Drug prescribing pattern in upper respiratory tract infections among the pediatric population attending outpatient clinics in pediatric hospitals

Abstract

BACKGROUND

Upper respiratory tract infections (URTIs) are one of the most frequent causes of childhood school leave and morbidity.

AIM

To study the present trend of medications’ prescribing pattern utilized in URTIs among the pediatric population attending outpatient clinics in pediatric hospitals.

METHODS

This analytical observational cross-sectional research was conducted in 200 children aged 1–10 years with URTIs attending the pediatric outpatient clinics in pediatric hospitals, one of which is an educational hospital, from July 2018 to August 2020.

RESULTS

Most of the prescriptions in our study included antibiotics (116/58%). The most commonly prescribed antibiotic family was ampicillin/sulbactam or amoxicillin/clavulanic acid (53/26.5%), followed by first-generation cephalosporin (25/12.5%) and third-generation cephalosporin (20/10%). Macrolides and second-generation cephalosporins were prescribed less frequently, in 16 (8%) and 2 (1%) patients, respectively. Most of our study population (155/77.5%) was satisfied with their prescriptions, whereas the rest of the study population (45/22.5%) was unsatisfied.

CONCLUSION

Overprescription of antibiotics is a significant issue among clinicians in pediatric outpatient clinics. Stewardship of drugs, particularly antibiotics, is a must to prevent the development of drug resistance. Most cases of URTIs were treated in accordance with the existing national treatment guidelines.

Key Words: Upper respiratory tract infection; Antibiotics’ prescribing pattern; School leave; Pediatric; Antibiotics’ stewardship

Core Tip: Overprescription of antibiotics is a significant issue among clinicians in pediatric outpatient clinics. Pediatric clinicians should aim to reduce antibiotic use by addressing three fundamental questions for each patient with a suspected infection: (1) Do antibiotics need to be prescribed; (2) What is the appropriate dose thereof; and (3) What is the optimal duration of treatment. Stewardship of drugs, particularly antibiotics is a must, to prevent the development of drug resistance.

INTRODUCTION

Acute respiratory illnesses are common in school-aged children, with approximately 30%-40% affected during the winter months. Upper respiratory tract infections (URTIs) are among the most prevalent causes of childhood school leave and morbidity, as well as the most frequent reasons for outpatient department (OPD) consultation. URTIs remain the clinical category for which antibiotics are most commonly prescribed. However, most URTIs are caused by viruses for which antibiotics have no role in treatment[1].

Bacterial etiology has been identified in just 10% of URTIs. The worldwide inappropriate usage of antibiotics in children with URTIs contributes to antibiotic resistance, which has become a serious public health problem. The consequences of antibiotic resistance are challenging to predict, but it is estimated that by 2050, it will cause about 10 million deaths and lead to a massive economic burden[2]. In 2019, the World Health Organization recognized antimicrobial resistance as one of the top 10 threats to global health[3].

The most common bacterial agents responsible for acute sinusitis are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Other organisms including Staphylococcus aureus, S. pyogenes, Gram-negative organisms, and anaerobes have also been recovered. Chronic sinusitis is commonly a mixed infection of aerobic and anaerobic organisms. Group A beta-hemolytic Streptococcus or St. pyogenes is the most important bacterial agent associated with acute pharyngitis and tonsillitis. Corynebacterium diphtheriae causes occasional cases of acute pharyngitis, as do mixed anaerobic infections (Vincent's angina), C. haemolyticum, Neisseria gonorrhoeae, and Chlamydia trachomatis. Outbreaks of Chlamydia pneumoniae (TWAR agent) causing pharyngitis or pneumonitis have occurred[4].

The initial treatment for cases diagnosed with bacterial URTIs is amoxicillin/clavulanic acid, while ceftriaxone is the preferred choice for those who are penicillin-sensitive. Other antibiotics that may be employed to treat URTIs include cefuroxime, cefpodoxime, azithromycin, cefdinir, cefixime, and cefadroxil[5].

The penicillin family of antibiotics remains a crucial component of our antimicrobial arsenal. These agents are generally well-distributed throughout the body, exhibit bactericidal activity, have low toxicity, and are effective against infections caused by susceptible bacteria[6]. A major pharmacologic milestone was the introduction of aqueous penicillin G for treating staphylococcal and streptococcal infections. In response to the emergence of penicillinase-producing S.aureus, penicillinase-resistant penicillins such as oxacillin, methicillin, and nafcillin were developed. These penicillins feature an acyl side chain that protects the β-lactam ring from disruption[7].

MATERIALS AND METHODS

This analytical cross-sectional research was performed on 200 kids aged 1–10 years with URTIs attending the pediatric outpatient clinics in pediatric hospitals, one of which is an educational hospital, from July 2018 to August 2020.

Inclusion criteria

Children with ages ranging from 1 to 10 years with URTIs.

Exclusion criteria

All patients between 1 and 10 years of age who attended the pediatric OPD and were diagnosed with URTIs were involved in the research, except those with intellectual disabilities, unconscious, and untreated cases; infants and kids with lower respiratory tract infections; infants and children with any other infections except URTIs; and those who needed inpatient admission.

Ethical considerations

The study was designed to confirm the requirements of the revised Helsinki Declaration of Bioethics (2013). The study protocol was presented to the Research Ethics Committee of the Faculty of Medicine, Cairo University for approval. Informed consent was obtained from the participants before enrollment in the study. The patients had the right to withdraw from the study at any time and for any reason without any consequences. Confidentiality of the data collected was protected.

Methods

The data were collected using an interview-based questionnaire. This data included a full medical history, vaccination history, physical examination involving anthropometry, laboratory investigations, and treatment given to children. The following was done based on the above-mentioned; the demographic characteristics of kids with URTIs were analyzed, focusing on the diagnosis and pharmacological information. This included the name of the drug (both its generic and brand names), dosage form, frequency of administration, duration of treatment, distribution of drug groups, antibiotics, and analgesic-antipyretics prescribed to the kids with URTIs.

Outcome measures

Primary outcome: Assessment of the pattern and rationale of drug prescription for URTIs in kids aged 1–10 attending outpatient clinics in pediatric hospitals.

Secondary outcomes: The prevalence of irrational drug use among children with URTIs; the correlation between antibiotic administration in kids with URTIs and their laboratory investigations; the correlation between the degree of fever and prescribing antibiotics for children; the correlation among children’s prescribed antibiotics, their temperature, and the extent of improvement of their condition; and the prevalence of prescribed antibiotics in kids with URTIs and antibiotic abuse.

Statistical analysis

The Excel 2013 program was used to acquire, code, and enter the data into the computer. The data analysis was conducted using the Statistical Package for the Social Sciences program. The data were analyzed and presented as percentages and numbers in tables and graphs; with a 95% confidence interval. The P value of 0.05 was utilized as the threshold for statistical significance. The quantitative values were given by the Student’s t-test, while the qualitative values were given by the χ² test. The results were tabulated, and statistical significance was determined.

RESULTS

Table 1 shows that 52.0% of the studied patients were males. In total, 29.5% of the participants had acute pharyngitis, 19.0% had acute tonsillitis, 13.5% had acute sinusitis, 6.5% had acute otitis media, and 31.5% had acute rhinitis and/or common cold. Seventy percent (70.0%) of the physicians were specialists, and 80.5% of the enrolled prescriptions were collected from pediatric outpatient clinics. Most of the prescriptions in our study included antibiotics (116/58%). The most commonly prescribed antibiotic family was ampicillin/sulbactam or amoxicillin/clavulanic acid (53/26.5%), followed by first–generation cephalosporin (25/12.5%) and third–generation cephalosporin (20/10%). Macrolides and second-generation cephalosporins were prescribed less frequently, in 16 (8%) and 2 (1%) patients, respectively.

Table 1 Baseline characteristics, n (%).

Baseline characteristics		Count
Gender	Male	104 (52.0)
	Female	96 (48.0)
Current diagnosis	Acute pharyngitis	59 (29.5)
	Acute tonsillitis	38 (19.0)
	Acute sinusitis	27 (13.5)
	Acute otitis media	13 (6.5)
	Acute rhinitis and/or common cold	63 (31.5)
Physician grade	General practitioner	60 (30.0)
	Specialist (pediatrician and ENT)	140 (70.0)
Outpatient clinic	Pediatric	161 (80.5)
	ENT	39 (19.5)
Type of drug (antibiotics)	No	84 (42)
	Yes	116 (58)
Family of antibiotic prescribed	Penicillin family "ampicillin/sulbactam or amoxicillin/clavulanic acid"	53 (26.5)
	First-generation cephalosporin	25 (12.5)
	Macrolides	16 (8.0)
	Second-generation cephalosporin	2 (1.0)
	Third-generation cephalosporin	20 (10.0)
	No	84 (42.0)

ENT: Ear, nose and throat.

Table 2 shows that 32.5% of patients were prescribed antihistaminic drugs. The most commonly prescribed antihistamines were from the second-generation family (24%), followed by those from the first-generation group (8.5%). Of the enrolled patients, 48.5% were prescribed oral nasal decongestants, of whom 72.2% had oral nasal decongestants containing pseudoephedrine, 26.8% had phenylephrine containing forms, and only 1% had a phenylpropanolamine-containing type. In all, 30.5% of patients had antitussive medicines, while 85.0% had antipyretics. According to the type of antipyretic, 48% and 22.8% of patients had received ibuprofen and paracetamol, respectively, whereas 14.6% had received diclofenac Na/K and combinations in each group. According to the route of administration of antibiotics, 37.0% of them were prescribed orally, 10.5% by injection and both routes in each individual category. Seventy-two percent of patients had laboratory investigations in the form of complete blood count (CBC) and C-reactive protein (CRP).

Table 2 Baseline characteristics regarding type of prescribed drug, n (%).

Baseline characteristics regarding type of prescribed drug		Count
Antihistamines	Yes	65 (32.5)
	No	135 (67.5)
Family of antihistamines	First-generation antihistaminic	17 (8.5)
	Second-generation antihistaminic	48 (24.0)
	No	135 (67.5)
Oral nasal decongestant	Yes	97 (48.5)
	No	103 (51.5)
Type of oral nasal decongestant	Oral nasal decongestant containing pseudoephedrine	70 (72.2)
	Containing phenylephrine	26 (26.8)
	Containing phenylpropanolamine	1 (1.0)
Antitussive medicine	No	139 (69.5)
	Yes	61 (30.5)
Antipyretic medicine	Yes	170 (85.0)
	No	30 (15.0)
Type of antipyretics	Paracetamol	39 (22.8)
	Ibuprofen	82 (48.0)
	Diclofenac Na/K	25 (14.6)
	Combinations	25 (14.6)
Route of administration of antibiotics	Orally	74 (37.0)
	Injection	21 (10.5)
	Both	21 (10.5)
	No	84 (42.0)
Laboratory investigations: Complete blood count and C-reactive protein	Not done	56 (28.0)
	Done	144 (72.0)

According to seeking other medical services, 19.5%, 12.5%, and 5.5% of patients sought pharmacies, private clinics, and hospitals, respectively. According to parents’ satisfaction, 77.5% of them were satisfied. According to vaccination history, 84.5% of patients had received compulsory immunization schedule only, while 15.5% had received additional recommended vaccines. According to the family education, 97.5% of patients had educated mothers, while 92.0% of them had educated fathers, as shown in Table 3.

Table 3 Summary of study population attitude and practice regarding the provided medical service, n (%).

Attitude and practice regarding the provided medical service		Count
Seeking other medical service	No	125 (62.5)
	Pharmacy	39 (19.5)
	Hospital	11 (5.5)
	Private clinic	25 (12.5)
Parents’ satisfaction	Satisfied	155 (77.5)
	Unsatisfied	45 (22.5)
Vaccination history	Compulsory immunization schedule only	169 (84.5)
	Additional recommended vaccines	31 (15.5)
Mother's education	Educated	195 (97.5)
	Uneducated	5 (2.5)
Father's education	Educated	184 (92.0)
	Uneducated	16 (8.0)

There was a significant relationship between antibiotic prescription and antitussive medicine, antipyretics, type of antipyretic, route of administration of antibiotics, laboratory investigations (CBC and CRP), total leukocyte count (TLC) in number, TLC (differential count), and CRP (Table 4).

Table 4 Intergroup comparison between the study populations when classified according to antibiotic administration status, n (%).

		Antibiotic prescription		P value
		Yes	No
Antitussive medicine	No	88 (76.5)	51 (60.0)	0.012
	Yes	27 (23.5)	34 (40.0)
Antipyretics	Yes	107 (93.0)	63 (74.1)	< 0.001
	No	8 (7.0)	22 (25.9)
Type of antipyretic	Paracetamol	12 (11.1)	27 (42.9)	< 0.001
	Ibuprofen	57 (52.8)	25 (39.7)
	Diclofenac Na/K	16 (14.8)	9 (14.3)
	Combinations	23 (21.3)	2 (3.2)
Route of administration of antibiotics	Orally	73 (63.5)	1 (1.2)	< 0.001
	Injection	21 (18.3)	0 (0.0)
	Both	21 (18.3)	0 (0.0)
	No	0 (0.0)	84 (98.8)
Laboratory investigations: Complete blood count and CRP	Not done	41 (35.7)	15 (17.6)	0.005
	Done	74 (64.3)	70 (82.4)
TLC in number	High	20 (26.7)	6 (8.6)	0.005
	Normal	55 (73.3)	64 (91.4)
TLC (differential count)	Normal	52 (69.3)	57 (81.4)	0.002
	Neutrophilia	18 (24.0)	3 (4.3)
	Lymphocytosis	5 (6.7)	8 (11.4)
	Eosinophilia	0 (0.0)	1 (1.4)
	Monocytosis	0 (0.0)	1 (1.4)
CRP	Positive	31 (41.3)	3 (4.6)	< 0.001
	Negative	44 (58.7)	62 (95.4)

CRP: C-reactive protein; TLC: total leukocyte count.

Table 5 shows a significant relationship between antibiotic prescription and father’s education.

Table 5 Correlation between antibiotic administration in children with upper respiratory tract infections and other parameters.

		Antibiotic prescription		P value
		Yes	No
Compliance to treatment	Regular	102 (88.7)	79 (92.9)	0.311
	Irregular	13 (11.3)	6 (7.1)
Response to treatment	Good	90 (78.3)	65 (76.5)	0.764
	Not good	25 (21.7)	20 (23.5)
Side effects appearance (rash, diarrhea, gastrointestinal upsets, etc.)	No	96 (83.5)	77 (90.6)	0.146
	Yes	19 (16.5)	8 (9.4)
Seeking other medical service	No	75 (65.2)	50 (58.8)	0.638
	Pharmacy	19 (16.5)	20 (23.5)
	Hospital	6 (5.2)	5 (5.9)
	Private clinic	15 (13.0)	10 (11.8)
Parents’ satisfaction	Satisfied	91 (79.1)	64 (75.3)	0.521
	Unsatisfied	24 (20.9)	21 (24.7)
Vaccination history	Compulsory immunization schedule only	102 (88.7)	67 (78.8)	0.057
	Additional recommended vaccines	13 (11.3)	18 (21.2)
Mother's education	Educated	112 (97.4)	83 (97.6)	1
	Uneducated	3 (2.6)	2 (2.4)
Father's education	Educated	101 (87.8)	83 (97.6)	0.011
	Uneducated	14 (12.2)	2 (2.4)

DISCUSSION

This study shows that 52.0% of the enrolled patients were males. In total, 29.5% of the study population had acute pharyngitis, 19.0% had acute tonsillitis, 13.5% had acute sinusitis, 6.5% had acute otitis media, and 31.5% had acute rhinitis and/or common cold. Seventy percent of physicians were specialists, and 80.5% of the enrolled prescriptions were collected from pediatric outpatient clinics. Fifty-eight percent of patients had antibiotics in their prescriptions.

In a study by Butt et al[8] on the outpatient pediatric population with URTIs, it was found that 45% of them had antibiotics in their prescriptions. The majority of antibiotics were prescribed by general/family practice physicians, followed by pediatricians, and otolaryngologists.

Most of the prescriptions in our study included antibiotics (116/58%). The most commonly prescribed antibiotic family was ampicillin/sulbactam or amoxicillin/clavulanic acid (53/26.5%), followed by first-generation cephalosporin (25/12.5%) and third-generation cephalosporin (20/10%). Macrolides and second-generation cephalosporins were prescribed less frequently in 16 (8%) and 2 (1%) patients, respectively.

The highest use of antibiotics was reported in the penicillin group (26.5%). These agents are suggested by the standard guidelines for URTIs[9].

In another study by Eibach et al[10], cephalosporins are widely utilized as empirical treatments in primary care clinics due to their low toxicity. However, it is important to note that they might also contribute to the development and spread of multi-drug-resistant infections.

Most of our study population did not have antitussive medications (139/69.5%); regarding the pattern of oral nasal decongestant prescription, 48.5% of our study population had this type of drug. Of those 97 patients, most of them had decongestants containing pseudoephedrine (70/72.2%), followed by those containing phenylephrine and phenylpropanolamine (26/26.8% and 1/1%), respectively.

Cheng et al[11] revealed that antihistamines for systemic use have been the most often prescribed drugs for cough and cold in viral respiratory tract infections, followed by mucolytic agents, across all age groups. Although studies have not demonstrated any therapeutic advantages of antihistamines compared to placebos in relieving cold-induced sneezing or nasal symptoms in children, it is still not advisable to use antihistamines alone in kids due to the potential for adverse reactions.

Most of the prescriptions (135/67.5%) included in our study did not involve antihistamines, while only 65 (32.5%) patients had antihistamines. These findings are in accordance with Lakshmi et al[12], who also reported a lower percentage of population with URTIs who had an antihistaminic prescription.

There was a significant relationship between antibiotic prescription and antitussive medicine, antipyretics, type of antipyretic, route of administration of antibiotics, laboratory investigations (CBC and CRP), TLC in number, TLC (differential count), CRP, and father’s education. According to the pattern of antipyretic drug prescriptions, most of our study population had antipyretics (170/85%). The most commonly prescribed antipyretic drug was ibuprofen (82/48%), followed by paracetamol (39/22.8%). Diclofenac Na/K or drug combinations were prescribed in (25/14.6%) of the enrolled prescriptions for each group.

Lakshmi et al[12] observed that 130 cases (71.8%) received antipyretic therapy. Particularly, the proportion of preschoolers (76.7%) receiving the therapy was greater than schoolchildren (57.4%). The prevalent pattern observed was the prescription of a single antipyretic medication, whereas a combination of two alternating medicines was administered in 25.3% of cases. The most recommended medications were paracetamol and ibuprofen, either used alone or in alternating doses. Ibuprofen was provided to 54% of preschoolers and 64.7% of schoolchildren.

Most of our study population (155/77.5%)was satisfied with their prescriptions, while the rest of our study population (45/22.5%) was unsatisfied.

The results are consistent with those reported by Zyoud et al[13], who found that pediatricians and parents have a trusting relationship. Most parents have confidence in the prescriptions and information provided by pediatricians, and only a few of them would change pediatricians if antibiotics were overprescribed or underprescribed for URTIs in kids.

We recommend that future studies include private healthcare facilities. More treatment details should be recorded such as the appropriateness and length of antibiotic use, with the indication for culture before antibiotic therapy. This will provide significant information to guide antibiotic stewardships strategies. Future surveys should be conducted throughout multiple time points for a more robust estimate of inpatient antibiotic prescribing in Egypt. Studies should also be conducted to assess the relationship of attitudes to actual antimicrobial prescribing; thus, there may have been information bias toward providing answers that the respondents thought the investigators wanted to hear, leading to underestimates of the prevalence of inappropriate attitudes, and prescribing behaviors. Measuring antibiotic consumption and prescription audit to determine the appropriate use of antibiotics and whether or not the interventions are effective.

CONCLUSION

Overprescription of antibiotics is a significant issue among clinicians in pediatric outpatient clinics. Pediatric clinicians should aim to reduce antibiotic use by addressing three fundamental questions for each patient with a suspected infection: (1) Do antibiotics need to be prescribed; (2) What is the appropriate dose thereof; and (3) What is the optimal duration of treatment. Stewardship of drugs, particularly antibiotics is a must, to prevent the development of drug resistance.