By making lethal infections readily treatable, antibiotics have led the development of modern medicine. Prompt initiation of appropriate antibiotic therapy to treat infectious diseases reduces morbidity and save lives. Moreover, antibiotics also enables multiple advances in the area of medical technology, such as organ transplants and cancer chemotherapy (Beyar-Katz et al., 2017; Versporten et al., 2018). However, about 30%–50% of all antibiotics prescribed in hospitals are either unnecessary or suboptimal worldwide (Denny et al., 2019; Rowe and Linder, 2019). In recent years, antimicrobial resistance (AMR) has been recognized as a growing public health problem of huge concern to countries around the world (Huemer et al., 2020). Inappropriate antibiotic use contributes greatly to the development of AMR (Bohmer et al., 2021), leading to ineffective therapy, increase in adverse reactions, and escalation in health care costs. In order to optimize antibiotic use in medical care, many different antimicrobial stewardship (AMS) initiatives have been conducted in some developed countries recently. Several studies have shown that AMS can help physicians increase infection cure rates, improve treatment outcomes, and reduce antibiotic resistance by improving antibiotic prescribing (Dellit et al., 2007; Rice, 2018).

According to the Centers for Disease Control and Prevention (CDC) of the United States, core elements of hospital AMS programs are as follows: 1) Hospital leadership commitment. AMS programs should be supported from the senior leadership of the hospital, especially the director of pharmacy. 2) Pharmacy expertise. AMS programs should appoint a physician or pharmacist as the coleader to improve antibiotic use. 3) Accountability. As a leader or coleaders, a physician or pharmacist should be responsible for program management. 4) Interventions. The prospective audit and feedback or preauthorization should be implemented to improve antibiotic use. 5) Education. AMS should educate clinicians, pharmacists, nurses, and patients about adverse reactions caused by antibiotics, AMR, and optimal prescribing (CDC, 2019).

A recent study found that 25% (21%–29%) of antibiotic prescriptions in the United States ambulatory care clinics were inappropriate in 2015 (Ray et al., 2019). The rates of inappropriate prescriptions were highest for otitis externa (67.3%) and upper respiratory tract infection (38.7%) in the United Kingdom general practice between January 2010 and June 2015 (Nowakowska et al., 2019). Due to its huge antibiotic consumption (Zhao et al., 2018), strong economic incentives (Lin et al., 2020), and limited knowledge about antibiotics (Liu et al., 2019) for overprescribing, inappropriate antibiotic use in China is common. The proportion of inappropriate antibiotic prescriptions among outpatients and inpatients was 60.6% and 75.4% in primary health care settings in China from 2009 through 2011, respectively (Wang et al., 2014). A recent survey conducted on the use of antibiotics in 52 hospitals of China reported that the proportion of antibiotic prescription in surgical inpatients in 2016 was 69.03% (Li et al., 2019), which did not meet the goal of not more than 60% set by the National Health Commission of the People’s Republic of China (National Health Commission of China, 2011). This report also showed that the percentage of antibiotic use in inpatients for acute upper respiratory infections and fever or cough symptoms all exceeded 55%, which was unnecessary for these infectious diseases mostly caused by viruses (WHO, 2011).

Thus, to promote rational use of antibiotics, it is necessary to implement AMS programs in hospitals. In 2011, AMS policy was formally implemented by the National Health Authority in medical institutions nationwide. Successful implementation of AMS requires a multidisciplinary organizational approach, with pharmacists as the core members that deliver the interventions to optimize antimicrobial use.

Several studies provided evidence that pharmacist-led interventions can improve adherence to guidelines and reduced the duration of antimicrobial therapy with substantial cost savings for patients (Mahmoudi et al., 2019; Monmaturapoj et al., 2021). Furthermore, implementation of pharmacy-based interventions in AMS programs can reduce antibiotic consumption, length of hospital day, and 30-day mortality (Xin et al., 2019; Du et al., 2020).

Previous studies assessed the effectiveness of AMS intervention on surgical antibiotic prophylaxis (Zhang et al., 2014; Abubakar et al., 2019), upper or lower respiratory tract infection (Shen et al., 2011; Foolad et al., 2018), nonspecified indications (Li et al., 2017; May et al., 2021) in those priority departments, such as the department of urology, department of obstetrics and gynecology, department of respiratory medicine, intensive care unit, and emergency department, given high antimicrobial prescribing for prophylaxis or treatment and concerns with inappropriate antibiotic use. However, the previous studies pay little attention to some emerging departments with innovative technology; for instance, as the number and breadth of vascular and interventional radiology procedures grow, it is critical to promote rational use of antibiotics in the department of vascular and interventional radiology to avoid serious infectious complications. So far, only one study on the use of antibiotics for perioperative interventional surgery was retrieved. Yang et al. (2017) conducted a clinical pharmacist-led guidance team intervention for the rationality of prophylactic antibiotic usage for eight interventional procedures in a Chinese tertiary teaching hospital. However, it did not focus on a specific department, and the intervention included mainly with prescription reviews and administrative approach. Moreover, it was only limited to perioperative antimicrobial prophylaxis, rather than comprehensive intervention involving antibiotic prophylaxis and antibiotic therapy in surgical wards. The research design of the study was that of a before-and-after intervention trial to evaluate the effectiveness.

To date, there is no evidence to demonstrate the effectiveness of pharmacist-led AMS interventions on the rational use of antibiotics in the department of vascular and interventional radiology in a Chinese tertiary hospital. Therefore, the aim of this study was to improve the rational antibiotics use in the department of vascular and interventional radiology, and assess the value of pharmacist-led AMS programs during the study period. For this purpose, we used a quasi-experimental study design with a difference-in-differences (DID) analysis comparing outcomes before and after the AMS intervention between intervention group and control group, to determine whether intervention would lead to changes in the following outcomes: irrationality of antibiotic prescribing, antibiotic utilization, cost of antibiotics, and length of hospital stay.

To our knowledge, this is the first study to evaluate the impact of a pharmacist-led AMS program in the department of vascular and interventional radiology. The DID analysis indicated that the multifaceted pharmacist-led AMS intervention was associated with a significant decline in the antibiotic use, cost of antibiotics, and irrationality of antibiotic prescribing. Comparison of pre- and post-intervention changes between the intervention group and the control group, rather than merely levels before and after the intervention in the intervention group, necessarily adjusted for the possibility that the outcome was changing without the benefit of the intervention (Gerber et al., 2013).

There was a significant reduction in antibiotic utilization after the interventions in our study. This decline was attributed to reduction of unnecessary antimicrobial prescribing and increase in compliance with duration of antibiotic use. This observation was consistent with studies conducted in hospital and clinic settings (Hwang and Kim, 2018; Lee et al., 2018; Abubakar et al., 2019; Haseeb et al., 2020). The current study also found that the implementation of antibiotic stewardship interventions led to cost savings of antibiotics, which was similar to that found in prior studies (Butt et al., 2019; Xin et al., 2019). Some studies reported that the length of hospital stay significantly was shortened after the intervention of a pharmacist-directed antimicrobial stewardship (Mahmoudi et al., 2019; Xin et al., 2019; Arensman et al., 2020; Mahrous et al., 2020), while some studies indicated that the intervention had no effect on the length of stay (Wenzler et al., 2017; Abubakar et al., 2019; Monmaturapoj et al., 2021), which may be related to differences in the study design and analytical methods.

Inappropriate antibiotic prescribing was evaluated using a scoring system consisting of different items regarding three categories. Compared with the scoring system constructed by Shen et al. (2011), the relative weight values of each item were determined on the basis of utilizing the Saaty1–9 scale method, which can quantitatively judge the importance of each item on the inappropriate antibiotic prescribing. The result implies that indication had the largest impact for irrationality of antibiotics, regardless of antibiotic use for prophylaxis or treatment. Several studies showed that intervention has a significant impact on the appropriateness of antibiotic use after the implementation of the AMS program (Brink et al., 2017; Foolad et al., 2018; Butt et al., 2019; Calò et al., 2021; Jantarathaneewat et al., 2021). Our study was consistent with these findings, as we observed that the irrationality of antimicrobial prescriptions decreased in perioperative antimicrobial prophylaxis, non-surgical antimicrobial prophylaxis, and therapeutic use of antibiotics.

Inappropriateness of antimicrobial use in perioperative prophylaxis significantly decreased, especially in first-choice antibiotics, which was similar to that found in a previous study (Yang et al., 2017). Regarding the choice of antimicrobial prophylaxis, cefazolin definitely became the first choice in the post-intervention period with a concomitant decrease in cefathiamidine. Indeed, cefazolin was recommended as the first-line antibiotic according to the evidence-based trials (National Health Commission of China, 2015). Previous studies have reported that implementation of antibiotic stewardship program in surgeries was associated with reduction in the prescription of broad-spectrum and expensive antibiotics (Dona et al., 2019; Mahmoudi et al., 2019).

Inappropriateness score of antimicrobial prescribing for non-surgical prophylaxis decreased, manifested by improvement in correct antibiotic choice. The current study observed an increased use of ceftriaxone instead of cefoxitin for cirrhotic patients with esophageal and gastric variceal bleeding. Cirrhotic patients presenting with acute variceal bleeding have a high risk of developing bacterial infections; therefore, initiation of prophylactic antibiotic treatment at the time of admission is necessary (Lee et al., 2014). According to the guidelines (Korean Association for the Study of the, 2020), short-term antibiotic prophylaxis with intravenous ceftriaxone is recommended in cirrhotic patients with variceal bleeding.

A significant reduction in inappropriate prescribing for therapeutic use of antibiotics was also found after the intervention, manifested by a reduction in inappropriate prescribing in conditions for which antibiotics were generally not indicated, such as superficial thrombophlebitis of the lower extremities. Other antimicrobial stewardship efforts also have demonstrated improvements in unnecessary antibiotic prescribing for viral acute respiratory infection and asymptomatic bacteriuria (Meeker et al., 2016; Akpan et al., 2020; Calò et al., 2021; May et al., 2021). Antibiotic prescribing for these conditions where antimicrobials are not indicated puts them at unnecessary risk for adverse events and should be a target for quality improvement in interventional radiology wards.

In the intervention period, the acceptance rate of interventions was 80.00%, which was similar to that described in other studies at hospitals (Li et al., 2017; Hurst et al., 2019). The highest proportion of intervention types for surgical prophylaxis during the intervention period was stopping antimicrobial treatment, but the acceptance rate was the lowest. The reason is as follows: first, according to the Clinical Practice Guidelines for antibiotic prophylaxis during vascular and interventional radiology procedures (Chehab et al., 2018), a single preprocedural dose of cefazolin is an effective regimen for arterial endografts in the management of aortic aneurysm or dissection. Chinese Guidelines also suggest a single dose for prophylaxis (National Health Commission of China, 2015). However, the aortic stent graft surgery involves important viscera, an endograft infection that carries high morbidity and mortality rates (as high as 27%) (Cernohorsky et al., 2011). Therefore, doctors are unwilling to use a single dose of antibiotics. Second, postoperative inflammatory response syndrome may occur after aortic stent graft procedures and hepatic artery chemoembolization, which is characterized by fever, leukocytosis, and elevated C-reactive protein (CRP) and other inflammatory markers (Blackburn and West, 2016; Daye and Walker, 2018). Sometimes it is difficult for doctors to distinguish it from infection, so they dare not easily stop the antibiotics. Compared with perioperative antimicrobial prophylaxis, non-surgical antimicrobial prophylaxis had a lower acceptance rate for intervention, which was mainly manifested in the recommendation of using preferred evidence-based drug. That is probably because clinicians in the surgical ward might pay more attention to perioperative antimicrobial prophylaxis that resulted in change of prescribing behavior. In terms of therapeutic use of antibiotics, the lowest acceptance rate of intervention type was discontinuation of therapy without indication. For example, superficial thrombophlebitis is characterized by the appearance of tenderness, pain, redness, and swelling in the affected veins, which refers to an inflammation of superficial veins. Nonsteroidal anti-inflammatory drugs are suggested to reduce inflammation rather than antibiotics (Di Nisio et al., 2018). However, the strained relationship between doctors and patients in China has made doctors hesitant to not use antibiotics.

Our study has several strengths. Although the AMS program was performed in a surgical ward, a comprehensive intervention implemented not only focused on perioperative antimicrobial prophylaxis but also on non-surgical antimicrobial prophylaxis and therapeutic use of antibiotics. Notably, a scoring system was developed for assessment of rationality of antimicrobial prescriptions in antimicrobial prophylaxis and treatment based on consultation of multidisciplinary experts experienced in the management of infectious diseases. Previous studies usually emphasized on the analysis of change trend in antimicrobial utilization and cost savings after the implementation of AMS, whereas a comprehensive evaluation of antimicrobial prescriptive appropriateness was conducted as well as antimicrobial consumption and cost in our study.

There were also some limitations. First, it was a nonrandomized, retrospective pre–post analysis that carry a risk of selection bias. However, a quasi-experimental design with a DID methodology is often used to estimate the net effect of the intervention. Second, the present study investigated only the short-term effects of a pharmacist-led AMS intervention in the department of vascular and interventional radiology. It is unclear whether these effects would sustain after the interventions had finished. Third, this study was limited by its sample size. Finally, this was a single center study conducted in a tertiary teaching hospital; hence, the possibility of generalizing our results to other hospitals was limited. Future study with a larger sample size and a more rigorous design over an extended period needs to be confirmed. In spite of the limitations, this study has demonstrated that implementation of pharmacist-led AMS program significantly decreased the antibiotic use, cost of antibiotics, and irrationality of antibiotic prescribing in the department of vascular and interventional radiology.

This study provides important evidence from a pre-post intervention study that implementation of AMS interventions was associated with a marked reduction of antibiotic use, cost of antibiotics, and irrationality of antibiotic prescribing in the department of vascular and interventional radiology in a Chinese hospital. Our data indicate that departments that are not a priority for antimicrobial administration also need attention. It is essential for surgeons to be aware of the importance of adherence to guidelines. The findings of our study indicate that the beneficial AMS intervention led by clinical pharmacists can help to promote the rational use of antibiotics and decrease the antibiotic utilization.