Prospective Observational Study of Antimicrobials Utilization Prescriptions Audit in Pediatric Patients at District General Hospital in Maharashtra

Introduction

The rational use of antimicrobials involves prescribing medications only when they are clinically justified, in appropriate doses, and for the correct duration. In addition to minimizing side effects and lowering the chance of antibiotic resistance, this method guarantees that antimicrobials treat infections successfully.^1-2 A major global problem, irrational drug usage can result in the growth of microbes resistant to antibiotics, which can lengthen hospital stays, increase mortality and morbidity, put a financial strain on the healthcare system and put more strain on already-existing hospital resources. In India, the extensive misuse of antibiotics by humans has been recognized as a significant factor contributing to antibiotic resistance.³ Thus, it is important to improve rational antimicrobial use, where irrational drug use is widely prevalent in India. Limited research studies from India have focused on the prescription utilization of antimicrobial drugs as well as adherence level to medication guidelines aimed at enhancing prescribing practices and regulating the inappropriate use of antimicrobials. The prevalence of infections among patients admitted to the pediatric ward is significant, primarily due to the presence of severe illnesses and the occurrence of nosocomial infections, resulting in increased utilization of antibacterial agents.^4,5 Accurate data regarding the patterns of antimicrobial usage and the requirement to reduce resistance has become essential for effectively addressing the issues stemming from the improper use of antimicrobials, particularly within the pediatric population.⁶ An antimicrobial prescription audit is a systematic review and evaluation of antimicrobial prescribing practices to ensure they align with established guidelines and best practices. The audit aims to encourage the proper utilization of antimicrobials, decrease the occurrence of antimicrobial resistance, and improve patient outcomes. Historically, the overuse and misuse of antimicrobials have been significant drivers of antimicrobial resistance, a global public health threat. In the past, audits of antimicrobial use were sporadic and often lacked standardization, which limited their effectiveness in curbing inappropriate prescribing practices.^7,8 A prospective drug usage study of antibacterials may provide valuable data for evaluating prescription trends and developing future policies on antibacterial usage. There is insufficient data on antimicrobial prescribing trends in the pediatric population. Therefore, the present study was conducted to evaluate the antimicrobial prescribing habits of the prescribers, systematically review antimicrobial prescriptions, and assess the antimicrobial utilization audit to promote more judicious use.

Materials and Methods

Study Design

A prospective observational study was conducted at the District General Hospital pediatric ward in Amravati, Maharashtra, for six months, from October 2023 to April. Patients receiving antimicrobial drugs of either sex who were admitted to the Pediatric Department and were younger than twelve years old were chosen. The ethical approval of the IEC of the hospital (IEC/8) was obtained for the study. A written informed consent form was received in the local language before the participation of subjects from the parent and legal guardian of the patient. Patients were informed about the study's purpose, and the data's confidentiality was maintained successfully. Patients unwilling to participate and not prescribed antimicrobial agents were excluded from the study.

Data collection and analysis

Patient information pertinent to the study has been gathered from treatment records and case sheets and through interviews with patients or their caregivers, utilizing a patient data collection form. Demographic data, clinical diagnosis, details of antibacterial use (name, dose, frequency, route), length of treatment, generic or brand prescription, switch in antibacterial agent, total number of drugs prescribed, and length of stay were recorded in a spreadsheet. The data collected was analyzed for predictors such as age, gender, length of hospital stay, and it was classified according to the antimicrobials prescribed. It was then quantitatively analyzed using World Health Organization (WHO) prescribing indicators.^8,9 Antimicrobials' frequency and rationality were assessed based on their selection criteria, dose, frequency and drug interaction. Using Medscape as the reference, the analysis of drug interactions categorized them into minor, moderate and major interactions. Statistics are expressed in frequency, percentage, mean, and standard deviation computed by MS-Excel. Correlation analysis between the age group of pediatric patients and the number of antimicrobials prescribed was analyzed using GraphPad Prism ver. 10.2.3.

Results

The study included 209 pediatric patients who received antimicrobial treatment in the inpatient pediatric ward of the district general hospital in Amravati during the study period. A total of 112 (53.58%) male patients received antimicrobials during the study period. The demographic characteristics of the patients across various age groups indicated a mean age of 5.47±3.13 years (Table 1). Out of 209, the majority of patients, 150 (71.77%), were hospitalized for <5 days, followed by 51 (24.40%) patients hospitalized for 5-10 days and 7 (3.34%) patients hospitalized for 10-15 days. Only 1 patient (0.47%) was hospitalized for more than 15 days with a mean duration of 4.48±2.77 days.

The majority [N=90 (43.06%)] of patients received dual antimicrobial therapy, followed by 56 (26.79%) patients who received one drug therapy and 54 (25.83%) patients who received triple drug therapy; the patients who received four-drug therapy were only 8 (3.82%). 105 (50.23%) patients were diagnosed with bacterial disease, whereas 83 (39.71%) patients were diagnosed with viral disease (Table 1). A total of 435 antimicrobials were prescribed in the collected data of 209 patients, while the percentage of generic drugs prescribed was 90.80%. Out of 435 antimicrobials, 310 (71.24%) were administered in the form of injectables, followed by 123 (28.27%) orals, and the least was topical 2 (0.45%). The majority, 308 (70.80%), were vials, followed by 80 (18.39%) oral suspension and 37 (8.50%) tablets (Table 2). Among 435 antimicrobials, the most frequently prescribed antimicrobial was amoxclav/amoxicillin+clavulanic acid among 107 (24.59%) patients, followed by cefotaxime among 63 (14.48%) and ceftriaxone among 58 (13.33%) patients.

Fifty-six patients were on monotherapy, among which Amoxclav was the highest prescribed antibiotic among 27 (48.21%) patients, followed by cefotaxime among 17 (30.35%) and ceftriaxone among 6 (10.71%) patients. Ninety patients were on two-drug combination therapy, among which amoxclav+azithromycin was the highest prescribed 11 (12.22%) patients, followed by cefotaxime+albendazole 9 (10.0%) patients. Within the context of combination therapy, a total of 54 patients were administered a regimen consisting of piperacillin and tazobactam, amikacin and either amoxicillin with clavulanic acid, resulting in a three-drug combination therapy (Figure 1).

From the correlation analysis between the age group of pediatric patients and number of antimicrobials prescribed (Figure 2a), it was observed that there was a significant correlation for 1, 2 and 3 drug therapy (P < 0.05) and no significant correlation between age group of pediatric patients and antimicrobials prescribed for 4 and 5 drug therapy (P > 0.05). Figure 2b illustrates the relationship between disease patterns (x-axis), which include malarial (n=2), fungal (n=3), amoebic (n=16), viral (n=80), and bacterial (n=105) and (y-axis) corresponding numeric data for the number of antimicrobials prescribed for each disease pattern. The antimicrobial prescription data for the malarial disease pattern was as follows: 1 drug therapy (0), two drug therapy (0), three-drug therapy (2), four drug therapy (0), and five drug therapy (0). Similarly, the data for other disease patterns was fungal (1, 0, 1, 0, 1), amoebic (2, 9, 5, 0, 0), viral (25, 35, 18, 2, 0), and bacterial (25, 46, 28, 6, 0). The data showed a significant positive correlation between disease patterns and using 1, 2, 3 or 4 antimicrobial drugs (P < 0.05). However, there was no significant correlation between the five drug therapies. The 1, 2, 3 and 4 drug regimens were commonly used to treat malarial, fungal, amoebic, viral, and bacterial infections.

The utilization of antimicrobials in this research demonstrates both rational and irrational aspects regarding drug selection, dosage, and frequency. In terms of selecting an antimicrobial agent, 152 (72.72%) prescriptions were rational, and 57 (27.27%) prescriptions were irrational. Based on the dose of the antimicrobial agent, 197 (94.25%) prescriptions were rational, and 12 (5.74%) prescriptions were irrational.

On the basis of the frequency of the antimicrobial agent, 203 (97.12%) prescriptions were rational, and 6 (2.87%) prescriptions were irrational (Table 3). In the study, out of 209 cases, 57 total drug interactions were found, which were classified into major (15.75%), moderate (47.36%), and minor (36.84%) interactions. Table 4 presents the WHO core prescribing indicators.

Discussion

Of the 209 patients studied, 112 (53.58%) were male, while 97 (46.41%) were female. The study found a higher prevalence of infectious diseases among male patients, leading to increased antimicrobial prescriptions and contributing to the overall higher disease burden in this group. Similarly, a study conducted by Rajalingam et al., in a private tertiary care teaching hospital in western India assessed the rational use of antibiotics. The study found that out of 200 patients, 126 (63%) were male, compared to 74 (37%) female patients.¹⁰ The reasons for the male predominance during the study period remain ambiguous; however, earlier research conducted in India has indicated a societal preference for male children and a selective prioritization in the care provided to them.¹¹

Majority of patients 153 (73.20%) received combination therapy and 56 (26.79%) patient’s received monotherapy. Similar results were found in study conducted by Gupta et al., reported that antimicrobial >1 was received around half of patients (50%). It is advisable to minimize the average number of drugs per prescription in order to reduce the risk of drug interaction, bacterial resistance, and hospital expenses.¹² Among 153 patients, 90 (43.06%) patients received two drugs, and 1 (0.47%) patient received five drugs combination therapy. Similarly, Abidi et al. reported that out of 237 patients having antimicrobial therapy, the majority, 93 (39.24%) of patients received four-drug therapy, followed by 47 (19.83%) patients received three-drug therapy, and 17 (7.17%) patients received two drug therapy, the patients who received five drug therapy were 33 (13.92%).¹³

The study monitored data on a range of clinical conditions. Infectious and parasitic diseases were the leading cause of hospital admissions, accounting for 74 patients (35.40%). This was followed by gastrointestinal infections 57 (27.27%), respiratory infections 47 (22.47%), blood infections 9 (4.30%), and urinary tract infections 6 (2.87%). A similar study conducted by Abidi et al., reported that the respiratory system was predominantly maximum (44.72 %) followed by infectious and parasitic diseases (16.03 %) and diseases of digestive system (13.92 %).¹³

The antimicrobials were prescribed by generic names in 90.80% of cases which was in line with WHO recommendations. The percentage in this study is greater than that found in other Indian research. A study by Karande et al., reported that 73.4% of drugs were prescribed by generic name.¹⁴ Generic prescribing reduces the chances of dispensing errors, which may be due to misinterpretation of like-sounding names of drugs, and also decreases the economic burden on the patients. WHO recommends that physicians prescribe medications in generic names, as they are cost-effective and provide flexibility in procuring drugs from the central medical store.⁸ The injectable type was used by the majority of patients 310 (71.24%), which is significantly higher than the acceptable range of 13.4-24.1%. Karande et al., reported that the majority of drugs prescribed were in the type of syrups (60.8%), 14 while similarly, Rishi et al., and Maini et al., reported that 7% and 6.8% of patients were given injectables, respectively, in their study.^{15, 16} Excessive utilization of injectable antimicrobial drugs may result in an increased likelihood of blood-borne diseases, the emergence of complications and elevated costs.¹⁷

Amoxicillin + clavulanic acid was the most frequently prescribed antimicrobial in the drug class of penicillin+β-lactamase inhibitor. The research conducted by Prakasam et al., revealed that among the population examined, a variety of antibiotic combinations were prescribed. These included penicillin paired with β-lactamase inhibitors, tetracycline, nitroimidazole, macrolide in conjunction with cephalosporins, lincosamide combined with penicillin, fluoroquinolones alongside β-lactamase, fluoroquinolones with linco-samide, cephalosporin paired with glycopeptides, cephalosporin in combination with fluoroquinolones, and β-lactamase inhibitors with lincosamide, each representing 0.42% of the prescriptions.¹⁸ In Iran, a study conducted by Safaeian et al., reported that penicillin was the most prescribed antibiotic.¹⁹ Borade et al., reported, among his study population, mostly prescribed antimicrobial agents to neonates admitted in NICU was cefotaxime (35.8%).²⁰

A total of 90 patients received a two-drug combination therapy, with amoxclav (clavulanic acid + amoxicillin) administered intravenously, along with azithromycin being the most frequently prescribed combination, accounting for 11 patients (12.22%). Additionally, 54 patients were treated with a three-drug combination therapy, where the combination of piptaz (piperacillin + tazobactam), amikacin, and amoxclav (amoxicillin + clavulanic acid) was the most prescribed, involving three patients (5.55%).

The correlation analysis between the age group of pediatric patients and a number of antimicrobials prescribed were significant for 1, 2, and 3 drug therapies (P < 0.05). Infants, toddlers, preschoolers, and children are most treated with one, two, or three-drug therapies, demonstrating a positive correlation. The correlation between disease pattern and the number of antimicrobials prescribed was significant for 1, 2, 3 and 4 drug therapy (P < 0.05). There was a positive correlation of 1, 2, 3 and 4 drug therapies for malarial, fungal, amoebic, viral, and bacterial, as these therapies were most frequently used to treat these diseases. Antimicrobial utilization audit for rationality and irrationality considered the criteria of drug selection, dose, and frequency. Based on the antimicrobial agent's application, dosage, and frequency, 57 (27.27%), 12 (5.74%), and 6 (2.87%) of the prescriptions were unreasonable.

The major interaction between antimicrobials was 9 (15.75%), monitor closely was 27 (47.36%), and minor interactions were 21 (36.84%). The mean of 2.08 drugs per patient encounter in this research indicates the existence of polypharmacy, which involves the prescribing of a greater number of drugs than what is clinically required or essential.²¹ The World Health Organization recommended a standard for the average number of drugs per patient encounter, which is between 1.6 and 1.8.²² However, in the studies conducted by Sudan et al. and Joseph et al., the average number of drugs recorded was found to be 2.0 and 2.6, respectively.^23,24 In our study, 100% antimicrobials were prescribed from hospital formulary, exactly like standard WHO prescribing indicators. Formulary drugs are carefully selected based on their safety, efficacy, and cost-effectiveness, ensuring patients receive high-quality treatment. This standardization streamlines the prescribing process, reduces medication errors, and enhances overall patient safety.

The study's shortcomings include the lack of a hospital information system that would enable quick data collection and antimicrobial prescription tracking, as well as the absence of a single point of contact for hospital-prescribed antimicrobials. As a result, a cost-benefit analysis of antimicrobial consumption could not be performed. It is advisable to organize continuous educational and training initiatives for physicians on the topic of rational prescribing practices for injectable medications. Enhancing public awareness and sensitizing medical practitioners are crucial for improving antimicrobial therapy. The research was restricted to the pediatric ward, excluding other medical wards and the intensive care unit. The sample size was relatively small, with only 209 participants, impacting the statistical power and robustness of the conclusions.

Conclusion

In our study, males were found to be more prone to antimicrobial prescription utilization compared to females. The antimicrobial prescribing trend deviates from WHO guidelines, indicating a need for close monitoring of antimicrobial therapy due to the higher utilization of injectable medications. The selection of antimicrobials, at 72.72%, was rational and adhered to the drug formulary. Research also indicates a significant use of antimicrobials, with broad-spectrum antimicrobials such as penicillin+β-lactamase inhibitor frequently prescribed. The audit of antimicrobial patterns in pediatrics serves as benchmark data for further studies in similar settings to identify trends in drug consumption over the years.

Conflicts of Interest

None