Gram-negative bacteria (GNB) mediated infections are a major burden in developing countries, with Klebsiella pneumoniae, Escherichia coli, Enterobacter cloacae and nonfermentable bacteria (Acinetobacter baumannii and Pseudomonas aeruginosa) being the major clinical opportunistic pathogens. Multiple antibiotic resistance in these bacteria can have serious clinical and socioeconomic consequences, as it often causes hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), bloodstream infections (BSI), urinary tract infection (UTI) and complex intraperitoneal infections [14, 15].

In our study, the incidence of NI after cardiac surgery was 20.1%, and the incidence of MDRO infection was 8.6%. The high morbidity of MDR bacteria infection after cardiac surgery, and multiple bacterial co-infection occurred in more than half of patients. Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa were the most common, and clinical specimens showed more co-infection of the above isolates. Enterobacter cloacae, Escherichia coli and Serratia clay were relatively rare. A study of VAP caused by MDR bacteria after adult surgery showed that Acinetobacter baumannii infection accounted for up to 40% and Klebsiella pneumoniae 16.7% [16]. A single-centre retrospective study of a hospital in Guangzhou showed that GNB were the most common pathogens of hospital-acquired infections in the centre, with Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae being the most common [17]. Meanwhile, Acinetobacter baumannii was found to be highly resistant to meropenem (82.7%). Although different clinical studies have revealed that the proportion of MDRO infection varies in different regions, hospitals and wards, the total burden of MDRO infection is similar. The situation of bacterial drug resistance was very severe, and the emergence and prevalence of MDR, extensively drug-resistant (XDR) and even pandrug-resistant (PDR) bacteria brings great challenges to clinical anti-infection treatment. Clinicians, especially cardiac surgeons, need to be on high alert.

A previous study of MDR bacterial infections from Brazil showed that the target population of MDR bacteria was mainly males and hospitalized patients over 60 years of age (55.1%) [18]. Similarly, in Lorenzoni et al. [19], the incidence was reportedly higher in male and patients over 60 years of age. In this study, the majority of hospitalized patients in the MDRO infection group were male and aged more than 65 years. The common causes requiring cardiac surgery were coronary heart disease, valvular heart disease, and aortic disease, and the majority of patients had coexisting diabetes mellitus and cerebrovascular diseases. These similarities indicate that men are often accompanied by smoking, drinking and other undesirable lifestyles and are prone to cardiovascular and cerebrovascular diseases as they grow older, leading to a decline in immune function, and that MDRO infections are likely to occur after hospitalization and surgical treatment. In this study, the main type of MDRO infection in patients after cardiac surgery were LRTI, among which 26.7% patients progressed to severe pneumonia, sepsis or even septic shock (14.8%) with exacerbation of the disease, which was mainly due to the weakened respiratory defence mechanisms caused by endotracheal intubation during surgical treatment. With a decreased ability to clear airway secretions, 11 patients were complicated with fungal infection, which was considered to be related to the weakened immune function of the patients during the perioperative period and the ease of occurrence of opportunistic pathogen infection caused by the prophylactic application of a large number of broad-spectrum antibiotics. An observational study of 31 patients with candidaemia infection in New York reported a 30-day mortality of 39% and a 90-day mortality of 58%. Additionally, candida often colonizes most parts of the body, such as the skin surface, groin, and armpit, and is prevalent in hospital settings, causing opportunistic fungal infections at appropriate times [20, 21]. The high morbidity and mortality of fungal infection in susceptible populations also need to arouse wide attention from clinicians. Other types of infection including BSI, mediastinal infection, UTI, and skin soft tissue infection were relatively rare in this study. A number of studies have also shown that UTI, LRTI and BSI are common clinical presentations of MDRO infections, which are often associated with patients staying in the ICU for a long time and frequent exposure to invasive operations, including catheter induration, tracheal intubation and deep vein catheterization. Such patients are often complicated with many underlying diseases and immune suppression and are prone to induce MDRO infections. After the occurrence of infection, it is more likely for patients to progress to severe or septic shock [18, 22, 23].

Our study shows that the probability of developing MDRO infections increases with length of in-hospital stay. Other studies have also shown that patients with MDR bacteria have significantly longer post-operative ICU stays and higher hospitalization costs than those infected with non-MDR bacteria [16]. Some studies have confirmed that the duration of CPB is a risk factor for postoperative VAP infection in patients [24]. Due to the particularity and complexity of cardiac surgery, every patient in this study underwent different duration of CPB. No causal relationship between the duration of CPB and the occurrence of MDRO infection was found, but it was found that pre-infection exposure to vancomycin, combined use of antibiotics and the use of glucocorticoids were risk factors for infection with MDR bacteria. The most common combination of antibiotics is cephalosporins, carbapenems combined with beta-lactamase inhibitors and vancomycin. Further analysis of our study found that with the increase of the number of antibiotics used in combination, the risk of inducing MDR bacterial infections also increased, especially the combination of four antibiotics. In this study, no patients who used five or more antibiotics in combination were found. However, from the research results, as the types of antibiotics exposed increased, the risk of MDR infection increased. MDRO infection leads to adverse clinical outcomes and prognosis, mainly characterized by significantly longer hospital stays after infection and total hospital stays, and increased all-cause mortality, which indicates the importance of strengthening perioperative management of high-risk patients and ensuring rational and prudent use of antibiotics for the prevention and treatment of post-cardiac infection. Previous studies have shown that long-term use of high-dose glucocorticoid is associated with infection and other adverse effects, but a recent retrospective cohort study also found that even low-dose glucocorticoid were associated with a statistically significant increased risk of clinical in-patient infection [25, 26]. Therefore, patients undergoing open cardiovascular surgery should avoid long-term use of high doses of glucocorticoid, while the pros and cons of low doses of glucocorticoid should be weighed for patients with an underlying risk of infection. Albumin was involved in immune function, tissue repair after surgery and drug co-transport. Therefore, the level of serum albumin has been shown to be correlated with the improvement or deterioration of clinical symptoms [27]. The existence of hypoalbuminemia not only weakens the immune function of the body and easily induces various infections but also weakens tissue repair function, which significantly affects the prognosis of in-hospital patients. Joseph et al. [28] and Hassoun-Kheir et al. [29] found that longer hospital stay before diagnosis of VAP was a risk factor for MDRO infection, and HAP after cardiac surgery resulted in higher mortality and longer hospital stay. All 409 patients in this study were admitted to the ICU for post-operative observation and simultaneously received tracheal intubation, deep vein catheterization, indwelling urinary catheter and thoracic drainage tube. Combined with previous research results, it was speculated that exposure to the above invasive operations would inevitably increase the chance of post-operative drug-resistant bacterial infection, leading to a high incidence of MDRO infection.

Multivariate regression analysis showed that underwent CABG, secondary operation and linezolid exposure during hospitalization were independent risk factors for MDRO infection. Although valve operation and aorta-related operation have no statistical significance for the occurrence of MDRO infection, considering that CABG was the most frequently performed operation in this research center, accounting for about half of the annual operation volume, and patients underwent CABG often present with severe multi-vessel cardiovascular lesions, with clinical characteristics such as poor cardiac function before surgery, long stay in ICU after surgery, and frequent exposure to invasive operations, leading to a higher risk of MDRO infection. However, compared with CABG, the risk of MDRO infection after valvuloplasty or replacement and aorta-related surgery remains, despite the small number of post-operative infections. Considering the difficulty of cardiac surgery and the greater intraoperative trauma to the body, some patients needed to underwent a second thoracotomy due to post-operative bleeding, which undoubtedly increased the possibility of MDRO infection. This result support surgeons to devote more attention to high-risk patients to reduce the morbidity and mortality of infection and improve the prognosis of in-hospital patients after cardiac surgery through early identification of risk factors for MDRO infection and early intervention. Linezolid is approved in the United States and Europe for the treatment of adults with HAP, community-acquired pneumonia (CAP), and complex bacterial skin and skin structure infections (SSIs) [30]. In our study, pre-infection linezolid exposure was independently associated with the development of MDRO infections. This result takes into account the fact that linezolid is generally only used to treat infections caused by drug-resistant bacteria, especially Gram-positive bacteria such as vancomycin-resistant Enterococcus (VRE) and methicillin-resistant Staphylococcus aureus (MRSA), and its prophylactic, widespread, and irrational use increases the chance of MDRO infection [30].

According to surveillance data from the hospital-based infection prevention and control office, no cluster outbreaks of MDRO infections were detected during the study period. The WHO has clearly highlighted the importance of effective and targeted infection prevention and control (IPC) measures in responding to outbreaks and epidemics of NI with MDR pathogens such as carbapenem-resistant enterobacteriaceae (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant pseudomonas aeruginosa (CRPA) [31]. Previous studies have reported effective interventions including strict contact precautions, active surveillance cultures (i.e. not only passive surveillance of CRE infection), monitoring, audit and feedback of preventive measures, patient isolation or cohorting, hand hygiene, and environmental cleaning [32]. Infection prevention and control office of the research center and infectious disease experts have formulated IPC measures for MDRO infection for patients after cardiac surgery according to the research progress of IPC measures for MDRO infection in ICU in China and the actual situation of the research center [33]. Specifically, it includes hand hygiene, contact prevention, patient isolation, active monitoring, environmental monitoring, environmental cleaning and disinfection, clinical application management of antibiotics and multidisciplinary collaborative management mode, regularly carrying out MDRO supervision and inspection of various departments, giving feedback and guidance to problems found, and simultaneously carrying out special treatment of NI in 2022. The annual report has made some achievements, and the detection rate of MDR bacteria has decreased significantly, but there is still a long way to go to control the spread and prevalence of MDR pathogens, and more efforts are needed in the future.

This study also has some limitations. First, This study is a single-center retrospective observational study. The findings are not conclusive and future studies involving multi-centers are warranted to verify our results and provide more robust data. Second, this study found that the short-term in-hospital outcomes of MDRO infection was poor, but there is a lack of analysis of the impact of MDRO infection on the long-term prognosis, and more cases need to be analyzed and explained.

In conclusion, this study highlighted the high morbidity and mortality of MDRO infection after adult patients with cardiac surgery and the major challenges facing clinical anti-infection treatment and evaluated the risk factors for MDRO infection. These data provide an important clinical reference for cardiac surgeons to strengthen the management of perioperative patients and enable early identification of high-risk patients of MDRO infection and early intervention. In the future, multi-disciplinary efforts are still needed to strengthen the implementation of IPC measures to curb the spread of MDRO, and achieve the purpose of reducing the morbidity and mortality of NI and improving the prognosis of in-hospital patients.