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Home , Cefluprenam, Epicillin, Metampicillin, Oxacephem, Quinolone antibiotic

April 30, 2019

Newsletter • 2019 • vol.1 • 117-148

SURVEY ON RATIONAL USE OF ANTIBACTERIALS INCLUDING MRSA IN A RURAL AREA OF BANGLADESH Shaheen Sharif M.*1 Rimu Sharmin S.1And Haque M Anamul1 1Daffodil International University, Daffodil Tower (DT)-054/2 Sobahanbag, Mirpur Road Dhanmondi, Dhaka-1207, Bangladesh. Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Sobahanbag Daffodil Tower (DT)-054/2, Mirpur Road Dhanmondi, Dhaka-1207, Bangladesh. Tel. +8848111639, Ext.355 [email protected], [email protected]

Abstract Antibiotics including antibacterials are most commonly used in the present world against pathogenesis. The present study was aimed to analyse the current status of rational use of antibiotics in the prescriptions surveyed in a rural area named Gazipur of Bangladesh and threat against MRSA ( resistant aureas) antibiotics misuse in rural area. resistance has increasingly been recognized as a major issue in healthcare. Antibiotic use is viewed as a key driver for the increase and spread of antibiotic resistance. To examine the level of rational use about antibiotic treatment and awareness of antibiotic resistance among the general public in Bangladesh. The records were collected for the people suffering with different type of . Generally, Antibiotics are used against bacterial infections and the rational use of antibiotic 54%, Less rational use 25%, Irrational use 17%, Misuse 4 % were found in this area selected here. Antibiotics are good medicine in infectious diseases and it should be prescribed and monitored carefully by registered pharmacist. However, it is so costly and difficult to continue long time for a rural people. The result of this survey indicates that the antibiotics are used among the doctor in improper way. To overcome this situation physician should be aware and careful about the safety of antibiotics. People must be following the prescription strictly to avoid antibiotic resistances. It is high time that the professional bodies should take up the project of increasing awareness about antibiotic use among the practicing physicians to dispel the inappropriate information caused by pharmaceuticals and initiate necessary steps to deliver the latest advances of the knowledge to every practicing physician through academic activities in order to check over this emerging problem of antibiotic resistance.

Keywords: Antibacterial , -resistant, antibiotics, MRSA antibiotics, prescription survey

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Introduction the above-mentioned criteria are not fulfilled. It An antibiotic or antibacterial is an agent that has calculated that half of the drugs are sold, inhibits bacterial growth or kills bacteria. dispensed inappropriately and also half of the Antibiotic is any substance produced by a patient fails to take the medicines as prescribed microorganism that is antagonistic to the by the physician. Irrational use may include Poly growth of other microorganisms in high pharmacy, over use of antibiotics and injection dilution. Rational use of a drug means when the failure to prescribe in accordance with clinical patients receive the drug which is appropriate, guide lines or wrong guideline. It is a global in doses that meet their individual requirement, problem of wrong use of drugs, some countries for an adequate period of time at the lowest taking action to make correct the problem. cost both to them and the community and irrational use of Medicine is that when one or Over use or miss use of antibiotics has more of the above condition is not met .This is significant consequences such as increased cost very much a medical-model definition. , bacterial resistance, therapeutic failure drug The definition implies that rational use of drugs, toxicity and drug inter action .Excessive use of especially rational prescribing, should meet antibiotic is a well-documented risk factor for certain criteria as follows: the selection of resistant bacteria and in general  Appropriate indication: The decision to a close association exists between the rate of prescribe drug(s) is entirely based on resistance development and the quantities of medical science agents used. The modern age of antibiotic therapeutics was launched in the  Appropriate drug: The selection of drugs 1930s with sulfonamides and the 1940s with is based on efficacy, safety, suitability, .Since then, many antibiotic drugs and cost considerations. have been developed, most aimed at the treatment of bacterial infections .These drugs  Appropriate patient: No have played an important role in the dramatic contraindications exist, the likelihood of decrease in morbidity and mortality due to adverse reactions is minimal, and the infectious diseases .While the absolute number drug is acceptable to the patient. of antibiotic drugs is large, there are few unique  Appropriate patient information: antibiotic targets. Patients are provided with relevant, Increasing is now a accurate, important and clear worldwide problem, compounded by the lack of information regarding their conditions development of new antimicrobial medicines. and the (s) that are This leaves the prudent use of antimicrobial prescribed. medicines, along with control, as the  Appropriate evaluation: The anticipated major strategies to counter this emerging and unexpected effects of threat. are appropriately monitored and A safe and effective strategy for antibiotic use interpreted. involves prescribing an antibiotic only when it is Unfortunately, in the real world, prescribing needed and selecting an appropriate and patterns do not always conform to these effective medicine at the recommended , criteria and can be classified as inappropriate or with the narrowest spectrum of antimicrobial irrational prescribing. Irrational prescribing may activity, fewest adverse effects and lowest cost. be regarded as "pathological" prescribing when

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General principles of antibiotic prescribing  Co-trimoxazole

1. Only prescribe antibiotics for bacterial 2. Diaminopyrimidines infections if: 3. Quinolones  Symptoms are significant or severe  There is a high risk of complications  First generation:  The infection is not resolving or is  Second generation unlikely to resolve , ,  Third generation: 2. Use first-line antibiotics first  Fourth generation: , 3. Reserve broad spectrum antibiotics for indicated conditions only 4. Beta lactam

We have undertaken the work to find 5. : out some vital information about antibiotic and the rational use of  antibiotics in a rural area of several  Doxycycline conditions. The specific objectives of the  Minocycline work were:-  6. Nitrobenzene Derivatives  To provide the public with a better understanding of the natural course of 7. Aminoglycosides: an infection  To understand whether the proper use  of antibiotics is going or not   To determine the risks associated with  Kanamycin the rapid emergence of resistance to  antibiotics  Spectinomycin To aware the patient for a useful discussion 8. : with his/her doctor on the need to use  antibiotics appropriately.  Clarithromycin Classification of antibiotics and antibacterials  Dirithromycin  Erythromycin Antibiotic can be classified according to the  Spiramycin following way: 9. Polypeptide A. According to Chemical Structure: 10. Glycopeptide 1. Sulfonamides and related drugs 11. Oxazolidinone  12. derivatives  13.

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14. Nicotinic acid derivatives E. Antibiotics are obtained from:

15. Polyene 1. Fungi: Penicillin, Griseofulvin

15. Azole derivatives 2. Bacteria:

B. According to mechanism of action: 3. Actinomycetes: Aminoglycosides, Macrolides 1. Inhibit synthesis: The Penicillin

 Penicillin’s Penicillin is a group of antibiotics that are  commonly used to treat different types of gram  (+) and gram (-) bacterial infection. Penicillin  antibiotics were among the first medications to  be effective against many bacterial infections  Penicillin G caused by staphylococci and streptococci. They  Penicillin V are still widely used today, though many types of bacteria have developed resistance following 2. ’s extensive use. About 10% of people report that 3. Inhibit protein synthesis: Tetracycline, they are allergic to penicillin; however, up to 90% of this group may not actually be allergic Serious allergies only occur in about 0.03%. All 4. Inhibit DNA gyrase: Ciprofloxacin penicillin are β-lactam antibiotics.

5. Interfere with DNA function: , Penicillin was discovered in 1928 by Scottish Rifampin scientist Alexander Fleming. People began using it to treat infections in 1942. There are 6. Interfere with DNA synthesis: Acyclovir several enhanced penicillin families which are 7. Cause leakage from cell membranes: effective against additional bacteria; these , include the anti-staphylococcal penicillin, and the anti-pseudomonal C. According to spectrum antibiotic: penicillin. They are derived from Penicillium fungi. 1. Broad Spectrum: Tetracycline, chloramphenicol

2. Narrow Spectrum: Penicillin G, Erythromycin D. According to mode of action:

1. Bacteriostatic: , Tetracycline, and chloramphenicol

2. Bactericidal: Penicillin, Rifampin, and Cephalosporin Chemical structure of the Penicillin core

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Classification of Penicillin wall; this is achieved through binding of the Penicillin can be classified into the following four-membered β-lactam ring of penicillin to the groups: enzyme DD-transpeptidase. As a consequence, 1. Natural Penicillin DD-transpeptidase cannot catalyze formation of 2. Beta Lactamase resistant penicillin these cross-links, and an imbalance between 3. Aminopenicillins cell wall production and degradation develops, 4. causing the cell to rapidly die. 5. The enzymes that hydrolyze the 6. penicillin / inhibitor combination cross-links continue to function, even while 1. Natural penicillin: those that form such cross-links do not. This  Penicillin V weakens the cell wall of the bacterium, and  Penicillin G osmotic pressure becomes increasingly  Penicillin VK uncompensated—eventually causing cell death (cytolysis). 2. Beta Lactamase Resistant penicillin:  Methicillin In addition, the build-up of peptidoglycan  Nafcillin precursors triggers the activation of bacterial  Oxacillin cell wall hydrolases and autolysins, which  further digest the cell wall's .  The small size of the penicillin’s increases their potency, by allowing them to penetrate the 3. Aminopenicillins: entire depth of the cell wall. This is in contrast  to the glycopeptide antibiotics and  Amoxicillin , which are both much larger than  the penicillin.   Bacamcillin Gram-positive bacteria are called protoplasts  when they lose their cell walls. Gram-negative  bacteria do not lose their cell walls completely  and are called spheroplasts after treatment 4. Carboxypenicillins: with penicillin. Penicillin shows a synergistic  Carcenicillin effect with aminoglycosides, since the inhibition  Ticalcillin of peptidoglycan synthesis allows aminoglycosides to penetrate the bacterial cell 5. Ureidopenicillins: wall more easily, allowing their disruption of  bacterial protein synthesis within the cell. This  results in a lowered MBC for susceptible Mechanism action of penicillin organisms.

Bacteria constantly remodel their Penicillin, like other β-lactam antibiotics, block peptidoglycan cell walls, simultaneously not only the division of bacteria, including building and breaking down portions of the cell cyanobacteria, but also the division of cyanelles, wall as they grow and divide. β-Lactam the photosynthetic organelles of the antibiotics inhibit the formation of glaucophytes, and the division of chloroplasts peptidoglycan cross-links in the bacterial cell of bryophytes. In contrast, they have no effect

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on the plastids of the highly developed vascular reaction. Anaphylaxis will occur in plants. This supports the end symbiotic theory approximately 0.01% of patients. of the evolution of plastid division in land Pain and inflammation at the injection site is plants. also common for parentally administered benzathine benzyl penicillin, benzyl penicillin, The chemical structure of penicillin is triggered and, to a lesser extent, procaine benzyl with a very precise, pH-dependent directed penicillin. mechanism, affected by a unique spatial assembly of molecular components, which can activate by protonation. It can travel through The Cephalosporin bodily fluids, targeting and inactivating Cephalosporin is a beta lactam antibiotic that enzymes responsible for cell-wall synthesis in inhibits the cell wall of bacteria. Cephalosporin gram-positive bacteria, meanwhile avoiding the was first isolated from a fungus named as surrounding non-targets. Cephalosporium acremonium by Dr.Abraham in 1948. The aerobic mould which yielded Penicillin can protect itself from spontaneous cephalosporin was found in the sea near a hydrolysis in the body in its anionic form, while sewage outfall in Su Siccu, by Cagliari harbour in storing its potential as a strong acylation agent, Sardinia, by the Italian pharmacologist Giuseppe activated only upon approach to the target Brotzu in July 1945. trans-peptidase enzyme and protonated in the active center. This targeted protonation mainly used in general practice neutralizes the carboxylic acid moiety, which is are; , cephalexin and weakening of the β-lactam ring N–C (=O) bond, (injection). Other cephalosporin’s available on resulting in a self-activation. Specific structural the Pharmaceutical Schedule are; , requirements are equated to constructing the and – these medicines are perfect mouse trap for catching targeted prey. usually prescribed for patients undergoing dialysis and for patients with .

Side effecst of penicillin Common (≥ 1% of people) adverse drug Classification of Cephalosporin reactions associated with use of the penicillin Cephalosporin can be classified by different way include diarrhoea, hypersensitivity, nausea, such as classification based upon: rash, neurotoxicity, urticarial, and super  Spectrum infection (including candidiasis). Infrequent  Generation adverse effects (0.1–1% of people) include fever,  Chemical structure vomiting, erythema, dermatitis, angioedema,  Resistance to beta lactamases seizures (especially in people with ),  Clinical Pharmacology and pseudomembranous colitis. Penicillin can also induce serum sickness or a serum sickness- like reaction in some individuals. Serum sickness But most renowned type of classification is is a type III hypersensitivity reaction that occurs based on generation. Cephalosporin drugs are one to three weeks after exposure to drugs divided into five generations depending upon including penicillin. It is not a true drug allergy, their microbial spectrum. because allergies are type I hypersensitivity 1. First generation: It is active against gram reactions, but repeated exposure to the (+) positive bacteria such as staphylococci and offending agent can result in an anaphylactic

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streptococci. It also have little gram (-) negative spectrum. Mechanism action of Cephalosporin  Cephelexin Cephalosporins are bactericidal and have the  Cephalothin same mode of action as other β-lactam  Cephradine antibiotics (such as penicillin’s), but are less  Cefazolin susceptible to β-lactamases. Cephalosporins  disrupt the synthesis of the peptidoglycan layer forming the bacterial cell wall. The 2. Second generation: It is active against peptidoglycan layer is important for cell wall gram (-) negative bacteria (Haemophilus structural integrity. The final transpeptidation influenza, aerogenes). step in the synthesis of the peptidoglycan is  Cefaclor facilitated by penicillin-binding proteins (PBPs).  Cefuroxime PBPs bind to the D-Ala-D-Ala at the end of  muropeptides (peptidoglycan precursors) to  Cefoxitin crosslink the peptidoglycan. Beta-lactam  Cafotetan antibiotics mimic the D-Ala-D-Ala site, thereby  irreversibly inhibiting PBP crosslinking of  peptidoglycan. 3. Third generation: It is active against gram (-ve) negative bacteria but has less activity Cephalosporins side effects against gram (+ve) positive bacteria. Cephalosporins generally cause few side  effects. Common side effects associated these  drugs include: diarrhoea, nausea, mild stomach  Moxalactam cramps or upset. Approximately 5-10% of  Ceftazidine patients with allergic hypersensitivity to  penicillin’s will also have cross-reactivity with  Cefiazidime cephalosporins.  Ceftriaxone Thus, cephalosporin antibiotics are 4. Fourth generation: It is active against contraindicated in people with a history of gram (-ve) negative bacteria and also effective allergic reaction (Urticaria, anaphylaxis, against streptococci and staphylococci. interstitial nephritis, etc.) to penicillin or  Cafepime cephalosporins. Cephalosporin antibiotics are  classed as pregnancy category B.   Cefclidine Macrolides  The macrolides are a class of natural products  that consist of a large macrocyclic lactone ring 5. Fifth generation: It is extended spectrum to which one or more deoxy sugars, usually clad antibiotic. nose and desosamine may be attached. The  lactone rings are usually 14-, 15-, or 16-  membered. Macrolides belong to the  Ceftolozane

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polypeptides class of natural products. Some in their chemical structure and are effective macrolides have antibiotic or antifungal activity against both Gram-negative and Gram-positive and are used as pharmaceutical drugs. There bacteria. One example is ciprofloxacin, one of are a couple of new relatives of erythromycin the most widely used antibiotics worldwide. (azithromycin and clarithromycin) that work the same way, but kill more bugs and have slightly fewer side effects. The erythromycin-like Fluoroquinolone group includes: antibiotics are also known as macrolides.  Ciprofloxacin  levofloxacin  antibiotics are:   Erythromycin   Clarithromycin   Azithromycin  Gatifloxacin  Dirithromycin  Ofloxacin  Roxithromycin   Troleandomycin

Mechanism action of macrolides Mechanism action of Fluoroquinolone Macrolides are protein synthesis inhibitors. The The mode of action of quinolones involves mechanism of action of macrolides is inhibition interactions with both DNA gyrase, the of bacterial protein biosynthesis, and they are originally recognised drug target, and thought to do this by preventing IV, a related type II peptidyltransferase from adding the growing topoisomerase. In a given bacterium these 2 peptide attached to tRNA to the next amino enzymes often differ in their relative acid (similarly to chloramphenicol) as well as sensitivities to many quinolones, and commonly inhibiting ribosomal translation. Another DNA gyrase is more sensitive in gram-negative potential mechanism is premature dissociation bacteria and topoisomerase IV more sensitive in of the peptidyl-tRNA from the ribosome. gram-positive bacteria. Usually the more Macrolide antibiotics do so by binding reversibly sensitive enzyme represents the primary drug to the P site on the 50S subunit of the bacterial target determined by genetic tests, but poorly ribosome. This action is considered to be understood exceptions have been documented. bacteriostatic. Macrolides are actively The formation of the ternary complex of concentrated within leukocytes, and thus are quinolone, DNA, and either DNA gyrase or transported into the site of infection. topoisomerase IV occurs through interactions in which quinolone binding appears to induce Quinolone changes in both DNA and the topoisomerase A quinolone antibiotic is any member of a large that occur separately from the DNA cleavage group of broad-spectrum that that is the hallmark of quinolone action. X-ray share a bicyclic core structure related to the crystallographic studies of a fragment of the compound 4-quinolone. They are used in human gyrase A subunit, as well as of yeast and veterinary medicine to treat bacterial topoisomerase IV, which has homology to the infections, as well as in . subunits of both DNA gyrase and Nearly all quinolone antibiotics in use are topoisomerase IV, have revealed domains that fluoroquinolones, which contain a atom are likely to constitute quinolone

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binding sites, but no topoisomerase crystal extensive research on chemically modified structures that include DNA and quinolone have or CMTs (like incyclinide) for the been reported to date. Inhibition of DNA treatment of rosacea, acne, diabetes and synthesis by quinolones requires the targeted various types of neoplasms. Incyclinide was topoisomerase to have DNA cleavage capability, announced to be ineffective for rosacea in and collisions of the replication fork with September 2007. reversible quinolone-DNA-topoisomerase Several trials have examined modified and complexes convert them to an irreversible unmodified tetracyclines for the treatment of form. However, the molecular factors that human cancers; of those, very promising results subsequently generate DNA double-strand were achieved with CMT-3 for patients with breaks from the irreversible complexes and that Kaposi Sarcoma. probably initiate cell death have yet to be Factors Underlying Irrational Use of Drugs defined. Many different factors affect the irrational use Tetracycline of drugs. In addition, different cultures view Tetracycline got their name because they share drugs in different ways, and this can affect the a chemical structure that has four rings. They way drugs are used. The major forces can be are derived from a species of Streptomyces categorized as those deriving from patients, bacteria. are broad- prescribers, the workplace, the supply system spectrum bacteriostatic agents and work by including industry influences, regulation, drug inhibiting the bacterial protein synthesis. information and misinformation, and Tetracyclines may be effective against a wide combinations of these factors. variety of microorganisms, including rickettsia and amoebic parasites. Tetracyclines are used in • Patients - drug misinformation the treatment of infections of the respiratory -misleading beliefs tract, sinuses, middle ear, urinary tract, skin, -patient demands/expectations intestines. Tetracyclines also are used to treat • Prescribers - lack of education and training Gonorrhoea, Rocky Mountain spotted fever, -inappropriate role models Lyme disease, typhus. Their most common -lack of objective drug information current use is in the treatment of moderately -generalization of limited experience severe acne and rosacea. -misleading beliefs about drugs Tetracycline antibiotics are: efficacy  Tetracycline • Workplace - heavy patient load  Doxycycline - pressure to prescribe  Minocycline - lack of adequate lab capacity  Oxytetracycline - insufficient staffing • Drug Supply System Mechanism of Action Tetracycline - unreliable suppliers Tetracycline antibiotics are protein synthesis -drug shortages inhibitors, inhibiting the binding of amino acyl- -expired drugs supplied tRNA to the mRNA-ribosome complex. They do so mainly by binding to the 30S ribosomal • Drug Regulation subunit in the mRNA translation complex. - nonessential drugs available Tetracyclines also have been found to inhibit -informal prescribers matrix metalloproteinase. This mechanism does -lack of regulation enforcement not add to their antibiotic effects, but has led to • Industry

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• Protozoan infection, e.g., metronidazole and -promotional activities Bactrim are effective against -misleading claims several parasitic All of these factors are affected by changes in • Immunomodulation, e.g., tetracycline, which national and global practices. For example, the is effective in periodontal inflammation, frequent use of injections is declining in many and , which is effective in autoimmune African countries because of the fear of AIDS. In diseases such as oral mucous some countries, however, the use of injectable membrane pemphigoid remains high due to false assumption of • No operative resource for patients who have prescribers that injections will improve patient non-complicated acute appendicitis. satisfaction and that they are always expected Treatment with antibiotics has proven to work, by the patients. with almost no cases of remission. Prevention of infection: Antibacterial Indications • Surgical wound Definitive Therapy: This is for accurate Antibiotic Resistance diagnose bacterial infection. Antibiotic are Antibiotic resistance occurs when an antibiotic effective against bacteria and it is important to has lost its ability to effectively control or kill restricted only for treatment of bacterial bacterial growth; in other words, the bacteria infections. So, it is important that first take the are “resistance” and continue to multiply in the sample either blood, fluid secretion and tested presence of therapeutic levels of an antibiotic. it on the basis of clinical testing i.e. cyst testing There are three main ways by which resistance microorganisms should be recognized and can occur: narrow spectrum, least toxic and cheap  by natural resistance in certain types of antibiotics should be prescribed. bacteria Empirical Therapy: Blind or empirical therapy of  by genetic antibiotics should be given in certain critical  by one species acquiring resistance from condition where immediate use of antibiotics is another very necessary before any laboratory findings Diagram showing the difference between non- available for example syndrome, resistant bacteria and drug resistant bacteria. becterimia, raise ESR, neutrophil leucocytosis, Non-resistant bacteria multiply, and upon drug hectic temperature etc. in such critical condition treatment, the bacteria die. Drug resistant the most appropriate class of antibiotic should bacteria multiply as well, but upon drug be prescribed mostly broad spectrum treatment, the bacteria continue to spread. antibiotics should be use such is combination of amoxicillin gentamicin both gram positive and Why do bacteria become resistance to gram negative microorganism are covered. antibiotics? Prophylactic Therapy: Prophylactic antibiotic Antibiotic resistance is a natural phenomenon. should be given to patient having risk of When an antibiotic is used bacteria that can infection for example antiburcular drugs to T.B resist that antibiotic have a greater chance of patient, propylacsis such is antirheumatic, survival than those that are “susceptible”. propylacsis for patient having heart deases. Susceptible bacteria are killed or inhibited by an

antibiotic , resulting in a selective pressure for Use of Antibiotic the survival of resistant strains of bacteria. Treatment: Bacterial infection:

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Some resistance occurs without human action, infections in humans. MRSA is any strain of S. as bacteria can produce and use antibiotics aureus that has developed, through horizontal against other bacteria, leading to a low-level of gene transfer and natural selection, multiple natural selection form resistance to antibiotics. to beta-lactam antibiotics. β- However lactam antibiotics are a broad spectrum group The current higher-levels of antibiotic-resistant which includes some – penicillin bacteria are attributed to the overuse and derivatives such as methicillin and oxacillin, and abuse of antibiotics. such as the cephalosporins. Strains unable to resist these antibiotics are classified Developing Resistance as methicillin-susceptible S. aureus, or MSSA. Dates are based upon early reports of resistance in the literature. In the case of pan What Causes a MRSA Infection? drug-resistant (PDR)- and , the date is based upon reports MRSA bacteria can be transmitted by direct of healthcare transmission or outbreaks. Note: (though skin and body fluids) and indirect penicillin was in limited use prior to widespread contact (from towels, diapers, and toys) to population usage in 1943. uninfected people. Also, some individuals have MRSA on their body (on their skin or in their Antibiotic resistance indentified nose or throat) but show no symptoms of  Penicillin-R Staphylococcus -1940 infection; these people are termed MRSA  Tetracycline-R Shigella-1959 carriers (see above) and can transmit MRSA to  Methicillin-R Staphylococcus- 1962 others. CA-MRSA is the predominant MRSA  Penicillin-R pneumococcus -1965 type found in the population. Most carriers are  Erythromycin-R Streptococcus -1968 best detected by culturing MRSA from nasal  Gentamicin-R Enterococcus -1979 swabs.  -R Enterobacteriaceae-1987  Vancomycin-R Enterococcus -1988 Signs and symptoms of MRSA  Levofloxacin-R pneumococcus -1996  -R Enterobacteriaceae-1998 In humans, S. aureus is part of the normal  XDR tuberculosis -2000 macrobiotic present in the upper respiratory  -R Staphylococcus -2001 tract, and on skin and in the gut mucosa.  Vancomycin-R Staphylococcus -2002 aureus, along with similar species that can  PDR-Acinetobacter and Pseudomonas - colonize and act symbiotically but can cause 2004/5 disease if they begin to take over the tissues  Ceftriaxone-R Neisseria gonorrhoeae- they have colonized or invade other tissues, 2009 have been called "pathobionts"  PDR-Enterobacteriaceae  Ceftaroline-R Staphylococcus -2011 After 72 hours, MRSA can take hold in human tissues and eventually become resistant to Methicillin-resistant Staphylococcus aureus treatment. The initial presentation of MRSA is Methicillin-resistant Staphylococcus aureus small red bumps that resemble pimples, spider (MRSA) refers to a group of gram-positive bites, or boils; they may be accompanied by bacteria that are genetically distinct from other fever and, occasionally, rashes. Within a few strains of Staphylococcus aureus. MRSA is days, the bumps become larger and more responsible for several difficult-to-treat painful; they eventually open into deep, pus-

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filled boils. About 75 percent of CA-MRSA  Resistance: MRSA is becoming infections are localized to skin and soft tissue increasingly resistant to in and usually can be treated effectively the United States.  Side Effects and Precautions: Diarrhea is MRSA tests and diagnosis the most common side effect, and it can promote C. difficile overgrowth Healthy people are sometimes tested to infections in the colon. C. difficile identify if they have MRSA on their skin before infections appear to occur more being admitted to the hospital. The test frequently with clindamycin than other involves swabbing the inside the patient's antibiotics. Other side-effects are nostrils or skin. pseudomembranous colitis, nausea, vomiting, abdominal cramps, skin rashes If the person is found to be colonized with and more. MRSA, removal (decolonization) of the bacteria is possible by using: 2. Linezolid (Brand Names: Zyvox, Zyvoxid or Zyvoxam)  antibacterial body wash or powder for the skin (Chlorhexidine baths) Approved for use in the year 2000, Linezolid is  cream for inside the nose (intranasal FDA approved for treating soft tissue and skin ) infections, including those caused by MRSA. It is  antibacterial shampoo for the scalp often prescribed for CA-MRSA and (Chlorhexidine soap shower/bath in particular, HA-MRSA pneumonia. It’s procedure) commonly prescribed to people of all ages and is one of the most expensive treatment options, Germ-killing soaps and ointments used in for a single course costing upwards of $1-2,000 intensive care units (ICU) have been found to for 20 tablets. reduce cases of MRSA by 40 percent.  Resistance: To minimize resistance, this Top 5 MRSA antibiotic therapies for skin infections is a “last resort” antibiotic and is not usually prescribed unless Vancomycin or Below are the five commonly prescribed other antibiotics don’t work. antibiotics for MRSA skin infections, which are  Side Effects and Precautions: Common commonly picked up in communities as adverse events when used for short community type MRSA or CA-MRSA. durations are: diarrhea, vomiting, headache, dizziness, and nausea. Long- 1. Clindamycin term use has led to serious effects including bone marrow suppression, It has been successfully and widely used for the myelosupression, low platelet counts, treatment of soft tissue and skin infections as , optic nerve well as bone, joint and abscesses caused by damage and lactic acidosis. It’s also Staph and MRSA. MRSA is becoming associated with C. difficile infections in increasingly resistant to clindamycin in the the colon. United States. 3. Mupirocin (Brand Name: Bactroban)

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Commonly used as a topical cream for minor myelosupression, acute renal failure, skin infections and skin lesions for Staph severe liver damage and more. aureus, MRSA and Streptococcus infections. Mupirocin ointment is applied to reduce or 5. Tetracyclines (Doxycycline and Minocycline) eliminate MRSA colonization in the nose (see also “MRSA carriers”). It’s commonly used Data suggests these drugs are effective in before surgical procedures to help prevent the treatment of soft tissue and skin infections, but surgical site from becoming infected with not for deeper or more severe infections. MRSA. It is commonly prescribed for children and adults and there is limited safety data for  Side Effects and Precautions: Not pregnant and nursing mothers. recommended during pregnancy or lactation. Not recommended for children  Resistance: It has been reported that under 8 years old because of potential MRSA resistance to mupirocin is decreased bone growth and tooth occurring in some communities. discoloration. Doxycycline side effects  Side Effects and Precautions: Possible can include an increased risk of side effects include headache, rash and when exposed to sunlight, diarrhea, and nausea as well as burning, dizziness and allergic reactions. Minocycline side secondary wound infection. Like other effects can include risk of sunburn (like antibiotics, prolonged use may result in doxycycline), upset stomach, diarrhea, overgrowth of bacteria that are not dizziness, headache, tinnitus, vomiting, susceptible to it, as well as an allergic reaction and more. Serious but overgrowth of fungal organisms (such as rare side effects for minocycline can yeast infections). include fever, yellowing of the eyes or skin, vision changes and more 4. - (Brand Name: Septra or Bactrim) Antibiotic resistant inBangladesh It is not FDA-approved for the treatment of  typhi Staphylococcal infections (including MRSA).  S typhimurium However, laboratory tests have shown most  Shigelladysenterae type 1 CA-MRSA strains are susceptible and so this  Neisseria gonorrhoeae drug has become a treatment option for Staph  Staphylococcus species and MRSA. It is commonly used for skin and  Enterococcus species wound infections, urinary tract infections, lung  Mycobacterium tuberculosis infections, ear infections, septicemia, and other  Streptococcus pneumonia types of infections.  Plasmodium species  Nosocomial pathogens  Side Effects and Precautions: Not  Pseudomonas spp. recommended for women in their third  Acinetobacter spp. trimester of pregnancy or infants less  Klebsiella spp. than 2 months old. Side effects can include mild allergic reactions, fever, In Bangladesh, misuse and waste of antibiotics sore throat, skin rashes, cough, diarrhea, appear to be frequent. Over the-counter and serious adverse effects can include availability of all types of Plasmodium SI

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antibiotics makes the situation worse. Antibiotic ―a pill for every ill. This may cause an prescribing by the physicians appears to be less apparent increased demand for drugs. than ideal. The widespread and inappropriate use of antibiotic results in the development of a progressively antibiotic-resistant microbial Importance of limited use of antibiotics ecosystem in Bangladesh. This is clearly The use of all medicines should be limited. But indicated by the high prevalence of antibiotic this is especially true of antibiotics, for the resistance. Salmonella, Vibriocholerae, following reasons: Escherichiacol, Neisseriagonorrhoe, Mycobacterium tuberculosis, Streptococcus 1. Poisoning and reactions. Antibiotics not only pneumonia and Haemophilus influenza kill bacteria, they can also harm the body, either infections in Bangladesh. For example, more by poisoning it or by causing allergic reactions. than 98% of 243 recent isolates of Shigella Many people die each year because they take dysenterictype 1 in Bangladesh were antibiotics they do not need. simultaneously resistant to ampicillin, 2. Upsetting the natural balance. Not all cotrimoxazole, nalidixic acid and 12% of them bacteria in the body are harmful. Some are were also resistant to pivmecillinum.And more necessary for the body to function normally. than 78% of Salmonella typhimuriumisolates Antibiotics often kill the good bacteria along from faecal samples were also resistant to with the harmful ones. Babies who are given ampicillin, chloramphenicol ,cotrimoxazole and antibiotics sometimes develop fungus or yeast ceftriaxone. A study on children from a rural infections of the mouth (thrush, p. 232) or skin. community of Bangladesh showed that 50% of This is because the antibiotics kill the bacteria children has enteric flora resistant to ampicillin, that help keep fungus under control. For similar cotrimoxazole and streptomycin throughout reasons, persons who take ampicillin and other the year. A high prevalence of resistant gut broad-spectrum antibiotics for several days may flora in healthy human and probably in animals develop diarrhoea. Antibiotics may kill some appears to be the source of antimicrobial kinds of bacteria necessary for digestion, resistance genes, the dissemination of which is upsetting the natural balance of bacteria in the enhanced by extensive use. gut. Impact of Inappropriate Use of Drugs 3. Resistance to treatment. In the long run, the most important reason the use of antibiotics The impact of this irrational use of drugs can be should be limited due to resistance. seen in many ways:

 Reduction in the quality of drug therapy leading to increased morbidity and Methods mortality The study was carried out some people who  Waste of resources leading to reduced had used antibiotic. Most people used availability of other vital drugs and antibiotics are Cephalosporin’s and Quinolone. increased costs But their knowledge of antibiotic resistance  Increased risk of unwanted effects such very low. Some people use antibiotic in case of as adverse drug reactions and the viral fever. Others use in case of GI tract emergence of drug resistance, e.g., infection, vomiting. But preferable use in malaria or multiple drug resistant Bacterial infection tuberculosis  Psychosocial impacts, such as when patients come to believe that there is

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Results and Discussion physician should have taken some necessary steps to rational use of antibiotics. From the selected prescription report it was found that significantly about various References prescription containing antibiotic prescribed by 1. Bowman WC, Rand MI, of Physician in several diseases. I found that Bacterial and Related Infection In: Text antibiotics were prescribed frequently. It is a Book: Pharmacology 2nd Edition. Pub: common problem for antibiotic resistance. Blackwell Scientific Publications 1980; pp Antibiotics used only for bacterial disease not 14. for viral disease. The Physician prescribed antibiotics the condition of cold and fever, skin 2. Australian Medicines Handbook. infection, respiratory tract infection. Adelaide; Australian Medicines Cephalosporins (40%), Quinolone (19%), Handbook Pty Ltd, 2011. (27%),Macrolides (10%) and MRSA (4%) 3. British Infection Association and Health antibiotics were prescribed. Second and third Protection Agency. Management of generation Cephalosporins were also used , All infection guidance for primary care for this type antibiotics have side effect that is very consultation and Public Health England. dangerous .MRSA antibiotics are preserve Available from: www.hpa.org.uk . local antibiotic and it should not prescribed easily. adaptation,2012 The result of this survey indicates that the 4. Nelson JD. 1996-1997 Pocket book of antibiotics are used among the prescription pediatrics antimicrobial therapy 12th frequently. To overcome this situation the Edition Pub: physician should have taken some necessary a. Williams and Wilkins 1996; pp1. steps to rational use of antibiotics. From the selected prescription report it was 5. Gonzalez-Estrada, A; Radojicic, C (May found that significantly about various 2015). "Penicillin allergy: A practical prescriptions containing antibiotics prescribed guide for clinicians". Cleveland Clinic by Physician in several diseases. I found that journal of medicine. 82 (5): 295–300. antibiotics were prescribed frequently. It is a doi:10.3949/ccjm.82a.14111. common problem for antibiotic resistance. PMID 25973877. Antibiotics used only for bacterial disease not 6. "Discovery and Development of for viral disease. The Physician prescribed Penicillin". American Chemical Society. antibiotics the condition of cold & fever, skin Retrieved 30 August 2015. infection, respiratory tract infection. 7. Oxford Handbook of Infectious Diseases Cephalosporins (40%), Quinolone (19%), and Microbiology. OUP Oxford. 2009. p. Penicillins (27%), Macrolides (10%) and MRSA 56. ISBN 978-0-19-103962-1. (4%) antibiotics were prescribed. Second and 8. "penicillin" – via The Free Dictionary. third generation Cephalosporins were also 9. Sweet man S, editor. Martindale: The used, All this type antibiotics have side effect Complete Drug Reference. that is very dangerous .MRSA antibiotics are preserve antibiotic and it should not prescribed a. London: Pharmaceutical Press, easily. 2011. The result of this survey indicates that the 10. "Cephalosporin spectrum of resistance". antibiotics are used among the prescription Retrieved 1 July 2012. frequently. To overcome this situation the

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College of Baltimore County. Retrieved 11. "Cephalosporins - Infectious Diseases - on July 31, 2009 Merck Manuals Professional Edition". 20. Drainas, D; Kalpaxis, DL; Merck Manuals Professional Edition. Coutsogeorgopoulos, C (1987). Retrieved 2018-06-14. "Inhibition of ribosomal 12. Narisada, Masayuki; Tsuji, Teruji (1990), peptidyltransferase by chloramphenicol. "1- Antibiotics", Recent Kinetic studies". European Journal of Progress in the Chemical Synthesis of Biochemistry / FEBS. 164 (1): 53–8. Antibiotics, Springer Berlin Heidelberg, doi:10.1111/j.1432-1033.1987.tb10991.x. pp. 705–725, doi:10.1007/978-3-642- PMID 3549307. 75617-7_19, ISBN 9783642756191, 21. Tenson, T.; Lovmar, M.; Ehrenberg, M. retrieved 2018-06-14 (2003). "The Mechanism of Action of 13. Weiss, Rick (4 March 2007). "FDA Rules Macrolides, Lincosamides and override Warnings about Drugs". March Streptogramin B Reveals the Nascent 4, 2007. Peptide Exit Path in the Ribosome". 14. The Antimicrobial Drugs, by Eric M. Journal of Molecular Biology. 330 (5): Scholar. Page 108. books.google.com 1005–1014. doi:10.1016/S0022- 15. Richard L Sweet; Ronald S. Gibbs (1 2836(03)00662-4. PMID 12860123. March 2009). Infectious Diseases of the 22. Bailly, S; Pocidalo, J J; Fay, M; Gougerot- Female Genital Tract. Lippincott Williams Pocidalo, M A (1991). "Differential & Wilkins. pp. 403–. ISBN 978-0-7817- modulation of cytokine production by 7815-2. Retrieved 8 September 2010. macrolides: Interleukin-6 production is 16. Wider AF (March 2008). "Ceftobiprole: a increased by spiramycin and new option for treatment of skin and erythromycin". Antimicrobial Agents and soft-tissue infections due to methicillin- Chemotherapy. 35 (10): 2016–9. resistant Staphylococcus aureus". Clin. doi:10.1128/AAC.35.10.2016. PMC Infect. Dis. 46 (5): 656–658. 245317 Freely accessible. PMID 1759822. doi:10.1086/526528. PMID 18225983. 23. Sathasivam, S.; Lecky, B. (November 17. Kosinski MA, Joseph WS (July 2007). 2008). "Statin induced myopathy". "Update on the treatment of diabetic British Medical Journal. 337: a2286. foot infections". Clin Podiatric Med Surg. doi:10.1136/bmj.a2286. PMID 18988647. 24 (3): 383–396. doi:10.1016/j.cpm.2007.03.009. PMID 24. Sanfilippo, A. (1976). "Infantile 17613382. hypertrophic pyloric stenosis related to 18. Hamilton-Miller, JM (1973). "Chemistry ingestion of erythromycin estolate: A and Biology of the Polyene Macrolide report of five cases". Journal of Pediatric Antibiotics". Bacteriological Reviews. Surgery. 11 (2): 177–180. doi:10.1016/0022- American Society for Microbiology. 37 3468(76)90283-9. PMID 1263054. (2): 166–196. PMC 413810 Freely 25. Honein, M. A.; Paulozzi, L. J.; Himelright, accessible. PMID 4578757 I. M.; Lee, B.; Cragan, J. D.; Patterson, L.; 19. Protein synthesis inhibitors: macrolides Correa, A.; Hall, S.; Erickson, J. D. (1999). mechanism of action animation. "Infantile hypertrophic pyloric stenosis Classification of agents Pharmamotion. after pertussis prophylaxis with Author: Gary Kaiser. The Community erythromcyin: A case review and cohort study". Lancet. 354 (9196): 2101–2105.

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doi:10.1016/S0140-6736(99)10073-4. (1997). Online corrected version: (2006– PMID 10609814. ) "tetracyclines" 26. Hautekeete, ML (1995). "Hepatotoxicity 33. "Mechanism of Action of Tetracyclines - of antibiotics". Acta gastro-enterologica Animations - PharmaXChange.info". 27 Belgica. 58 (3–4): 290–6. PMID 7491842 May 2011. Retrieved 13 March 2017. 27. Andriole, VT The Quinolones. Academic 34. H. Spreitzer (July 2, 2007). "Neue Press, 1989. Wirkstoffe - Incyclinid". Österreichische 28. Andersson MI, MacGowan AP (2003). Apothekerzeitung (in German) (14/2007): "Development of the quinolones". 655. Journal of Antimicrobial Chemotherapy. 35. Viera MH, Perez OA, Berman B (2007). 51 (Suppl. S1): 1–11. "Incyclinide". Drugs of the Future. 32 (3): doi:10.1093/jac/dkg212. 209–214. 29. Heeb, S.; Fletcher, M. P.; Chhabra, S. R.; doi:10.1358/dof.2007.032.03.1083308. Diggle, S. P.; Williams, P.; Cámara, M. 36. United States. Centers for Disease (2011). "Quinolones: from antibiotics to Control and Prevention. "Methicillin- autoinducers" (PDF). FEMS Microbiology Resistant Staphylococcus aureus Reviews. 35 (2): 247–274. (MRSA) Infections." Aug. 4, 2015. doi:10.1111/j.1574-6976.2010.00247.x. PMC . 3053476 Freely accessible. PMID 37. Liu, C., A. Bayer, S.E. Cosgrove, et al. 20738404. "Clinical Practice Guidelines by the 30. Hooper, DC. (Mar–Apr 2001). "Emerging Infectious Diseases Society of America mechanisms of fluoroquinolone for the Treatment of Methicillin- resistance". Emerging Infectious Resistant Staphylococcus aureus Diseases. 7 (2): 337–41. Infections in Adults and Children." Clin. doi:10.3201/eid0702.010239. PMC Infect. Dis. 52 (2011): 285-292. 2631735 Freely accessible. PMID 38. Welte, T., and M. Pletz. "Antimicrobial 11294736. Treatment of Nosocomial Methicillin- 31. Elsea, SH.; Osheroff, N.; Nitiss, JL. (July Resistant Staphylococcus aureus(MRSA) 1992). "Cytotoxicity of quinolones Pneumonia: Current and Future toward eukaryotic cells. Identification of Options." Int J Antimicrob Agents 36.5 topoisomerase II as the primary cellular (2010): 391-400. target for the quinolone CP-115,953 in yeast" (PDF). J Biol Chem. 267 (19): 13150–3. PMID 1320012. Retrieved 6 May 2011. 32. IUPAC, Compendium of Chemical Terminology, 2nd ed. (the "Gold Book")

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Table 1: Antibiotics that are used from the Essential Drug List in Bangladesh Drugs Dosage form Ampicillin Cap Chlorhexidine Cream Tetracycline Cap Aminophylline Inj Cotrimoxazole Tab Metronidazole tab/elixir/Inj Amoxicillin tab /cap Ciprofloxacin Azithromycin tab /cap Levofloxacin tab /cap Cotrimoxazole Tab/cap Cloxacillin Cap Salbutamol Inj Benzyl penicillin Inj Cephalosporin’s 1st, 2nd , 3rdgeneration Cap

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Table 2: Survey report on Rational use of antibiotic

Patient Pathological Used antibiotic Class of Rationality Comment condition Antibiotics Patient-1 Fever and Tab.Evo Quinolone(Levofloxacin) + - - Irrational Cough for 6 (500mg) use days Patient-2 Fever and Tab. Levox Quinolone(Levofloxacin) + - - Irrational nasal 500mg use obstruction Patient-3 Fever, Nausea, Cap. Cafexta Third generation + + + Rational use Swelling 300mg Cephalosporins around the affected bone Patient-4 Fever ,burning Tab. Furoclav Second generation + + - Less rational feeling when 500mg Cephalosporins use urinate Patient-5 Fever and Quinolone(Levofloxacin) + - - Irrational cough, nasal Tab.Asilee use obstruction 500mg Patient-6 Sharp Chest Quinolone + - - Irational use Pain , Tab. Gembax (Gemifloxacin) Increased 320 mg Shortness of Breath Patient-7 Swelling Second generation + + - Less rational around the Tab. Cefaclav Cephalosporins use affected bone 500mg Patient-8 Second generation + + - Less rational Switch therapy Tab. Cerox CV Cephalosporins use after surgery 500mg

Patient-9 Fever and Quinolone(Levofloxacin) + + + Rational use Cough for 6 Tab. Levox days, nasal 500mg obstruction, Tap sore throat,

Patient-10 Fever, Sharp Tab. Gembax Quinolone + + + Rational use Chest Pain , 320 mg (Gemifloxacin) Increased Shortness of Breath , Changes in Mucus Patient-11 throat and Cap. Flustar Penicillinase-resistant + + - Less rational nose 500mg penicillin use infections, (Flucloxacillin sodium chest pain

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Patient-12 Fever for 5 Tab.Moxaclav Penicillin + + + Rational use days, throat 375mg (Amoxicillin) pain , cough , ear problem Patient-13 Fever, skin Cap, Cleodin Clindamycin(Miscellaneous - - - Misuse rushes and 300 mg Antibiotics) irritating, acne produced in skin and allergy Patient-14 mild pain or Tab Amoclav penicillin + - - Irrational discomfort 500mg (Amoxicillin) use inside the ear, hearing loss, Patient-15 Fever and Tab. Evo Quinolone(Levofloxacin) + + + Irrational Cough for 6 (500mg) use days Patient-16 Fever, Nausea, Tab. Furoclav Second generation + + + Rational use Swelling 500mg Cephalosporins around the affected bone Patient-17 Second generation + + + Rational use Switch therapy Tab. Cerox CV Cephalosporins after surgery 500mg

Patient-18 Fever for 5 Tab.Moxaclav penicillin + + + Rational use days, throat 375mg (Amoxicillin) pain , cough , ear problem Patient-19 Headaches, Quinolone + + - Less rational sore throat, Tab. Gembax (Gemifloxacin) use runny or 320 mg blocked nose Patient-20 mild pain or Tab.Demoxicla penicillin + + - Less discomfort ve Forte 375mg (Amoxicillin) irrational inside the ear, use hearing loss, Patient-21 Cefotil plus Second generation + + + Rational use Throat infe - 250mg Cephalosporins ction , pain in throat, tonsillitis, fever. Patient-22 Fever for 5 Tab.Moxaclav penicillin + + + Rational use days, throat 375mg (Amoxicillin) pain , cough , ear problem Patient-23 Headaches, Quinolone(Levofloxacin) + + - Less rational sore throat, Tab. Levox use runny or 500mg blocked nose Tap

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Patient-24 Fever, Nausea, Second generation + + + Rational use Swelling Tab. Cefaclav Cephalosporins around the 500mg affected bone Patient-25 Cefotil plus Second generation + + + Rational use Throat infe - 250mg Cephalosporins ction , pain in throat, tonsillitis, fever. Patient-26 Second generation + + + Rational use Fever, Axim CV 500mg Cephalosporins diarrhea, nausea, vomiting Patient-27 Second generation + + + Rational use Switch therapy Axim CV 500mg Cephalosporins after surgery Patient-28 Fever for 3 Third generation + + + Rational days, burning Cap. Cafexta Cephalosporins use feeling when 300mg urinate, Pain or pressure in the back or lower abdomen, Patient-29 Fever, Nausea, Second generation + + + Rational use Swelling Tab. Cefaclav Cephalosporins around the 500mg affected bone Patient-30 Fever, Sharp Quinolone + + + Rational Chest Pain , Tab. Gembax (Gemifloxacin) use Increased 320 mg Shortness of Breath , Changes in Mucus Patient- 31 Second generation + + - Less rational Fever, Axim CV 500mg Cephalosporins use diarrhea, nausea, vomiting Patient-32 Fever for 5 Tab.Moxaclav penicillin + + + Rational use days, throat 375mg (Amoxicillin) pain , cough , ear problem Patient-33 neck Macrolides + - - Less rational tenderness Cap.Acos use due to swollen 500mg lymph nodes

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Patient- Fever, Nausea, Second generation + + + Rational use 34 Swelling Tab. Cefaclav Cephalosporins around the 500mg affected bone Patient- Pain or Third generation + + - Less rational 35 pressure in the Cap. Cafexta Cephalosporins use back or lower 300mg abdomen, stomachaches Patient-36 Fever, sore Macrolides + + + Rational use throat, a Cap. Acos scratchy- 500mg sounding voice, Patient- Second generation + + + Rational use 37 Throat infe - Tab. Furoclav Cephalosporins ction , pain in 500mg throat, tonsillitis, fever. Patient- Fever for 3 Third generation + + + Rational use 38 days,burning Cap. Cafexta Cephalosporins feeling when 300mg urinate, Pain or pressure in the back or lower abdomen, Patient- Fever and Tab. Evo Quinolone(Levofloxacin) + + + Rational use 39 Cough for 6 (500mg) days Patient- mild pain or Tab.Demoxicla penicillin + + - Less rational 40 discomfort ve Forte 375mg (Amoxicillin) use inside the ear, hearing loss, Patient- 41 Rocky Cap. Tetracycline ( MRSA) - - - Misuse Mountain Tetracycline spotted fever, 500mg Rashes, Fatigue, unexplained pain, heart problem Patient- Fever for 5 Tab.Moxaclav penicillin + + + Rational use 42 days, throat 375mg (Amoxicillin) pain , cough , ear problem

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Patient- cough with Penicillinase-resistant + + + Rational use 43 increase Cap. Flux penicillin mucus and 500mg (Flucloxacillin sodium blood, chest pain , shortness of breath Patient-44 Second generation + - - Irrational Fever, Tab. Cerox CV Cephalosporins use diarrhea, 500mg nausea, vomiting Patient- throat and Cap. Flustar Penicillinase-resistant + + + Rational use 45 nose 500mg penicillin infections, (Flucloxacillin sodium chest pain Patient- Fever , dental Azimex 500mg Macrolides + - - Irrational 46 pain , Runny tablet use nose Patient- Fever, sore Macrolides + + - Less rational 47 throat, a Cap.Acos use scratchy- 500mg sounding voice, Patient- Fever, cough Cap. Fluclox Penicillinase-resistant + + + Rational use 48 with increase 500mg penicillin mucus and (Flucloxacillin sodium blood, Patient- Fever, skin Cap, Cleodin Clindamycin(Miscellaneous - - - Misuse 49 rushes and 300 mg Antibiotics) irritating, acne produced in skin and allergy. Patient- neck Macrolides + + - Less rational 50 tenderness Cap.Acos use due to swollen 500mg lymph nodes Patient- 51 Second generation + + + Rational use Switch therapy Tab. Cerox CV Cephalosporins after surgery 500mg

Patient- mild pain or Tab.Demoxicla Penicillins + + - Less rational 52 discomfort ve Forte 375mg (Amoxicillin) use inside the ear, hearing loss, Patient- Fever and Tab. Evo Quinolone(Levofloxacin) + - - Irrational 53 Cough for 6 (500mg) use days

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Patient- throat and Cap. Flustar Penicillinase-resistant + + - Less rational 54 nose 500mg penicillin use infections, (Flucloxacillin sodium) chest pain Patient- Fever , dental Azimex 500mg Macrolides + + - Less rational 55 pain , Runny tablet use nose Patient-56 Cefotil plus Second generation + + + Rational use Throat infe - 250mg Cephalosporins ction , pain in throat, tonsillitis, fever. Patient-57 Fever , dental Azimex 500mg Macrolides + + - Less rational pain , Runny tablet use nose Patient-58 throat and Cap. Flustar Penicillinase-resistant + + - Less rational nose 500mg penicillin use infections, (Flucloxacillin sodium) chest pain Patient-59 Fever, Sharp Quinolone(Levofloxacin) + + + Rational use Chest Pain , Tab Asilee Increased 500mg Shortness of Breath , Changes in Mucus Patient-60 Fever, Nausea, Second generation + + + Rational Swelling Tab. Cefaclav Cephalosporins use around the 500mg affected bone Patient- 61 mild pain or Tab.Demoxicla Penicillins + + + Rational use discomfort ve Forte 375mg (Amoxicillin) inside the ear, hearing loss, Patient- throat and Cap. Flustar Penicillinase-resistant + + - Less rational 62 nose 500mg penicillin use infections, (Flucoxacillin sodium) chest pain Patient- fever, cough Penicillinase-resistant + + + Rational use 63 with increase Cap. Flux penicillin mucus and 500mg (Flucoxacillin sodium) blood,chest pain , Patient- Headaches, Quinolone(Levofloxacin) + + - Less rational 64 sore throat, Tab. Levox use runny or 500mg blocked nose Tap Patient- pain in throat, Second generation + + + Rational 65 tonsillitis, Tab. Furoclav Cephalosporins use fever. 500mg

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Patient- chest pain , Penicillinase-resistant + - - Irrational 66 shortness of Cap. Flux penicillin use breath 500mg (Flucoxacillin sodium) Patient- Rocky Cap. Tetracycline ( MRSA) - - - Misuse 67 Mountain Tetracycline spotted fever, 500mg Rashes, fatigue, unexplained pain, heart problem Patient- Fever for 3 Cap. Cef-3 Third generation + + + Rational use 68 days, burning 500mg Cephalosporins feeling when urinate Patient- Second generation + - - Irrational 69 Fever, Axim CV 500mg Cephalosporins use diarrhea, nausea, vomiting Patient- painful Cap. Emixef Third generation + + + Rational 70 swallowing, a 200mg Cephalosporins use scratchy- sounding voice, bad breath, fever, chills, earaches, Patient- 71 Fever for 5 Tab Amoclav Penicillins + + - Less rational days, throat 500mg (Amoxicillin) use pain , cough , ear problem Patient- Fever for 3 Cap. Cef-3 Third generation + + + Rational use 72 days, burning 500mg Cephalosporins feeling when urinate Patient- Fever, Nausea, Second generation + + + Rational use 73 Swelling Tab. Cefaclav Cephalosporins around the 500mg affected bone Patient- painful Cap. Emixef Third generation + + + Rational use 74 swallowing, a 200mg Cephalosporins scratchy- sounding voice, bad breath, fever, chills, earaches, Patient- throat and Cap. Flustar Penicillinase-resistant + - - Irrational 75 nose 500mg penicillin use infections, (Flucoxacillin sodium) chest pain

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Patient- Fever, Sharp Quinolone + + + Rational use 76 Chest Pain , Tab. Gembax (Gemifloxacin) Increased 320 mg Shortness of Breath , Changes in Mucus Patient- Second generation + + + Rational use 77 Switch therapy Tab. Cerox CV Cephalosporins after surgery 500mg

Patient- Fever for 5 Tab Amoclav Penicillins + + - Irrational 78 days, throat 500mg (Amoxicillin) use pain , cough , ear problem Patient- throat and Cap. Flustar Penicillinase-resistant + + + Rational use 79 nose 500mg penicillin infections, (Flucoxacillin sodium) chest pain Patient- Axim CV 500mg Second generation + - - Irrational 80 Fever, Cephalosporins use diarrhea, nausea, vomiting Patient- 81 painful Cap. Emixef Third generation + + + Rational use swallowing, a 200mg Cephalosporins scratchy- sounding voice, bad breath, fever, chills, earaches, Patient- Fever for 5 Tab Amoclav Penicillins + + + Rational use 82 days, throat 500mg (Amoxicillin) pain , cough , ear problem Patient- Fever , dental Azimex 500mg Macrolides + - - Irrational 83 pain , Runny tablet use nose Patient- Fever and Tab. Evo Quinolone(Levofloxacin) + - - Irrational 84 Cough for 6 (500mg) use days Patient- Fever, Nausea, Tab. Furoclav Second generation + + + Rational use 85 Swelling 500mg Cephalosporins around the affected bone Patient- mild pain or Tab.Demoxicla Penicillins + + - Less rational 86 discomfort ve Forte 375mg (Amoxicillin) use inside the ear, hearing loss,

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Patient- Fever , dental Azimex 500mg Macrolides + - - Less rational 87 pain , Runny tablet use nose Patient- Second generation + + + Rational use 88 Throat infe - Tab. Furoclav Cephalosporins ction , pain in 500mg throat, tonsillitis, fever. Patient- Fever, Sharp Quinolone(Levofloxacin) + + + Rational use 89 Chest Pain , Tab Asilee Increased 500mg Shortness of Breath , Changes in Mucus Patient- Fever for 5 Tab Amoclav Penicillins + + - Less rational 90 days, throat 500mg (Amoxicillin) use pain , cough , ear problem Patient- 91 Fever for 3 Cap. Emixef Third generation + + + Rational use days, burning 200mg Cephalosporins feeling when urinate, Pain or pressure in the back or lower abdomen, Patient- Cefotil plus Second generation + + + Rational use 92 Throat infe - 250mg Cephalosporins ction , pain in throat, tonsillitis, fever. Patient- Fever for 3 Cap. Cafexta Third generation + + + Rational use 93 days,burning 300mg Cephalosporins feeling when urinate, Pain or pressure in the back or lower abdomen, Patient-94 Tab. Furoclav Second generation + + + Rational use Throat infe - 500mg cephalosporin ction , pain in throat, tonsillitis, fever. Patient- Fever , dental Azimex 500mg Macrolides + - - Irrational 95 pain , Runny tablet use nose

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Patient – Fever for 5 Tab Amoclav penicillin + + + Rational use 96 days, throat 500mg (Amoxicillin) pain , cough , ear problem Patient-97 Fever, Nausea, Tab. Furoclav Second generation + + + Rational use Swelling 500mg cephalosporin around the affected bone Patient-98 Fever for 3 Cap. Cef-3 Third generation + + + Rational days, burning 500mg Cephalosporin use feeling when urinate, Pain or pressure in the back or lower abdomen, Patient- mild pain or Tab.Demoxicla penicillin + + - Less rational 99 discomfort ve Forte 375mg (Amoxicillin) use inside the ear, hearing loss, Patient- Fever, Sharp Quinolone + + + Rational use 100 Chest Pain, Tab. Gembax (Gemifloxacin) Increased 320 mg Shortness of Breath, Changes in Mucus

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Figure 1. Common mechanism of Penicillin

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Figure 2. Common mechanism of Cephalosporins

Figure 3. Common mechanism of Macrolides

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Figure 4. Mechanism of antibiotic resistance development

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Figure 5. Mechanism of Antibiotic spread

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