Analysis of the Distribution and Antibiotic Resistance of Pathogens Causing Infections in Hospitals from 2017 to 2019

Background Antibiotic resistance is a global public health problem, leading to high mortality and treatment costs. To achieve more efficient treatment protocols and better patient recovery, the distribution and drug resistance of pathogens in our hospital were investigated, allowing significant clinical guidance for the use of antimicrobials. Methods In this retrospective study (2017–2019), 3482 positive samples were isolated from 43,981 specimens in 2017; 3750 positive specimens were isolated from 42,923 specimens in 2018; and 3839 positive pathogens were isolated from 46,341 specimens in 2019. These samples were from various parts of the patients, including the respiratory tract, urine, blood, wound secretions, bile, and puncture fluids. The distribution and antibiotic resistance of these isolated pathogens from the whole hospital were analyzed. Results The results from pathogen isolation showed that Escherichia coli (12.8%), Staphylococcus aureus (11%), Klebsiella pneumoniae (10.8%), Pseudomonas aeruginosa (10.7%), and Acinetobacter baumannii (6.4%) represented the five main pathogenic bacteria in our hospital. Pseudomonas aeruginosa (16.2% and 17.5%) occupied the largest proportion in the central intensive care unit (central ICU) and respiratory intensive care unit (RICU), while Acinetobacter baumannii (15.4%) was the most common pathogen in the emergency intensive care unit (EICU). The resistance rate of Escherichia coli to trimethoprim and minocycline was 100%, and the sensitivity rate to ertapenem, furantoin, and amikacin was above 90%. The resistance rate of Pseudomonas aeruginosa to all antibiotics, such as piperacillin and ciprofloxacin, was under 40%. The sensitivity rate of Acinetobacter baumannii to tigecycline and minocycline was less than 30%, and the resistance rate to many drugs such as piperacillin, ceftazidime, and imipenem was above 60%. Extended-spectrum β-lactamases (ESBLs)-producing Klebsiella pneumoniae (ESBLs-KPN) and carbapenem-resistant Klebsiella pneumoniae (CRE-KPN), ESBLs-producing Escherichia coli (ESBLs-ECO) and carbapenem-resistant Escherichia coli (CRE-ECO), multidrug-resistant Acinetobacter baumannii (MDR-AB), multidrug-resistant Pseudomonas aeruginosa (MDR-PAE), and methicillin-resistant Staphylococcus aureus (MRSA) are all important multidrug-resistant bacteria found in our hospital. The resistance rate of ESBLs-producing Enterobacteriaceae to ceftriaxone and amcarcillin-sulbactam was above 95%. CRE Enterobacteriaceae bacteria showed the highest resistance to amcarcillin-sulbactam (97.1%), and the resistance rates of MDR-AB to cefotaxime, cefepime, and aztreonam were 100%. The resistance rates of MDR-PAE to ceftazidime, imipenem, and levofloxacin were 100%, and the sensitivity rate to polymyxin B was above 98%. The resistance rate of MRSA to oxacillin was 100%, and the sensitivity rate to linezolid and vancomycin was 100%. Conclusion The distribution of pathogenic bacteria in different hospital departments and sample sources was markedly different. Therefore, targeted prevention and control of key pathogenic bacteria in different hospital departments is necessary, and understanding both drug resistance and multiple drug resistance of the main pathogenic bacteria may provide guidance for the rational use of antibiotics in the clinic.


Introduction
Due to the complexity and universality of infectious diseases, antibacterial agents have been widely used in clinical practice. Since the application of antibacterial agents in clinical practice, they have saved the lives of countless patients. However, bacterial resistance caused by overuse not only has a negative impact on individual users but also on the social group as a whole. Globally, various institutes and agencies have recognized this serious public health issue.
Antibiotics are a subset of antimicrobial agents that play a key role in the inhibition of essential bacterial functions and are used widely to treat and prevent bacterial infections in humans and other animals [1]. Treatment by antibiotics is one of the main approaches used by modern medicine to combat infectious diseases [2]. Antibiotics have not only saved countless lives but also have played a pivotal role in achieving significant advances in medicine and surgery and have successfully prevented or treated infections that occur in patients [3]. However, antibiotic resistance has emerged because of their overuse and inappropriate prescribing, as well as their extensive use in agriculture [4]. A minimum of 700,000 people die from antimicrobial-resistant infections each year around the world, and drug-resistant infections are expected to kill 10 million people a year within 30 years, greatly exceeding deaths from cancer. It has also been estimated that this resistance problem will be the biggest challenge facing healthcare systems by 2050 [1]. e rapid and sustained spread of antibiotic resistance poses a growing threat to the public, animal, and environmental health worldwide. e abuse of antibiotics in clinical practice, poor public health conditions, and insufficient public awareness are the main causes cited [5].
Multidrug resistance (MDR) relates to bacteria becoming resistant to multiple classes of antibiotics and [6,7] is now classified as follows: multidrug resistance (MDR) that is not susceptible to at least one representative from each of the three categories of selected antimicrobial compound families [7]. Extreme drug resistance (XDR) is not susceptible to at least a single representative of all but very few categories of antimicrobial compounds. Pan-drug resistance (PDR) is not susceptible to any of the tested representatives of all known antimicrobial compound families [7]. Compared with other infections, MDR infections are associated with poorer clinical outcomes, resulting in increased morbidity and mortality rates and higher healthcare costs [8].
ere is concern that the emergence of pan-resistant strains (pathogens resistant to all available antibiotics) will render some infections untreatable. How to effectively slow down the emergence of multidrug-resistant bacteria and block the spread of multidrug-resistant bacteria has attracted extensive attention from the medical community, government, and society.
In this study, the isolation, culture, and identification of pathogenic microorganisms and antimicrobial sensitivity tests were carried out, the detection results for different pathogenic microorganisms were provided, and the changes to and the mechanism of drug resistance were analyzed. is study provides a theoretical basis for exploring the clinical application of antibacterial drugs and further monitoring bacterial resistance and multidrug-resistant bacteria.

Source of Pathogenic Samples.
Pathogen samples, including sputum, mid-section urine, blood, wound secretions, chest and gastric juices, bile, and puncture fluids, were taken from hospitalized patients from 2017 to 2019. To avoid overestimating antibiotic resistance, duplicate strains obtained from the same patient were deleted from the study. e study protocol was approved by the Ethics Committee of our hospital and given that medical records and patient information were anonymously reviewed and collected in this observational study, informed consent was not needed.
In 2018, the total number of microbial culture samples submitted for inspection was 42,923, a slight decrease from last year. e respiratory tract, urine, blood, stool, and female reproductive tract samples ranked in the top five, of which the respiratory tract samples, urine specimens, and blood specimens accounted for 43.93%, 12.35%, and 9.98% of the total, respectively. Stool specimens accounted for 6.73%, and female reproductive tract specimens accounted for 6.12%, a significant increase from last year by 4% and were related to Streptococcus agalactiae screening in obstetrics and gynecology. e total number of microbial culture specimens submitted for inspection in 2019 was 46,341, also representing an increase from last year. e lower respiratory tract, urine, and blood specimens ranked in the top three, accounting for 39.6%, 11.0%, and 8.8% of the total, respectively, and the female reproductive tract specimens accounted for 6.7%, an increase of 6.12% from 2018. e main reason is related to Streptococcus agalactiae screening in the obstetrics and gynecology department, and stool specimens accounted for 6.5% and were related to the decline in the number of intestinal outpatients in recent years.
In addition, instrument drug sensitivity cards and Kirby-Bauer agar diffusion methods were used to define antibiotic resistance. e results were interpreted according to the minimum inhibitory concentration (MIC) interpretive breakpoints recommended by the Clinical and Laboratory

Isolation of Pathogenic Bacteria.
According to the results from the pathogen bacteria isolation from the three hospital departments from 2017 to 2019 (Table 1), the top five pathogenic bacteria in three years were always Escherichia coli (12.8%), Staphylococcus aureus (11%), Klebsiella pneumoniae (10.8%), Pseudomonas aeruginosa (10.7%), and Acinetobacter baumannii (6.4%), which were relatively concentrated, and accounted for 51%, 53.4%, and 50.7% of the total cases each year. e average share of Enterococcus faecalis and Enterococcus faecium was 7.1% within three years.
From 2017 to 2019, the results of pathogenic bacterial isolation in the central intensive care unit (central ICU), respiratory intensive care unit (RICU), and emergency intensive care unit (EICU) were surveyed. Within the three ICU departments, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii were always in the top eight within the three years. In central ICU, Pseudomonas aeruginosa was ranked first over three years and had the highest proportion between 15.4% and 17.3%, followed by Klebsiella pneumoniae (36/13.7%), and both showed an upward trend from  Tables 5-7. From 2017 to 2019, the average proportion of Escherichia coli isolates (61/22.8%) in blood samples was the highest, showing a downward trend. At the same time, Staphylococcus epidermidis (48/18.1%) and Klebsiella pneumoniae (32/12%) occupied the second and third places in each of the three years. e mean proportion of Staphylococcus epidermidis in blood specimens was higher than that seen in urine within the three years, but it was not found in sputum specimens. e composition of blood samples in 2017 and 2019 ranked fourth and Acinetobacter baumannii accounted for about 6.7%, but Staphylococcus hominis ranked fourth in 2018, accounting for 7.5%, Staphylococcus hominis ranked fifth for the three years, accounting for 8.1%, and was unique to blood samples (Table 5).
It was found that Escherichia coli (39.7%), Enterococcus faecium (11.3%), Enterococcus faecalis (9.4%), and Klebsiella pneumoniae (9.1%) ranked in the top four pathogenic bacteria from urine sample isolates. e most predominant pathogen in the urine samples was Escherichia coli accounting for 42.2%, 39.3%, and 37.8% from 2017 to 2019. Within the three years, compared to the blood and sputum samples, Escherichia coli accounted for the highest proportion of the urine samples isolated strains. Enterococcus faecium and Enterococcus faecalis have a higher proportion in urine than in blood samples, and they were not present in samples (Table 6).

Antibiotic Resistance Analysis.
Combining the isolation of the pathogenic bacteria from the three hospital departments from 2017 to 2019 and the distribution of isolated strains from blood, urine and sputum specimens, it can be seen that the bacteria that are susceptible and have a high titer in each specimen were mainly Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and Acinetobacter baumannii and their antibiotic resistance was found to be unchanged. From 2017 to 2019, Escherichia coli was generally resistant to trimethoprim and minocycline, with a resistance rate of up to 100% and with high sensitivity to imipenem, amikacin, ertapenem, and other drugs (Table 8).
e resistance rate of Klebsiella pneumoniae to trimethoprim, cefuroxime, piperacillin, piperacillin-sulbactam, and  Evidence-Based Complementary and Alternative Medicine ampicillin was higher than 90%. However, its resistance to cefoperazone-sulbactam, ertapenem, and amikacin was lower than 40% (Table 9). e resistance of Pseudomonas aeruginosa to most antibiotics such as piperacillin, ciprofloxacin, amikacin, and tobramycin was less than 30%, and resistance to polymyxin B was less than 5%, and even reached a sensitivity of 100% in 2018 and 2019 (Table 10). Acinetobacter baumannii had high sensitivity to tigecycline  Evidence-Based Complementary and Alternative Medicine  and minocycline of less than 30%, and the resistance rate to tigecycline was zero but was greater than 60% resistant to many drugs such as piperacillin, ceftazidime, gentamicin, and imipenem (Table 11). Staphylococcus aureus had the highest resistance rate to penicillin, at more than 80%, and the resistance rate to erythromycin was approximately 60%. However, no strains were resistant to antibiotics such as vancomycin, teicoplanin, tigecycline, and linezolid (Table 12).

Multidrug Resistance Analysis.
Analysis of multiple drug resistance for the main pathogenic bacteria in our hospital in 2017 is shown in Figure 1. In 2017, a total of 1181 multidrugresistant bacterial strains of Enterobacteriaceae were isolated, accounting for the largest proportion of the detected multidrug-resistant strains; of which 491 strains of multidrug-resistant organisms (MDRO) accounted for 41.6%, and no XDR and PDR strains were found (Figure 1(a)). ESBLs-KPN is highly resistant to amoxicillin and ceftriaxone, with resistance rates of 100% and 99.4%, respectively, and the sensitivity to ertapenem, imipenem, and piperacillin/tazobactam was above 95% (Table 13). e resistance rate of CRE-KPN to all drugs was above 50%, among which ampicillin, cefoperazone-sulbactam, ampicillin-sulbactam, ceftazidime, and ceftriaxone were all resistant by 100%. e resistance rates to nitrofurantoin, ciprofloxacin, levofloxacin, aztreonam, and cefepime were all greater than 95% (Table 14) and the resistance rates of ESBLs-producing Escherichia coli (ESBLs-ECO) to ampicillin and ceftriaxone were over 99%, and sensitivities to drugs such as amikacin,   (Table 15). A total of 263 strains of Acinetobacter were isolated, including 150 strains of MDRO, accounting for 57%, and no XDR and PDR strains were found (Figure 1(b)). e resistance rate of MDR-Acinetobacter baumannii (MDR-AB) to levofloxacin, moxifloxacin, and ampicillin was up to 100%, and the drug resistance to cotrimoxazole, amikacin, and other drugs was also more than 70% (Table 16). Of the 395 strains of Pseudomonas aeruginosa isolated, 90 strains of MDRO accounted for 22.8%, and 21 strains of XDR accounted for 5.3%. No PDR strain was found (Figure 1(c)). MDR-Pseudomonas aeruginosa (MDR-PAE) showed more than 97% resistance to ciprofloxacin, piperacillin, and amtronam, among which the resistance rate for ceftazidime, imipenem, and levofloxacin     (Figure 1(d)). Methicillin-resistant Staphylococcus aureus (MRSA) was 100% resistant to benzacillin, 60% resistant to erythromycin, 50% resistant to ciprofloxacin, clindamycin, and tetracycline, but 100% sensitive to linezolid and vancomycin (Table 18). In 2018, a total of 1293 strains of multidrug-resistant bacteria such as Enterobacteriaceae were isolated, of which MDRO (574 strains) accounted for 44.4%, while XDR and PDR strains were not found (Figure 2(a)). A total of 270 strains of Acinetobacter were isolated, including 145 strains of MDRO, accounting for 53.7%, and no XDR and PDR strains were found (Figure 2(b)). A total of 406 strains of Pseudomonas aeruginosa were isolated, among which 107 strains of MDRO accounted for 26.4%, while 26 strains of XDR accounted for 6.4%, and no PDR strains were found (Figure 2(c)). A total of 704 strains of Staphylococcus bacteria were isolated, including 300 strains (42.6%) of MDRO, with no XDR and PDR strains being found (Figure 2(d)). e resistance rates of MRSA to benzacillin and penicillin were 100% and 99.2%, respectively. No strains were found to be resistant to linezolid, vancomycin, teicoplanin, and tigecycline (Table 19).
As shown in Figure 3(a), in 2019, a total of 1166 strains of Enterobacteriaceae were isolated, of which 484 strains were isolated by MDR, accounting for 41.5%, and no XDR and PDR strains were found. e high resistance of ESBLsproducing Enterobacteriaceae to ceftriaxone and amcarcillin-sulbactam was observed, both more than 95%. Its drug resistance to cephalosporin, tobramycin, and furantoin was less than 40%, among which the drug resistance rate for tigecycline, imipenem, and amikacin was less than 5% (Table 20). Carbapenem-resistant (CRE) Enterobacteriaceae bacteria showed the highest resistance to amcarcillin-sulbactam (97.1%), and the resistance rate to most drugs ranged from 70% to 90%, but they were sensitive to tigecycline and amikacin (Table 21). A total of 325 strains of Acinetobacter were isolated, of which 213 strains were isolated from MDR, accounting for 65.5%, and no XDR and PDR strains were    Evidence-Based Complementary and Alternative Medicine found (Figure 3(b)). A total of 409 strains of Pseudomonas aeruginosa were isolated, of which 86 strains were isolated by MDR, accounting for 21.0%, and 23 strains were isolated by XDR, accounting for 5.6%, with no PDR strain being found (Figure 3(c)). A total of 768 strains of Staphylococcus were isolated, of which 356 strains were isolated by MDRO, accounting for 46.4%, and no XDR and PDR strains were found (Figure 3(d)). Similar to 2018, MRSA showed 100% resistance to penicillin and benzacillin, and the sensitivity to tetracycline, ciprofloxacin, and other drugs was more than 60%, and no strains resistant to linezolid, vancomycin, and other four drugs were found (Table 22).

e Trend of Isolate Major Multidrug-Resistant Bacteria in
Our Hospital in the Past Four Years. As shown in Figure 4, the isolation rate of MDR-AB, which remained at the top for three years, declined in 2018 but increased again in 2019. ESBLs-ranked second in the three-year average separation rate, while MDR-PAB showed a continuous downward trend, whereas MRSA was the opposite, with a continuous increase being observed and CRE also exhibited a rise.

Discussion
e discovery of antibiotics in the last century is considered one of the most important achievements in the history of medicine, and its use has greatly reduced morbidity and mortality associated with bacterial infections [2]. However, the evolution of new bacterial strains, as well as the excessive use and reckless consumption of antibiotics, has led to the development of antibiotic resistance. Multidrug resistance is a potential threat worldwide and is escalating at an extremely high rate [9]. Poor public health conditions, lack of awareness concerning drug-resistant bacteria among the public, high incidences of disease, ease of access, and their misuse are the major factors exacerbating the problem [5]. In the context of antibiotic resistance, due to the emergence and increased prevalence of multidrug-resistant (MDR) superbugs such as Staphylococcus aureus, Escherichia coli, 266 20      most problematic clinical pathogens, were summarized as "ESKAPE" bugs by Louis Rice [11]. ESKAPEE pathogens have developed resistance mechanisms against most antibiotic treatments, including those that are the last line of defense, such as carbapenems and polymyxins [12].
According to the results of pathogen isolation in three ICU departments in the past three years, the five pathogens mentioned above always ranked among the top eight. e total number of isolates from central ICUs was always higher than that from specialized ICUs, namely RICUs and ICUs. e isolation rates of Pseudomonas aeruginosa, Klebsiella pneumoniae, and Stenotrophomonas maltophilia in the RICUs were the highest among the three ICU wards because they were all closely associated with lower respiratory tract infections [13]. In the last three years, the average proportion of Pseudomonas aeruginosa isolates was 17.5% in RICUs, similar to studies in the United States during the early years that found P. aeruginosa (17.0%) as a relatively common organism isolated in RICU with respiratory infections [14]. In EICUs, Acinetobacter baumannii occupies the highest isolation rate among the three ICU wards, and critically ill patients tend to be more susceptible to infection. Because Acinetobacter baumannii infection is associated with invasive surgery, the reason for hospitalization includes host factors, length of ICU stay, and prior use of broad-spectrum antibiotics [15]. e composition of isolates from different sources from 2017 to 2019 was analyzed, and we found that the isolation rate of Staphylococcus epidermidis was higher in blood samples than in urine samples, but no isolates were found in sputum samples. Staphylococcus hominis isolates were only present in blood samples, and as previously reported, these two bacteria both produce biofilms that allow them to adhere to internal medical devices and are commonly isolated from bloodstream infections [16,17]. Among the three sources, blood, urine, and sputum, Escherichia coli isolates accounted for the highest proportion in urine specimens. Enterococcus faecium and Enterococcus faecalis were distributed at higher levels in urine samples than in blood samples and were absent in sputum samples. As previously reported, the above three bacteria are the main pathogenic bacteria of urinary tract infections [18,19]. e top five frequent isolates from sputum samples are Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Staphylococcus aureus, and Stenotrophomonas maltophilia, and this is similar to previous findings [13].
Measures for the management and clinical application of antibiotics in China are as follows: according to the notice of the Health and Family Planning Commission of the People's Republic of China on further strengthening the management of the clinical application of antibacterial drugs to effectively curb bacterial resistance, medical institutions should carry out monitoring of bacterial resistance, establish bacterial resistance early warning mechanisms, and take the following corresponding measures: (1) If the antimicrobial drug resistance rate of the main target bacteria exceeds 30%, warning information should be reported to the medical staff of the institution in a timely manner; (2) Antibiotics with a resistance rate of more than 40% for the major target bacteria should be used cautiously and empirically; (3) Antibiotics with drug resistance rates of over 50% for the major target bacteria should be selected according to drug sensitivity test results; (4) Clinical application of antibacterial drugs with drug resistance rates exceeding 75% for the main target bacteria should be suspended, and clinical application should be decided according to results based on bacterial resistance.
Regarding antibiotic resistance, Escherichia coli showed low resistance to most third-generation cephalosporins and aminoglycoside antibiotics, the resistance rate is between 30% and 50%, which is similar to the study conducted by Miller et al. [20]. It is highly sensitive to imipenem, nitrofurantoin, piperacillin-tazobactam, and amikacin and is recommended for clinical use. Klebsiella pneumoniae, also belonging to the Enterobacteriaceae family, exhibited low  Figure 4: e trend of separation rate (%) of main multidrugresistant strains in our hospital in recent four years.
resistance to imipenem and cefoperazone-sulbactam. Similar antibiotic resistance rates have been reported by Liu et al. [21]. In 2018-2019, its resistance rate to amikacin, piperacillin-tazobactam, ertapenem, and other antibacterial drugs was less than 20%, indicating a wide range of drug choices that can be used as a good choice for current clinical treatment. Pseudomonas aeruginosa showed low to moderate rates of drug resistance to commonly used antipseudomonal drugs and most antibiotics such as carbapenems, amikacin, cefoperazone-sulbactam, piperacillin-tazobactam, and ceftazidime, were less than 30%, similar to the results of previous studies [22]. us, there are many options for medication. Especially in 2018 and 2019, no strains resistant to polymyxin B were found, and therefore, it is the recommended drug for clinical treatment. e drug resistance of Acinetobacter baumannii is relatively serious, and the resistance rate to most antibiotics is greater than 60%. erefore, carbapenems are not recommended for single Acinetobacter baumannii infections, which can easily increase the risk of multidrug resistance. Acinetobacter baumannii has relatively high sensitivity to cefoperazonesulbactam, which is the first choice for empirical medication in confirmed cases of infection to improve the curative effect. Staphylococcus aureus is resistant to penicillin by more than 85%, so the clinical application for these target bacteria should be suspended. No resistant strains were found to linezolid, vancomycin, teicoranin, and tigecycline. Hence they represent a good choice for empirical treatment. Acinetobacter baumannii, Enterobacteriaceae, and Pseudomonas aeruginosa are the common clinical carbapenem-resistant Gram-negative bacteria. Several drugs that are active against carbapenem-resistant Acinetobacter baumannii have been approved for clinical use or have entered late-stage clinical development, including eravacycline, cefiderocol, and plazomicin [23]. For MDR-AB, carbapenems are not recommended for empirical use, not only because of their high resistance rate, but more importantly, they further increase the risk of multidrug resistance caused by high intensity antimicrobial use. For pan-resistant Acinetobacter baumannii, some clinical departments have chosen tigecycline for treatment, but CLSI (American Institute of Clinical and Laboratory Standards) lacks the criteria for determining the susceptibility of Acinetobacter baumannii to tigecycline, and its efficacy remains to be validated. e detection rate of multidrug-resistant bacteria in the Enterobacteriaceae family was the highest and was mainly concentrated on the detection of ESBLs-ECO, ESBLs-KPN, CRE-KPN, and CRE-ECO. e number of ESBLs-KPN and CRE-KPN isolates ranked first in 2017, followed by MDR-AB, and these results are in agreement with those obtained by Talaat et al. [24], who showed that the most predominant Gram-rods in the hospital were Klebsiella pneumoniae (28.7%) and Acinetobacter sp. (13.7%). ESBLs-producing isolates showed resistance to β-lactam antibiotics, including third-generation cephalosporins; in addition, they often exhibit resistance to other classes of drugs such as aminoglycosides, cotrimoxazole, and fluoroquinolones [25]. Tigecycline and imipenem can be used as empirical drugs for ESBL-producing bacteria. It should be emphasized that ESBLs-ECO and ESBLs-KPN have high drug resistance rates to ceftriaxone and amcarcillin-sulbactam, and the risk of induced drug resistance is also very high. erefore, the drug sensitivity test results should be referred to for selection. e detection rate of CRE bacteria in 2019 was higher than the national average in 2018, and therefore, it is necessary to reduce the overuse of carbapenem antibiotics and prevent the spread of bacteria in hospitals and regions. e resistance rate of CRE bacteria to amcarcillin-sulbactam exceeded 95%, and their clinical use should be suspended. No strains sensitive to tigecycline have been found, and they can be used as clinically recommended drugs, usually in combination with other drugs. Enterobacteriaceae represents a key family of carbapenem-resistant bacteria. Colistin, tigecycline, ceftazidime-avibactam, plazomicin, eravacycline, and cefiderocol can all be used for their clinical treatment [23]. e average separation rate of MDR-PAE ranks third (31.7%), with no major fluctuations in recent years. It is also a common clinical carbapenem-resistant Gram-negative bacterium. Our results showed that MDR-PAE and XDR-PAE occupy 23.4% and 5.8% of the average proportion of Pseudomonas aeruginosa isolates, higher than the results from other studies. In 2015, the European Centers for Disease Prevention and Control stated that MDR-PAE and XDR-PAE isolates accounted for 13.7% and 5.5% [26]. e high prevalence of resistant species in developing countries could be due to noncompliance with infection control regulations and to the lack of or an imperfect antibiotic policy. Studies [26] have shown that multiple antibiotic combinations can be used as a clinical solution for MDR-PAE and XDR-PAE infections. Previous studies [27,28] have reported that combinations of polymyxins with these anti-pseudomonas drugs (such as imipenem, piperacillin, aztreonam, ceftazidime, or ciprofloxacin) are more effective than polymyxins alone against MDR-PAE, providing a reference for the treatment of MDR-PAE infection. Yadav et al. [29] demonstrated substantially enhanced death in vivo against an MDR-PAE clinical isolate with an optimized imipenem-plus-tobramycin combination regimen, which was an alternative to colistin therapy, especially in patients with renal insufficiency. In addition, drugs such as cefiderocol and fosfomycin are potential treatment options in the near future [26]. e available clinical solution for MDR-PAE infections requires a precise diagnostic and combination antibiotic therapy based on diagnostics. Several infections which are recurrent need additional care to stop the proliferation of MDR-PAE contaminating the surrounding environment.

Evidence-Based Complementary and Alternative Medicine 15
MRSA is a virulent and difficult-to-treat "superbug," and our results show that MRSA accounted for 30% to 50% of Staphylococcus aureus infections in hospital settings over the three-year period, which was slightly higher than the 25% to 50% reported in previous studies [30]. As previously reported [31], the infection rates of resistant Staphylococcus, Pseudomonas, Acinetobacter, and Klebsiella vary by country and region, with Asia being higher than North America and Western Europe. is may be due to the apparent wide variations in health care systems, ICU facilities, and policies for infectious disease control in the different geographical regions. Drug resistance, however, is consistent with previous research results, where MRSA is resistant to penicillinlike beta-lactam antibiotics [32], and the resistance to penicillin was observed to be as high as 99.2%, and clinical use of this target bacterium should be suspended. Many drugs remain active against MRSA, including glycopeptides (vancomycin and teicoranin), linezolid, and tigecycline, to which no resistant strains have been found and are, therefore, good choices for empirical treatment. Even some newer lactams, such as ceftazlorin and cefdipropanol, can be used as treatment options for MRSA [33].
With the promotion of rational applications for antibiotics, the isolation spectrum of pathogenic bacteria and the isolation rate of multidrug-resistant strains in our hospital have also changed accordingly, mainly reflected by the fact that although the isolation and drug resistance rates of MDR-AB always ranked first. After 2016, the separation rate of MDR-AB decreased significantly, which is probably due to the implementation of the Guiding Principles of Clinical Use of Antibiotics in 2015. e prevalence of CRE Enterobacteriaceae bacteria has increased in recent years, which is consistent with the national drug resistance monitoring information. e isolation rates of other bacteria did not fluctuate greatly, but the epidemiology of these bacteria still needs to be addressed. e emergence of multidrug-resistant bacteria, or superbugs, poses a serious threat to public health and requires multilevel efforts to prevent them from overcoming antibiotic resistance. Governments must allocate sufficient funds to improve and develop new drug products, monitor the use of antibiotics, and establish strict policies and regulations. In addition, infection control measures must be strictly implemented in hospitals, but management practices must be considered for the use of antibiotics and microbicides and appropriate disposal or discharge of medical waste. Clinicians should avoid prescribing unnecessary and excessive antibiotics to patients with normal infections and advise patients to follow good hygiene practices such as hand washing and appropriate infection control measures. As an individual, we can take antibiotics that are prescribed only by our doctors, take them exactly as prescribed, and use them sensibly. Efforts to address the spread of antibiotic resistance include limiting the overuse of antibiotics in the food and animal sectors.
Nonantibiotic strategies for the treatment of antibioticresistant pathogens have been reported, such as gene editing techniques, immunotherapies, and vaccines, and antivirulence inhibitor bacteriophages [5,10]. Antimicrobial adjuvants, fecal microbiota transplant (FMT), and competitive exclusion of pathogens through genetically modified probiotics and postbiotics are prospective alternative, unconventional strategies [5]. In addition, epidemiological and surveillance studies should be carried out and powerful tools should be used to deepen our understanding of antibiotic resistance and provide a timely and precise diagnosis of antibiotic use and consumption. erefore, a multidisciplinary approach is needed to eliminate the serious threat of multidrug resistance.
However, this study also has some limitations. When analyzing multiple drug resistance, multiple bacteria in the same family and genus were not studied separately. In the future, a specific analysis should be carried out for important multidrug-resistant pathogens.

Conclusion
e distribution of pathogenic bacteria in different hospital departments and sample sources is variable. erefore, targeted prevention and control of key pathogenic bacteria in different hospital departments must be carried out. Understanding the drug resistance and multiple drug resistance of the main pathogenic bacteria can provide guidance for the rational use of antibiotics in clinic.

Data Availability
e data used to support the findings of this study are available from the corresponding author upon request.
Ethical Approval e study protocol was approved by the ethics committee of our hospital.

Conflicts of Interest
e authors declare that there are no conflicts of interest.