Abstract Context: Pediatric patients require more care while prescribing antimicrobials in order to avoid the adverse drug events, resistance, drug-drug interactions. Rational use of antimicrobials is an important mode to decrease these issues.Aims: To generate a baseline data on antimicrobial prescribing pattern among pediatric patients.Settings and Design: Observational, descriptive, drug utilization studyMethods and Material: Pediatric patients of both gender and ≤12 years of age and receiving at least one antimicrobial were included in the study. A specially designed case record form was used to collect data regarding patient's details, drugs details, culture sensitivity reports.Results: Total 450 (43.65%) indoor patients prescriptions and 581 (56.35%) outdoor patients prescriptions were assessed. Antimicrobials were prescribed most commonly to the age group of 1 year to 4 years. Parenteral dosage form was commonly utilized in indoor patients (69.57%). Among indoor and outdoor patients 1.84 and 1.14 antimicrobials were prescribed per prescription respectively. Single antimicrobial was prescribed in (85.54%) outdoor patients and (42%) indoor patients, while two antimicrobial were prescribed in 14.46% of outdoor patients and 28% of indoor patients. Syrup Amoxicillin and Clavulanic acid combination was most frequently utilized antimicrobial (32.53%) in outdoor patients while cefotaxime injection (50%) was most commonly utilized among indoor patients. Brand names were more frequently used in indoor patients (64.88%) than outdoor patients (29.89%). Rational prescribing was observed in 84.85% of outdoor patients and 80% of indoor patients.Conclusions: the most of the prescribing pattern of antimicrobials in the pediatric patients of the hospital is found to be rational according to the guidelines while number of AMAs per prescription and duration of treatment warrant further awareness.Key-words: antimicrobial, pediatric, prescription pattern, outdoor, indoor.Introduction Drug utilization research is defined by WHO as “the marketing, distribution, prescription, and use of drug in a society, with special emphasis on the resulting medical, social and economic consequences” [1]. An antimicrobial agent (AMA) or an antibiotic is defined as any therapeutic agent produced by an organism or made synthetically that selectively destroys or inhibits the growth of micro-organisms, such as bacteria, fungi, or protozoa [2]. In India the infectious disease burden is among the highest in the world. Pneumonia and diarrheal diseases account for 50% of total 1.34 million deaths among Indian children of 1 month to 5 years of age [3]. Antimicrobials are among the most widely prescribed therapeutic agents across the world [4]. The use of antimicrobials among children is different from adults due to (i) lack of data on pharmacokinetics, pharmacodynamics, efficacy and safety of drugs (ii) different physiological spectrum among different age groups like preterm neonates, full term neonates, infants and toddlers, and older children, adolescents (iii) pediatrics populations being vulnerable to the majority of the illnesses and (iv) the adverse effect of irrational use of antimicrobials being more serious among children than adults [5]. Recent report showed the inappropriate and irrational use of antimicrobial agents, which led to increase in development of antimicrobial resistance. Antimicrobial resistance will result in difficulty in controlling the diseases in the community and ineffective delivery of the health care services [6]. Recent years, have seen an uncontrolled rise in antimicrobial-resistant infections, leading to increased morbidity, mortality, and healthcare costs [7].Thus, cautious use of antimicrobial is therefore an important mode to decrease an issue of antimicrobial resistance. So, detailed rationale knowledge of antimicrobial prescribing pattern must be implemented in the clinical practice. The study of prescribing pattern is a part of the medical audit and seeks to monitor, evaluate and if necessary, suggest change in prescribing practices to make medical care rational and cost effective. Pediatric patients require more care while prescribing antibiotics in order to avoid the adverse drug events, resistance, drug-drug interactions. A recent study highlighted the importance of rationalizing antibiotic use to limit antibiotic resistance in India [8]. Rational prescribing practices serve to combat this global public health challenge by preventing antibiotic overuse and misuse [9]. This study was planned with an aim to generate a baseline data on drug prescribing pattern, with main focus on antimicrobial drugs prescribing for patients of pediatric Inpatient (IPD) and outpatient Department (OPD) and To suggest necessary modifications in antimicrobial drugs prescribing practices in order to achieve the rational and evidence based therapeutic practices.Materials and MethodsThis observational, single center, descriptive, drug utilization study was conducted in Pediatric OPD and IPD of B. J. Government Medical College and Sassoon General Hospitals, Pune after getting an approval from Institutional Ethics Committee. Inclusion and Exclusion criteria were as follows:Inclusion criteria1.Age group 1 day to ≤12 years2.Patients visiting OPD 3.Patients admitted in pediatric intensive care units and pediatric wardsExclusion criteria1.Patients who don’t have antimicrobials in their prescription2.Age group > 12 yearsGuardian of the patients meeting eligibility criteria were briefed about the study and informed consent was obtained from those willing to participate, from guardians. Patients who were admitted in pediatric wards and those visiting pediatric OPD of both gender and ≤12 years of age with any diagnosis of their medical condition and at least one antimicrobial in prescription were included in the study. The data was collected after getting permission from respective head of the department for analyzing the prescriptions. Strict confidentiality of the prescriber and of the patient was maintained during the study period. Patient’s antibiotic prescription data was collected for period of 3 months from May 2017 to July 2017. A specially designed case record form was used to collect the required information from each patient. The following parameters were recorded for each prescription: patient's demographic details, diagnosis, drugs details (name, dose, route, dosage form, frequency and duration of therapy), culture sensitivity reports and adverse events due to current therapy. During the study period if patient revisited to hospital, included in study again as follow up patient. National Essential Drug List and List of Essential Medicines for Children of India [10, 11] have taken as reference to check availability of prescribed antimicrobials. Evaluation of prescription was done with help of WHO guidelines [12] and hospital antibiotic policy [13] to measure their rationality Data and results were represented in suitable graphical and tabular forms.ResultsTotal 1500 prescriptions of indoor and outdoor patients of pediatric department were screened. 1031 prescriptions were assessed, rest 469 prescriptions were excluded. It consisted of 450 (43.65%) indoor patients and 581 (56.35%) outdoor patients. Out of 450 indoor patients, 225 (50%) were male while 225 (50%) were female. Out of 581 outdoor patients, 343 (59%) were males and 238 (41%) were females. Majority of indoor as well as outdoor patients who had received antimicrobials were from age group of 1 year to 4 years (Table-1)It was observed that, parenteral dosage form of antimicrobials was commonly utilized in indoor patients (69.57%) followed by oral dosage form of antimicrobials (29.35%) while oral route was obviously preferred for antimicrobials administration (94.73%) followed by topical dosage form of antimicrobials (5.27%) in OPD patients. Parenteral dosage form was not at all used in outdoor patients (Figure 1).OPD patients were categorized on the basis of predominant systems involved. A total of 581 were further categorized according to diseases like respiratory tract infections which consisted of 44.67% patients followed by 15.67% gastrointestinal infections, 14.46% skin infections. (Table-2) The most common diagnosis which warranted antimicrobial prescription in the OPD was upper respiratory tract infection (280 cases) followed by diarrhea and skin infection. Table-2 also demonstrates system wise distribution of diagnosis among 450 pediatric IPD prescriptions. Respiratory system was the most commonly involved system in which bronchopneumonia (54 cases) and bronchiolitis (54 cases) were the major diseases which required antimicrobials use.During the study period, 1863 drugs were prescribed for 450 indoor patients (average 4.14 drugs per prescription), out of which 828 (44.44%) were antimicrobials. Hence, 1.84 antimicrobials were prescribed per prescription in indoor patients. 1680 drugs were prescribed for 581 outdoor patients (2.89 drugs per prescription), out of which, 665 (39.58%) were antimicrobials. Hence, 1.14 antimicrobials were prescribed per prescription in outdoor patients. When assessed about the number of antimicrobials per prescription, it was found that most commonly one antimicrobial per prescription was prescribed in 42% of prescriptions and two antimicrobials per prescription were prescribed in 28% of prescriptions in indoor patients. It was found that most of the outdoor prescriptions were consisted of one antimicrobial per prescription (85.54%) followed by two antimicrobials per prescription (14.46%) (Table-3).Antimicrobial drugs utilization pattern among OPD patients was shown in Figure 2. It was found that syrup Amoxicillin and Clavulanic acid combination was most frequently used antimicrobial agent (32.53%) followed by deworming agent syrup Albendazole (21.69%). Topical antimicrobials prescribed were clindamycin gel, permethrin cream, clotrimazole mouth paint, miconazole cream, fusidic acid cream. It was observed that, parenteral dosage form of antimicrobials was commonly utilized (69.57%) followed by oral dosage form of antimicrobials (29.35%) in IPD patients. Most frequently used oral antimicrobial was syrup oseltamivir (14%) followed by syrup Amoxicillin + Clavulanic acid while most commonly utilized parenteral injectable antimicrobial was cefotaxime (50%) among IPD patients. (Figure 3, 4.)It was observed that most of the antimicrobials were prescribed by brand names in indoor and outdoor patients. Statistically, higher percentages of prescriptions were found to contain brand names in indoor (64.88%) than outdoor (29.89%) patients of pediatric department. It was also observed that only 2.1% antimicrobials prescribed in outdoor patients were not found to be from NLEM 2015 while 19.66% antimicrobials prescribed in indoor patients were not from NLEM 2015. Among the different classes of antimicrobial, cefotaxime injection remained the most frequently prescribed injectable in indoor patients. In outdoor patients most frequently prescribed oral antimicrobial was Amoxicillin and Clavulanic acid combination syrup. Prescriptions were further assessed for their consistency with List of Essential Medicines for Children of India. Among OPD patient’s significant percentage of antimicrobials (93.7%) was found in this list but in IPD patients only 47.82% antimicrobials were from List of Essential Medicines for Children of India. Only 32% indoor patients had undergone microbial culture and sensitivity test, whereas this test was not at all used in outdoor patients to guide the treatment.Evaluation of antimicrobial prescriptions was done on the basis of hospital antibiotic policy to measure rationality of prescribing practices. Higher percentage of prescriptions were found to be rational among OPD as well as IPD patients (Table: 2.)Discussion Drug utilization studies may be defined as studies of the marketing, distribution, prescription and use of drugs in a society, with special emphasis on the resulting medical, social and economic consequences [14]. The present study was planned with an aim to generate a baseline data on drug prescribing pattern, with main focus on antimicrobial drugs prescribing for pediatric patients. In our study, a total of 1031 prescriptions containing antibiotics were recorded, Male pediatric patients were more (55.09%) compared to female (44.91%). Similar results were found in the studies conducted by Venkateswaramurthy N [15] (males 54.5% & female 45.5%), and Malpani et al [16] (males 58.4% & female 41.5%). This can be attributed to the gender discrimination as a result of which males are predominantly taken to tertiary care hospitals for treatment as compared to females. This study had shown majority of indoor as well as outdoor patients who had received antimicrobials were from age group of 1 year to 4 years. This was comparable with study conducted by Neha et.al in which 46.38% patients were from age group of 1 to 4 years [17]. This could be explained by UNICEF data which states, the leading causes of death among children under 5 years of age (in 2018) included preterm birth complications (18%), pneumonia (15%), intrapartum-related events (13%), congenital abnormalities (9%), diarrhoea (8%), neonatal sepsis (7%) and malaria (5%). It denotes that for leading causes of mortality in children under 5 years of age, antimicrobial agents will be mainstay of treatment [18].In our study respiratory tract infections (pneumonia, bronchiolitis) were most common reason for hospitalization which consisted of 44.67% patients followed by 15.67% gastrointestinal infections, 14.46% skin infections. This is in line with study conducted by Achalu T (19), which also showed pneumonia (38.7%) as a most common reason for hospitalization followed by Sepsis 49 (15.2%) and acute gastro enteritis 41(12.7%). Tadesse et al study in Ethiopia found that the major medical conditions for which antibiotics prescribed were severe pneumonia (31.23%) and late onset neonatal sepsis with meningitis (20.60%) [20]. Present study showed that 69.57% antimicrobial agents were prescribed by parenteral routes, while 29.35% were by oral use. In other study by Baidya S 84.1% antimicrobial agents were prescribed by parenteral route and only 15.7% by oral route [21] indicating parenteral administration was much higher than we observed in the current study. In present study, 1.84 and 1.14 antimicrobials were prescribed per prescription respectively in indoor patients and outdoor patients. This was less than indicated by Achalu T study, 2.37 antibiotic per prescription [19] and comparable with study by Kebede HK, [7] which denoted 1.7 ± 1.1 antibiotics per prescription while by Kanish R [22] research depicted average 1.9 AMAs were prescribed per patient. These differences may be due to variations in prescribing practice among different hospitals or among the different physicians, also availability and implementation of hospital antibiotic policy and effective infection control committee at our hospital responsible for more rational prescribing.In this study, 14.46% outdoor patients were prescribed two antimicrobial per prescription and58% indoor patients were administered two or more antimicrobials. Prajapati and Bhatt reported that 71% of prescriptions with two or more antimicrobial agents in their study[23] while Baidya S et al.[18] observed about 60% such prescriptions in pediatric cases. It is vital to maintain the number of antimicrobials per prescription as less as possible to minimize the risk of development of bacterial resistance, drug-drug interactions and costs of therapy. Thus, considering the situation in India, and particularly in our hospital, offers possibility for upgrading prescribing practices especially among indoor patients.Statistically, higher percentages of prescriptions were found to contain brand names in indoor (64.88%) than outdoor (29.89%) patients in current study. This finding was much contradictory to other studies where only 1.3% and 16.5% antimicrobials were prescribed by brand names in Baidya S et al. and Prajapati and Bhatt [23] studies respectively. Though most of the AMAs prescribed by brand name were from hospital drug store in our study still almost 100% generic prescribing is a desirable. Most commonly utilized parenteral injectable antimicrobial in this study was cefotaxime (50%) among indoor patients, however surprisingly cefotaxime is not included in the List of Essential Medicines for Children of India [11], this was contrary to other studies where most commonly prescribed antimicrobial was crystalline penicillin [24, 25]. Cephalosporin was a most frequently used group of AMAs in indoor patients as per reports of few studies [3, 26, 27]. Use of syrup containing Amoxicillin and Clavulanic acid combination in the present study was most frequent (32.53%) in outdoor patients while in other study by Malpani AK et al it was much less. Liquid preparations are usually recommended for infants and younger children so as to make swallowing easy and to mask unpleasant taste. As upper respiratory tract infection was the most common diagnosis found in this study Amoxicillin and Clavulanic acid combination is the most appropriate antibiotic to cover respiratory pathogens. Only 32% indoor patients had undergone microbial culture and sensitivity test was the matter of concern in this study. Limitations of study: This was cross-sectional descriptive study and it does not cover factors and causality for irrational prescribing. Study duration was of three months only so one could get environmental variation in predisposition for particular infections. Follow up of all indoor patients was difficult as few took discharge against medical advice. Hence long duration, follow up studies are needed.Conclusion:This study highlights antimicrobial prescription pattern in a pediatric population in West Maharashtra region. The present study concludes that the most of the prescribing pattern of antimicrobials in the pediatric patients of the hospital is found to be rational according to the guidelines while number of AMAs per prescription and duration of treatment warrant further awareness. There is a scope for improvement in utilization of culture and sensitivity facilities and promotion of generic prescribing. The study gives impetus to a national drive toward antimicrobial stewardship.Conflict of interest No conflict of interest is declared.References:WHO Expert committee report. The use of essential drug. WHO TRS 615, 1977. Available at http://apps.who.int/iris/bitstream/10665/41272/1/WHO_TRS_615.pdfTripathi KD. Antimicrobial drugs, Essentials of Medical Pharmacology. 7th Edition, 12. New Delhi JAYPEE Brothers medical, 2013; 688-704.Sharma M, Damlin A, Pathak A, Lundborg CS. Antibiotic Prescribing among Pediatric Inpatients with Potential Infections in Two Private Sector Hospitals in Central India. PloS one. 2015 Nov 5;10(11):e0142317.Sharma S, Bowman C, Alladin-Karan B, Singh N. Antibiotic prescribing patterns in the pediatric emergency department at Georgetown Public Hospital Corporation: a retrospective chart review. BMC infectious diseases. 2016 Apr 19;16(1):170Porta A, Esposito S, Menson E, Spyridis N, Tsolia M, Sharland M, Principi N. Off-label antibiotic use in children in three European countries. European journal of clinical pharmacology. 2010 Sep 1;66(9):919-27.Kumar SG, Adithan C, Harish BN, Sujatha S, Roy G, Malini A. Antimicrobial resistance in India: A review. Journal of Natural Science, Biology and Medicine. 2013 Jul 1;4(2):286.Kebede HK, Gesesew HA, Woldehaimanot TE, Goro KK. Antimicrobial use in pediatric patients in a teaching hospital in Ethiopia. PloS one. 2017 Mar 6;12(3):e0173290World Health Organization. The World medicines situation 2011: rational use of medicines. Geneva: WHO; 2011. Available from: http://www.who.int/medicines/areas/ policy/world_medicines_situation/WMS_ch14_wRational.pdf. [Assessed on 2017 march 10]Ganguly NK, Arora NK, Chandy SJ, Fairoze MN, Gill JP, Gupta U, et al., authors. GARP-India working group. Rationalizing antibiotic use to limit antibiotic resistance in India. Indian J Med Res. 2011; 134:281–94.National Essential Drug List [Internet]. Delhi; Ministry of Health and Family Welfare; Government of India; 2015; 1-117. Available from: http://cdsco.nic.in/WriteReadData/NLEM-2015/NLEM,%202015.pdf. [Assessed on 2017 March 11]Indian Academy of Pediatrics. List of Essential Medicines for Children of India, First List. Indian Academy of Pediatrics. 2011. Available: http://apps.who.int/medicinedocs/documents/s19040en/s19040en.pdf. [Assessed on 2017 March 11]Introduction to drug utilization research, WHO, 2013. Available at http://www.whocc.no/filearchive/publications/drug_utilization_research.pdf. Accessed 07 January 2017.Antibiotic policy Sassoon Hospital & BJGMC Pune 2015-16. Available at . Accessed 07 April 2017.Sacristén JA, Soto J. Drug utilisation studies as tools in health economics. Pharmacoeconomics. 1994 Apr 1;5(4):299-312.Venkateswaramurthy N, Murali R, Sampath Kumar R. The study of drug utilization pattern in pediatric patients. Int J Pharm Pharm Sci. 2013;5(3):140-4.Malpani AK, Waggi M, Rajbhandari A, Kumar GA, Nikitha R, Chakravarthy AK. Study on prescribing pattern of antibiotics in a pediatric out-patient department in a tertiary care teaching and non-teaching hospital. Indian Journal of Pharmacy Practice. 2016 Oct;9(4):253-9.Patel N, Shah S, Asari P Amin A . Prescription auditing and drug utilization pattern in indoor patients of pediatrics department. Int J Cur Res Rev. 2016 Dec;8(23): 39-46.Under-five mortality. Available at: Accessed 1 october 2019.Achalu T, Mensa M. Retrospective Drug Use pattern of antibiotics in Pediatric ward of Shenan Gibe Hospital, Oromia Region, EthiEthiopia. Journal of antibiotics Research. 2017;1(1):1-0.Tadesse Sheleme A, Belay Y, Tsegaye Melaku K. Antibiotics Utilization Pattern in Pediatric Ward: The Case from Tertiary Teaching Hospital, South West Ethiopia. Int J Adv Multidisciplinary Res 2015; 2: 54–61.Baidya S, Hazra A, Datta S, Das AK. A study of antimicrobial use in children admitted to pediatric medicine ward of a tertiary care hospital. Indian journal of pharmacology. 2017 Jan;49(1):10.Kanish R, Gupta K, Juneja S, Bains HS, Kaushal S. Prescribing pattern of antibiotics in the department of pediatrics in a tertiary care medical college hospital in Northern India. Asian Journal of medical sciences. 2014 May 17;5(4):69-72.Prajapati V, Bhatt JD, authors. Study of prescribing pattern of antimicrobial agents in the pediatric wards at tertiary teaching care hospital, Gujarat. Indian J Pharm Sci Res. 2012;3:2348–55Alemnew G, Atnafie SA. Assessment of the pattern of antibiotics use in pediatrics ward of Dessie Referral Hospital, North East Ethiopia. International journal of medicine and medical sciences. 2015 Jan 31;7(1):1-7.Soleimani M, Karamian S. Antibiotic Utilization Pattern in Surgery and Pediatric, Bhagwan Mahaveer Jain Hospital, Bangalore, India. IOSR Journal of Pharmacy. 2017 July ;7(7):06-10.Choudhury DK, Bezbaruah BK. Antibiotic prescriptions pattern in pediatric in-patient department gauhati medical college and hospital, Guwahati. Journal of Applied pharmaceutical science. 2013 Aug 1;3(8):144.Shamshy K, Begum IM, Perumal P. Drug utilization of antimicrobial drug in pediatrics population in a tertiary care hospital in Erode, Tamilnadu, India. Int J Pharm Tech Res. 2011 Jul;3(3):1530-6.
