Bloodstream infection (BSI) is a severe systemic infectious disease characterized by the invasion of pathogenic microorganisms into the body. These microorganisms circulate in the bloodstream, where they undergo transient, intermittent, or continuous reproduction, releasing toxins and metabolic products that trigger the release of cytokines, ultimately resulting in damage to organs. In severe cases, BSI can lead to shock, multiple organ failure, disseminated intravascular coagulation, and death (Tajima et al., 2021; Fabre et al., 2022). Globally, BSIs account for an estimated 20-30% of sepsis cases and are associated with mortality rates exceeding 40% in critically ill populations, particularly in intensive care units (ICUs) (Fleischmann-Struzek et al., 2020). The rising prevalence of antimicrobial resistance (AMR) has further complicated BSI management, with the World Health Organization declaring AMR one of the top 10 global public health threats, projected to cause 10 million annual deaths by 2050 if unchecked (World Health Organization [WHO], 2021).

The diagnoses of BSIs, infective endocarditis, unexplained infections, catheter-related BSIs, arthritis, and bacterial pneumonia rely on blood culture (Gonzalez et al., 2020) to identify the causative pathogens and provide antibiotic susceptibility profiles. These data are critical for guiding evidence-based antibiotic therapy, especially as multidrug-resistant (MDR) pathogens reduce treatment efficacy and increase healthcare costs (Cheng et al., 2020; Mazi et al., 2021). Recent data reveal alarming global shifts: while gram-negative bacteria historically dominated BSI etiology, gram-positive pathogens such as Staphylococcus aureus, coagulase-negative staphylococci, and enterococci now prevail in many regions (Lan et al., 2021). Concurrently, resistance mechanisms like methicillin resistance in S. aureus (MRSA), vancomycin resistance in enterococci (VRE), and extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae have escalated, driven by antibiotic overuse in clinical and agricultural settings (Antimicrobial Resistance Collaborators, 2022). For instance, MRSA accounts for > 35% of S. aureus BSIs in high-income countries, while carbapenem-resistant Klebsiella pneumoniae infections in ICUs exceed 60% in some endemic regions (Centers for Disease Control and Prevention [CDC], 2023; European Centre for Disease Prevention and Control [ECDC], 2022).

These trends underscore the urgency of region-specific pathogen surveillance and resistance profiling. This study retrospectively analyzed the distribution of pathogens and their antibiotic resistance in blood culture specimens collected from an intensive care unit (ICU) between 2019 and 2022. By correlating our findings with global antimicrobial resistance dynamics, we aim to establish a scientific foundation for optimizing empirical antibiotic therapy, informing stewardship programs, and mitigating resistance escalation in critical care settings.

Blood culture remains the gold standard for diagnosing bloodstream infections (BSIs) due to its accessibility, clinical utility, and ability to guide antibiotic susceptibility testing (Bai et al., 2022). While emerging molecular diagnostics (e.g., PCR-based assays) offer rapid pathogen identification, blood culture remains indispensable for capturing viable pathogens and resistance profiles, particularly in critically ill ICU patients requiring timely targeted therapy (El Haddad et al., 2018). The isolation of clinically-relevant pathogens via blood culture indicates that the defense mechanisms of the host and/or prior clinical interventions were unsuccessful in eradicating the infecting pathogens at the primary infection site. Moreover, the specific types of pathogens identified via blood culture offer important prognostic insights (El Haddad et al., 2018; Wildenthal et al., 2023). When multidrug-resistant organisms are identified in blood cultures, the patient mortality rate is as high as 35% (Abu-Saleh et al., 2018; GBD 2019 Antimicrobial Resistance Collaborators, 2022).

From 2019 to 2022, a total of 1,282 distinct strains were isolated from the positive blood cultures of patients in the ICU at the Second Affiliated Hospital of Xi’an Jiaotong University. gram-positive bacteria (52.0%) slightly outnumbered gram-negative isolates (48.0%), aligning with global ICU trends (Li et al., 2022; Van An et al., 2023). However, the data in this study may be biased due to a lower number of strains in 2021. Among the gram-positive bacteria, coagulase-negative staphylococci were the most common, followed by Enterococcus faecalis and Staphylococcus aureus. MRSA displayed a decreasing resistance to gentamicin, levofloxacin, moxifloxacin, trimethoprim-sulfamethoxazole, and erythromycin from 2019 to 2022. No resistance to vancomycin, linezolid, or rifampicin was observed in Staphylococcus aureus. However, coagulase-negative staphylococci (CoNS) accounted for 28.0% of isolates, raising questions about their clinical significance. While CoNS are frequent blood culture contaminants due to improper skin disinfection (Wang et al., 2023), they may represent true pathogens in immunocompromised patients or those with indwelling devices (Heilmann et al., 2019). In our cohort, standardized blood culture collection were followed, yet persistent CoNS isolation underscores the need for rigorous clinical correlation to distinguish contamination from true infection. The resistance rates of MRCNS to gentamicin, rifampicin, levofloxacin, moxifloxacin, and erythromycin did not change significantly throughout the study period, though the resistance of MRCNS to trimethoprim-sulfamethoxazole increased slightly. MRCNS were not resistant to vancomycin or linezolid; therefore, these are the preferred antibiotics for clinical Staphylococcus infections. The Enterococcus genus constituted 11.0% of the isolated strains in our hospital, with Enterococcus faecium displaying higher resistance rates than Enterococcus faecalis. More specifically, Enterococcus faecium exhibited high resistance to ampicillin, while Enterococcus faecalis was sensitive to ampicillin. The resistance of Enterococcus faecium decreased from 2019 to 2022, while Enterococcus faecalis was slightly resistant to penicillin and erythromycin. Neither Enterococcus faecium nor Enterococcus faecalis displayed resistance to vancomycin, though two Enterococcus faecium strains were resistant to linezolid.

The rising carbapenem resistance in Enterobacterales is alarming. Escherichia coli exhibited a carbapenem resistance increase from 0% (2019) to 2.3% (2022), while Klebsiella pneumoniae maintained resistance rates exceeding 20% throughout the study period. Nevertheless, the overall resistance rates decreased from 2019 to 2022. According to the 2023 CHINET China Bacterial Resistance Surveillance data, Klebsiella pneumoniae had resistance rates of 26.2 and 27.1% to imipenem and meropenem, respectively, which are similar to the national resistance levels (Hu et al., 2022). These trends are likely driven by horizontal gene transfer of blaKPC carbapenemases (Han et al., 2021) and prolonged carbapenem use in critically ill patients. Enterobacter cloacae demonstrated an increase in resistance rates to carbapenem antibiotics from 2019 to 2022. No resistance to tigecycline or polymyxin B was observed among bacteria in Enterobacterales. Therefore, it is imperative to prioritize the identification and management of risk factors associated with carbapenemase-induced nosocomial infections.

Among non-fermenting gram-negative bacteria, Pseudomonas aeruginosa displayed relatively high sensitivity to piperacillin-tazobactam, cefotiam, cefepime, amikacin, and tobramycin. However, its resistance rates to imipenem and meropenem decreased during the study period. Pseudomonas aeruginosa did not display resistance to polymyxin B. In contrast, Acinetobacter baumannii remained sensitive to tigecycline and polymyxin B. However, resistance rates to imipenem and meropenem were high from 2019 to 2022. The rise in carbapenem resistance aligns with global trends (GBD 2019 Antimicrobial Resistance Collaborators, 2022), particularly in A. baumannii (100% resistance in 2022), surpassing national averages reported by CHINET (26od.%) (Hu et al., 2022). It is likely due to various factors, including compromised immunity in patients in the ICU and prolonged use of broad-spectrum antibiotics (Teerawattanapong et al., 2018; Kaye et al., 2023). This phenomenon may also be linked to the production of carbapenemase hydrolytic enzymes, decreased outer membrane permeability or loss of porins, reduced affinity of penicillin-binding proteins, and overexpression of efflux pumps (Abdi et al., 2020; Somily et al., 2022).

The ICU is a high-incidence area of multidrug-resistant organisms and carries a considerable disease burden. Research shows that the six leading pathogens for deaths associated with resistance-related deaths—Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa—were responsible for approximately 929,000 (660,000–1,270,000) deaths ascribed to AMR and 3.57 million (2.62–4.78) deaths associated with AMR in 2019. Due to various factors, the number of detected strains in individual years is relatively small, and some drug resistance rates may be skewed. Clinical implications of resistance patterns demand urgent action. For gram-positive infections, vancomycin and linezolid remain effective against staphylococci and enterococci, though two Enterococcus faecium linezolid-resistant strains highlight emerging threats. For gram-negative infections, carbapenem-sparing regimens (e.g., ceftazidime-avibactam for K. pneumoniae) should be prioritized where susceptibility permits, while polymyxins and tigecycline serve as last-resort options. For critically ill patients in the ICU, who often undergo invasive medical procedures and have multiple underlying conditions and compromised immune function, the detection of CRO in blood specimens is associated with an increased risk of mortality, emphasizing the need for prompt, effective, and precise treatment (Yi and Kim, 2021; Martínez et al., 2023).

Study limitations include its single-center, retrospective design and small annual sample sizes (e.g., 2021), which may skew resistance rates due to stochastic variation. To mitigate this, we aggregated data across the 4-year period to identify overarching trends. Additionally, infection control measures (e.g., enhanced environmental decontamination, antimicrobial stewardship programs) were implemented during the study period, potentially influencing resistance dynamics. Future multicenter studies with larger cohorts are needed to validate these findings.

The pathogens responsible for BSI and their antimicrobial resistance profiles are constantly changing. Timely surveillance of pathogen distribution and resistance trends in blood cultures remain indispensable for guiding empirical antibiotic choices in ICU patients with infections. The resistance patterns reported here offer actionable insights to optimize treatment regimens and inform antimicrobial stewardship efforts in critical care settings.