Terminal cancer patients often experience infectious complications toward the end of their lives. Consequently, many end-of-life (EOL) cancer patients who are hospitalized continue to receive antibiotics until their passing [1–3]. Even when physician orders for life-sustaining treatment (POLST) dictate minimal treatment, antibiotics are frequently administered continuously as an exception [4]. The common reasons for the ongoing administration of antibiotics to EOL cancer patients include: (1) presence of an actual infection in the patient; (2) difficulty in determining whether patients are infected because typical symptoms of infection such as fever or elevated inflammatory markers can also manifest in non-infected cancer patients; and (3) medical staff may feel guilty if a patient deteriorates or dies after discontinuing antibiotics. In addition to these three reasons, various factors contribute to the continued use of antibiotics, such as caregivers’ requests [5].

Antibiotic use is associated with adverse drug effects, drug interactions, injection site inflammation, intravenous catheter-related infections, Clostridioides difficile infection, and the emergence of multidrug-resistant organisms (MDRO) [1,2,6]; therefore, antibiotics should be administered cautiously in EOL care, which prioritizes patient comfort over cure. Accordingly, the Infectious Diseases Society of America has recommended implementing antimicrobial stewardship programs (ASP) for EOL patients [7].

There are limited studies on antibiotic use in patients nearing death in Korea. In 2006, one study reported that 84.4% of terminal cancer patients received antibiotics within a month of their death, with 63.8% continuing to receive antibiotics until their last day [1]. Another study found that 90.6% of patients continued to receive antibiotics after their POLST decision and 60.1% received antibiotic combination treatment [8]. A recent nationwide multicenter cohort study found that 88.9% of terminally ill patients received antimicrobial agents during the last two weeks of their lives [9]. Of these patients, 63.6% received inappropriate antibiotic treatment [9]. However, no studies to date have assessed the medical staff’s perception of antibiotic use in EOL patients, particularly among internal medicine residents, specialists, and hospitalists who primarily manage hospitalized patients.

This study aimed to evaluate the pattern of antibiotic use in hospitalized cancer patients receiving EOL care and determine whether there were changes in antibiotic use patterns before and after POLST decisions. Additionally, we investigated the perceptions of medical staff who prescribe and administer antibiotics to EOL cancer patients.

This study is to examine the patterns of antimicrobial use and perceptions of medical staff in cancer patients with EOL care in Korea, and is the first study on perception of antibiotics in Korean medical staff. In our study, 96.0% of EOL cancer patients received antibiotics, and 81.1% were administered antibiotics until within 24 hours of death. A total of 77% were treated with combination antibiotics. The decision on the administration of antibiotics in EOL cancer patients was mainly determined by the medical staff. The results of a questionnaire-based survey showed that many medical staff were not aware of ASP, and even those who thought ASP was important did not properly utilize it in the actual clinical setting. We believe that our findings may provide valuable data for considering how ASP can be applied to EOL cancer patients in South Korea.

Infection and fever are the most common acute complications experienced by terminally ill patients. It is challenging to distinguish between normal parts of the dying process and aspects that are reversible or clinically treatable [6]. For this reason, antibiotics are often administered until the day of death for EOL cancer patients [1,2,9]. Antibiotics use in EOL care could have some benefits for improving infection related symptoms (e.g., pain, dysuria), signs (e.g., fever), inflammatory marker [12,13]. However, in our study, no improvement in fever or inflammatory markers was observed even if antibiotics were administered during the EOL period, and a previous study reported that there was no significant difference in time to mortality if antibiotics were stopped in terminally ill patients [14]. Since EOL patients are often cared for with the goal of “comfort” rather than “cure”, it is necessary to make a decision to properly use or stop antibiotics, considering various benefits (e.g., long-term survival effects, symptom improvement) and risks (e.g., drug side effects, occurrence of MDRO).

Excessive antibiotic use in patients with EOL care could increase the incidence of antibiotic resistance, which leads to increases in hospitalization days, mortality, and medical costs [15–17]. One study reported that antibiotics were continued to be administered even after Do-Not-Resuscitate requests, and more MDRO were isolated from those who died [18]. As MDRO can spread to other patients, this can ultimately lead to increased global healthcare costs. C. difficile infection can occur during or after antibiotic administration, which is also on the rise worldwide, causing problems such as extended hospitalization, increased re-admission rates, and overall medical costs [19–21]. Additionally, antibiotic injections can cause side effects, such as injection site inflammation, phlebitis, and catheter-related bloodstream infection [22–24]. There are also side effects of antibiotics themselves, such as drug fevers, skin rash, urticaria, hypersensitivity reactions, and gastrointestinal upsets [25–28]. Although patients may not be able to complain of discomfort because they are in the EOL course, they could still experience various side effects. Moreover, antibiotics may interact with the drugs being administered at the EOL care, leading to additional problems such as increased workload for nurses who perform antibiotic administration and increased decision-making for doctors. Considering these downsides of antibiotics use, antibiotics should be properly administered, de-escalated, or stopped altogether in patients with EOL. Determining the use of antibiotics can result in better treatment services for patients and benefit both medical institutions and the nation.

In our study, only 31.7% of medical staff discussed the use of antibiotics with patients and caregivers when writing POLST, and decision-making on the use of antibiotics in EOL cancer patients was largely determined by the attending physician. The situation regarding antibiotic use in EOL cancer patients is complex and can be a source of ethical and practical challenges for healthcare professionals. In some patients, continuing to use antibiotics might be seen as prolonging the dying process rather than providing comfort and dignity in the final stages of life. In the POLST state, it is necessary to consider the life dignity of patients in EOL care and give patients or caregivers the right to decide on the use of antibiotics. To this end, it is important to provide accurate information to patients and caregivers first, and to fully explain the scenarios that may occur regarding antibiotics use or cessation [2]. Ethical judgment is a very complicated and difficult issue when it comes to the use of antibiotics in patients who are rapidly progressing to their death. We think that it is necessary to allow cancer patients to decide on the use of antibiotics based on their dignity when writing POLST. It is time to clarify that antimicrobial therapy is considered as life-sustaining treatment which can be withdrawn or withheld in EOL cancer patients [6]. We also suggest that the context about benefits and risks of antibiotics should be included in POLST documentation. In addition, the use of antibiotics in EOL patients depends on a combination of factors, such as ambiguity of therapeutic effectiveness, physician perception, and attitudes and opinions of patients and caregivers. Therefore, it should be recorded when writing POLST if the decision is made not to use antibiotics during EOL care [3], which would help reduce antibiotic use in the EOL phase. A study revealed that indicating a preference for limited antimicrobials on a POLST form ≥ 30 days before death may lead to less inpatient antimicrobial use in the last 30 days of life [3]. Therefore, we think that the medical law revision are required, including discussions on the use or discontinuation of antibiotics when writing POLST.

There have been studies on medical staff’s perceptions of antibiotic stewardship in EOL patients. One survey study found that many doctors who provide palliative care tend to initiate and maintain or extend antibiotics use in EOL patients, even in cases where antibiotics might not be appropriate or where the risks might outweigh the benefits [4]. Another study found that physicians have divergent attitudes toward the management of infectious diseases in terminally ill patients with cancer [29]. Our survey reveals a significant lack of awareness about ASP among internal medicine residents and specialists, and that doctors found it difficult to use antibiotics appropriately in EOL patients. We believe the reasons why antibiotics are prescribed so frequently, used for long periods, and not easily discontinued are likely due to doctors’ personal concerns of stopping antibiotics and the unclear benefits and risks of antibiotics cessation. In particular, regular education on palliative care is still insufficient before and after POLST implementation. In South Korea, doctors face many practical difficulties in the clinical field before and after POLST [30]. There is limited education related to antibiotic use guidelines for EOL patients in medical schools and clinical settings. Although a few tertiary centers have ASP support teams or hospice palliative care teams, there are no practical guidelines on appropriate antibiotic use in EOL patients. It is necessary for physicians to develop the ability to use antibiotics appropriately in cancer patients with EOL and make informed decisions regarding the proper use or discontinuation of antibiotics, considering the benefits and risks of antibiotics for hospitalized cancer patients with EOL aiming for “comfort” and not “cure”. We believe this ability could be developed through appropriate ASP activities [9]. Moreover, proper education on the use of appropriate antibiotics is needed from the time of medical school and throughout residency training, and clear guidance for ASP in EOL care is essential.

We acknowledge some limitations to our study. First, there is potential selection bias as this study is a retrospective study conducted at a single institution. A more accurate analysis and results would be achieved through a multicenter study. Second, this study focused on hospitalized patients with solid organ cancer and internal medicine doctors. Additional research is needed on EOL cancer patients with hemaologic malignancy and medical staff belonging to departments other than internal medicine. Third, this study excluded patients who showed improvement after receiving antibiotics during the EOL stage, and therefore cannot determine the effectiveness of antibiotic use during this period or provide guidance on whether to initiate or discontinue their use.

Despite these limitations, we were able to determine the status of antibiotic use and medical staff perception among hospitalized EOL cancer patients. This study could provide hospital antibiotic management specialists with a direction for ASP development and serve as valuable data to enhance the ability of residents, specialists, and hospitalists who primarily manage inpatients to use antibiotics appropriately. Additionally, there is a need to improve medical staff’s awareness of ASP, which may be achieved by actively implementing ASP, adding antibiotic education in EOL situations to medical school curricula, or actively guiding the use of antibiotics in patients with EOL in hospitals.

In conclusion, most cancer patients with EOL continued to receive antibiotics until just before death, and antibiotic use in these patients should be carefully determined by comprehensively considering the benefits, potential problems, and the patient’s right to self-decision. During EOL care discussions for hospitalized patients with terminal cancer, antibiotics usage should be taken into consideration, and efforts should be made to increase medical staff awareness on appropriate usage of antibiotics.