In the present study, we synthesized data from the CARSS and BRICS surveillance systems to depict the epidemiology and resistance profile of S. maltophilia in China. The analysis included data on 514,768 S. maltophilia strains collected from 2014 to 2021. The overall prevalence rate of S. maltophilia among all bacterial pathogens, including both Gram-negative and Gram-positive bacteria, was 2.1%, which is comparable to other countries [21, 22]. However, it is noteworthy that the prevalence rates were higher in certain departments, such as intensive care units, including specific care units, the respiratory department, and the hematology department. Such high prevalence aligns with findings from other studies [8, 23,24,25,26]. Since S. maltophilia is an opportunistic pathogen, it often colonizes medical devices, indwelling catheters, and respiratory epithelial cells [23]. Moreover, patients in these departments are typically at high risk of S. maltophilia infections [27, 28]. Given these two facilitators, it is unsurprising to observe the high prevalence of S. maltophilia in these departments. However, in the present study, apart from blood culture isolates which could provide reliable pathogenic evidence, the high recovery rates from other specimen types should be interpreted cautiously as they may not necessarily represent the actual burden of S. maltophilia infections [29]. Therefore, future epidemiological studies should focus on accurately measuring the true infection burden of this pathogen in infectious syndromes beyond bloodstream infections to provide a more precise understanding of its clinical impact.

Although colonization does not equate to true infection, the clinical impact of S. maltophilia colonization in certain populations should not be overlooked. In intensive care unit patients, colonization by S. maltophilia is associated with an increased risk of infection [26]. McDaniel et al. have shown that being colonized with S. maltophilia could lead to notable weight loss, immune cell infiltration, and elevated inflammatory responses in the lungs [30]. Furthermore, this colonization could increase the density of Pseudomonas aeruginosa in the lungs, potentially resulting in co-infection of these two problematic pathogens, and in turn leads to increased mortality and longer hospital stays [30]. In patients with cystic fibrosis, S. maltophilia colonization can exacerbate lung function deterioration more significantly than those without colonization [31]. Therefore, it is important to monitor and manage S. maltophilia colonization to mitigate its potential adverse effects on the vulnerable patient populations.

Regarding infection sources, the respiratory system is the primary infection site for S. maltophilia. In our study, the highest prevalence rate of S. maltophilia was observed in bronchoalveolar lavage fluid cultures, aligning with findings from the European Antimicrobial Resistance Surveillance Network (EARS-Net) annual report, which identifies S. maltophilia as a predominant cause of hospital-acquired pneumonia [32]. In contrast, the prevalence of S. maltophilia in bloodstream infections is comparatively low, with an average rate of 0.93% reported in our study. Despite this low prevalence, it remains the most common carbapenem-resistant Gram-negative bacterium causing bloodstream infections in the USA [33]. Moreover, the mortality associated with S. maltophilia in bloodstream infections is strikingly high, particularly among patients with underlying conditions. In China, a retrospective study of 56 patients with acute myeloid leukemia and bloodstream infections from 2019 to 2021 found a 30-day mortality rate of 71.4% for those infected with S. maltophilia [8]. Similarly, a study conducted in South Korea reported a comparable mortality rate, with an overall mortality of 64.5% [33]. Given the high mortality and nosocomial infection nature of S. maltophilia, effective infection prevention and control measures, along with effective therapy regimens, are urgently needed.

The intrinsic resistance of S. maltophilia to various classes of antibiotics, including carbapenems, poses great challenges to clinical treatment. As indicated in our study, the resistance rates to ceftazidime, ticarcillin-clavulanic acid, and chloramphenicol were significantly high, with 46.2%, 25.1%, and 22.1% reported in 2021, severely restricting their clinical use. Similar high resistance rates of these antibiotics have also been reported globally [34, 35]. Therefore, therapies for S. maltophilia infections primarily rely on sulfamethoxazole-trimethoprim, fluoroquinolones, and tetracyclines (tigecycline and minocycline) owing to their comparatively lower resistance rates [15]. However, alarming increases in resistance to these recommended antibiotics have been reported in other countries [34,35,36]. A recent retrospective study of 4466 S. maltophilia strains revealed that resistance rates to levofloxacin reached 27.7% in 2019–2022, while resistance to sulfamethoxazole-trimethoprim increased from 6.2% in 2004–2008 to 20.0% in 2019–2022 [36]. In contrast, our findings demonstrated that the overall resistance rates to these antibiotics remained stable at below 10%, with no significant increasing trends. However, we observed concerningly high resistance rates to levofloxacin and sulfamethoxazole-trimethoprim in specific specimen types, particularly in blood cultures. This highlights the need for cautious consideration when selecting these antibiotics for treating bloodstream infections caused by S. maltophilia.

Two factors may explain this discrepancy. Firstly, the higher resistance rates in other studies might be attributed to the predominance of S. maltophilia isolates originating from intensive care units, where the use of broad-spectrum antibiotics and invasive procedures could facilitate the selection of resistant strains [37]. In contrast, our study included data from the entire country across different provinces, hospitals, and departments, along with a large sample size, therefore providing a more comprehensive analysis. Secondly, the limited availability of these tested antibiotics, coupled with stringent antimicrobial stewardship programs in Chinese hospitals, likely contributes to lower resistance rates in clinical settings [18]. This hypothesis is further supported by a study of S. maltophilia isolates in China between 2005 and 2019 [38]. The study observed increased resistance to sulfamethoxazole-trimethoprim and minocycline from 2005 to 2014, followed by a decreasing trend from 2014 to 2019. This shift coincides with the enhancement of national action plans against antimicrobial resistance in 2012 [39]. Despite geographical variations in the resistance profiles of S. maltophilia, sulfamethoxazole-trimethoprim, tetracyclines (tigecycline and minocycline), and levofloxacin remain the most effective antibiotics against S. maltophilia in vitro on a global scale [34].

In addition to the aforementioned antibiotics, newly marketed antibiotics, like cefiderocol and ceftazidime-avibactam, also present good in vitro activity against S. maltophilia [40, 41]. Several in vitro studies indicate that combining two effective agents would enhance the bactericidal effect on S. maltophilia compared to monotherapy [42, 43]. Moreover, a multicenter observational study involving 307 patients with S. maltophilia pneumonia found that combination therapy was linked to reduced mortality rates among immunocompromised and critically ill patients [44]. Although combination therapy was not associated with reduced mortality in the overall patient cohort, the 2024 Infectious Diseases Society of America (IDSA) guidelines panel still recommends either using at least two active agents or the specific combination of ceftazidime-avibactam and aztreonam for S. maltophilia infections until clinical improvement is achieved, after which monotherapy may be considered [45]. However, given the relatively limited strength of the current evidence, further clinical studies evaluating various treatment regimens for S. maltophilia infections are strongly encouraged. At the current stage, it is better to follow these latest guidelines, even though it is not always the practice in many Chinese hospitals because of local constraints [18].

There are several limitations to this study. First, while we collected data on S. maltophilia strains isolated from various medical institutions across China on a large scale, we could only measure its prevalence among all isolated pathogens. Although blood culture isolates provide reliable pathogenic evidence, the high recovery rates from other specimen types should be interpreted cautiously as they may not necessarily represent the actual burden of S. maltophilia infections. Second, in the present study, we were only able to collect data specific to the pathogen itself, including the time of isolation, the department of isolation, the specimen type, and antimicrobial susceptibility testing results. This limitation restricts us to provide insights into its role in mixed infections, which is a common clinical scenario. Moreover, in the present study, we report only resistance rates rather than exact MIC values, which could provide more detailed information for clinicians. Third, although we have provided comprehensive resistance profiles across different departments, specimen types, hospital levels, and elderly patient populations, other key demographic factors and clinical outcomes were still absent. Fourth, our analysis focused primarily on susceptibility to conventional antibiotics, and information regarding the newly introduced antibiotic cefiderocol was absent. As cefiderocol is widely used in clinical settings globally, incorporating such data in future studies would aid in selecting appropriate regimens for treating S. maltophilia infections. Fifth, data sourced from the CARSS and BRICS surveillance systems may not fully represent the entire spectrum of S. maltophilia infections across all healthcare settings in China. The participating hospitals may have varying levels of resources, patient populations, and infection control practices, which could influence the resistance profiles and prevalence rates observed. However, despite these limitations, this study represents the largest analysis to date reporting the epidemiology and resistance profile of S. maltophilia in China. The insights gained from this research could significantly inform clinical practice, guiding antibiotic stewardship and optimizing treatment strategies for infections caused by this opportunistic pathogen.