The following trend was observed in this study: the total amount of antibiotics used decreased; oral third-generation cephalosporins were no longer prescribed; and amoxicillin became the most commonly used medications at the Department of Oral and Maxillofacial Surgery, Kobe University Hospital. Additionally, the amount of macrolides used also decreased, and the general appropriateness of antibiotic use improved based on the action plan for AMR. Our study is relevant because thus far, only few reports, especially in the dental surgery field, have evaluated the impact of the global action plan on AMR on the appropriate use of antibiotics [27,28,29].
In the present study, educational interventions and conscious and habitual practice of appropriate antibiotic use could reduce the use of antimicrobials. In addition, the use of antimicrobials need not be broad-spectrum [15,16,17], and as narrow a range of beta-lactams (e.g. AMPC) as possible was considered preferable. The results of this study suggest that prophylactic antimicrobials should be administered in 1–2 days, but further investigation is necessary because the administration of prophylactic antimicrobials may vary depending on the target surgery. In contrast, there is no conclusion from this study about the necessity of antimicrobial administration, the type of antimicrobial agent, and the duration of treatment for dental infections due to differences in the type and degree of disease addressed. Therefore, more detailed studies are needed in the future. By actively addressing these issues, we believe that we can contribute to the proper use of antimicrobials in the field of dentistry and oral and maxillofacial surgery.
In this study, for outpatients, there was almost no prescription of oral third-generation cephalosporins in 2018. Moreover, macrolides and quinolones prescriptions in 2018 were much less than that in 2013, because of the adoption of the National Action Plan on AMR in Japan [6]. The introduction of educational intervention by the AST was considered to have contributed significantly in this regard [24]. In addition, we consider that these results reflect the high compliance following the introduction of the guidelines in Japan (e.g., guidelines for the treatment of odontogenic infection [30] or guidelines for the prevention of postoperative infection [25]). The sharing of knowledge and creation of awareness about appropriate antimicrobial agents contributed significantly to the appropriate antibiotic use observed in our department. All members of our department participated in clinical conferences where guidelines on the appropriate use of antibiotics for surgical patients were discussed in the department’s conference room (a staff member (SF) specialized in odontogenic infection who is an “infection control doctor” certified in Japan as a specialist in infection control must attend). Thus, this probably influenced our routine daily clinical practice even though a departmental antibiotic policy was not adopted. However, we still came across cases of inappropriate use of antibiotics, and we would like to investigate this further in a subsequent study.
For inpatients, there were no prescriptions of oral third-generation cephalosporins in our department in 2018. Thus, oral third-generation cephalosporins were removed from the formulary for inpatients in our hospital, and the educational intervention by the AST contributed significantly in this regard [24]. Penicillins, which are highly effective against odontogenic infection, have supplanted oral third-generation cephalosporins in terms of the appropriate use of antibiotics [18, 19]. However, the prescription of quinolones, particularly Sitafloxacin, increased in 2018 compared to that in 2013. This might have been influenced by change in disease pattern encountered in our department. The number of surgical treatments performed for inpatients with intractable osteomyelitis, medication-related osteonecrosis of the jaw (MRONJ), and osteoradionecrosis in our department increased since 2016. Hence, it was considered that the residual cases of infectious symptom had increased postoperatively, with increased postoperative use of antimicrobial agents. Owing to its good antibacterial bone penetration [31] and significant effect in treatment-resistant osteomyelitis [32], there seemed to be an increase in the use of quinolones. Sitafloxacin was found to be particularly effective for MRONJ [33]. However, this report had a low evidence level, and the results were not validated against narrower spectrum antibiotics such as penicillins (amoxicillin or clavulanate/amoxicillin). This subject should be the research agenda for future studies since there is possibility of the persistence of inappropriate use of antibiotics.
The clinical outcomes and prevalence of adverse effects with changes in antibiotic use were investigated among inpatients. We observed an SSI incidence of 6.2% in 2013 and 1.8% in 2018. In addition, the prevalence of adverse effects due to antibiotics was 1.8% in 2013, but no adverse effects were observed in 2018. It has previously been reported that the prevalence of SSI after surgery for mandibular impacted third molar extraction was around 10% [34]; postoperative SSI developed in 4% of patients in the antibiotic group and 6.1% of patients in the placebo group in a meta-analysis assessing the effectiveness of antibiotic prophylaxis [35]. Prevalence of adverse effects of antibiotics reported for penicillins and cephems was 6–7% [36]. Amoxicillin was the safest antibiotic prescribed by dentists [37]. In this study, although the sample size was small, there was not much difference in the findings when compared to past reports [34,35,36], and the incidence of SSI and adverse effects were also similar. These findings suggest that these negative impacts (SSI and adverse effects) exist in clinical practice despite the change in antibiotics. Although the need for prophylactic antibiotic administration for third molar extraction is controversial, its use is currently favored [38]. Presently, postoperative oral antibacterial agents are not prescribed for the prevention of SSI in our department, and further investigation needs to be undertaken to determine the influence of not prescribing oral antibacterial agents on the onset of SSI.
There were several limitations in this study. Since the investigation included data from a single department, the results do not reflect the entirety of the Japanese dental institutions. However, we consider that the results might be a useful starting point in promoting appropriate use of antibiotics. Further, it was difficult to evaluate the posology of antibiotics since “DOT” was the measure for evaluating the amount of antibiotics used in this study. It was further difficult to evaluate an appropriate posology in this study, since the dosage of antibiotics used in Japan is generally lower than the world standard (approximately 1/3–1/2 in almost antimicrobial agent according to a package insert). Especially, there are strict restrictions on antibiotics prescription and dosages in dentistry. In contrast, the defined daily dose (DDD), which is based on the total number of grams of the antimicrobial agent used, is an indicator for evaluating other antimicrobial amounts. In “DDDs,” it is not possible to determine which factors are problematic in the case of large doses, such as the daily dose, the number of days of the administration, or the number of people treated. In addition, it is difficult to determine changes in the amount of antimicrobial agents used when the dosage is changed because many Japanese medical departments (not dentistry and oral surgery) have recently been administering antimicrobial agents according to global standards. In this study, not a few hospitalized cases have been intervened by the medical doctors, and the dosage of antimicrobial agents must be reduced due to the inclusion of elderly patients and those with impaired renal function. Therefore, in the present study, we determined that DOT, without taking into account the daily dose, was appropriate for the evaluation of antimicrobial use, as per previous reports [23, 24]. Another limitation was the switch from intravenous to oral antibiotics for some patients which could have potentially altered the results. Therefore, inappropriate prescription of oral antibiotics continues to plague Japan warranting further impetus to this issue.