1. Background
The rational use of antibiotics is an important issue worldwide, especially in low-income and middle-income countries. Irrational antibiotic use can lead to the emergence of antibiotic-resistant bacteria, increased patient morbidity and mortality, and a heightened economic burden. Notably, antibiotics are among the most commonly prescribed drugs globally (1, 2). The high rate of antibiotic prescriptions (68.2%) compared with the World Health Organization (WHO) ideal prevalence of antibiotic prescribing (20 - 26.8%) is a critical issue in both outpatient and inpatient settings in Iran (3). Significantly, the emergency department (ED) is a high-risk area for inappropriate antibiotic prescriptions due to its fast-paced, high-pressure, and unpredictable nature (4). In line with relevant guidelines, the irrational prescription of antibiotics is defined as inappropriate antibiotic prescribing concerning indication, drug selection, administration route, usage, dosage form, dosage, duration, interactions, incompatibility, and cost (5, 6). The primary reasons for irrational antibiotic prescriptions include patients’ demand for antibiotics, physicians’ attitudes, inadequate knowledge, prescribing behavior to satisfy patients, and suspicion of unproven infections (1, 7).
Educational interventions are effective methods for promoting knowledge and awareness among physicians to reduce irrational antibiotic prescriptions (8). Another strategy to enhance this knowledge and awareness is the involvement of clinical pharmacists and pharmacists in antibiotic stewardship teams, as previous studies have demonstrated their importance in this area (9-11). Clinical pharmacists play a vital role in evaluating antibiotic prescriptions for both outpatients and inpatients and in providing educational programs (10). Pharmacists are also often involved in antibiotic stewardship programs by developing and revising antibiotic guidelines, educating medical staff, and monitoring antibiotic use and expenditure (11).
2. Objectives
Considering the above, this study was designed to evaluate the effect of an educational intervention led by pharmacists on rational antibiotic prescribing in an outpatient ED.
3. Methods
3.1. Ethical Considerations
This study (99000168) was approved by the Ethical Committee of Kerman University of Medical Sciences under the number IR.KMU.REC.1399.384. In the present study, all patients provided written informed consent. Additionally, the confidentiality of all patients' and physicians' data was strictly maintained.
3.2. Study Type, Setting and Patients
This pre-post intervention study was conducted in the outpatient ED of Shahid Bahonar Hospital, affiliated with Kerman University of Medical Sciences, Kerman, Iran, from February to June 2020. Non-random (convenience) sampling was employed. All patients referred to the outpatient ED at triage and those prescribed antibiotics were included in this study.
3.3. Medical Doctors
In the outpatient ED, ten medical doctors (MDs) worked in rotating 8-hour shifts. Among them, 2 (20.00%) were female, and 8 (80.00%) were male. Their mean age was 41.60 ± 6.04 years. Before the study commenced, all the doctors were informed about the research and agreed to participate in conducting the study.
3.4. Study Design
This study was divided into two phases: Pre-intervention and post-intervention. In the first phase (pre-intervention), which was observational, a pharmacist was present in the doctor's office during the morning shift (8:00 AM to 4:00 PM) for one month. The pharmacist observed the process of prescribing antibiotics for patients and recorded key details, such as the duration of antibiotic use. All the doctors were asked to write their final diagnosis on the back of the patient's prescription. After the morning shift, the pharmacist visited the ED satellite pharmacy to record information from prescriptions containing antibiotics, including the patients’ age, sex, diagnosis, and details of the prescribed antibiotics, such as their indication, dose, and duration, in a checklist.
The pharmacist then assessed the irrational prescribing of antibiotics based on reliable references, such as UpToDate® (UptoDate, Waltham, MA, USA, http://www.uptodate.com), and through consultation with an infectious disease specialist and a clinical pharmacist. The educational topics were determined based on the most common diagnoses associated with irrational antibiotic prescribing and were finalized in consultation with the clinical pharmacist and infectious disease specialist. The topics included antibiotic treatment for periodontitis, pharyngitis, urinary tract infection, sinusitis, animal bites, and wounds.
Subsequently, a 20-minute educational video with clear audio and visuals featuring the pharmacist was prepared as the educational tool and provided to the doctors. The content of the video was approved by the clinical pharmacist and the infectious disease specialist. The video covered key points regarding the appropriate indication, dose, and duration of antibiotics for the aforementioned infections, based on UpToDate®. The doctors were given one week to watch the video.
Two weeks after the educational intervention, the post-intervention (second) phase was conducted in the same manner as the first phase over one month. During this phase, the pharmacist again evaluated the patients' prescriptions for irrational antibiotic prescribing.
3.5. Statistical Analysis
The present study was conducted as a pilot study to assess the efficacy of the intervention, enhance the researchers' experience with the study method, and validate the feasibility of the study. Based on the results of this pilot study, a large-scale multicenter study will be planned. The irrational antibiotic prescription rate was assumed to be approximately 38% (4), and it was anticipated that this rate would decrease to 20% following the pharmacist-led educational intervention. Therefore, a sample size of 96 prescriptions containing antibiotics in each phase was required to detect the change between the two mentioned proportions with a 95% confidence level and 80% power.
All data were analyzed using SPSS 25 software. Descriptive statistics were applied to all variables. Independent samples t-test and chi-square test were used to compare quantitative and qualitative variables, respectively, between the pre- and post-intervention phases. A P-value < 0.05 was considered statistically significant.
4. Results
During the first phase of the present study, out of 314 prescriptions, 100 (31.85%) contained antibiotics. Similarly, in the second phase, among a total of 235 prescriptions, 100 (42.55%) contained antibiotics. It is noteworthy that 112 antibiotics were prescribed for the 100 patients in the first phase, while 110 antibiotics were prescribed for the 100 patients in the second phase. Some prescriptions included more than one antibiotic.
Among the 100 patients prescribed antibiotics during the first phase, 52 (52.00%) were male, and 48 (48.00%) were female. In the second phase, among the 100 patients, 47 (47.00%) were male, and 53 (53.00%) were female. The mean age of the patients was 36.65 ± 15.73 years in the first phase and 37.30 ± 15.71 years in the second phase. There was no significant difference in the patients’ age (P = 0.758) and gender (P = 0.887) between the two phases of the study.
Antibiotics with inappropriate indications (21 in the first phase and 3 in the second phase) were excluded from the evaluation of proper dose and duration. The analyses demonstrated that the educational intervention had a statistically significant effect on reducing irrational antibiotic prescribing with respect to indication (P = 0.0001), dose (P = 0.005), and duration (P = 0.0001) (Table 1).
Table 1.
The Effect of Education on the Rational Prescription of Antibiotics a
| Variables | Pre- intervention | Post- intervention | P-Value b |
|---|---|---|---|
| Indication of antibiotics | N = 112 | N = 110 | 0.0001 |
| Appropriate | 91 (81.25) | 107 (97.27) | |
| Inappropriate | 21 (18.75) | 3 (2.73) | |
| Dose of antibiotics | N = 91 | N = 107 | 0.005 |
| Appropriate | 68 (74.73) | 96 (89.72) | |
| Inappropriate | 23 (25.27) | 11 (10.28) | |
| Duration of antibiotics treatment | N = 91 | N = 107 | 0.0001 |
| Appropriate | 36 (39.56) | 92 (85.98) | |
| Inappropriate | 55 (60.44) | 15 (14.02) |
a Values are expressed as No. (%).
b Based on chi-square test.
In Table 2, the prescribed antibiotics during the pre- and post-intervention phases are presented. The educational intervention did not have a statistically significant effect on the types of prescribed antibiotics (P = 0.143). The most frequently prescribed antibiotics were cephalexin (28.57%), azithromycin (15.18%), and ciprofloxacin (15.18%) in the pre-intervention phase, and amoxicillin/clavulanic acid (20.91%), cephalexin (20.91%), and azithromycin (17.27%) in the post-intervention phase.
Table 2.
The Prescribed Antibiotics in the Pre and Post-intervention Phases a
| Prescribed antibiotics | Pre-intervention (n = 112) | Post-intervention (n = 110) | P-Value b |
|---|---|---|---|
| Amoxicillin | 3 (2.68) | 1 (0.91) | 0.143 |
| Amoxicillin/clavulanic acid | 14 (12.50) | 23 (20.91) | |
| Azithromycin | 17 (15.18) | 19 (17.27) | |
| Cephalexin | 32 (28.57) | 23 (20.91) | |
| Cefixime | 12 (10.71) | 12 (10.91) | |
| Ciprofloxacin | 17 (15.18) | 12 (10.91) | |
| Levofloxacin | 1 (0.89) | 3 (2.73) | |
| Metronidazole | 13 (11.61) | 7 (6.36) | |
| Penicillin | 3 (2.68) | 10 (9/09) |
a Values are expressed as No. (%).
b Based on chi-square test.
The infectious diseases diagnosed by the doctors during the pre- and post-intervention phases are presented in Table 3. The most common infectious diseases in the first phase were wounds and urinary tract infections, while wounds and animal bites were the most common in the second phase.
Table 3.
The Infectious Diseases Diagnosed by the Doctors in the Pre and Post-intervention Phases a
| Infectious Diseases | Pre-intervention (n = 100) | Post-intervention (n = 100) | P-Value b |
|---|---|---|---|
| Acute otitis media | 0 | 3 (3.00) | 0.0001 |
| Animal bites | 11 (11.00) | 23 (23.00) | |
| Cellulite | 1 (1.00) | 0 | |
| Diabetic foot | (1.00) | 0 | |
| Gastrointestinal infection | 2 (2.00) | 3 (3.00) | |
| Mastitis | 1 (1.00) | 0 | |
| Pelvic inflammatory disease | 0 | 1 (1.00) | |
| Periodontitis | 3 (3.00) | 1 (1.00) | |
| Pharyngitis | 8 (8.00) | 17 (17.00) | |
| Respiratory tract infection | 7 (7.00) | 13 (13.00) | |
| Scorpion sting | 1 (1.00) | 0 | |
| Sinusitis | 9 (9.00) | 5 (5.00) | |
| Urinary tract infection | 24 (24.00) | 8 (8.00) | |
| Vaginal infection | 0 | 1 (1.00) | |
| Wounds | 32 (32.00) | 25 (25.00) |
a Values are expressed as No. (%).
b Based on chi-square test.
Examples of irrational antibiotic prescribing are summarized in Table 4.
Table 4.
Some Examples of Irrational Antibiotics Prescribing
| Clinical Cases | Irrational Prescription Type | Appropriate Prescription |
|---|---|---|
| For a patient diagnosed with periodontitis, metronidazole 250 mg every 8 hours, 30 tablets, and amoxicillin 500 mg every 8 hours, 30 tablets, were prescribed. | Inappropriate dose | The correct dose of metronidazole for periodontitis is 500 mg three times a day. |
| For a patient, who suffered from wounds and lacerations, cephalexin 500 mg every 6 hours, 30 tablets, was prescribed. | Inappropriate duration of treatment | The correct treatment duration for wounds and lacerations is 3 to 5 days. Twenty tablets were enough for the recommended duration. |
| For a patient with pharyngitis, cefixime 400 mg every 12 hours, 10 tablets, was prescribed. | Inappropriate duration of treatment and dose | For pharyngitis, cefixime 400 mg once daily for ten days should be prescribed. |
| Metronidazole and cefixime were prescribed for treatment of uncomplicated urinary tract infection in a patient. | Inappropriate indication | Metronidazole should not be used for treatment of uncomplicated urinary tract infection. |
| Azithromycin was prescribed for a patient with sinusitis | Inappropriate indication | Azithromycin is not recommended for treatment of sinusitis because of high rates of Streptococcus pneumonia resistance. |
5. Discussion
The present study demonstrated that the pharmacists’ educational intervention effectively reduced irrational antibiotic prescribing with respect to indication, dose, and duration in the outpatient ED. The strength and novelty of this study lie in the approach where the pharmacist first identified the specific diseases for which physicians lacked knowledge regarding rational antibiotic prescribing, and then designed the educational intervention based on these findings. In essence, a targeted educational intervention was implemented in this study.
It is worth noting that a targeted educational intervention addressing specific knowledge gaps is more effective than interventions based on generic information (12). As previously suggested in a study, assisting physicians in decision-making related to antibiotic prescribing can be an effective strategy to reduce irrational antibiotic use (2). Additionally, involving pharmacists in antibiotic decision-making can lead to more appropriate antibiotic choices and regimens (13). Moreover, educational interventions have been shown to enhance physicians’ knowledge and behaviors concerning the appropriate use of antibiotics (14).
Several studies have demonstrated that decision-support strategies based on pharmacists’ interventions can promote rational antibiotic prescribing. Pharmacists’ interventions, such as attending ward rounds, training physicians, reviewing medical orders, and providing feedback to physicians, have been shown to positively influence physicians’ prescribing behaviors and their knowledge of antibiotic use (15).
In a study conducted in an ED, a pharmacist’s intervention, including participation in ward rounds, review of medical records, and communication with physicians, resulted in identifying 78 (43.33%) inappropriate antibiotic prescriptions out of 180 and correcting 51 (52.56%) of them within one month (4).
In another study conducted in Iran, it was demonstrated that a pharmacist’s educational programs, particularly when delivered interactively over nine sessions, had a significant impact on improving the rational use of surgical antibiotic prophylaxis. The improvements were observed in terms of indication, timing of administration, dose, duration of prophylaxis, and cost-effectiveness (16).
Similarly, a study in Pakistan evaluated the impact of a pharmacist’s educational intervention (10 - 15 days of training) on post-surgical antibiotic prophylaxis based on clinical practice guidelines for antimicrobial prophylaxis in surgery. The study found that the pharmacist’s intervention significantly improved the rational prescribing of prophylactic antibiotics, particularly regarding dose, frequency, and duration in post-surgical procedures. Moreover, the intervention notably reduced antibiotic use and hospitalization costs (17).
Additionally, Fesus et al. reported that a pharmacist-led intervention increased rational antibiotic use in surgical antibacterial prophylaxis in Hungary, emphasizing the critical role of clinical pharmacists in antibiotic stewardship teams (18). Furthermore, Radhakrishnan et al. found that video-based consultations provided by a clinical pharmacist increased public knowledge about appropriate antibiotic use. They concluded that video-based consultation is an effective educational tool for raising awareness about antibiotic use (19).
Thus, it is evident that a pharmacist’s educational interventions can effectively enhance rational antibiotic prescribing.
It should be noted that the majority of antibiotic prescriptions in medicine occur in outpatient settings (14), where 30% to 50% of them may be irrational (20). Moreover, previous studies have demonstrated that educational interventions can significantly reduce inappropriate antibiotic prescribing in outpatient departments (14). Craddock et al. reported that an educational intervention involving guideline development resulted in a nearly 24% reduction in irrational outpatient antibiotic prescriptions for acute upper respiratory tract infections (21). Similarly, Yadav et al. found that educational interventions could reduce inappropriate antibiotic prescribing by 33% for acute respiratory infections in outpatient EDs (22).
The current study showed a relative decrease of 15% in inappropriate dose and indication of antibiotics and a 45% reduction in inappropriate antibiotic duration following the implementation of the pharmacist’s educational intervention in the outpatient ED.
Furthermore, long-term monitoring of the effectiveness of educational interventions is recommended. It has been reported that educational interventions aimed at improving the rational use of antibiotics are often difficult to sustain; therefore, they should be continuous, flexible, and evolving. Additionally, the continuous availability of guidelines and standard antibiotics has been identified as essential for the sustainability of educational interventions (23).
The limitations of the present study include its implementation in a single medical center and one outpatient department over a short period of time, which may limit the generalizability of the findings to other centers or settings. As this was a small-scale study, it is suggested that similar, larger multicenter studies be conducted in both outpatient and inpatient settings to definitively establish the effectiveness of pharmacist-led educational interventions. Moreover, it is recommended that future studies assess the long-term impact of such educational interventions.
Seniority and specialty of antibiotic prescribers have also been associated with rational antibiotic prescribing in EDs (24). Additionally, a seasonal pattern in antibiotic use has been reported previously (25). As these factors could influence the results of similar studies, they should be considered in future research.
In conclusion, the pharmacists’ educational intervention was shown to improve rational antibiotic prescribing in the outpatient ED.
