Drug Utilization Evaluation of Aminoglycosides, Gentamicin and Amikacin: A Retrospective study in pediatric patients at secondary care public hospital

 

Keerthana Chandrasekar¹, Shruthi Jaya Saju², Brisha Hana Zechariah², Jenny Ann John², Sadagoban GK³, Arun KP⁴*

¹Resident, Department of Pharmacy Practice, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu, India.

²Department of Pharmacy Practice, JSS College of Pharmacy, JSS Academy of Higher Education &  Research, Ooty, Nilgiris, Tamil Nadu, India.

³Lecturer, Department of Pharmacy Practice, JSS College of Pharmacy, JSS Academy of Higher Education &  Research, Ooty, Nilgiris, Tamil Nadu, India.

⁴Assistant Professor, Department of Pharmacy Practice, JSS College of Pharmacy, JSS Academy of Higher Education &  Research, Ooty, Nilgiris, Tamil Nadu, India.

 

ABSTRACT:

Background: Antibiotics are potent drugs which are usually used in the treatment of bacterial infections. Aminoglycosides are powerful, broad spectrum antibiotics that exhibits both gram positive and gram-negative coverage and are often used for treatment of bacterial infections in the pediatric patients. Gentamicin and Amikacin are broad spectrum aminoglycoside antibiotics with bactericidal activity and is widely used in the treatment of bacillary infections in infants and children. Clinical effects of gentamicin-related toxicity such as ototoxicity, nephrotoxicity is well known. The incorrect use of aminoglycosides has deleterious effects such as of nephrotoxicity and ototoxicity and can result in the development of resistant pathogens. Therefore, drug utilization evaluation of aminoglycosides can significantly improve their usage. Methods: This study is a retrospective pilot study carried out in a secondary care public hospital, Ooty to understand the Aminoglycoside usage in the pediatric population. A total of 133 cases were collected with aminoglycoside usage during the period of one year from January 2018 to December 2018. The data was collected in the structurally designed data collection form which included patient demographic data such as name, age, gender, body weight, treatment plan including drug, dose, duration, frequency and route of administration, length of hospitalization along with laboratory data such as, microbiological culture sensitivity and renal function test. Results: Among 133 cases, the aminoglycoside commonly prescribed was gentamicin (100) and amikacin (34) which constitutes for 74.6 and 25.4 percentages respectively. The Defined Daily Dose of Gentamicin and Amikacin was calculated and compared with WHO DDD value which was found to be comparable. The DDD per patient and DDD per 1000 patients were calculated respectively to understand the drug utilization pattern of aminoglycosides. The study findings suggested that Aminoglycosides are widely used in Infants and Children and was commonly prescribed for Lower Respiratory Tract Infections and Upper Respiratory Tract Infections, followed by Fever, Viral Fever, Febrile Seizures, Tonsillitis, Acute Gastro Enteritis, Adenoiditis and Urinary Tract Infections. Once daily was more commonly prescribed followed by Twice daily followed by combination therapy. Among the 100 cases of gentamicin prescribed, a total of 18 prescriptions were found to be stopped earlier with 1 day (n=10) or 2 days (n=08). Among the total 39 cases of renal function test done, the patients (n=11) prescribed with Amikacin constitutes about 32.4% and the patients (n=29) prescribed with gentamicin constitutes around 29% respectively.

Conclusion: The study findings concluded that Gentamicin and Amikacin usage was appropriate in pediatric population with reference to the DDD values.

 

 

 

INTRODUCTION:

Antibiotics are one of the most powerful medicines and are commonly prescribed for the treatment of both mild and severe bacterial infections. They are most extensively prescribed drugs in the latest era of medicine¹. They are profoundly specific in terms of the type of bacteria being treated and substantially cannot be switched from one infection to another. Experimentation on antibiotic and its significance began in the late 1800s². With the discovery of Quinine for Malaria and Emetine for amebiasis, the use of antimicrobial agents for the treatment of infectious diseases began³. Aminoglycosides are broad spectrum and potent antibiotics that exerts action through inhibition of protein synthesis by binding to the 30S ribosomal subunit^4,5. Streptomycin isolated from Streptomyces griseus was the first aminoglycoside which was established into routine clinical practice in 1944^4,6,7. Aminoglycosides were developed at the dawn of the antibiotics era and it was the first antibiotics to be discovered and made known for conventional clinical use. They found prevalent use as a corner stone drug in the primordial days of antimicrobial chemotherapy^4,8,9. Aminoglycosides have added benefits of supplemental gram-negative coverage and are typical antimicrobial agents used in pediatric patients¹⁰. They exhibits both gram positive and gram negative coverage.

 

Aminoglycosides are markedly potent against ample variety of gram-negative bacilli such as members of Enterobacteriaceae family, including Escherichia coli, Klebsiella pneumoniae., Salmonella spp., Shigella spp, Pseudomonas spp., Enterobacter aerogenes, Providencia spp., Proteus spp., Serratia spp., Morganella spp^4,7.

 

Irrational drug use is a commonly encountered problem globally¹¹. Rational drug use (RDU) gives an account of unharmful, affordable and economically feasible use of drugs¹². The fundamental target of RDU is to promote quality pharmaceutical care, to lessen the cost of drug therapy, to encourage patient adherence by helping patient receive appropriate drugs for their health conditions at optimal dose and for adequate time and at the cost that the community and individual can afford^12,13,14,15.

 

 

Country like India, due to factors like poor community illiteracy regarding safe use of drugs along with failures in pharmaceutical regulatory environment and ease of access to numerous drugs including many without ample evidence to support their safe use potentiates irrational drug use which leads to high treatment cost, ill health antibiotic resistance, and widespread health hazards^16,17.

 

Drug utilization evaluation (DUE) studies have become a quality check tool in evaluating the health care system, which aims on various dimensions of appropriate drug use¹⁸. DUE programs aids in further evaluations of prescribing practices and guides to achieve rational drug use by providing appropriate recommendations¹⁹.

 

Micro-organisms are the major cause of infectious diseases and the worldwide prevalence of microbial infections is likely to increase every year²⁰. Infectious diseases and their treatment is a commonly encountered problem in the pediatric population^21,22.

 

Acute respiratory infections are the most common infections in the young and comprises 50% of all illnesses in children²³. Aminoglycosides as preferred treatment choice for this condition is highly associated with side effects such as nephrotoxicity and ototoxicity^6,21,10.

 

Gentamicin and Amikacin are broad spectrum aminoglycoside antibiotics with bactericidal activity and is widely used in the treatment of bacillary infections in infants and children. Gentamicin is widely used for the treatment of gram-negative bacillary infections and is cheaper than the other drugs of the same class²⁴. Due to its chemical stability, rapid bactericidal action and broad coverage, gentamicin often is the drug of choice in diverse clinical situations²⁵. Clinical effects of gentamicin-related toxicity such as ototoxicity, nephrotoxicity are well known^26,27. Nephrotoxicity due to aminoglycosides accounts for 10-15% of all cases of acute renal failure²⁸.

 

Nephrotoxicity induced by aminoglycosides is outlined by targeting the proximal tubule epithelial cells of the renal cortex which ultimately leads to disruption in the electron transport and ATP synthesis after a series of events resulting in nephrotoxicity via apoptosis⁶. Aminoglycoside induced ototoxicity occurs due to death of inner ear sensory hair cells selectively triggered by aminoglycosides. These adverse drug reactions correlate with aminoglycoside blood concentrations. Studies also have shown cumulative period of therapy can be prognosticative of ototoxicity²⁹. The improper use of aminoglycosides has adverse effects such as of nephrotoxicity and ototoxicity and can also result in development of resistant pathogens. Thus, drug utilization evaluation of aminoglycosides can remarkably improve their usage³⁰. This throws light to the significance of drug utilization evaluation of aminoglycosides.

 

OBJECTIVES:

To understand about the drug utilization evaluation of aminoglycosides - gentamicin and amikacin in pediatric patients at secondary care public hospital.

 

MATERIALS AND METHODS:

A Retrospective Pilot Study was carried out at the, secondary care public hospital, Ooty to understand the Aminoglycoside usage in the pediatric population. A total of 133 cases were collected with aminoglycoside usage during the period of one year from January 2018 to December 2018. The study included the patients receiving parenteral aminoglycosides and pediatric patients aged below 14 years. The following patients were excluded from the study:

·       Patients with cystic fibrosis, renal failure or burns being treated with aminoglycosides.

·       Patients who are immunocompromised.

·       Patients with disease contraindicated to aminoglycoside treatment.

 

The data was collected retrospectively from Medical Records Department and transcribed to the designed data collection form. The data collected comprised of patient demographic data such as name, age, gender, body weight, treatment plan including drug, dose, duration, frequency and route of administration, length of hospitalization along with laboratory data such as, microbiological culture sensitivity and renal function test.

 

RESULTS AND DISCUSSION:

Among 133 cases, the aminoglycoside commonly prescribed was gentamicin (100) and amikacin (34) which constitutes for 74.6 and 25.4 percentages respectively. The Defined Daily Dose of Gentamicin and Amikacin was calculated and compared with WHO DDD value. The DDD per patient and DDD per 1000 patients were calculated respectively to understand the drug utilization pattern of aminoglycosides.

 

The study composed of 77 males and 56 females, who constitute 57.9 and 42.1 percentage of the population respectively. Among the 133 pediatric cases, the pediatric patients were classified as Infants and Toddlers, Young Child, Old Child, Adolescents and their percentages is shown in Figure 1.

 

Our study findings suggested that Aminoglycosides are widely used in Infants and children which were in accordance with the finding in other articles^26,27,31.

 

Figure 1- Age Distribution

 

 

In the total of 133 cases, Aminoglycosides was commonly prescribed for Lower Respiratory Tract Infections and Upper Respiratory Tract Infections, followed by Fever, Viral Fever, Febrile Seizures, Tonsilitis, Acute Gastro Enteritis, Adenoiditis and Urinary Tract Infections which signifies the importance of implementation of the therapeutic guidelines for the prescribing of gentamicin at the secondary care public hospital. [Figure 2]

 

Figure 2- Disease Distribution

 

The sub analysis of disease distribution was performed. Among the various diseases, Gentamicin was prescribed either as Once Daily or Twice Daily or in combination. [Figure 3].

 

Once daily was more commonly prescribed followed by Twice daily followed by combination. Among the 100 cases of gentamicin prescribed, a total of 18 prescriptions were found to be stopped earlier with 1 day (n=10) or 2 days (n=08). Among the 133 patients who were prescribed with aminoglycosides, a total of 39 cases, Renal Function Test was assessed. Since Gentamicin has a higher risk of nephrotoxicity and ototoxicity, the renal function test should be monitored after 3 days of gentamicin administration. A total of 39 cases, renal function test was done, the patients (n=11) prescribed with amikacin constitutes about 32.4% and the patients (n=29) prescribed with gentamicin constitutes around 29% respectively.

 

Figure 4- Gentamicin Disease Frequency Relation

Since it is a retrospective study, the data regarding the renal function test monitoring, post administration of aminoglycoside was lacking. This is one of limitations of our study.

 

However, Renal Function Tests and Ototoxicity should be monitored for the pediatric patients prescribed with aminoglycosides as it is associated with higher risk of toxicity^{6,21,29,26,27}. This could improve appropriate drug usage to a greater extent.

 

CONCLUSION:

Our study findings concluded that Gentamicin and Amikacin usage was appropriate in our study population with reference to the defined daily dose (DDD) values.

 

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Accepted on 17.03.2020           © RJPT All right reserved

Research J. Pharm. and Tech 2021; 14(3):1247-1250.