J Young Pharm, 2022; 14(2) : 165-168

A multifaceted peer reviewed journal in the field of Pharmacy Review Article

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Rational Use of Antibiotics: An Area of Concern

Sougata Sarkar,1 Vartika Srivastava,2,* Shambo Samrat Samajhdar,1 Chaitali Pattanayak,2 Santanu Tripathi3
1
Department of Clinical and Experimental Pharmacology, School of Tropical Medicine, Kolkata, West Bengal, INDIA.
2
Department of Pharmacology, Kalinga Institute of Medical Sciences, Bhubaneswar, Odisha INDIA.
3
Department of Pharmacology, Netaji Subhas Medical College and Hospital, Patna, Bihar, INDIA.

ABSTRACT
Most of the IPD (Inpatient department) and OPD (Outpatient department) Chemical (ATC) codes and WHO Essential Medicines List status. One
patients receive a course of antibiotics either for treatment or prevention health approach is the collaborative effort of multiple health science
of infection or during discharge. The therapeutic outcome with an antibiotic professions to attain optimal health for people, domestic animals, wildlife,
depends mostly on choice of appropriate agent. The selection of antibiotic plants, and environment. Recently, WHO issued new guidelines regarding
depends on causative agent, patient factors, clinical pharmacology of the use of antimicrobials in animals producing food, recommending the
antibiotics and its cost effectiveness. Antimicrobial resistance (AMR) restricted use of such medicines in growth promotion or prevention of
occurs when microbes like bacteria, parasites, viruses and fungi become disease in healthy animals. Hence rational use of antibiotics is important for
resistant to antimicrobial drugs that are used for treatment of various successful treatment outcome and prevention of emerging drug resistance
diseases leading to decreased effectiveness, difficulty in treatment of for broader community.
disease and hence requiring multiple therapeutic options. Antimicrobial Key words: Antibiotics, Antibiotic resistance, Antibiotic stewardship,
stewardship is a coordinated intervention, designed to improve and AWaRe Classification, One health approach.
measure the appropriate use of antimicrobial agents, by promoting the Correspondence
selection of optimal antimicrobial drug regimen including dosing, duration
Dr. Vartika Srivastava,
of therapy and route of administration. To strengthen the implementation
of rational antibiotic use and reduction of antimicrobial resistance, WHO Assistant Professor, Department of Pharmacology, Kalinga Institute of Medical
Sciences (KIMS), Bhubaneswar-751001, Odisha, INDIA.
(World Health Organisation) in 2019 introduced “AWaRe” classification
of antibiotics that includes details of 180 antibiotics classified as Access, Email id: vartika.srivastava@kims.ac.in
Watch or Reserve, their pharmacological classes, Anatomical Therapeutic DOI: 10.5530/jyp.2022.14.31

INTRODUCTION
Recently, antibiotics are that group of drugs which are often prescribed, patterns that helps in starting empirical therapy) and laboratory support.
both in IPD and OPD. Most of the IPD patients receive a course of Laboratory reports should always be viewed in the light of clinical
antibiotics either for treatment or prevention of infection; this is also findings to distinguish normal flora, colonizers or contaminants from
true during discharge. The antibiotics share a major part of hospital’s true pathogens.2
drug budget. Rational use of antibiotics is therefore extremely important The patient factors which are taken into consideration while selecting
to achieve desired patient outcome, prevent appearance of antibiotic an antibiotic are age, pregnancy, allergic history, organ function, genetic
resistance and increased cost of health care. factors and compliance. For example, chloramphenicol is unsafe in
neonates, tetracyclines and quinolones may cause adverse effects in
RATIONAL PRESCRIBING OF AN ANTIBIOTIC - growth of tissues and organs in children. Aminoglycosides leads to
THE ISSUES nephrotoxicity in elderly patients. Antibiotics selection in pregnancy is
Necessity of Antibiotics a major area of concern to safeguard the growing fetus. Allergy history
Bacterial infections are always treated by an antibiotic. One must should always be taken before selecting an appropriate antibiotic. Safer
remember that infection is one of the many causes of fever and not all antibiotics selection and dosage modifications should be done for
infections are caused by bacteria. A considerable portion of infections patients with hepatic or renal impairment. Genetic factors can raise
seen in general practice are of viral origin and antibiotics have no role the risk of adverse reaction (e.g. the acetylation and G6PD status).3
in these patients. Even after establishment of bacterial infections, not The patient’s adherence and compliance to antibiotics are important
necessarily an antibiotic is required because some bacterial infections factors required to achieve desirable outcome and preventing resistance.
resolve spontaneously.1 Generally, compliance is better with once daily dosing and shorter
duration regimen.4
Selection of most appropriate antibiotic The physician should have proper knowledge of the pharmacokinetic
The therapeutic outcome with an antibiotic depends mostly on choice profile of the prescribed antibiotic, especially its ability to attain
of appropriate agent. This appropriate selection of antibiotic depends therapeutic concentrations at the site of infection. For example,
on causative agent, the patient factors, the clinical pharmacology of moxifloxacin and gemifloxacin are not effective for the treatment of
antibiotic and cost effectiveness of the antibiotics. urinary tract infections, as they do not achieve adequate concentration in
Determination of the causative agent depends on a combination of urine. Concentration dependent killing (CDK), time dependent killing
clinical skill (and a knowledge of both universal and local sensitivity (TDK), post antibiotic effect (PAE) and bactericidal-bacteriostatic

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 Sarkar, et al.: Rationality of Antibiotic usage

interaction are also the area of concern. The drug-drug interactions ANTIBIOTIC RESISTANCE
of antibiotics with other non-antibiotic drugs may produce barrier in
optimum response.5 Antimicrobial resistance (AMR) takes place when microbes (like bacteria,
parasites, viruses and fungi) become resistant to antimicrobial drugs that
Nevertheless, a major concern remains the cost burden caused by
are used for treatment of various diseases. Irrational use (over use, under
prescribed antibiotics. While calculating costs, one should consider
use, miss use and abuse) of antibiotics not only expose the patients at
the total cost of therapy rather than the unit value of antibiotic i.e the
risk for therapeutic failure and serious adverse events but also endanger
cost per dose. In addition to this, the cost of drug administration, the
the entire globe by introducing antimicrobial resistant pathogens. Once
requirement for performing TDM and the duration of hospital stay must
the microbe develops resistance, the effectiveness of some common
also be taken into consideration. antimicrobials is decreased and even completely ineffective, the disease
becomes difficult to treat, requires different/multiple therapeutic options
Appropriate regimen of antibiotics (dose, route, that could be more toxic and expensive. In addition to this, lack of clean
frequency and duration of use) water, improper sanitation and continuous environmental exposure of
In patients who are unable to take oral treatment, parenteral therapy is pharmaceuticals and personal care products (PPCPs) also increases the
obviously indicated. But preferring parenteral treatment for severe sepsis, chances of resistance. Treatment of common infections like pneumonia,
is not always true when antibiotics having good oral bioavailability are diarrhoea, gonorrhoea, tuberculosis, HIV/AIDS and malaria, get
readily available (eg. Linezolid has 100% bioavailability). Studies showed affected due to this AMR. WHO has declared AMR as top 10 global
that oral antibiotics are as good as parenteral antibiotics in specific public threats that need to be addressed urgently.
infections.6 The dose, frequency and duration depend on PK of drug, Many new initiatives have been launched by various agencies in India to
CDK or TDK, MIC and PAE. combat this problem like Indian Clinical Epidemiology Network (Clen)
Oral therapy has several advantages. This eliminates the risk of has produced some quality data on antibiotic resistance in pathogens
intravenous access related bacteraemia, phlebitis and pulmonary like pneumococcus, H. influenzae across the country, Indian Initiative
embolism, ancillary costs related to intravenous injections apart from for Management of Antibiotic Resistance (IIMAR started in March
pain. Oral therapy reduces the duration of hospitalization and the cost 2008) for promoting the rational use of antimicrobials, INSAR (Indian
of treatment.7 Network for Surveillance of Antimicrobial Resistance) consisting of
The ideal term of antibiotic treatment is unclear in many situations. Most 20 private and public laboratories generates quality data on AMR all
of the antibiotics are usually prescribed for a span of 5-7 days. However, it over the country etc. An ICMR expert committee was formed in 2009
is unreasonable to stop the prescribed therapy, if the patient’s symptoms to combat the problem of antibiotic resistance, while an Indo-Swedish
have resolved, even after 3 to 5 days.8 workshop was organised in New Delhi on 2 February 2010 to evaluate a
joint strategy for confinement of AMR.
Monitoring of effectiveness of therapy
An early evaluation (preferably 3rd or 4th day of treatment) of the response
ANTIMICROBIAL STEWARDSHIP
is essential to ensure if the patient is receiving suitable treatment and “It is a coordinated intervention, designed to improve and measure the
to further determine whether to stop, continue, change, modifying the appropriate use of antimicrobial agents, by promoting the selection of
dose or regimen. If the patient is responding well there is no necessity optimal antimicrobial drug regimen including dosing, duration of therapy
to change antibiotic even if the laboratory reports a resistant organism and route of administration” (definition by SHEA, IDSA, PIDS – April
(the isolate may be a colonizer or a contaminant). On contrary, if there 2012).11
is no improvement in patient’s condition, then a change in antibiotic An effective antimicrobial stewardship program relies on appropriate
should be considered, even if the laboratory reports claims it as sensitive • appropriate drug selection,
organism. Sometimes, a patient might not respond to an antibiotic
• optimum dosing,
due to incorrect diagnosis and improper antibiotic selection, resistant
• suitable route of administration and,
strain, secondary infection, non-compliance to treatment etc. Whenever
feasible intravenous therapy should be changed to oral therapy and vice • proper duration of antimicrobial therapy,
versa if the patient’s condition warrants it without hesitation.9 The oral For a successful antibiotic stewardship program, a team work of
antibiotic should be selected based on clinical and laboratory findings. knowledge regarding scope and areas of unmet needs, effective strategies
Four types of changing from intravenous (IV) to oral treatment are:10 and updated recommendations as well as guidelines, are required.
Pharma industries, international organizations and governmental health
• Streamlining - here the IV antibiotic is changed to one with
policy makers have all those competency and skills for implementing
narrower spectrum which specifically targeting the offending
effective antimicrobial stewardship. When this antimicrobial stewardship
pathogen confirmed by culture-sensitivity reports e.g., a
program coupled with comprehensive infection control program it
third generation cephalosporin is changed to cloxacillin for
maximally curbs the emergence as well as transferal of antimicrobial
staphylococcal infection.
resistant pathogens. WHO, national and international organization (like
• Sequential - the use of oral formulation of the IV antibiotic without SHEA, IDSA, and PIDS), and government now strongly encourages
any loss in potency e.g., changing from IV to oral ciprofloxacin. healthcare institutions to develop stewardship programs.
• Step-down – Here, the IV antibiotic is changed to an oral agent of In 2012, the first initiative was taken in India to combat antimicrobial
the same or different class of similar antibiotics with a reduction resistance by formulating a document, known as the “Chennai
in potency e.g., changing from IV cefuroxime to oral cefuroxime Declaration”, to improve the overall awareness regarding AMR. After this,
axetil. ICMR started a program named “Antimicrobial Resistance Surveillance
• Switch - here the IV antibiotic is changed to an oral formulation of and Research Network” (AMRSN) in 2013 to accumulate nationwide
another antibiotic without any loss in potency e.g., changing from evidence on antimicrobial resistance. Grounding on this data, in 2016,
IV ceftazidime to oral ciprofloxacin. National Antimicrobial Treatment Guidelines document was released.

166 Journal of Young Pharmacists, Vol 14 Issue 2, Apr-Jun, 2022

 Sarkar, et al.: Rationality of Antibiotic usage

These guidelines were helpful in using antibiotics more judiciously and source and spread of antimicrobial resistance, introduce the logical
have strengthened the antimicrobial stewardship practices. notion of ‘One Health approach’ to address this global threat.
In these upcoming years, other stewardship programs like Indian Clinical “One Health is the collaborative effort of multiple health science professions
Epidemiology Network, and IIMAR (in collaboration with WHO) to attain optimal health for people, domestic animals, wildlife, plants, and
have been launched to generate more standard data on antimicrobial our environment” (Definition). This is aimed to safeguard the existing
resistance. Initiatives were also taken to get rapid diagnostics which antimicrobials by (1) limiting their irrational use (by adopting regulation
could be affordable in combating AMR. India has also implemented and policy, surveillance, stewardship etc), (2) implementing regulation
National Action Plan (NAP) on Antimicrobial Resistance, from 2017 and guidelines on animal husbandry (3) restricting propagation of
to 2021, for improving antibiotic prescribing by doctors and health care infection (by improving sanitation and hygiene), (4) reduction of
workers. Another step that was taken in this respect, was by the hospital environmental pollution (from industrial, domestic, and farm contains
accreditation bodies like National Accreditation Board for Hospitals antimicrobials waste); to reduce emergence of antimicrobial resistance,
(NABH), Joint Commission International (JCI), etc., i.e these bodies are to achieve continuous and assured antimicrobial effectiveness and
to implement Antimicrobial Stewardship Program (AMSP), which is effective health outcomes.
now an essential prerequisite for a hospital to get accredited. Recently, focusing on ‘one health approach’, guidelines are introduced
by WHO on use of therapeutically important antimicrobials in animal
AWARE CLASSIFICATION husbandry. This aims to prevent apperance of antimicrobial resistance
and to protect effectiveness of antimicrobial, used in human disease.
Rational use of antibiotics, through antimicrobial stewardship, is one of
According to the recommendations, the antimicrobials used to promote
the most relevant interventions that ensure appropriate treatment, limits
growth and prevent disease in healthy animals, should be stopped.
further development and outspread of antimicrobial resistance.12
To strengthen the implementation of rational antibiotic use and reducing CONCLUSION
antimicrobial resistance, WHO in 2019 introduced the “AWaRe” (Access,
Extravagant use of antibiotics has resulted in the rapid rise of multi-drug
Watch, Reserve) classification of antibiotics, those are in its Essential
resistant bacteria - the so called “superbugs” whereas the production
Medicines List. Total 180 antibiotics are classified as Access, Watch or
of newer antibiotics to combat those is till slower. The infections
Reserve, with details of their pharmacological classes, ATC (Anatomical
caused by these superbugs are difficult to treat, leading to increase
Therapeutic Chemical) codes and WHO Essential Medicines List
complications and fatality rates. Recently, universal and national battles
status. This classification can be used as an interactive tool for antibiotic
draw an attention globally to the rational use of the available antibiotics
stewardship, at national and international levels for adequate support of
and antibiotic stewardship programs. The goal of these stewardship
antibiotic monitoring and its appropriate use.13
programs is to maintain the effectiveness of antibiotics by implementing
• Access group includes 48 antibiotics like amoxicillin, ampicillin, their appropriate and optimum use. The therapeutic aim of antibiotics
nitrofurantoin, doxycycline, gentamicin, clindamycin, metronidazole therapy is not limited to only the successful treatment outcome in a
etc. These antibiotics are effective against numerous commonly given patient, rather it also encompassing the prevention of emerging
susceptible microorganisms and have less resistance potential than drug resistance for broad community. Recently WHO has issued new
antibiotics in the other two groups. guidelines regarding the use of antimicrobials in animals producing
• The Watch group includes 110 antibiotics like azithromycin, food, recommending the restricted use of such medicines in growth
cifixime, ceftriaxone, ciprofloxacin, vancomycin, meropenem etc. promotion or prevention of disease in healthy animals. Therefore, it is
These antibiotics have higher risk of bacterial resistance and are essential to use the available antibiotics in an optimal manner to limit the
recommended for some specific infectious disease, as an essential spread of these superbugs.
first or second-choice empiric treatment options. The antibiotics of
this group should be regarded as the essential targets of stewardship ACKNOWLEDGEMENT
programs and monitoring. We are thankful to the staff of department of Clinical and Experimental
• Reserve group antibiotics should be used as “last resort” options. Pharmacology, School of tropical Medicine, Kolkata as well as staff of
The antibiotics and antibiotic classes of this group should be Department of Pharmacology, Kalinga Institute of Medical Sciences,
reserved for the treatment of confirmed or suspected infections due Bhubaneswar, who were constantly involved with us in this project.
to multi-drug-resistant organisms, to highly specific patients and
situations when no suitable alternatives are available. For examples CONFLICT OF INTEREST
- linezolid, polymyxin etc. The authors declare that there is no conflict of interest.

ONE HEALTH APPROACH ABBREVIATIONS

This is worth mentioning, the emergence of antimicrobial resistance AMR: Antimicrobial resistance; WHO: World Health Organization;
is not only due to irrational antimicrobial use in human, but also ATC: Anatomical Therapeutic Chemical; IPD: Inpatient department;
irresponsible use of antimicrobial in animal, live stocks and various OPD: Outpatient department; CDK: Concentration dependent killing;
environmental sectors; and then the dissemination of resistant bacteria TDK: Time dependent killing; PAE: post antibiotic effect; TDM:
between these sectors and across the world. This is because of similarity Therapeutic drug monitoring; MIC: Mean inhibitory concentration;
in antimicrobials (or antimicrobials classes) used in humans and animals. PPCPs: Pharmaceuticals and personal care products; INSAR: Indian
For example, the mass medication (for prevention or treatment) of Network for Surveillance of Antimicrobial Resistance; AMRSN:
animals with critically important antimicrobials for humans, like third- Antimicrobial Resistance Surveillance and Research Network; ICMR:
generation cephalosporins and fluoroquinolones; and the long-term Indian council of medical research; NABH: National Accreditation
use of medically important antibiotics, such as colistin, tetracyclines, Board for Hospitals; NAP: National Action Plan; JCI: Joint Commission
and macrolides, for growth promotion. This overriding interconnecting International; AMSP: Antimicrobial Stewardship Program.

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 Sarkar, et al.: Rationality of Antibiotic usage

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Article History: Received: 18-02-2022; Revised: 18-02-2022; Accepted: 18-02-2022.

Cite this article: Sarkar S, Srivastava V, Samajhdar SS, Pattanayak C, Tripathi S. Rational Use of Antibiotics: An Area of Concern. J Young Pharm.
2022;14(2):165-8.

168 Journal of Young Pharmacists, Vol 14 Issue 2, Apr-Jun, 2022