Discussion

There are several notable findings in our study. First, APB varied based on specialties, inclusive of investigations prior to antibiotic administration in both the initial and on-treatment stages, the pattern of antibiotic prescription, and further management of patients with infections not responding to therapy. Notably, the use of biomarkers was more commonly reported in the initial stage, while participants who were in the MT stage of TTM were more likely to prescribe appropriate antibiotics in the de-escalation stage. Second, adequate investigation, inclusive of source control during the on-treatment stage, was only reported by ID specialists. Third, antibiotic de-escalation was commonly reported only by ID specialists, while successful carbapenem de-escalation was reported by 41%–80% of respondents as categorized by specialty. To the best of our knowledge, this study is the first to explore APB among different specialties by a multinational survey in Asia. This knowledge will help identify the gap of antibiotic administration in different stages to help promote appropriate antibiotic prescriptions among physicians in different specialties. Further investigation should be conducted to determine why Japanese physicians are much more accepting of the concept of de-escalation of empiric therapy compared to other Asian nationalities.

APB, including the choice of empiric antibiotics and the use of biomarkers to help with empirical in the initial stage, can vary by specialty. ^{Reference Cusini, Rampini and Bansal7,Reference Fridkin, Baggs and Fagan15} While broad-spectrum antibiotics are usually prescribed for empiric treatment among internists, the use of narrow spectrum antibiotics followed by escalation to broader-spectrum antibiotics are usually observed among surgeons. ^{Reference Naeem, Alshamrani, Aseeri and Khan16} Additionally, several studies found that incorrect antibiotic dosing and inappropriate use of broad-spectrum antibiotics such as carbapenems and vancomycin are common practices in treating patients with febrile neutropenia and those in critical care settings. ^{Reference Naeem, Alshamrani, Aseeri and Khan16,Reference Rhodes, Evans and Alhazzani17} Similarly, our study found that the patterns of empiric antibiotic prescription among specialties can differ based on common sites of infections as well as the adopted international guidelines in each country. Inappropriate APB was commonly reported by trainees, and these young physicians were influenced by their role models suggesting the importance education in younger groups of physicians in all specialties. Several guidelines and consensus suggest the benefit of RDTs and biomarkers, including procalcitonin to help reduce inappropriate antibiotic use during the initial, on-treatment, and de-escalation/cessation stage. ^{Reference Apisarnthanarak, Kim and Moore18,Reference Liew, Chlebicki, Lee, Hsu and Kwa19} These RDTs and biomarkers can be integrated in antibiotic stewardship to improve the diagnostic and therapeutic management for various indications, including acute respiratory infections and sepsis. ^{Reference Lee, Kwa and Apisarnthanarak20} However, our study found that use of these RDTs and biomarkers was limited to procalcitonin and mostly only used in the initial stage. It is therefore imperative that more education is provided for the appropriate use of RDTs and biomarkers in all stages.

During the on-treatment stage, adding or switching to broader-spectrum antibiotics is the most common practice if the patients fail to respond to antibiotics therapy. ^{Reference Bassetti, Montero and Paiva21} Failure to respond to antibiotic therapy may occur due to a miss diagnosis, an infectious complication, or the lack of source control. ^{Reference Gonçalves-Pereira, Conceição and Póvoa22} Our study found that only ID specialists consistently consider source control, while other specialties chose to step up to broader-spectrum antibiotics with/without appropriate investigations. Several studies have shown the benefit of ID consultation to assist with appropriate investigation and antibiotics administration in different clinical sites. ^{Reference Fariñas, Saravia and Calvo-Montes23–Reference Nagao, Iinuma and Saito25} ID consultation may include recommending the appropriate choice of antibiotics and reducing the use of broad-spectrum antibiotics, which result in the reduction in antibiotic expenditure as well as improved clinical outcomes. ^{Reference Pavese, Sellier, Laborde, Gennai, Stahl and François26} Likewise, we found that ID consultation was associated with appropriate management for patients who fail to respond during the on-treatment stage. National antibiotic guidelines and policies have been shown to increase awareness of the harm of over prescription of antibiotics and reduce the inappropriate use of antibiotics. ^{Reference Wathne, Harthug and Kleppe27} In Japan, implementation a national antibiotic policy was associated with reducing in total antibiotics use. ^{Reference Kusama, Tsuzuki, Muraki, Koizumi, Ishikane and Ohmagari28} Our data emphasize the important role of the implementation of national guidelines to help with appropriate management of antibiotics during the on-treatment stage.

Antibiotic de-escalation has been shown to reduce the risk of antimicrobial resistance and adverse effects from unnecessary antibiotic use. ^{Reference De Bus, Depuydt and Steen29} Predictors for antibiotic de-escalation include positive microbiological culture results, consultation with an ID specialist, and adherence to national guidelines. ^{Reference Byl, Clevenbergh and Jacobs24,Reference Tabah, Cotta and Garnacho-Montero30} Carbapenem de-escalation has been reported to be 45%–50% by several studies. ^{Reference Morel, Casoetto and Jospé31,Reference Gonzalez, Cravoisy and Barraud32} In our study, the rate of de-escalation was reported to be 10%–60% depending on the specialty. Notably, de-escalation was less commonly reported by hematologists and intensivists, and this may be due to the severity of illness among their patient population. Adherence to national prescribing guidelines has been shown to help with carbapenem de-escalation. ^{Reference Tabah, Cotta and Garnacho-Montero30} Likewise, our study found that adherence to national prescribing guidelines is associated with appropriate de-escalation. In addition, several studies have reported on the use of behavioral theories to evaluate APB. ^{Reference Warreman, Lambregts and Wouters33} A Thai study showed a strong correlation between the TTM stages and appropriate antibiotic prescriptions in surgical wards during the initial stage. ^{Reference Jantarathaneewat, Chansirikarnjana, Tidwong, Mundy and Apisarnthanarak6} Likewise, our study found that participants who are in the MT stage were more likely to report appropriate APB in the de-escalation stage. Therefore, it is important to provide more education on the appropriate use of APB among participants who belong to the earlier TTM stages during de-escalation.

Our study had several limitations. First, the nature of a self-reported survey lends to a situation in which the actual practice may not reflect what participants report. However, we were very clear to potential participants that the survey is de-identified and completely anonymous and so the reported behavior is more reflective of the practice. Second, the nature of a convenience sample survey may be subject to selection biases. Third, as the majority of the participants were staff, being internists and ID specialists, and were from Korea, Thailand, and Japan, it is possible that our results may skew toward the practices in these specialties and countries. Lastly, the small sample size may limit our ability to identify other factors associated with APB in the initial, on-treatment, and de-escalation stages.

In conclusion, this study shows that there are differences in APB in the initial, on-treatment, and de-escalation stages among different specialties. These differences in behaviors can be reduced by educating prescribers on the use of RDTs and biomarkers during the initial stage, consulting ID specialists during the on-treatment stage, and increased adherence to national antibiotic prescribing guidelines during the de-escalation stage.