The Open Biotechnology Journal




ISSN: 1874-0707 ― Volume 14, 2020
REVIEW ARTICLE

Antimicrobials Misuse/Overuse: Adverse Effect, Mechanism, Challenges and Strategies to Combat Resistance



Amit K. Mittal1, 2, *, Rohit Bhardwaj1, Priya Mishra3, Satyendra K. Rajput1, 2
1 Amity Institute of Pharmacy (AIP), Amity University-Uttar Pradesh, Sector-125, NOIDA, Uttar Pradesh, India
2 Amity Institute of Indian System of Medicine (AIISM), Amity University-Uttar Pradesh, Sector-125, NOIDA, Uttar Pradesh, India
3 Amity Institute of Neuropsychology and Neurosciences (AINN), Amity University-Uttar Pradesh, Sector-125, NOIDA, Uttar Pradesh, India

Abstract

Overuse and misuse of antibiotics are the first risk factors for the development of antibiotics resistance. Inadequate professional competence of health care physicians might worsen the complications associated with antibiotics resistance. Antibiotic resistance is a global issue; however, the epicenter of this misfortune is Asian regions due to the easy accessibility of the strongest antibiotics without prescriptions or diagnoses. High effectiveness and easy accessibility of antibiotics lead to overuse/misuse and encouraging bacteria to develop the resistance. The over-usage and mis-usage of antibiotics are antibiotic abuse, which increase the potentially serious impact on human health. Bestowing to WHO guidelines, the resistance has led to spread worldwide and classifying resistance is a serious health problem. Furthermore, resistance claims uncertainty to predict the future. This review summarizes the major antibiotics involved in drug resistance, mechanism, prescribed dosage with a disease condition, proposed policies and guidelines to combat antibiotic resistance associated problems.

Keywords: Antimicrobials misuse, Antibiotics, AMR, Bacteria, Antimicrobial resistance, MDR.


Article Information


Identifiers and Pagination:

Year: 2020
Volume: 14
First Page: 107
Last Page: 112
Publisher Id: TOBIOTJ-14-107
DOI: 10.2174/1874070702014010107

Article History:

Received Date: 3/3/2020
Revision Received Date: 21/4/2020
Acceptance Date: 27/4/2020
Electronic publication date: 08/09/2020
Collection year: 2020

© 2020 Mittal et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: (https://creativecommons.org/licenses/by/4.0/legalcode). This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


* Address correspondence to this author at the Amity Institute of Pharmacy (AIP), Lab no-G-01, Block-L-1, Amity Institute of Pharmacy, Amity University, Noida, Uttar Pradesh (UP), India -201313; Tel: 0120-4735655; E-mail: akmittal@amity.edu; amitkrbiotech@gmail.com





1. INTRODUCTION

Antimicrobial Resistance (AMR) has emerged as a major risk to public health estimated to cause 1 crore deaths annually by 2050 [1Dixit A, Kumar N, Kumar S, Trigun V. Antimicrobial resistance: Progress in the decade since emergence of New Delhi metallo-β-lactamase in India. Soc Med (Soc Med Publ Group) 2019; 44(1): 4.]. Annually, more than 50,000 newborns die from sepsis due to resistance against first-line antibiotics [1Dixit A, Kumar N, Kumar S, Trigun V. Antimicrobial resistance: Progress in the decade since emergence of New Delhi metallo-β-lactamase in India. Soc Med (Soc Med Publ Group) 2019; 44(1): 4., 2Sidjabat H, Nimmo GR, Walsh TR, et al. Carbapenem resistance in Klebsiella pneumoniae due to the New Delhi Metallo-β-lactamase. Clin Infect Dis 2011; 52(4): 481-4.
[http://dx.doi.org/10.1093/cid/ciq178] [PMID: 21258100]
]. The overuse and misuse of antibiotics are vital issues contributing to the development of antibiotic resistance, causing potentially serious effects on human health [3de Carvalho CC, Caramujo MJ. Ancient procedures for the high-tech World: health benefits and antimicrobial compounds from the Mediterranean Empires. Open Biotechnol J 2008; 2(1)
[http://dx.doi.org/10.2174/1874070700802010235]
]. Several countries are facing the emergence of drug-resistant bacteria, which are completely resistant to available antibiotics. Most of the countries are preparing a country-specific action plan for the management of AMR globally, according to WHO guidelines [1Dixit A, Kumar N, Kumar S, Trigun V. Antimicrobial resistance: Progress in the decade since emergence of New Delhi metallo-β-lactamase in India. Soc Med (Soc Med Publ Group) 2019; 44(1): 4., 2Sidjabat H, Nimmo GR, Walsh TR, et al. Carbapenem resistance in Klebsiella pneumoniae due to the New Delhi Metallo-β-lactamase. Clin Infect Dis 2011; 52(4): 481-4.
[http://dx.doi.org/10.1093/cid/ciq178] [PMID: 21258100]
]. Asian countries have the largest burdens of drug-resistant strains worldwide [4Porter G, Grills N. Medication misuse in India: A major public health issue in India. J Public Health (Oxf) 2016; 38(2): e150-7.
[http://dx.doi.org/10.1093/pubmed/fdv072] [PMID: 26060236]
]. Furthermore, India is one of the major consumers of antibiotics in the world and their overuse and misuse are rambling [4Porter G, Grills N. Medication misuse in India: A major public health issue in India. J Public Health (Oxf) 2016; 38(2): e150-7.
[http://dx.doi.org/10.1093/pubmed/fdv072] [PMID: 26060236]
]. Besides, India is at one of the top rates of resistance against antimicrobials that are used for the treatment of humans and farm animals [5Van Boeckel TP, Brower C, Gilbert M, et al. Global trends in antimicrobial use in food animals. Proc Natl Acad Sci USA 2015; 112(18): 5649-54.
[http://dx.doi.org/10.1073/pnas.1503141112] [PMID: 25792457]
]. Currently, antibiotics are also utilizing against the treatment of several species of fungi and protozoans infections, but the impact of these is very toxic to humans and animals [6Waksman SA. The role of antibiotics in nature. Perspect Biol Med 1961; 4(3): 271-87.
[http://dx.doi.org/10.1353/pbm.1961.0001]
]. Antibiotics' effectiveness and easy access can lead to overuse or misuse prompting to develop resistance in microorganisms. In addition, inappropriate antibiotic dosages have also contributed to the emergence of antibiotic-resistant bacterial strains [7Lewis R. The rise of antibiotic-resistant infections. FDA consumer magazine 1995; 29(1)]. Unappropriated practices of antibiotics have long been believed to fuel AMR, but newer research showed that simply lowering consumption is not enough [8Cunha CB. Antimicrobial stewardship programs: Principles and practice. Med Clin North Am 2018; 102(5): 797-803.
[http://dx.doi.org/10.1016/j.mcna.2018.04.003] [PMID: 30126571]
]. Significant problems are arising due to the development of antibiotic-resistant strains of bacteria and further creation of multidrug-resistant bacterial spp [9Magiorakos AP, Srinivasan A, Carey RB, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 2012; 18(3): 268-81.
[http://dx.doi.org/10.1111/j.1469-0691.2011.03570.x] [PMID: 21793988]
]. The multidrug-resistant bacterial spp., having resistance to multiple antibiotics, can cause life-threatening infections [10Bassetti M, Righi E. Multidrug-resistant bacteria: what is the threat? ASH Education Program Book 2013; 2013(1): 428-32.]. For example, overuse of fluoroquinolone and other associated antibiotics can also lead to such kind of antibiotic resistance in bacteria [11Fair RJ, Tor Y. Antibiotics and bacterial resistance in the 21st century. Perspectives in medicinal chemistry 2014.]. Developments of superbugs are the result of such kinds of antibiotic associated evils [12Alpert PT. Superbugs: antibiotic resistance is becoming a major public health concern. Home Health Care Manage Pract 2017; 29(2): 130-3.
[http://dx.doi.org/10.1177/1084822316659285]
]. In addition, few antibiotics have been associated with adverse side effects, including mild to very serious symptoms that depend upon treated microbial sps and individual patients [13Török E, Moran E, Cooke F. Oxford handbook of infectious diseases and microbiology 2016.
[http://dx.doi.org/10.1093/med/9780199671328.001.0001]
]. The antibiotics can sometimes alter the host microbiota and lead to chronic infection and inflammation [14Langdon A, Crook N, Dantas G. The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation. Genome Med 2016; 8(1): 39.
[http://dx.doi.org/10.1186/s13073-016-0294-z] [PMID: 27074706]
]. Usually, antibiotics side-effects are fever, nausea and major allergic reactions, including photo-dermatitis and anaphylaxis. The common side-effect of antibiotics is diarrhea, due to the misbalancing of the intestinal flora species or overgrowth of pathogenic bacteria [15Bhattacharya S. The facts about penicillin allergy: a review. J Adv Pharm Technol Res 2010; 1(1): 11-7.
[PMID: 22247826]
]. Additional side-effects included the interaction with other drugs, such as the elevated risk of damage of tendon when quinolone antibiotic is given with a corticosteroid [16Lewis T, Cook J. Fluoroquinolones and tendinopathy: A guide for athletes and sports clinicians and a systematic review of the literature. J Athl Train 2014; 49(3): 422-7.
[http://dx.doi.org/10.4085/1062-6050-49.2.09] [PMID: 24762232]
]. The overuse of fluoroquinolone and other antibiotics leads to antibiotic resistance in bacteria, which might inhibit the treatment of antibiotic-resistant infections [16Lewis T, Cook J. Fluoroquinolones and tendinopathy: A guide for athletes and sports clinicians and a systematic review of the literature. J Athl Train 2014; 49(3): 422-7.
[http://dx.doi.org/10.4085/1062-6050-49.2.09] [PMID: 24762232]
]. The article summarizes the adverse effect of antibiotics, mechanisms of resistance, challenges and future strategies to combat antimicrobial resistance to manage the health care system.

2. ADVERSE EFFECTS OF ANTIBIOTICS

A side effect of antibiotics is a reaction that occurs in the patients, along with the therapeutic action [17Heta S, Robo I. The side effects of the most commonly used group of antibiotics in periodontal treatments. Med Sci (Basel) 2018; 6(1): 6.
[http://dx.doi.org/10.3390/medsci6010006] [PMID: 30720776]
]. If the dosage of antibiotics is used appropriately, antibiotics are relatively safe, with very few side effects. However, these side effects can range from mild allergic reactions to severe adverse, which may be extremely variable from patient to patient and from antibiotic to antibiotic [18Thong BYH. Update on the management of antibiotic allergy. Allergy Asthma Immunol Res 2010; 2(2): 77-86.
[http://dx.doi.org/10.4168/aair.2010.2.2.77] [PMID: 20358021]
]. Moreover, many antibiotics may interfere with the individual patient’s ability to tolerate and complete the course [19Saradamma RD, Higginbotham N, Nichter M. Social factors influencing the acquisition of antibiotics without prescription in Kerala State, south India. Soc Sci Med 2000; 50(6): 891-903.
[http://dx.doi.org/10.1016/S0277-9536(99)00380-9] [PMID: 10695985]
]. Fewer patients having any previous allergic reaction to any kind of antibiotics are not recommended for the same. The allergic reactions may include symptoms like a skin rash and allergic reactions, called anaphylaxis, which can lead to difficulties in breath and swelling of the lips or tongue and face. Here, the common side-effects of major antibiotics are given below [20Warrington RJ, McPhillips S. Independent anaphylaxis to cefazolin without allergy to other β-lactam antibiotics. J Allergy Clin Immunol 1996; 98(2): 460-2.
[http://dx.doi.org/10.1016/S0091-6749(96)70171-9] [PMID: 8757224]
].

(1) Penicillin: Rash, diarrhea, abdominal pain, nausea/ vomiting, drug fever, hypersensitivity (allergic) reactions, etc. [15Bhattacharya S. The facts about penicillin allergy: a review. J Adv Pharm Technol Res 2010; 1(1): 11-7.
[PMID: 22247826]
, 21Golembiewski JA. Allergic reactions to drugs: Implications for perioperative care. J Perianesth Nurs 2002; 17(6): 393-8.
[http://dx.doi.org/10.1053/jpan.2002.36669] [PMID: 12476405]
].

(2) Cephalosporin: Diarrhea, nausea/vomiting, hypersensitivity reactions, serum sickness, etc. [22Mitropoulos IF, Rotschafer JC, Rodvold KA. Adverse events associated with the use of oral cephalosporins/cephems. Diagn Microbiol Infect Dis 2007; 57(3)(Suppl.): 67S-76S.
[http://dx.doi.org/10.1016/j.diagmicrobio.2006.12.002] [PMID: 17292575]
].

(3) Aminoglycosides: Nausea/vomiting, nystagmus, etc. [23Gregory D, Hirschmann JV. Prudent use of the aminoglycosides. Postgrad Med 1978; 64(3): 97-102, 104.
[http://dx.doi.org/10.1080/00325481.1978.11714923] [PMID: 704499]
].

(4) Erythromycin, azithromycin, clarithromycin: abdominal pain, diarrhea, anorexia, nausea/vomiting, taste alterations, etc. [24Shoukath U, Khatoon F, Mahveen S, Uddin MN. Iatrogenic Disease. Asian J Pharm Res 2018.].

(5) Tetracycline: Nausea/vomiting, diarrhea, anorexia, abdominal pain, tooth discoloration in children < 8 years, liver toxicity, etc. [25Greer ND. Tigecycline (Tygacil): the first in the glycylcycline class of antibiotics. Baylor University Medical Center Proceedings 2006; 19(2): 155-61.].

(6) Quinolones ciprofloxacin (cipro), levofloxacin (levaquin), moxifloxacin (avelox), ofloxacin (floxin): nausea/vomiting, diarrhea, abdominal pain, headache, lethargy, insomnia, etc. [26Tribble DR. Antibiotic therapy for acute watery diarrhea and dysentery. Military medicine 2017; 182(suppl_2): 17-25.].

(7) The environments, especially the water bodies, have also reported the presence of resistant organisms or their genes. Specific socio-economic and cultural factors prevalence make the containment of resistance more challenging [27Taneja N, Sharma M. Antimicrobial resistance in the environment: The Indian scenario. Indian J Med Res 2019; 149(2): 119-28.
[http://dx.doi.org/10.4103/ijmr.IJMR_331_18] [PMID: 31219076]
].

3. COMMON MECHANISM TO DEVELOP RESISTANCE IN MICROORGANISM

The key mechanisms of antimicrobial resistance include enzymatic degradation of antimicrobial produced by bacterial cells, a mutation in the antimicrobial targeting agents and prohibition of antibiotic entry inside the bacterial cells via membrane (Fig. 1). The spread of antibiotic resistance occurs through genetic material (plasmid or the bacterial chromosome) [28Naguib MM, El-Gendy AO, Khairalla AS. Microbial diversity of mer operon genes and their potential rules in mercury bioremediation and resistance. Open Biotechnol J 2018; 12(1)
[http://dx.doi.org/10.2174/1874070701812010056]
, 29Pitton JS. Mechanisms of bacterial resistance to antibiotics.Ergebnisse der Physiologie Reviews of Physiology 1972; Vol. 65: 15-93.].

Fig. (1)
Representation of mechanisms involved in microbes resistance.


4. ANTIBIOTIC RESISTANCE RATE IN MICROORGANISM

World Health Organization, European Centre for Disease Control and World Health Assembly highlighted the antimicrobial resistance as a major public health issue and will be a big challenge to grip for health care workers [30Richardson E. The Role of Public Health Organizations in Addressing Public Health Problems in Europe: The Case of Obesity Alcohol and Antimicrobial Resistance 2018; 51]. An establishment of multi-resistant strains arises due to the production of a broad spectrum of β-lactamases using various bacterial spp. after continuous consumption and became very common [31van Duin D, Paterson DL. Multidrug-resistant bacteria in the community: trends and lessons learned. Infect Dis Clin North Am 2016; 30(2): 377-90.
[http://dx.doi.org/10.1016/j.idc.2016.02.004] [PMID: 27208764]
]. Antimicrobial resistance is an important public health concern at the global level. However, in India, recent hospital and community based reports showed an incensement of microbial resistance [32Kumar SG, Adithan C, Harish BN, Sujatha S, Roy G, Malini A. Antimicrobial resistance in India: A review. J Nat Sci Biol Med 2013; 4(2): 286-91.
[http://dx.doi.org/10.4103/0976-9668.116970] [PMID: 24082718]
]. The reports showed varied resistance in different antibiotic resistance rates of various organisms along with various parts of India, as shown in Table 1.

5. CHALLENGES FOR ANTIMICROBIAL RESISTANCE

AMR in the world and emergence of newer Multi-Drug Resistant (MDR) and Extreme Drug Resistance (XDR) strains pose newer diagnostic and therapeutic challenges [33Patil K, Bagade S, Bonde S, Sharma S, Saraogi G. Recent therapeutic approaches for the management of tuberculosis: Challenges and opportunities. Biomed Pharmacother 2018; 99: 735-45.
[http://dx.doi.org/10.1016/j.biopha.2018.01.115] [PMID: 29710471]
]. However, developed and developing countries are still striving to combat deep-rooted diseases such as tuberculosis, malaria and cholera pathogens, which are becoming with more drug resistant strains [34John TJ, Dandona L, Sharma VP, Kakkar M. Continuing challenge of infectious diseases in India. Lancet 2011; 377(9761): 252-69.
[http://dx.doi.org/10.1016/S0140-6736(10)61265-2] [PMID: 21227500]
]. Several factors such as poverty, illiteracy, overcrowding and malnutrition further contribute to such kind of situation [35Bajpai V. The challenges confronting public hospitals in India, their origins, and possible solutions. Adv Public Health 2014; 2014.
[http://dx.doi.org/10.1155/2014/898502]
]. Lower healthcare professional to patient ratios is also involved for such kind of concern.

6. CASE STUDIES OF RESISTANCE DEVELOPMENT AND AFFECTING FACTORS

1. A study published by the Indian Council of Medical Research (ICMR) has found antibiotic resistant organisms of the digestive tracts in about 66% of the Indian population. The study was performed on 207 individuals with an analysis of stool samples, who had not taken any antibiotic from at least last month. Individuals selected were not suffering from any chronic illness. Isolates taken from 139 out of these 207 individuals were found to be resistant to one or more types of antibiotic classes. The maximum resistance rate was seen for cephalosporin (60%) and fluoroquinolones (41.5%) [36Gupta M, Didwal G, Bansal S, et al. Antibiotic-resistant Enterobacteriaceae in healthy gut flora: A report from north Indian semiurban community. Indian J Med Res 2019; 149(2): 276-80.
[http://dx.doi.org/10.4103/ijmr.IJMR_207_18] [PMID: 31219094]
].

Table 1
List of some common well-reported cases of antibiotics resistance rate in India.


2. A group of All India Institute of Medical Science (AIIMS), New Delhi, India researcher analyzed the water samples from seven different places in Delhi NCR regions along with the river, including its entry and exit points in the city, 35 bore wells and water percolating through waste. They found the concentration of dissolved drugs/antibiotics in the river water increased at an exit point rather than an entry point into the city. This case story concludes that either stopping or recommended use of the drugs/antibiotics by humans, animals and proper disposal method needs to be recommended to save the environment and welfare [37Velpandian T, Halder N, Nath M, et al. Un-segregated waste disposal: an alarming threat of antimicrobials in surface and ground water sources in Delhi. Environ Sci Pollut Res Int 2018; 25(29): 29518-28.
[http://dx.doi.org/10.1007/s11356-018-2927-9] [PMID: 30136185]
].

7. ANTIBIOTIC DOSE RECOMMENDED

Resistances against various classes of antibiotics were detected among various parts of the world [38Global Antibiotic Resistance Partnership (GARP)-India Working Group, 2011. Rationalizing antibiotic use to limit antibiotic resistance in India The Indian journal of medical research 2011; 134(3): 281.]. However, the main reasons for this situation are either antibiotic doses not used under prescription or with proper treatment duration [18Thong BYH. Update on the management of antibiotic allergy. Allergy Asthma Immunol Res 2010; 2(2): 77-86.
[http://dx.doi.org/10.4168/aair.2010.2.2.77] [PMID: 20358021]
, 38Global Antibiotic Resistance Partnership (GARP)-India Working Group, 2011. Rationalizing antibiotic use to limit antibiotic resistance in India The Indian journal of medical research 2011; 134(3): 281., 39Gawande U, Deshmukh S, Kadam S, Potdar G, Salvitthal H. Prescription audit of patients attendees in public health facilities in Maharashtra, India with special reference to rational use of antibiotics. Int J Res Med Sci 2015; 3: 3655-64.
[http://dx.doi.org/10.18203/2320-6012.ijrms20151418]
]. Increasing antimicrobial resistance is now a worldwide problem, compounded by the lack of development of new antimicrobial medicines [40Reardon S. Antibiotic resistance sweeping developing world. Nature 2014; 509(7499): 141-2.
[http://dx.doi.org/10.1038/509141a] [PMID: 24805322]
]. Penicillin medication is used to treat several kinds of bacterial infections. It is also used for the treatment of a number of infections like pneumonia, bronchitis, gonorrhea and infections of the ears, nose, throat, urinary tract and skin [41Venkatesh S, Chauhan LS, Gadpayle AK, Jain TS, Ghafur A, Wattal C. National treatment guidelines for antimicrobial use in infectious diseases. India: National Centre For Disease Control, MOHFW, Government of India 2011; 1-64.]. Such type of treatments led to develop a resistance and side-effects against the penicillin class of drugs, when un-appropriate doses are given with no medical healthcare supervision/guidance [42Miller EL. The penicillins: a review and update. J Midwifery Womens Health 2002; 47(6): 426-34.
[http://dx.doi.org/10.1016/S1526-9523(02)00330-6] [PMID: 12484664]
]. The antibiotic should be prescribed only in case of bacterial infections, when the symptoms are severe, high risk of complications, and infection is not resolving [43Reese RE, Betts RF, Gumustop B, Betts R. Handbook of antibiotics 2000.]. Furthermore, in the case of severe infections, combinations therapy of antibiotics should be followed to achieve the synergistic effect of antibiotics at a lower dose under medical supervision.

8. GUIDELINES TO FOLLOW ANTIBIOTICS PRESCRIPTION

To prevent the development of antibiotic resistance, it is important to use antibiotics in the right way, to use the right drug with the right dose, at the right time for the right duration as per disease condition after diagnosis [44Doron S, Davidson LE. Antimicrobial stewardship. Mayo Clin Proc 2011; 86(11): 1113-23. [). Elsevier.].
[http://dx.doi.org/10.4065/mcp.2011.0358] [PMID: 22033257]
]. Prescribe the drug only where necessary, and consider benefits versus risks according to patient. The dosage should be prescribed carefully and be followed by manufacturer’s instructions [45De Vries TPG, Henning RH, Hogerzeil HV, Fresle DA, Policy M. Guide to good prescribing: a practical manual (No WHO/DAP/9411) 1994.]. The manufacture recommended doses are determined using clinical trial studies and assume one dose fits all [46Shen J, Swift B, Mamelok R, Pine S, Sinclair J, Attar M. Design and Conduct Considerations for First-in-Human Trials. Clin Transl Sci 2019; 12(1): 6-19.
[http://dx.doi.org/10.1111/cts.12582] [PMID: 30048046]
]. The newer drugs are launched and necessary to review the patient to assess for effect, side-effects (Adverse Event; AE and Serious Adverse Events; SAE) and the need to continue [47Gliklich RE, Dreyer NA, Leavy MB. Adverse event detection, processing, and reporting.Registries for Evaluating Patient Outcomes: A User’s Guide 3rd ed. 2014. Internet].

9. PRECAUTIONS DURING ANTIBIOTICS UTILIZATION

1. Antibiotics are life-saving drugs, should be used safely and effectively [48Centers for Disease Control and Prevention (CDC) and Aware. Smart Use, Best Care CDC website 2017.]. During the entire course of any prescribed antibiotic, complete the course so that it can be fully effective and does not induce resistance [49National Collaborating Centre for Women’s and Children’s Health. Antibiotics for early-onset neonatal infection: antibiotics for the prevention and treatment of early-onset neonatal infection 2012.]. It is required that necessary precautions should be taken by health care professionals to minimize the unnecessary prescribing and overprescribing of antibiotics [48Centers for Disease Control and Prevention (CDC) and Aware. Smart Use, Best Care CDC website 2017., 50Fleming-Dutra KE, Linder JA, Hyun D, Iskander JK, Thorpe P, Laird S. Be antibiotics aware: smart use, best care 2018.]. Many antibiotics such as amoxicillin, ampicillin, cephalosporin, etc. cause mild side effects such as diarrhea and abdominal pain, and need to be prescribed with appropriate stomach care supplement or probiotics [51Visone DNP. The Use of Probiotics to Prevent Antibiotic Associated Diarrhea: Current Primary Care Practice and Introduction of an Evidence Based Practice Protocol 2012.]. It is recommended that, the prescribed treatment should be continuous, the side-effects of medicine may occur and subside gradually after a few days [52Cunha BA. Antibiotic side effects. Med Clin North Am 2001; 85(1): 149-85.
[http://dx.doi.org/10.1016/S0025-7125(05)70309-6] [PMID: 11190350]
]. Try to practice good hygiene and use appropriate infection control procedures. Additional precautions should be taken for patients or suspected to be infected or colonized with highly infectious pathogens [53Leblebicioglu H, Rodriguez-Morales AJ, Rossolini GM, López-Vélez R, Zahar JR, Rello J. Management of infections in critically ill returning travellers in the intensive care unit-I: Considerations on infection control and transmission of resistance. Int J Infect Dis 2016; 48: 113-7.
[http://dx.doi.org/10.1016/j.ijid.2016.04.019] [PMID: 27134158]
]. The usage of combination therapy would provide prevention against drug-resistant bacterial strains [54Worthington RJ, Melander C. Combination approaches to combat multidrug-resistant bacteria. Trends Biotechnol 2013; 31(3): 177-84.
[http://dx.doi.org/10.1016/j.tibtech.2012.12.006] [PMID: 23333434]
].

10. GOVERNMENT INITIATIVE POLICIES TO CONTROL ANTIBIOTICS RESISTANCE

(1) To prevent the misuse of important antibiotics, the Central Drugs Standard Control Organization (CDSCO), Govt of India has implemented Schedule H1 in India [55Ahmad A, Patel I. Schedule H1: Is it a solution to curve antimicrobial misuse in India? Ann Med Health Sci Res 2013; 3(Suppl. 1): S55-6.
[http://dx.doi.org/10.4103/2141-9248.121228] [PMID: 24349854]
].

(2) Implementation of the National Health Policy, 2017 to public health and creating the awareness [56Prinja S, Downey LE, Gauba VK, Swaminathan S. Health technology assessment for policy making in India: current scenario and way forward 2018.
[http://dx.doi.org/10.1007/s41669-017-0037-0]
].

(3) Hospital infection control and prevention program [57Pai M, Kalantri S, Aggarwal AN, Menzies D, Blumberg HM. Nosocomial tuberculosis in India. Emerg Infect Dis 2006; 12(9): 1311-8.
[http://dx.doi.org/10.3201/eid1209.051663] [PMID: 17073077]
].

(4) The regulation of antimicrobial’s sale [58Shet A, Sundaresan S, Forsberg BC. Pharmacy-based dispensing of antimicrobial agents without prescription in India: Appropriateness and cost burden in the private sector. Antimicrob Resist Infect Control 2015; 4(1): 55.
[http://dx.doi.org/10.1186/s13756-015-0098-8] [PMID: 26693005]
].

(5) Training program to control antibiotic usage [59Chandy SJ, Michael JS, Veeraraghavan B, Abraham OC, Bachhav SS, Kshirsagar NA. ICMR programme on antibiotic stewardship, prevention of infection & control (ASPIC). Indian J Med Res 2014; 139(2): 226-30.
[PMID: 24718396]
].

(6) An establishment of the National Centre for Disease Control (NCDC) [60Choudhry A, Singh S, Khare S, et al. Emergence of pandemic 2009 influenza A H1N1, India. Indian J Med Res 2012; 135(4): 534-7.
[PMID: 22664503]
].

(7) Antimicrobial stewardship (AMS) to prevent the emergence of antimicrobial resistance and decrease preventable healthcare-associated infections [61Walia K, Ohri VC, Mathai D. Antimicrobial stewardship programme (AMSP) practices in India. Indian J Med Res 2015; 142(2): 130-8.
[http://dx.doi.org/10.4103/0971-5916.164228] [PMID: 26354210]
].

11. POSSIBLE STRATEGIES TO COMBAT THE PROBLEM ASSOCIATED WITH ANTIBIOTICS RESISTANCE

Followings strategies can be followed

(1) Understanding the emergence and spread of antibiotics resistance and key factors influencing it [62Berger-Bächi B, Rohrer S. Factors influencing methicillin resistance in staphylococci. Arch Microbiol 2002; 178(3): 165-71.
[http://dx.doi.org/10.1007/s00203-002-0436-0] [PMID: 12189417]
-65Pollack M, Charache P, Nieman RE, Jett MP, Reimhardt JA, Hardy PH Jr. Factors influencing colonisation and antibiotic-resistance patterns of gram-negative bacteria in hospital patients. Lancet 1972; 2(7779): 668-71.
[http://dx.doi.org/10.1016/S0140-6736(72)92084-3] [PMID: 4115815]
].

(2). Establishing a nationwide well-coordinated antibiotics program with well-defined and interlinked responsibilities and functions of different arms of the program [66Huttner B, Harbarth S. The French national campaign to cut antibiotic overuse. PLoS Med 2009; 6(6)e1000080
[http://dx.doi.org/10.1371/journal.pmed.1000080] [PMID: 19492081]
-70Lutters M, Harbarth S, Janssens JP, et al. Effect of a comprehensive, multidisciplinary, educational program on the use of antibiotics in a geriatric university hospital. J Am Geriatr Soc 2004; 52(1): 112-6.
[http://dx.doi.org/10.1111/j.1532-5415.2004.52019.x] [PMID: 14687324]
].

(3) Rationalizing the usage of available antibiotics [38Global Antibiotic Resistance Partnership (GARP)-India Working Group, 2011. Rationalizing antibiotic use to limit antibiotic resistance in India The Indian journal of medical research 2011; 134(3): 281., 71Ghafur A, Mathai D, Muruganathan A, et al. The Chennai Declaration: a roadmap to tackle the challenge of antimicrobial resistance. Indian J Cancer 2013; 50(1): 71-3.
[http://dx.doi.org/10.4103/0019-509X.104065] [PMID: 23713050]
].

(4) Reducing the antibiotic selection pressures by appropriate control measures [72Tenover FC, McGowan JE Jr. Reasons for the emergence of antibiotic resistance. Am J Med Sci 1996; 311(1): 9-16.
[http://dx.doi.org/10.1097/00000441-199601000-00003] [PMID: 8571988]
].

(5) Promotion of discovery of newer and effective antibiotics based on current knowledge of resistance mechanisms [73Holmes AH, Moore LS, Sundsfjord A, et al. Understanding the mechanisms and drivers of antimicrobial resistance. Lancet 2016; 387(10014): 176-87.
[http://dx.doi.org/10.1016/S0140-6736(15)00473-0] [PMID: 26603922]
-75Jindal AK, Pandya K, Khan ID. Antimicrobial resistance: A public health challenge. medical journal armed forces india 2015; 71(2): 178-81.].

(6) Rapid and accurate diagnosis of infections and infectious diseases [76Byington CL, Castillo H, Gerber K, et al. The effect of rapid respiratory viral diagnostic testing on antibiotic use in a children’s hospital. Arch Pediatr Adolesc Med 2002; 156(12): 1230-4.
[http://dx.doi.org/10.1001/archpedi.156.12.1230] [PMID: 12444835]
, 77Christ-Crain M, Müller B. Biomarkers in respiratory tract infections: diagnostic guides to antibiotic prescription, prognostic markers and mediators. Eur Respir J 2007; 30(3): 556-73.
[http://dx.doi.org/10.1183/09031936.00166106] [PMID: 17766633]
].

(7) Prescribe multiple antibiotics to achieve a synergistic effect at a lower dose.

CONCLUSION AND FUTURE PROSPECTS

AMR has increased the burden worldwide in pathogenic microbes, leading to the spread of microbial resistance across the globe. However, appropriate usage of respective antibiotics is the only way to prolonging life. A novel class of antibiotics needs to be discovered and introduced for better safety against severe microbial infection against drug-resistant species. Furthermore, novel molecular tools and diagnostics methods need to be explored to inhibit and develop the resistance in microbes. Additionally, the interaction of antibiotics with others should be studied in the laboratory to investigate the synergistic and antagonistic effects of antibiotics.

FUNDING

None.

CONFLICT OF INTEREST

The author declares no conflict of interest, financial or otherwise.

ACKNOWLEDGEMENTS

The authors greatly acknowledge Amity University, Noida, Uttar Pradesh, India, for providing the infrastructural support and opportunity to write this review.

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