were significantly older than those in the control group (mean age 73 vs. 67 years; p = 0.005). In addition, these patients more frequently received proton pump inhibitors, statins, β-blockers, and acetylsalicylic acid preoperatively (p = 0.008, p = 0.012, p = 0.004, and p = 0.001, respectively). Furthermore, a history of atherosclerosis, coronary artery disease, and malignant neoplasms was associated with CDAD development (p = 0.012, p = 0.036, and p = 0.05, respectively) [35]. No differences were identified between the study groups regarding the type or duration of surgical procedures, aortic cross-clamp time, cardiopulmonary bypass duration, postoperative drainage volume, or blood product transfusion. CDAD recurrence was more frequently observed in patients with overweight, elevated postoperative glucose levels, increased C-reactive protein concentrations during the first CDAD episode, and in those with a history of coronary artery disease or diabetes mellitus (p = 0.005, p = 0.030, p = 0.009, p = 0.049, and p = 0.025, respectively) [35].

It has been established that NIs in cardiac surgery patients may result from endogenous infection caused by microbial translocation from the intestine or chronic infectious foci. Endogenous infection complicates the course of noninfectious pulmonary complications in cardiac surgery [36, 37]. In SSIs, S. aureus (30%) and coagulase-negative Staphylococcus spp. demonstrate the greatest potential. Other Gram-positive pathogens, including streptococci and enterococci, account for approximately 10% of the etiologic distribution on average. Enterococcus spp. exhibit multidrug resistance to antimicrobial agents, notably complicating the treatment of deep enterococcal SSIs. Aerobic bacteria of the Enterobacteriaceae family: Escherichia coli, Klebsiella spp., Proteus spp, and anaerobes (Bacteroides spp., Peptostreptococcus spp.) are most frequently isolated from purulent wound specimens. Non-fermenting Gram-negative bacteria, including P. aeruginosa and A. baumannii, cause severe infections with a tendency toward systemic inflammatory response and sepsis [38]. Virtually all of the listed pathogens are components of the intestinal microbiome, indirectly supporting the endogenous origin of NIs. The presence of MDR microorganisms in the colon is considered an independent risk factor for surgical site infection (risk ratio [RR] 3.95; 95% confidence interval [CI] 2.79–5.60).

Methicillin-resistant S. aureus (MRSA) and MRSE strains have a high epidemic potential and are associated with severe, difficult-to-treat BSIs and VAP. In 48% of cases of SSI caused by MDR microorganisms (predominantly carbapenem-resistant Enterobacterales), concordance between pathogens isolated from rectal screening cultures and clinical specimens was identified. Multivariable logistic regression analysis demonstrated that the presence of MDR microorganisms in rectal swabs was an independent risk factor for the development of acute intestinal infections (RR, 3.95; 95% CI, 2.79–5.60). Other independent risk factors included female sex, chronic dialysis, diabetes mellitus, a history of previous cardiac surgery, prior myocardial infarction, overweight/obesity, and prolonged intubation. Intestinal colonization with MDR microorganisms was more frequently observed in patients with SSIs (69.6% vs. 33.3%; p < 0.001). Approximately half of SSIs were caused by Gram-negative bacteria (52.7%; n = 97). More than one quarter of SSI cases were attributable to MDR microorganisms (27.1%), including extended-spectrum β-lactamase–producing Enterobacterales (8.7%; n = 16) and carbapenem-resistant Enterobacterales (14.1%; n = 26) [38]. In immunocompromised patients, who are more susceptible to infectious complications, persistence of opportunistic bacteria in the respiratory tract is considered a significant risk factor for BSI. In 28 of 97 patients (35%) with Stenotrophomonas maltophilia infection, the respiratory tract was identified as the source of bacteremia. Central venous catheters were used in 75% of patients, and catheter replacement was required in 23 patients within five days after detection of S. maltophilia bacteremia [39]. Antimicrobial susceptibility testing identified 71 S. maltophilia isolates, of which 9 (11.3%) were resistant to trimethoprim–sulfamethoxazole. Thirty-day mortality was 33.8%. Non-survivors differed significantly from survivors with respect to central venous catheter use (p = 0.020), mechanical ventilation (p = 0.006), urinary catheterization (p = 0.021), hypoalbuminemia (p = 0.026), and thrombocytopenia (p = 0.039). S. maltophilia bacteremia was independently associated with mortality in patients with hypoalbuminemia, whereas replacement of the central venous catheter was associated with reduced mortality [39]. Prolonged postoperative antibiotic use not only fails to reduce the risk of nosocomial infections but also increases toxicity, promotes bacterial superinfection, and contributes to the development of antimicrobial resistance [40].

Fungal pathogens of the genus Candida represent a considerable cause of healthcare-associated bloodstream infections. In a case–control study, predictors of candidemia following open-heart surgery were evaluated. Among patients who developed candidemia at a median of 23 days after surgery (14–36 days), multivariable analysis identified the following independent predictors: CHF class III or IV according to the NYHA classification (p < 0.001), prior exposure to carbapenems (p = 0.001), and fluoroquinolone therapy (p = 0.007). The overall 30-day mortality attributable to candidemia was 53% (39 of 74 cases). No association was identified between the duration of cardiopulmonary bypass and the development of candidemia [41]. The incidence of candidemia in this patient population was 0.2%. C. albicans accounted for 65% of cases. C. parapsilosis and C. glabrata were isolated in 14% and 9% of cases, respectively [41].

Thus, when assessing the risk of NI in an individual cardiac surgery patient, several key criteria should be considered:

• Patient microbiological status, including:
  
  • persistence of opportunistic bacterial and fungal microorganisms;
  • presence of chronic infectious foci;
  • transient dysbiosis;
  • presence of a stable intestinal pathobiome;
• Patient immune status, including:
  
  • primary or secondary immunodeficiency;
  • pharmacological immunosuppression;
• Medical history and perioperative factors associated with an increased risk of NI.

ROLE OF ANAMNESTIC RISK FACTORS

Preoperative risk factors have a substantial impact on the severity of NIs in patients undergoing cardiac surgery, notably increasing the length of hospital stay and mortality rates during the first two months after surgery.

In addition to the primary cardiac condition requiring surgical intervention, cardiac surgery patients commonly present with concomitant cardiovascular diseases, including rhythm and conduction disorders, as well as ischemic heart disease. In some cases, these conditions are combined with gastrointestinal conditions and metabolic disorders. According to a study by Pérez-Granda et al. (2024), the most frequent underlying comorbidity identified in 24.9% of patients was T2DM. The next most frequent conditions were CHF (22.6%), prior ischemic heart disease (13.5%), and COPD (13.1%) [4].

When assessing the risk of postoperative NIs, clinicians often underestimate the importance of anamnestic factors. Meanwhile, the proportion of cardiac surgery patients with multiple comorbid conditions continues to increase. This trend is largely attributable to population aging, the growing prevalence of insulin resistance, and the high incidence of post-COVID complications affecting the cardiovascular and respiratory systems. In addition, the proportion of patients with malignant hypertension accompanied by target-organ damage, multifocal atherosclerosis, cerebrovascular disease, and renal failure is increasing [5].

The combination of cardiac condition with bronchopulmonary diseases, as well as baseline respiratory system status, represents an important prognostic determinant of both early and long-term postoperative outcomes. Risk factors associated with an increased likelihood of NI include preoperative therapy with corticosteroids, immunosuppressive agents, antibiotics, and antineoplastic drugs [42], as well as the presence of type 2 diabetes mellitus [15] and postoperative hyperglycemia with glucose levels exceeding 10.1 mmol/L within the first 48 hours after surgery [33]. Smoking is associated with a higher risk of postoperative complications, including respiratory failure, infectious processes, and the need for intensive care unit admission [43].

In international emergency surgery practice, postoperative mortality risk assessment may incorporate up to 22 anamnestic parameters with varying degrees of influence. These include patient age at the time of surgery, sex, body weight, height, body mass index, total leukocyte count, absolute neutrophil and platelet counts, hemoglobin concentration, C-reactive protein level, procalcitonin, albumin, ALT, AST, blood glucose concentration, and other laboratory indicators [44].

In most of the cited studies, the authors do not analyze the frequency of combinations of multiple risk factors. Analysis of the available statistically processed data indicates that patients in the studied cohorts usually have more than three risk factors in their medical history. It can therefore be assumed that the combination of pre-existing and perioperative factors contributes to the development of NIs not in an additive manner but to a substantially greater extent.

The use of artificial intelligence (AI) enables the prediction of the risk of infectious complications after surgical procedures. For example, Zhang et al. developed a machine-learning–based algorithm to predict the risk of infections and complications in patients undergoing mitral valve surgery. The authors analyzed 91 demographic and perioperative parameters and identified key variables, including age, body weight, length of hospital stay, erythrocyte, platelet, and leukocyte counts, volume of infused fluids, volume of intraoperative autologous blood, NYHA class of CHF, preoperative serum creatinine, left ventricular ejection fraction, prothrombin time, total blood loss, aortic cross-clamp time, postoperative leukocyte count, and serum AST and ALT levels. Based on these data, predictive models for postoperative infection after mitral valve surgery were developed and demonstrated good accuracy (AUC > 0.79) [45]. Recently published reviews [46, 47] describe the application of machine-learning approaches in the management of patients with high cardiovascular risk. AI-based models have shown promise in integrating imaging data, such as coronary computed tomography angiography and cardiac magnetic resonance imaging, to identify early signs of subclinical atherosclerosis and plaque stability, thereby providing more accurate predictions of future cardiovascular events. In addition, incorporation of genetic information through AI models allows for identification of polygenic risk scores that may stratify individuals with a high genetic predisposition to cardiovascular disease [46]. Biomarker profiles, including levels of inflammatory markers and cardiac-specific proteins such as troponins, may also be integrated to enhance the predictive performance of machine-learning–based cardiovascular risk models. Over time, this approach may transform the management of cardiac surgery patients by enabling personalized strategies for the prevention and treatment of various conditions, NIs. However, at present, the use of AI both in Russia and worldwide is limited by regulatory frameworks and unresolved technical challenges; therefore, AI systems are applied only as clinical decision support tools.

The development of new AI-based approaches requires evidence of their effectiveness and safety, which may improve early diagnosis, risk stratification accuracy, and timely detection of NIs in cardiac surgery patients. To date, there is no conclusive evidence that investments in AI have increased the effectiveness or safety of treatment. It is possible that future methods will optimize and personalize preoperative preparation, postoperative management, and early rehabilitation of patients undergoing cardiac surgery. Nevertheless, the final decision regarding patient management will always remain with the physician, who bears responsibility for the patient’s life and health.

CONCLUSION

The scientific data analysis confirms the significance of risk factors that are predominantly present in patients prior to surgery. Available evidence indicates that the accumulation of clinically relevant risk factors in cardiac surgery patients markedly increases the likelihood of developing NIs in the postoperative period.

After cardiac surgery, clinicians tend to focus more on cardiac complications than on other disorders. At the same time, the risk of NIs may be underestimated until their clinical manifestations become life-threatening, leading to prolonged hospitalization, deterioration of patient condition, and poorer outcomes. This underscores the need to develop an effective tool for risk assessment and prognostication of NIs in cardiac surgery patients, as well as for subsequent monitoring of high-risk individuals. Such a tool would enable clinicians to make evidence-based decisions regarding the choice of antimicrobial agent, its dosage, and duration of therapy. Based on the data reviewed, the most significant risk factors for the development of nosocomial infections after cardiac surgery include age over 60 years, BMI greater than 24 kg/m², smoking, hypertension, diabetes mellitus, COPD, CHF of NYHA class III–IV, peripheral vascular disease, and a history of previous cardiac surgery.

Upon hospital admission, the likelihood of developing NIs may be influenced by pronounced preoperative hypoalbuminemia, anemia, low hematocrit, and elevated serum creatinine. Intraoperatively, the risk of NIs is associated with cardiopulmonary bypass duration exceeding 120 minutes, intraoperative blood loss greater than 2000 mL, and infusion of large volumes of blood substitutes, packed red blood cells, and donor blood.

Further studies are required to clarify the role of endogenous sources of infection in the development of NIs, including baseline gut microbiome status, bacterial colonization, and the presence of chronic infectious foci, particularly in patients colonized with opportunistic pathogens exhibiting multidrug resistance on mucosal surfaces.

ADDITIONAL INFORMATION

Author contributions: T.I. Khomyakova: writing—original draft; Yu.N. Khomyakov: writing—review & editing; E.A. Ponomarenko: methodology; V.A. Mkhitarov: resources; L.V. Ozeretskaya: writing—review & editing. All the authors approved the version of the manuscript to be published and agreed to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Acknowledgments: The authors express their gratitude to Prof. O.V. Makarova, Dr. Sci. (Medicine), Head of the Laboratory of Inflammation Immunomorphology at the A.P. Avtsyn Research Institute of Human Morphology, for her scientific guidance and valuable comments.

Ethics approval: Not applicable.

Funding sources: This work was part of state assignment FURG-2023-038, Search for Novel Biomarkers to Predict Individual Risk of Multiple Organ Dysfunction in Cardiac Surgery Patients.

Disclosure of interests: The authors have no relationships, activities, or interests for the last three years related to for-profit or not-for-profit third parties whose interests may be affected by the content of the article.

Statement of originality: No previously published material (text or images) was used in this work.

Data availability statement: The editorial policy regarding data sharing does not apply to this work.

Generative AI: No generative artificial intelligence technologies were used to prepare this article.

Provenance and peer review: This paper was submitted unsolicited and reviewed following the standard procedure. The peer review process involved two members of the editorial board.

About the authors

Tatiana I. Khomyakova

Russian Scientific Center of Surgery named after academician B.V. Petrovsky; Synergy University

Author for correspondence.
Email: tatkhom@yandex.ru
ORCID iD: 0000-0003-3451-1952
SPIN-code: 5059-1414

MD, Cand Sci. (Medicine)

Russian Federation, 3 Tsyurupa st, Moscow, 117418; Moscow

Yuri N. Khomyakov

Synergy University

Email: khomyakovyuri@yandex.ru
ORCID iD: 0000-0003-0540-252X
SPIN-code: 2405-6712

MD, Dr. Sci. (Biology), Cand Sci. (Medicine)

Russian Federation, Moscow

Vladimir A. Mkhitarov

Russian Scientific Center of Surgery named after academician B.V. Petrovsky

Email: mkhitarov@mail.ru
ORCID iD: 0000-0002-4427-1991
SPIN-code: 3998-2748

Cand. Sci. (Biology)

Russian Federation, 3 Tsyurupa st, Moscow, 117418

Elena A. Ponomarenko

Russian Scientific Center of Surgery named after academician B.V. Petrovsky

Email: ponomarenkoea75@mail.ru
ORCID iD: 0000-0002-9672-7145
SPIN-code: 7193-7254

MD, Cand Sci. (Medicine)

Russian Federation, 3 Tsyurupa st, Moscow, 117418

Liubov V. Ozeretskaya

Russian Scientific Center of Surgery named after academician B.V. Petrovsky

Email: lozloz.o@yandex.ru
ORCID iD: 0009-0007-8646-3952
SPIN-code: 6376-3060
Russian Federation, 3 Tsyurupa st, Moscow, 117418

References

Supplementary files