INTRODUCTION:

Any infectious disease on the respiratory tract is termed as Respiratory Tract Infections. RTIs remain as a challenge to the public health in both industrialized and developing countries because of their frequency and economic impact [1].

Infections of the respiratory tract are grouped according to their symptomatology and anatomic involvement. (Figure 1) It is usually classified as URTIs (Infection site includes nasal cavity, pharynx and larynx) and LRTIs (Infection site includes trachea, primary bronchi and lungs).

Depending on the Global Burden of Disease 2015 study (GBD 2015), the upper respiratory tract infections (URTIs) such as chronic obstructive pulmonary disease (COPD) and lower respiratory tract infections (LRTIs) such as acute bronchitis, pneumonia and bronchiectasis ranks the third and fourth place for the causes of death, after cardiac diseases and cerebrovascular diseases respectively [2]. The aetiological cause of RTI being viral, it is noted that some doctors prescribe newer and broad-spectrum antibiotics early before diagnosis because they believe that, these antibiotics would give patients the best option of fast cure and it could help the patient to prevent hospital admissions.

Classification of RTIs:

		Respiratory Tract Infection

Upper Respiratory Tract Infection			Lower Respiratory Tract Infection

	Sinusitis			Bronhitis
	Common Cold			Brochiolitis
	Pharyngitis			Pneumonia
	Epigottis and Laryngotracheitis

Figure 1. Classification of RTIs

Table 1 and 2 discusses the microbes responsible for URTIs and the recommended treatment guidelines in children.

Table 1. The microbes responsible for URTIs and the recommended treatment guidelines in children

Sl. No	RTI	Causative agents	Recommended Treatment	Ref. no
1.	Sinusitis	• Streptococcus • Pneumoniae • Haemophilus • Influenza • Moraxella catarrhalis	• Amoxicillin (45 mg per kg, twice daily) is the antimicrobial agent of choice for first-line treatment of uncomplicated acute bacterial sinusitis in situations in which antimicrobial resistance is not suspected. • Patients presenting with moderate to severe illness as well as age less than two years, amoxicillinclavulanate (80–90 mg/kg per day, maximum of 2g /dose).	[3]
2.	Common Cold	• Rhinoviruses • Coronaviruse • Parainfluenza viruses • Respiratory syncytial virus • Adenoviruses • Influenza viruses	• Acetylcysteine • High-dose inhaled corticosteroids in children who are wheezing (Budesonide, 1,600 mcg) • Nasal irrigation with saline (3 - 9 mL / nostril) Zinc sulphate (Syrup, 15 mg / 5 ml)	[4]
3.	Pharyngitis	• Type A coxsackie viruses • Streptococcus	• No Antibiotic treatment in case of Viral Pharyngitis, Symptomatic treatment with	[5]
		• Corynebacterium diphtheria • Corynebacterium haemolyticum • Neisseria gonorrhoeae	• Over-the-counter pain relievers such as oral acetaminophen or ibuprofen may be helpful in relieving discomfort from pharyngitis • In case of bacterial pharyngitis, Penicillin 40mg per kg, twice daily for 10 days (orally). • For penicillin allergic patients, Clindamycin- oral route (20mg per kg three times a day for 10 days) or Erythromycin- oral route (40mg per kg three times a day for 10 days) is preferred.
4.	Epigottis and Laryngotracheitis	• Haemophilus influenzae type b • Beta-hemolytic streptococcus • C diphtheriae	• Ceftriaxone (50 mg/kg once daily) slow IVover 3 minutes. • Intramuscular injections should be avoided as it can agitate the child and precipitate a respiratory arrest. • The IV treatment should be administered for at least 5 days then it can be changed to amoxicillin/clavulanic acid (co-amoxiclav). • It should be taken orally for at least 7-10 days as recommended.	[6]

Table 2. The microbes responsible for LRTIs and the recommended treatment guidelines in children

Sl.

RTI

Causative agents

Recommended Treatment

Ref.

Bronhitis and

Brochiolitis

• H influenzae

• S pneumonia

• Parainfluenza viruses

• Influenza viruses

• Adenoviruses

• Amoxcillin 20-40mg/kg/day in three divided doses

(or)

• Sulfamethoxazoe with trimethoprim 80 mg, twice daily for seven days

(or)

• Erythromycin: 30 – 50 mg/kg in four divided doses; 15- 20 mg per kg, IV over 5 minutes, thrice or quads daily as recommended.

[7]

Pneumonia

• Streptococcus pneumoniae

• Pseudomonas aeruginos

• Escherichia coli

• Enterobacter

• Proteus,

• Klebsiella

• Chlamydia

• Legionella

• Ampicillin: 50 mg per kg, or benzyl penicillin: 50 000 units per kg IM/IV every 6 hours for at least five days

• Gentamicin: 7.5 mg per kg IM/IV once a day for at least five days

• Ceftriaxone should be used as a second-line treatment in children with severe pneumonia having failed on the first-line treatment.

[8]

Deviation from recommended treatment guidelines:

The prescribing rate of antibiotics for respiratory tract infections seems to be increasing, while the proper follow-up of guidelines is been decreased tremendously. The selection of the appropriate antibacterial therapy should be based on the organisms which are isolated and on the emerging resistance to the conventional therapies [9]. Even though many of the hospitals have their own antibiotic policy manual for rational use of antibiotics, it is noted that a lag remains in implementing those guidelines.

Use of antibiotics, including irrational and unnecessary antibiotic treatment, contributes to the development of antibiotic resistance in paediatrics from their childhood itself. [10, 11].

Table 3 discusses the various studies conducted to analyse the prescription rate of antibiotics for RTIs in children.

Table 3. Various studies in analysing the prescription pattern of antibiotics for RTI

Sl. No	Author	Study Method	Study Type	Most used antibiotics	Ref no.
1.	Nimbagiri et al.,	Observational study	Drug Utilization	Cephalosporin (33.33%)	[12]
2.	Jinish J et al.,	Observational study	Prescription Pattern	Azithromycin, Amoxicillin, Cephalexin and Cefixime (73.18%)	[13]
3.	Mirza AB et al.,	Observational study	Irrational Prescribing Pattern	56.56% of antibiotics was prescribed	[14]
4.	Mona M et al.,	Observational study	Prescription Pattern of antibiotics for LRTI	45% of quinolone antibiotics was prescribed	[15]
5.	Chandra N et al.,	Observational study	Prescription Pattern	Co-amoxyclav (37.5%), Ceftriaxone (13.75%), Moxifloxacin (12.50%) and Clarithromycin (12.55%)	[16]

The above studies shows that the use of antibiotics varies as the bacteriological profiles for the RTI are different in different countries, which vary with time within the same country and the aetiologies of respiratory infections plays an important role in making decision, which is considered for choosing the appropriate antibiotics, isolation and hospitalization measures.

The causes for antibiotic resistance:

Especially India being a lower middle income country and being the highest antibiotic consumption country in the world, antibiotic resistance has been a critical threat to healthcare sector [17]. When RTIs are treated with antibiotics, virus/bacteria come in contact with an antibiotic, the weaker bacteria die, but the strong bacteria/virus multiplies and become resistant to the antibiotic, this makes some bacteria very hard to kill. Antibiotic resistance is a problem because we need antibiotics to treat bacterial infections which our body needs to get rid off. When bacteria become resistant to antibiotics, physicians finds a tough time to treat the infection, which means when the child gets an infection from antibiotic-resistant bacteria, they become very sick and more hard to treat. Therefore, Taking an antibiotic when it is not needed (such as to treat a viral illness) or taking the wrong antibiotic, or the wrong dose, or stopping an antibiotic too soon can lead to antibiotic resistance. [18]

The reasons behind the failure to adhere the guidelines have also been the major cause for inappropriate antibiotic use in children. Kuehlein T et al., acknowledg that the guideline recommendation still remains unknown to some of the general physicians and therapeutic decisions were mainly driven by what was perceived as prevailing practice [19].

Livorsi et al., identified three barriers to guideline-concordant care such as physician’s lack of awareness of specific guideline recommendations; tension between adhering to guidelines and the desire to individualise patient care; and scepticism of certain guideline recommendations [20]. Even though, the guideline recommendations are known by the physicians, their level of acceptance is undignified. Lugtenberg et al., [21] found that “lack of agreement with guideline recommendations” was the most prominent barrier in applying guidelines in general practice.” (Figure 2)

Ways to limit antibiotic resistance:

Tracking antibiotic consumption patterns over time and across countries could inform policies to optimize antibiotic prescribing and would help in minimizing antibiotic resistance, which includes setting and enforcing per capita consumption targets for the patients or aiding investments in alternatives to antibiotics.

Vaccination uptake in children should be increased by providing accurate information about the benefits of vaccines and by dispelling myths. Healthcare professionals should motivate parents with children who have not taken or missed immunization at their younger age. Cattaneo A [22] conducted a study to understand role of vaccination in preventing acute RTIs in children in developing countries and it was noted that vaccines against Haemophilus influenzae type b, could reduce acute LRTIs deaths by 4% and Streptococcus pneumonia vaccine reduced the death by 10%.

Antibiotic use in India can also be limited by implementation of Antimicrobial Stewardship programmes which helps in improving the antibiotic use, quality of patient care, safety through increased infection cure rates, reducing treatment failures, and increasing the frequency of correct prescription for therapy and prophylaxis [23].

Usage of alternative aids such as Vitamin D supplementation was found useful in decreasing the events related to respiratory tract infections, this theory was supported by Jaykaran C et al., but they also suggest more clinical trials for evidence [24]. In the same way, zinc supplement was found useful in reducing the events of pneumonia in children who was taking vitamin A supplement along with it [25].

Khaled S et al., conducted a study to understand the efficacy and tolerability of Bovine Colostrum in preventing recurrent URTIs in children. Due to its direct antimicrobial and endotoxin-neutralizing effects, Bovine colostrum was found effective in the prophylaxis of recurrent URTI and diarrhoea as it reduces the number of episodes and the hospitalization in children [26].

Mortality rates in children caused due to irrational antibiotic prescription and antibiotic resistance:

The actual number of deaths related to antibiotic resistance is unknown, since such information is usually missing from medical reports and death certificates. However when an estimate is taken, In every 4 minutes, a person dies from an infection caused by bacteria which have become resistant to antibiotics (as per the combined data from the EU, the USA and for children in India) and at least 25,000 patients in Europe and 23,000 patients in the USA die each year as a result of antibiotic-resistant infections [27, 28].

Therefore, it’s the responsibility of the healthcare professionals to provide rational prescription for the patients by providing the right drug with the right dose in order to reduce the mortality rate

CONCLUSION:

This review clearly indicates the importance of prescribing right antibiotics for respiratory tract infection in children as per the guidelines provided because as mentioned in this review, unnecessary prescribing of antibiotics for viral illness of respiratory tract in children results in irrational prescription and antibiotic resistance from their early age itself. Hence, follow-up of treatment and implementation of hospital polices should be a mandatory.

REFERENCE:

1. Pragti C, Geetanjali S, Anjur T. Prevalence of Respiratory Disease and Associated Factors in an Urban Area of Delhi. Indian Journal of Community Medicine. 2008; 33(4):229-232.

2. GBD 2015 Mortality and Causes of Death Collaborators. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: A systematic analysis for the global burden of disease study 2015. Lancet. 2016; 388(1):459-544.

3. Ellen R, Kimberly E, Clay B, Mary P, Richard M, Michael J, et al., Clinical Practice Guideline for the Diagnosis and Management of Acute Bacterial Sinusitis in Children Aged 1 to 18 Years. Pediatrics. 2013; 132(1):262-280.

4. Julia F, Kevin E, Sarah W. Treatment of the Common Cold in Children and Adults. American Family Physician. 2012; 86(2):153-159.

5. TOP. Guideline for the Diagnosis and Management of Acute Pharyngitis. http://www.topalbertadoctors.org/download/368/acute_pharyngitis_guideline.pdf. Updated February 2008. Accessed on October, 2018.

6. Medecins Sans Frontiers. Epiglottitis. https://medicalguidelines.msf.org /viewport/CG english/epiglottitis-16689226.html. Accessed on October, 2018

7. Standard Treatment Guidelines for General Hospital. Food, Medicine and Healthcare Administration and contro authority of ethioia; 3^rd edition, 2014.

8. WHO. Revised WHO classification and treatment of childhood pneumonia at health facilities.http://apps.who.int/iris/bitstream/handle/sequence. Accessed on October, 2018.

9. Syed M, Ramakrishna P, Shaniya K, Arya B, Shakir V. Lower respiratory tract infection: An insight into the prevalence and the antibiogram of the gram negative, respiratory and bacterial agents. Journal of Clinical and Diagnostic Research. 2013, 7(2): 253-256.

10. Goossens H, Ferech M, Stichele Vander R, Elseviers M. Outpatient antibiotic use in Europe and association with resistance: a cross-national database study. Lancet. 2005; 365:579–587.

11. Bassani DG, Kumar R, Awasthi S, Morris SK, Paul VK, Shet A, et al. Causes of neonatal and child mortality in India: a nationally representative mortality survey. Lancet. 2010; 376(9755):1853–1860.

12. Nimbagiri ST, Uday VM, Raju B. Drug utilization pattern in South Indian pediatric population: A prospective study. Perspectives in Clinical research. 2014; 5(4):178–183.

13. Jinish J, Denny D. Paediatric Prescription Analysis in a Primary Health Care Institution. Journal of Clinical and Diagnostic. 2016:10(11):5–8.

14. Mirza AB, Shakti BD, Shalu B, Amanjot K, Subhash V, Upendra K. Prescribing trends in respiratory tract infections in a tertiary care teaching hospital. International Journal of Research in Medical Science. 2017; 5(6): 17-23.

15. Mona M, Ashraf A, Engy W. Study of prescription patterns of antibiotics in treating lower respiratory tract infections at Sohag Chest Hospital. Egyptian Journal of Chest Diseases and Tuberculosis . 2016; 65(1):143-155.

16. Chandra NG, Kripasindhu C. Prescription pattern of antibiotics in respiratory disorders in a tertiary care teaching hospital in Eastern part of India. International Journal of Research in Medical Science. 2017; 5(4):1430-1433.

17. Ashok J. Determinants of Antibiotic Consumption - Development of a Model using Partial Least Squares Regression based on Data from India. Scientific reports. 2018; 8(6421):1-9.

18. Sickkids. Antibiotic Resistance. https://www.aboutkidshealth.ca/Article?Contentid =2317&language=English . Updated June 29, 2015. Accessed on October, 2018.

19. Kuehlein T, Goetz K, Laux G, Gutscher A, Szecsenyi J, Joos S. Antibiotics in urinary tract infections. Sustained change in prescribing habits by practice test and self-reflection: a mixed methods before-after study. British Medical Journal. 2011; 20(6):522-530.

20. Livorsi D, Comer AR, Matthias MS, Perencevich EN, Bair MJ. Barriers to guideline concordant antibiotic use among inpatient physicians: A case vignette qualitative study. Journal of Hospital Medicine. 2016; 11(3):174-180.

21. Lugtenberg M, Zegers JS, Wester G. Burgers, Why don’t physicians adhere to guideline recommendations in practice? An analysis of barriers among Dutch general practitioners, Implemention. Science. 2009; 4(1):54-60.

22. Cattaneo A. Current role of vaccination in preventing acute respiratory infections in children in developing countries. Monaldi Archives for Chest Disease .1994; 49(1):57-60.

23. Kamini W, Ohri VC, Dilip M. Antimicrobial stewardship programme (AMSP) practices in India.Indian Journal of Medical Research. 2015; 142(2): 130–138.

24. Jaykaran C, Jagdish PG, Deepak S, Preeti Y. Vitamin D for prevention of respiratory tract infections: A systematic review and meta-analysis. Journal of Pharmacology and Pharmacotherapeutics. 2012; 3(4): 300–303.

25. Nita Bhandari, Rajiv Bahl, Sunita Taneja, Tor Strand, KåreMølbak, Rune Johan Ulvik, Halvor Sommerfelt, Maharaj K Bhan. Effect of routine zinc supplementation on pneumonia in children aged 6 months to 3 years: randomized controlled trial in an urban slum. British Medical Journal. 2002; 324(1358):1-5.

26. Khaled S, Mohamed GM. Abo Elela. Effects of bovine colostrum on recurrent respiratory tract infections and diarrhea in children. Medicine. 2016;95(37):1-5

27. A gobal impact. The antibiotic resistance challenge. www.antimicrobial resistance.biomerieux.com/popup/global -impact. Accessed on October,2018

28. Laxminarayan et al. Antibiotic resistance – the gobal solutions. Lancet Infectious Disease. 2013; 13:1057-1098.

Received on 25.02.2019 Modified on 18.03.2019

Research J. Pharm. and Tech. 2019; 12(10):5126-5130.

DOI: 10.5958/0974-360X.2019.00888.6