Our data show that the main concentration of S. marcescens infections is in ICU (40.98%), which is similar to the results of Bo-Huang17 and Şimşek18; however, our percentage is higher than that in their studies. For sample types of S. marcescens, our study showed that sputum (79.30%) was the dominant sample type, which is consistent with the trend observed by Bo-Huang17; however, the proportion was markedly higher in our study than the latter. Analysis of sputum specimens showed that almost half were colonized (data not shown). In addition, previous studies have confirmed that S. marcescens is easily colonized in the respiratory and urinary tracts in adult patients19,20. The total number of detected strains and the total number of isolated pathogens increased every year. The highest number of detected strains was 175 in 2020, but the total proportion was <1%, which is slightly lower than the results reported by Xiaoli Wang in China21. This finding indicates that the prevalence of S. marcescens in some regions of China is low. To the best of our knowledge, our study is the first to classify detected S. marcescens strains into HA, CA, and colonization bacteria according to infection type, to further analyze the possible patterns and sources. Our results showed that HAI S. marcescens remarkably decreased from 51.2% to 22.3% during the 7 years. CAI S. marcescens infections accounted for approximately 30% infections, while colonization with S. marcescens showed an increasing trend, which may indicate that HAI S. marcescens infections reduced to a certain extent. However, due to the widespread presence of S. marcescens in nature and the hospital environment, more patients acquired S. marcescens from the environment but did not develop a disease. In addition, in immunocompromised, young, and elderly populations, colonization bacteria have considerable invasive power to cause infection22. Therefore, the surveillance and analysis of the trend of an S. marcescens epidemic should be actively performed, along with reasonable interpretation of data. Furthermore, active screening can be conducted for high-risk groups, such as newborns, and prevention and control measures should be taken in advance and at the earliest20.
Our results showed that the detection rate of multidrug-resistant S. marcescens reached 16.89% in 2019. In addition to the innate resistance to tetracycline and polymyxins, the production of β-lactamases, including ESBL and cephalosporin enzyme (AmpC enzyme), are the main reasons for resistance of S. marcescens to β-lactamases23. In this study, piperacillin had the highest drug resistance rate (35.45%) in 2017, which ranged from 17% to 29.06% in other years. However, the drug resistance rate of piperacillin and tazobactam was remarkably lower than that of piperacillin, ranging from 2.95% to 13.13%, which was lower than the results of 19.6%18. As a β-lactamase inhibitor, tazobactam reduced the drug resistance rate of related S. marcescens strains to a certain extent, but the change of the membrane pore protein and active pumping system were mechanisms contributing to a certain degree of resistance to the drugs. For cephalosporin antibacterial drugs, S. marcescens resistance rates, first to cephalosporin and second to cephalosporin, were >99%, closely related to the innate drug resistance24. The drug resistance rate of ceftriaxone of the third-generation cephalosporins (18.8%–37.7%) was higher than that of ceftazidime (3.7%–9.0%), which was similar to that of the fourth generation cephalosporins.
The quinolone antibacterial drugs levofloxacin and ciprofloxacin had an increasing trend in resistance for 7 consecutive years, and the highest resistance rate was approximately 30% in 2017; this is similar to the results by Gonzalez22 but markedly higher than the results by Şimşek18. All samples from the latter study were obtained from blood, indicating that the drug resistance rates of S. marcescens is different from different sample sources. Multiple results12,18 have shown that aminoglycosides such as amikacin had strong antibacterial activity against S. marcescens, which is consistent with the results of our study. No drug-resistant strains were detected in 2019 and 2020. However, previous studies25 suggested that aminoglycoside resistance was high, which may be related to the frequency of the use of aminoglycoside antibacterial drugs. The use of aminoglycoside was limited in recent years and the drug resistance decreased. In addition, the side effects with aminoglycoside use such as ototoxicity and nephrotoxicity affect its application in clinical practice13.
Carbapenems are a class of atypical β-lactam antibacterial drugs that are characterized by strong antibacterial activity and stability to ESBLs and AmpC enzymes. According to a report released by the China Antimicrobial Resistance Surveillance System in 2016, drug resistance rates of Serratia (dominated by S. marmaris, 87.5%) to carbapenems such as meropenem and ertapenem increased from 0.5% and 1.6% in 2005 to 7% and 6.8% in 2014. It ranks first in the growth rate of common antimicrobial drug resistance, and the situation is not optimistic26. In addition, the results of our study showed that the drug resistance rate of S. marmaris to meropenem and imipenem increased considerably after 2017–2018. The drug resistance rate of >10% was similar to the results by Şimşek18 but markedly higher than those by GM Gonzalez, which showed a drug resistance rate of <5%22. Zhang27 showed that the drug resistance rate of S. marcescens to imipenem was as high as 25.6%, which completely demonstrates the severity of carbapenem-resistant S. marcescens in some regions of China. The main mechanism of S. marcescens resistance to carbapenems is the production of carbapenase19,28. Furthermore, S. marcescens is naturally resistant to polymyxin, which makes treatment difficult13. To further explore the trend of carbapenem-resistant S. marcescens, this study classified S. marcescens into three sources, HAI, CAI, and colonization, and compared the drug resistance rates to carbapenem antibiotics. We observed that the drug resistance rate of CAI S. marcescens to carbapenem was remarkably higher than that of HAI and colonization. One possible reason for this could be that patients with CAI may have been referred to our facility from other hospitals. therefore, the patient could have acquired the infection at another hospital. As a regional medical center, it is common for our institution to accept transferred patients; therefore, from the perspective of other hospitals, the patient is likely to have a HAI. In addition, the patient may have used a several antibacterial drugs at the previous medical institution, which may have exacerbated drug resistance. Although the drug resistance rate of S. marcescens is low, it can result in an infection under favorable conditions. In addition, the drug resistance rates of S. marcescens to imipenem and meropenem showed a steep downward trend from 19.23% to 1.74% and 16.22% to 1.71% in 2019 and 2020, respectively. We believe that the strict prevention and control measures due to the COVID-19 pandemic may have played a role in the decreasing rates.
Limitations
Despite the promising findings, our study has some limitations. First, ours was a single-center study; therefore, most research categories were not represented. Second, our study was a traditional epidemiological study, without in-depth analysis of drug resistance of S. marcescens by molecular biological methods. Further in-depth analysis is required to explore this topic in the future.