INTRODUCTION:

Paediatrics is a field of medicine that is concerned with health of children.¹ The anatomical development and physiological function vary in pediatrics depending on their age bracket.

Children are prone to RTI as compared to adults because they do not have adequate immunity against certain viruses and bacteria that cause these infections. RTI is one of the leading causes of increased paediatric hospitalisation and mortality.²

Respiratory tract infection is the infectious disease of upper or lower respiratory tract.^3,4Acute Respiratory Tract Infections (ARTI) are a major burden to child health in developing countries like India.⁵ ARTI mainly of LRTI are leading cause of death among children below 5 years of age in such countries, resulting in 1.9 million childhood death per year, of which 20% are estimated to occur in India. Worldwide, about 85-88% of ARTI episodes are acute URTI, while the remaining are acute LRTI.⁶

The vast majority of URTIs have a viral aetiology. Rhinoviruses account for 25-30 percent of URTIs. RSVs, para-influenza and influenza viruses, human metapneumovirus and adenoviruses account for 25-35 percent; corona viruses for 10 percent and unidentified viruses for the remainder. Currently, the most common causes of viral LRTIs are RSVs. They tend to be highly seasonal, unlike parainfluenza viruses, the next most common cause of viral LRTI. ⁷Streptococcus pneumoniae, Haemophilus influenza and Moraxella catarrhalis are the most common bacterial pathogens in upper and lower RTI.⁸

RTI transmits through direct contact with droplets of saliva or mucosal secretion. These are prevalent in children below 5 years of age. A weakened immune system, overcrowding, malnutrition, poor immunisation status are other predisposing factors.⁶

Most of the RTIs are self-resolving. Symptomatic relief can be given through anti-pyretic, analgesics, non-prescription lozenges and sprays, bulb suction, nebulisation, mist therapy and other supportive care. Other treatment option includes beta adrenergic agonist, anti-histamines, antitussives, bronchodilators, expectorants, oral and nasal decongestant. Vaccinations and the availability of antibiotics substantially reduced the mortality caused by bacterial RTI. However, due to the limited availability of antiviral medications and effective vaccines the burden of viral RTI remains high.⁹

Antibiotics are the most commonly prescribed drugs (60%) in RTI. According to WHO, antibiotics used against many diseases are rapidly losing their effectiveness and microorganisms develop resistance to them due to misuse or overuse leading to the emergence of Superbugs.¹⁰Globally, antibiotic resistance has become a major clinical and public health problem.¹¹Therefore, antibiotic regimen should be selected based on presumed causative pathogen.

Rational prescription of antibiotics is very important to avoid treatment failure, non-compliance, multiple drug resistance and increased cost of treatment.¹² Therefore, antibiotics should be prescribed in appropriate route, dosage and frequency.

In view of the higher burden of RTI among paediatrics in this area, a study is taken up to analyse the prescribing pattern of antimicrobials in RTI.

MATERIALS AND METHODS:

Study Design: The prospective study was carried out for a period of six months fromMay 2022 to October 2022.

Study Population:

The study was conducted in the paediatric ward of a tertiary care teaching hospital in the southern part of India.

Ethical considerations:

Ethical approval was obtained from Institutional Ethics Committee (IEC). (Ref.no.: FMIEC/CCM/683/2022)

Source of data:

The data source needed for the study was collected from the case reports, laboratory data and treatment charts in a suitably designed documentation form.

Study Sample:

Case records of 156 patients with RTI were selected based on the study criteria. A suitably designed data collection form was used to collect the required data.

Statistical analysis: Collected information was analysed by descriptive statistical tools like frequency, percentage, mean, standard deviation and Microsoft excel.

Sample size:

n ≥ z²p (1-p)

d²

n ≥ 150

z = 1.96@ 5% level of significance

p = 0.11 (proportion from reference study)

d =0.05 (margin of error)

Study Criteria:

All the inpatients from paediatric ward and PICU with RTI aged 18 and below irrespective of gender and other comorbidities were included in this study. Exclusion criteria include patients with structural defects of lungs causing other respiratory disorders, patients under palliative care, patients with COVID-19 and HIV and patients receiving anti-tubercular drugs.

RESULTS:

The study included records of 156 patients ranging from 0-18 years, with a slight female predominance. The most prevalent and least prevalent age groups were 0- 3 and 10- 12 years respectively. The distribution in other paediatric age groups are summarized in table 1.

Table 1: Age wise distribution of the patients

Age (Years)	Frequency (%)
0-3	70 (44.88%)
3-6	47 (30.12%)
7-9	12 (7.7%)
10-12	07 (4.48%)
13-15	10 (6.41%)
16-18	10 (6.41%)

Of 156 patients, 40 were diagnosed with Wheeze Associated Lower Respiratory Tract Infections (WALRTI), 37 with unspecified URTI, 16 with pneumonia, 15 with unspecified LRTI, 12 with bronchitis [7-acute and 5- wheezy], 11 with otitis media [3- Chronic Suppurative OM, 2- Serous OM, 6- Acute OM], 9 with tonsilitis, 7 with viral URTI, 4 with bronchiolitis, 3 with pharyngotonsillitis, 1 with sinusitis and 1 with pharyngitis.

Figure 1: Distribution of RTI

Penicillin was the most frequently prescribed class of antimicrobials, followed by cephalosporins, antivirals, macrolides, aminoglycosides, carbapenems and others (fluoroquinolones, glycopeptides, sulphonamides, nitroimidazole). Amoxicillin- clavulanate (26.02%) was the most frequently prescribed antibiotic followed by ceftriaxone (21%). Oseltamivir (16.67%), Cefpodoxime (11.86%), Azithromycin (4.56%), Cefotaxime (3.19%), Cefixime (3.19%), Amikacin (2.73%), Meropenem (2.2%), Piperacillin- Tazobactam (1.82%), Clindamycin (1.36%) and Cefuroxime (0.91%) were the other antimicrobials prescribed. The least recommended antimicrobials include Cotrimoxazole, Clarithromycin, Ciprofloxacin, Cefoperazone- Tazobactam, Vancomycin, Metronidazole, erythromycin, Moxifloxacin, Amoxicillin and Tobramycin (0.45% each).

Figure 2: Percentage utilisation of class of antimicrobials

Table 2: Distribution pattern of antibiotics prescribed for RTI

Disease Antibiotics	URTI	Viral URTI	OM	Tonsilitis	Pharyngo- tonsilitis	Sinusitis	LRTI	Bronchitis	Bronchiolitis	Pneumonia	WALRI	Total
Amoxicillin-Clavulanate	14	1	3	6	2	1	5	2	1	4	18	57
Azithromycin	1	0	0	0	0	0	1	1	1	1	5	10
Ceftriaxone	10	3	4	3	1	0	6	4	0	7	8	46
Cefpodoxime	6	0	8	2	0	0	5	0	0	4	1	26
Cefixime	2	0	0	0	0	0	2	0	0	1	2	7
Piperacillin-Tazobactam	0	0	0	0	0	0	1	0	0	2	1	4
Meropenem	0	0	0	0	0	0	0	0	0	5	0	5
Amikacin	1	0	0	0	0	0	0	0	0	5	0	6
Cefuroxime	0	0	0	1	0	1	0	0	0	0	0	2
Clindamycin	0	0	0	0	0	0	2	0	0	0	1	3
Cefotaxime	3	0	0	1	0	0	1	0	0	0	2	7
Others	0	0	2	1	0	0	0	0	0	0	0	3
Total	37	4	17	14	3	2	22	7	2	29	37	167

Amoxicillin-Clavulanate was the most prevalent antibiotic which was given to treat WALRTI (31.57%) followed by URTI (24.56%). Ceftriaxone was the second most commonly prescribed antibiotic given to treat URTI (21.73%), WALRTI (17.39%) followed by Cefpodoxime, Azithromycin, Cefixime, Cefotaxime, Amikacin, Meropenem, Piperacillin- Tazobactam, Clindamycin, Cefuroxime. Antibiotics which were least prescribed include Cotrimoxazole, Cefoperazone-Tazobactam and Metronidazole.

Figure 3: RTI distribution based on age group

In this study, 77.56% patients were treated with antibiotics, of which 62.18% received monotherapy, 12.17% received dual therapy, 1.93% received triple therapy, 1.28% received quadruple therapy. Of 156 patients, 22.44% patients had no antibiotics prescribed. Majority of antibiotics were prescribed intravenously. (Figure 4). The mean number of drugs per encounter was found to be 5.19 (Table 3). The average duration of hospital stay was found to be 8.89±3.47 days.

Table 3: Number of drugs prescribed

Parameter	Number
Total number of prescriptions analysed	156
Total no. of drugs prescribed	811
Average no. of drugs per prescription	5.19

Figure 4: ROA of antibiotics

Figure 5: Other drugs prescribed

In addition to antimicrobials, other drugs prescribed were also analysed. The most common antipyretic used was paracetamol. Bronchodilators such as salbutamol, levo-salbutamol, ipratropium bromide and theophylline were prescribed. The antihistamines cetirizine and levocetirizine were given to patients. Nasal decongestion was managed using xylometazoline, oxymetazoline and saline drops. A combination of antihistamine and decongestant (chlorpheniramine maleate+phenylephrine and ebastine+phenylephrine) were used. An antihistamine and leukotriene antagonist combination (Montelukast+levocetirizine) was also given. NSAIDs such as aceclofenac, ibuprofen, mefenamic acid were also advised. Corticosteroids prescribed were budesonide, prednisolone, hydrocortisone, dexamethasone and fluticasone. Cough medications included mucolytics, expectorants and antitussives. Antiemetics were prescribed as well but to a lesser extent.

Table 4: Distribution of underlying comorbidities in patients

Comorbidities	No. of Prescriptions
Endocrine disorders	2
GI disorders	2
Cutaneous	4
Cardiovascular disorders	5
Musculoskeletal disorders	6
Global Developmental Delay	6
Neuromuscular disorders	7
Anaemia	8
Others	11
Seizures	18
Malnutrition	32
None	89

89 patients out of 156 had no comorbidities and a total of 101 comorbidities were identified from 67 patients. 32 patients (16.80%) had malnutrition which makes it the most common comorbidity identified during study. Other comorbidities in our study include blepharitis, nasal septal deviation, dehydration with hypovolemic shock, exotropic squint, hypocalcaemia, urinary tract infection, tuberous sclerosis, allergic rhinitis, hepatic failure, dissociative disorder with abnormal movements and Downs syndrome.

DISCUSSION:

RTI in paediatrics are one of the major reasons for hospital visits. RTI mainly of LRTI are leading cause of death among children below 5 years of age, resulting in 1.9 million childhood death per year, of which 20% are estimated to occur in India. Worldwide, about 85 - 88% of RTI episodes are acute URTI, while the remaining are acute LRTI.⁶Though RTIs of viral origin are self-limiting, rational use of antibiotics are necessary for bacterial infections. An appropriate prescription of antibiotics in children is necessary to avoid resistance and any unintended effects.

The study results give an overview of the prescribing pattern of antimicrobials for RTI among paediatrics which helps in planning an effective therapy and identification of drug related problems (antibiotic resistance, safety, effectiveness) and their appropriateness in comparison with standard guidelines. An antimicrobial is a chemical compound that destroys or inhibits microorganisms, especially pathogenic.¹³

In our study, there was a slight female preponderance (50.64%). Contradictory results were found in studies conducted.^2,14,15 Majority of the patients were in the age group of 0-3 years (44.88%). High incidence of RTIs among this age group is due to a weakened immune system. A study conducted by Hussaini et.al. in Telangana, India categorised 60 patients into 5 groups of which 0-3 years were more infected.¹⁶

There was a high prevalence of LRTI in our study (55.77%). An earlier study conducted in Chennai by Ramya et al. found similar results.¹⁷ It was observed that most of the patients were diagnosed with WALRTI (25.65%) followed by unspecified URTI (23.71%) and pneumonia (10.26%) while sinusitis and pharyngitis (0.64%) constitute the least. Unspecified LRTI (29.9%) was the most frequent and rhinitis (2.4%) was the least diagnosed disease in a study conducted by Naik AV et al. ¹⁸

Of prescriptions analysed, penicillins (33.15%) were the most frequently prescribed class of antibiotics followed by cephalosporins (38.51%). Similar results were found in previous studies^16,18. In contrary to these results, the studies conducted by Mustafa ZU et al. in Pakistan and Xue F et al. in China showed the use of cephalosporin class of antibiotics followed by penicillins.^19,20A study conducted by Joseph N et al. among paediatric outpatients with URTI reported the use of penicillins (69%) followed by cephalosporins (21.4%) and macrolides (9%).²¹

A total of 26.02% of antimicrobial prescriptions were amoxicillin-clavulanate and 21.0% were ceftriaxone. This result are in favour of study conducted by Hussaini et al.¹⁶and Pranay W et al.²²In contrast to these results, third generation cephalosporins (34.9%), macrolides (24.3%) and second generation cephalosporins (23.3%) were most common antibiotics prescribed for paediatric patients in a study carried out by Xue F et al. in China.²⁰

In the present study, amoxicillin-clavulanate was often used to treat WALRTI and URTI. Badar V et al. and Malo S et al. performed a study which revealed the maximum use of amoxicillin-clavulanate in the treatment of WALRTI followed by bronchiolitis and otitis media followed by bronchitis respectively.^23,24

Of 121 patients prescribed with antibiotics, 64.66% received monotherapy and 15.38% received polytherapy. This observation is different from that of prior studies.^23,25,26 It was found that most of the antibiotics were given intravenously followed by oral route. These findings are in accordance with the studies conducted by Hemamalini et al.²⁶ and Isaac S et al.²⁷

Along with antibiotics, other drugs prescribed were also examined. Antipyretics, antihistamines and bronchodilators accounted for majority of drugs used. Antipyretics were prescribed in 75% of patients with RTI. The study carried out by Jadhav et al. reported the use of antipyretics in 98.3% of patients which was higher compared to the present study.²⁸

The average number of drugs per prescription was found to be 5.19 in the present study. This is due to the prescription of cough medications, saline drops, antipyretics, bronchodilators and antihistamines along with antimicrobials. Similar trend was reported in a study conducted in Bangalore by Vishwanath M et al. and found that the average number of drugs per prescription to be 5.69.²⁹

One of the limitations of our study is that empirical treatment with antibiotic was initiated before the culture sensitivity test. Therefore, most of the culture reports were negative and might have restricted the identification of organisms.

Antibiotic treatment should be discouraged in symptomatic treatment of RTIs. Since most of the RTIs are viral in origin, the prescription pattern of antimicrobials should comply with the guidelines. The dose, dosage and frequency of drugs used varied in accordance with age and type of infections.

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Received on 05.12.2022 Modified on 01.05.2023

Research J. Pharm. and Tech 2023; 16(12):5972-5977.

DOI: 10.52711/0974-360X.2023.00969