The impact of pharmacist behavioral intervention on antibiotics prescribing in pediatric wards

Introduction

The introduction of antibiotics in medicine has resulted in one of the most successful medical advances of the 20^th century, i.e. a significant reduction in morbidity and mortality.¹ Globally, antibiotics are among the most commonly used medicines, both in the community and hospital settings; however, this has been frequently associated with irrational use (prescription of incorrect doses, self-medication and treatment of non-bacterial illness). This irrational use of antibiotics not only increases the risk of unnecessary adverse effects but also contributes to the development of antimicrobial resistance (AMR) which is a leading cause of serious health and economic problems.^2,3 High rates of bacterial resistance to broad spectrum antibiotics have been recorded in Iraq. In a study conducted in Babel, Iraq, all isolated bacteria showed high rates of resistance to the evaluated cephalosporin, and 100% and 87% resistance to cefotaxime and ceftriaxone, respectively.⁴ Globally, about 1.27 million deaths were directly attributable to AMR in 2019, which was considered the third leading cause of death that year, and it was estimated that AMR may kill 10 million people per year by 2050.⁵

Infants and children frequently experience infections, which may predispose them to unnecessary antibiotic use due to the viral origin of most of these infections.⁶ This may predispose children to unnecessary adverse effects, particularly during the first year of life.⁷ Therefore, rational antibiotic use is very essential in this population.

The rational use of antibiotics was defined by World Health Organization (WHO) as “the cost-effective use of antimicrobials which maximizes clinical therapeutic effect while minimizing both drug related toxicity and the development of antimicrobial resistance.”⁸ Another definition by the Center for Disease Control and Prevention (CDC) is “prescribing antibiotics only when they are likely to be beneficial to the patient, selecting agents that will target the likely pathogens and using these agents at the correct dose and for the proper duration.”⁹

Various studies have been conducted to assess antibiotic prescribing both in adult and pediatric populations. In a study conducted in a Neonatal Intensive Care Unit, Pune, India, it was shown that 55.9% of neonates received between one and two antibiotics, 37.3% received three to five antibiotics and 6.7% neonates were prescribed more than five antibiotics.¹⁰ In Iraq, several studies were conducted to describe the antibiotic prescribing pattern in hospitals. A study conducted in Medical City Teaching Hospitals, Baghdad, has shown that 87% of patients had received the antibiotics at incorrect time and proper antibiotic selection was found only in 11% of patients.¹¹ Additionally, a study conducted in Al-Elwia Pediatric Teaching Hospital in Baghdad has shown that 87.56% of the patients who visited the hospital have received antibiotics, and amoxicillin was the antibiotic preferred by pediatricians.¹² Another study that surveyed five teaching hospitals in Baghdad has found that 66.7% of patients were treated with at least one antimicrobial agent and the neonatal intensive care unit had the highest antimicrobial prescription rate (97.2%) where ceftriaxone was the most frequently used antibiotic.¹³

Clinical pharmacist intervention (CPI) is one of the most important interventions used to optimize medication prescription, prevent drug-related issues and lower drug costs for both the patient and the hospital.¹⁴ A study conducted in Oman has demonstrated that CPIs on antimicrobial use had positive impact both on the clinical and economic outcomes by increasing the efficacy of the treatment, avoiding unnecessary exposure to an antibiotic, reducing the toxicity of the treatment and the net cost savings was close to $200,000 USD annually.¹⁵ Besides, a prospective interventional study conducted in Babel, Iraq showed that pharmacist intervention increased surgeons’ awareness of the proper use of the National Institute of Health and Care Excellence (NICE) guidelines of fluid therapy, subsequently improving prescription practice and decreasing the incidence of fluid-associated complications including fluid overload, weight gain, increased creatinine levels and electrolyte disturbances.¹⁶

This study was the first to evaluate the impact of pharmacist interventions on antimicrobial use in pediatric wards of an Iraqi hospital. This study aimed to evaluate the current clinical practice of antimicrobial agents’ prescription in pediatric wards and to assess the clinical and economic impact of pharmacist interventions on antibiotic use.

Methods

Results

The study recruited 500 children who received antibiotic treatments: 250 patients in the pre-intervention phase and 250 patients in the post-intervention phase. Most of the patients were male in both study phases (56% and 59.6% in the pre- and post-intervention phases, respectively). However, according to Chi-square test, there was no significant (p-value ˂0.05) difference between the two phases in terms of patient sex. The age of the pediatric patients ranged from one to 12 months in both phases. Pneumonia was the most frequent diagnosis in the pre-intervention phase (40.8%) whereas gastroenteritis was the most frequent one in the post-intervention phase (24.4%). These frequencies were comparable between the two study phases (Table 1).

Regarding antibiotic use, four antibiotics (amoxicillin, cefotaxime, vancomycin and meropenem) were significantly more frequently prescribed for children in the pre-intervention phase compared to the post-intervention phase. Two antibiotics (ceftazidime and amikacin) were only prescribed in the post-intervention phase (Table 2).

Regarding the pattern of the antibiotics prescribed, double antibiotic treatment was mostly used in the pre-intervention phase (58.4%), whereas single antibiotic treatment was the most frequent in the post-intervention phase (59.6%). The difference in the number of antibiotics prescribed in the pre- and post-intervention phases was statistically significant (Table 3).

Both length of therapy and days of therapy were significantly longer in the pre-intervention phase compared to post-intervention phase. The total cost of the antibiotics used in the pre-intervention phase was significantly higher than that in the post-intervention phase, since the cost per single vial/bottle of antibiotic was the same across the two phases (Table 4).

The culture and sensitivity (C/S) test were not performed for any patient during the pre-intervention phase. In contrast, 28% of the participating patients in the post-intervention phase did have a C/S test. Three types of samples were tested: urine (35.7%), throat swab (35.7%) and stool (28.6%). Among the seventy C/S tests in the post-intervention phase, only 18 samples had bacterial growth. Urine samples had the highest percent of bacterial growth (40%), while throat swap had the lowest growth rate (8%) (Table 5).

Escherichia coli (E. coli) was the most commonly (61%) identified bacteria in the C/S test, followed by Staphylococcus epidermidis (Staph. epidermidis) (16.6%) (Table 6).

Not all antibiotics were tested in each C/S test. The frequency of antibiotic testing ranged from 13 to 18 times. Four antibiotics had sensitive results in more than half of the conducted C/S tests: nitrofurantoin (100%), meropenem (81.25%), amikacin (70.6%) and gentamicin (53%) (Table 7).

Discussion

Irrational antibiotic use is a global problem that requires special attention to reduce its adverse consequences. Pharmacists, being medication experts, can play a critical role in enhancing antibiotic prescription. To the best of the authors’ knowledge, this is the first study conducted in Iraq that has evaluated the impact of pharmacist intervention on antibiotic prescription in the pediatric population.

Most of the patients were males in both study phases and in the age range of 1-12 months. This may be expected because infants in this age are more prone to infections due to their still-developing immune system. It was estimated that infants during their first year of life may be subjected to five to 11 episodes of infections.¹⁹ Pneumonia was the most frequent diagnosis in the pre-intervention phase whereas gastroenteritis was the most frequent one in the post- intervention phase (Table 1). This may be related to the time period during which the data was collected (winter months in the pre-intervention phase versus summer months during the post-intervention phase) where the risk of these kinds of infections increases. Similar results were obtained from other studies in Baghdad, Iraq and India, where gastroenteritis and respiratory tract infections were the most commonly reported diagnoses.^12,20

Regarding the type of antibiotics prescribed, amoxicillin, ceftriaxone and gentamicin were the most commonly prescribed drugs (Table 2). These are broad spectrum antibiotics and frequently used as empiric therapy, which could explain the obtained results. In the study conducted in AL- Elwia Pediatrics Hospital in Baghdad, the results have shown that amoxicillin was the most predominant antibiotic prescribed (72.24%) in the emergency departments of the hospital.¹² Similarly, results from a study in the United Arab Emirates have shown that amoxicillin was the most frequently prescribed antibiotic (40%).²¹ In contrast, a study conducted in Saudi Arabia has shown that cephalosporin were more frequently (38%) prescribed in the pediatric intensive care unit (ICU) and aminoglycosides were frequently (45.4%) prescribed in the neonatal ICU.²²

In the current study, results have shown that prescribing broad spectrum antibiotics, including meropenem and vancomycin, significantly decreased after pharmacist intervention (Table 2). Similar results were observed in an interventional study conducted in China in which the prescription of these antibiotics also significantly decreased in the post-intervention phase (p<0.05).²³ Similarly, differences in the number of antibiotics prescribed in the two phases was statistically significant. Double antibiotic treatment was mostly used in the pre-intervention phase whereas single antibiotic treatment was the most frequent in the post-intervention phase (Table 3). On the other hand, LOT, DOT and the total cost of the antibiotics prescribed clearly decreased in the post-intervention phase (Table 4). This clearly shows the pivotal role of pharmacists’ intervention in enhancing antibiotic prescribing by the physicians. In Oman, the annual net cost savings from pharmacist interventions on antimicrobial use was close to $200,000 USD.¹⁵

In the current study, antibiotic prescribing was mostly based on the physicians’ experience and the availability of antibiotics at the hospital. C/S test was not done for any patient in the pre-intervention phase of the study. Nearly similar results were obtained in two studies conducted in AL-Elwia Pediatric hospital and five hospitals in Baghdad, where culture and sensitivity tests were only conducted on 0.08% and 1.2% of the patients, respectively.^12,13 In comparison, during the post-intervention phase, the C/S test was done for 28% of the participating patients of which only 25.7% had bacterial growth (Table 5). These results show that antibiotics may be frequently prescribed for conditions that may not require their use.

Regarding bacterial sensitivity to antibiotics, four antibiotics had sensitive results in more than half of the conducted C/S tests: nitrofurantoin, meropenem, amikacin and gentamicin. On the other hand, third-generation cephalosporin had a resistance rate of more than 90%, while ampicillin and amoxicillin showed full resistance (Table 7). Highly similar results were obtained from a study conducted in Al-Shomali General Hospital, Babel, Iraq from October 2019 to May 2020. The study showed a high rate of resistance to cefotaxime and ceftriaxone 100% and 87%, respectively, while low resistance was recorded against gentamicin and amikacin; 22% and 19%, respectively.⁴ In comparison, another study conducted in Bagdad, Iraq in 2012 showed that the rate of resistance to cefotaxime and ceftriaxone was 71.5% and 66.7%, respectively.²⁴ On the other hand, a retrospective study conducted in Al-Diwaniyah Tertiary Hospital from in 2022 found that Staphylococcus species showed high resistance to ampicillin (92.9%) followed by ceftazidime (87.5%), and were highly sensitive to vancomycin. Additionally, E. coli showed high resistance to ampicillin (97.9%) and ceftriaxone (81.3%) while it was highly susceptible to meropenem (97.9%) and amikacin (97.6%).²⁵ This increase in the rate of resistance to these antibiotics can be attributed to their irrational use as they are frequently used as empiric therapy based on their availability and broad spectrum of activity, with no limitation and without relying on culture and sensitivity test results.

This study had a number of limitations. The study included a relatively small number of patients and was conducted in one hospital. Additionally, this study focused on antimicrobial prescribing practices in the governmental sector without including any data from the private sector.

Conclusions

This study demonstrates that the pharmacist intervention on antimicrobial use in pediatrics resulted in favorable clinical and economic outcomes. These results indicate that clinical pharmacists can play an essential role in enhancing the practice of antimicrobial use in hospitals.