Medical Students' Understanding, Attitudes, and Awareness of Antibiotic Resistance

Background: Antimicrobial agents are potent medication that can stop or significantly limit bacterial development. Misuse of antibiotics


INTRODUCTION
Antimicrobial agents are medication and lifesaving used to prevent infection caused by bacteria while wrong use of antibiotics play a major role in developing drug-resistant microorganisms.Drug-resistant bacteria cause major health issues in underdeveloped nations [1,2].Antibiotic resistance can affect humans and animals of any age in any nation, making bacterial illnesses difficult to cure.WHO releases sixpoint antimicrobial resistance policy [2,3].WHO recommends education as integral part of stopping irrational use of antibiotics to decrease the resistant germs.There is misunderstanding that taking antibiotics can help faster to improve an illness and prevent infections [9].Antibiotics are also misunderstood to treat viral infections [5,7,8].Irrational use of antibiotics enhances to make the drugs ineffective very soon which is a serious healthcare problem in global societies [3,7].Inappropriate, Incomplete course, and illogical antibiotic treatment increases the risk of antibiotics resistance [1, 2, 3 4,5,7,8, 10, 11, 12].In addition, noncompliance in the use of antibiotics promotes the emergence of resistant bacteria even during treatment course [4].Irrational antibiotic use also produces resistant germs, which lead to increase hospital stays and treatment costs [5,6,1].Unfortunately, antibiotic misuse and overuse accelerate antibiotic resistance.Around 50 % of antibiotics worldwide are obtained privately from pharmacies without prescription [1,3,10].Many factors can increase antibiotic misuse [1,2,5].Thus, many studies linked inappropriate antibiotic use to public, healthcare worker, and student awareness, attitude, practice, and knowledge [1,2,3,5,6,7,10].Demographic factors such age, gender, race, education, residence, and family income affect knowledge [2,12].Self-medication is another important component in antibiotic resistance [1,2,5,6].Optimal use of antimicrobial agents leads to getting a high level of health for individual and communities [7].

History of antibiotics
In World War II, antibiotics were discovered to treat infectious diseases, a global event.Penicillin, developed by Sir Alexander Fleming in 1928, was the first antibiotic given for serious illnesses in the 1940s.WII soldiers treated bacterial illnesses using penicillin.By the 1950s, penicillin resistance threatened many of the previous decade's advances.New beta-lactam was found, developed, and trusted.In 1962, the UK reported the first MRSA case.Unfortunately, antibiotic resistance is widespread.MRSA in S.aureus and coagulase-negative staphylococci was controlled with vancomycin in 1972.However, vancomycinresistant coagulase-negative staphylococci were reported in 1979 and 1983 [13].Three generations of spectrum-active cephalosporins emerged in 1960.Journals published the first antimicrobial prescription in 1975-1976 discovered β-lactamase inhibitors.Thienamycin became imipenem, which was useful in vitro and animals but short-lived in humans.Meropenem, approved in 1995, had fewer side effects [14].Some antimicrobial drugs increased resistance bacterial infections.
When we look at the evolution in the manufacture and discovery of a new antibiotic and the ability of bacteria to resist, we find that several factors help overcome bacteria resistance and these factors can be deduced or highlighted as the central part, which is optimal antibiotic use.

Global Burden
Antibiotic resistance is a major public health problem.It can render antibiotic-resistant illnesses.Antimicrobial resistance (AMR) is anticipated to kill 10 million people per year by 2050, costing $100 trillion [15].The World Health Assembly (WHA) agreed to address AMR in May 2015 [16].Understanding antibiotic use and AMR prevention is crucial to reducing AMR globally.The main causes of antibiotic resistance are improper usage and misuse [17,18].WHO recommend surveillance which plays a major tool to monitor the rising in AMR and to improve the usage of antibiotics through public and healthcare workers [19,20].Furthermore, rational usage, policies and restrictions can reduce AMR [19].Global studies showed the resistant bacteria are increasing and the urgent need to new antibiotics [21].World governments have one strategy to prevent AMR and limit antibiotic use which is focus on the follow experimentation policy, activating stewardship program, restricting the use of last-resort antibiotic, and establish public awareness campaigns [22].

Antibiotics resistance
Mechanism of action of antibiotic resistance and definition AMR occurs when microorganisms become immune to antimicrobials through intrinsic resistance, acquired resistance, or adaptive resistance [23].It is essential point to understanding how the mechanism of action is work before knowing how the antibiotic acts with bacteria.Antimicrobial agents proceed selectively on vital microbial functions with the last effects or without affecting host functions.Different medicines act in different ways, and the understanding of these mechanisms as well as the chemical nature of antibiotics is critical point in the knowledge of the methods of how resistance against them has been developed.The device of action of antibiotics can be classified based on a function of bacteria or the structure that is affected by the agents, and these include the following: Interfere with Cell Wall Synthesis Bacterial ribosome's, cytoplasmic structure on which protein synthesis takes place, are targets for some antibiotic such as Chloramphenicol and Macrolide because bacterial ribosomes differ in size and structure from human ( bacterial cell are prokaryotic and their ribosomes are 70S, whereas human cell are eukaryotic and their ribosomes are 80S ).[S represent Svedberg units, a measurement of sedimentation rate].

Interfere with protein synthesis
Bacterial ribosomes, cytoplasmic structure on which protein synthesis takes place, are targets for some antibiotic such as Chloramphenicol and Macrolide because bacterial ribosomes differ in size and structure from human ( bacterial cell are prokaryotic and their ribosomes are 70S, whereas human cell are eukaryotic and their ribosomes are 80S ).

Interfere with Cell Membrane Function
Cell membranes are crucial gatekeepers.They regulate cell access.Antibiotics like polymyxin alter membrane function, causing membrane permeability and fast cell death.

Interfere with Nucleic Acid Synthesis
DNA expression involves DNA replication and RNA synthesis.Quinolone antibiotics inhibit DNA gyrase in grampositive bacteria and topoisomerase IV in gram-negative bacteria.

Interfere with Metabolic Activity
Antimetabolites are medications that compete with metabolic enzymes and resemble natural substances.Sulfonamide work similarly.Bacteria generate folic acid for cell formation.Bacteria employ sulfa medicines to generate folic acid.Sulfa medicines can treat humans since mammalian cells don't synthesize folic acid [24].Infection happened and many of bacteria make you sick and some of these germs became resistant to antibiotics.
Antibiotics kill pathogens but not resistant bacteria.Antibiotics kill beneficial bacteria that prevent infection.
Antibiotic-resistant microorganisms have defenses.They multiply and sicken you.
Drug-resistant microorganisms can pass it on.Antimicrobials cannot treat your illness, and resistant organisms can spread [27].

Epidemiology of AMR Epidemiology of antibiotics resistance (Worldwide)
Antibiotics have greatly reduced death and morbidity.However, resistant bacteria have rapidly spread worldwide and locally, increasing mortality and morbidity.AMR causes 23,000 US and 25,000 EU deaths annually.In low-and middle-income areas, people use antibiotics unnecessarily, which increases the number of resistant bacteria.Other factors reinforce the frightening growth.Lack of infection control and over-the-counter medicine sales, poor surveillance, considered as main factors which driving the spread of antibiotics resistance [18][19][20][21][22][23][24][25][26][27][28][29].European Centers for Disease Prevention and control (ECDC), European Food Safety Authority (EFSA), and European Medicine Agency (EMA) found a link between human and animal antibiotic use and AMR in 2015.They give several findings linking antibiotic use to resistance in people and animals.Antibiotic use in humans, animals, and hospitals has to be assessed.This threat requires a crucial strategy.Identifying AMR transmission channels and sources requires active surveillance [28].The new WHO Global Antimicrobial Surveillance System (GLASS) found antibiotic resistance in 500 000 probable bacterial illness patients in 22 countries.Escherichia coli, Klebsiella pneumonia, Staphylococcus aurous, and Streptococcus pneumonia were the most prevalent resistant bacteria, followed by Salmonella spp.Among patients with suspected bloodstream infection, the percentage that had bacteria resistant to at least one of the most commonly used antibiotics ranged wonderfully between different countries from zero to 82%.Countries reported penicillin resistance from 0 to 51%.8% to 65% of urinary tract infection-associated E. coli were resistant to ciprofloxacin [30].Saudi Arabia joined GLASS recently.Antibiotic resistance kills 25,000 EU residents and adds 2.5 million hospital days.In India, resistant bacteria from mothers killed nearly 58,000 newborns in one year.Antibiotic resistance kills 38,000 Thais and costs 3.2m hospital days.Antibiotic resistance kills 23,000 Americans annually [31].

Epidemiology of antibiotics resistance (Local)
The Ministry of Health (MOTH) in the Kingdom of Saudi Arabia has begun to work hard to confront the danger of resistant germs to antibiotics, which has become a global health problem.Many epidemiological studies in KSA have shown an increase in bacterial resistance to different pathogens.From this perspective, the Ministry of Health organized a national committee comprising numerous national institutions to activate the WHO plan for antibioticresistant microorganisms.[32].Epidemiological data and continual surveillance can help regulate and determine bacterial drug resistance [33,34,35].Western KSA researchers found several drug-resistant microorganisms.This study reported 48.6% of E. coli resistant to SXT, 49.3% of Klebsiella isolated from respiratory secretions resistant to AMP, and 59.3% resistant to AMP and Piperacillin.20.1% of 244 respiratory Acinetobacter baumannii were resistant to SXT, 56.3% E. coli and 31.1% Klebsiella were positive for Extended-Spectrum Beta-Lactamases (ESBLs), 50.3% S. aureus from miscellaneous cultures, and 35.9% were methicillin resistant [33].Another study conducted in Saudi Arabia has shown the high level of antibiotics resistance for different pathogens.In that's study, they isolate gram-negative and gram-positive, and they found tin E.coli the resistance was 40% to ciprofloxacin, 30% to cefepime, 29% to ceftazidime, 8.5% to tazocin and amikacin, 40% to gentamicin and cefuroxime.In K. pneumonia, the resistance was 48%to ceftazidime, 49% to cefuroxime, 45.5% to cefepime, 38% to gentamicin, 30% to ciprofloxacin, 19% to istazocin, 7.5% to amikacin and 2.4% to imipenem /meropenem.In A.bumannii, 79% were resistant to ciprofloxacin, 68.5% to tazocin, 67% to cefepime, 66% to gentamicin and imipenem /meropenem, 65% to ceftazidime, 68% to amikacin and no resistance to colistin that reported.In Pseudomonas aeruginosa, almost 34% were resistant to ceftazidime, 31% to ciprofloxacin, 29% to cefepime, 26.5% to gentamicin, 19% to imipenem /meropenem, 17% to amikacin, and 15.5% were resistant to tazocin.In grampositive isolates, MRSA counted only for 4.6%, and no vancomycin-intermediate Staphylococcusaureus was detected [36].Due to lack of awareness and health culture, the KSA's resistant bacteria rate increased.The study found that private pharmacies are the main source of antibiotic abuse, especially among children.They need government regulation and a strategy to promote rational use.Riyadh pharmacy misused antibiotics 77%, Alkharj dental clinics 82%, Jeddah 97%, and Abha community hospital 72%.Many studies have shown that cultural factors, knowledge, behavioral traits, and education can influence antibiotic misuse [38].Research in multiple KSA regions found that 53% of individuals used antibiotics without a prescription and were unaware of antibiotic abuse.Thus, we need a medicine rationing program and an educational program to improve public and healthcare provider knowledge to reduce the antibiotics resistance [39].

Lack of new antibiotics
The WHO shows a severe problem toward the lack of new antibiotics and encourages creating a strong strategy for the regulation of the use of antibiotics.However, the rate of AMR is increasing globally.Therefore, the discovery of a new antibiotic is one of the priorities of the WHO and the desired goal through which experts from pharmacists or manufacturers work to achieve it.A critical solution of the emergence of antibiotics resistance is the development of new antimicrobial agents with high activity against multi-drug resistant bacteria which is a vital health need to cover the resistant bacteria that is a global health crisis now [40].The expected rate of emergence and spread of antimicrobial resistance yearly will reach 10 million deaths by 2050 with an estimated cost of $100 trillion [41].From this point of view, we can stress the urgent need of the health society to develop plans and strategies which may help to discover a new antibiotic because of the spread of infectious diseases and at the same time to regulate the irrational use of antibiotics strictly.

Policymakers
Antibiotic resistance needs to be addressing through national policies.An effective system is required to improve acting with antibiotics.Development countries started with a severe strategy based on evidence that reflects importance needs of new system or policy to rationing the use of antibiotics.A global burden toward challenges of increasing resistance bacteria to promotes standards to facing the most factors which accelerate the spread of AMR.Many factors are rapidly driving antibiotics resistance such as poor hygiene, misuse or abuse of drugs, malnutrition, crowded places, contaminated food, and contaminated water.Understanding the importance of international and national policy will help to reduce the antibiotics resistance.Effective efforts with strict strategies will help to optimize drugs as well as WHO recommendations.Effective efforts with strict strategies will help to optimize drugs as well as WHO recommendations [48].Controlling the spread of infections is one of the critical pillars of healthcare facilities.In this regard, there is an urgent need for education and complying with national guidelines to control and minimize the overuse of antibiotics even this policy not exited it should be creating and ongoing updating [49].The importance of policy at healthcare setting for many reasons such as eliminate the use of unnecessary antibiotics and restrict the use of unnecessary powerful ones, regulate and support the optimal use of drugs, improve patient care by promoting a high level of practice, make the information available at a healthcare setting, and creation a national action plan to prevent the spread of antibiotic resistance is in place.

Agriculture aspect
The resistant bacteria in agriculture sector being one of the global public health problems.Uses of antimicrobial agents without consultation will contribute and spread of antimicrobial populations with consequences for animal and public health.Antibiotics used in animal production and human medicine are very similar [50].The overuse of antimicrobial agents in food-producing animals has been accelerating of AMR in bacterial populations [18,51].The emergence of resistant bacteria organisms in animal populations can affect animal's health and their productivity.
It is essential that's rational antibiotics practice dependable in veterinary as well as in human medicine to minimize the selection pressures with the aim of minimizing the emergence of resistant bacteria [51].AMR may be spreading to the environment through farm waste which can reach human as a result of direct contact with animals, the consumption of contaminated foods of animal origin, water, and vegetables [50].A close relationship between resistant bacteria in human and antibiotics uses in agriculture sector which we need to understand how antimicrobial prescribing sits amongst other factors that might drive antimicrobial use in both human and agriculture aspect.Strong responsibility that's including pressure from clients and lack of roles and strategies such as management in the facility all may lead to irrational prescribing in some context.Interventions to improve or decrease antimicrobial use on farms will need to control and prevent the spread of this phenomenon at the human and agriculture sector [51].Moreover, better awareness of the consequences of AMR in disease control and farm productivity would be helpful to preclude the overuse or abuse of antibiotics in animal production [50].A recent WHO report emphasizes the importance of undergraduate training courses in prudent using of antibiotics [52].Education programs play an essential role in teaching and changing the behavior among students and healthcare workers, where physicians are well-informed and share suggestions.Many studies have shown that guidelines and education intervention programs in hospitals reduce antimicrobial consumption costs and minimize the emergence of resistant germs.A strategy that can be used to promote the rational use of antibiotics and decrease the resistant germs through ongoing education programs, ongoing drug-auditing practices, work on formulations restriction, pharmacy justification, surveillance, and work by multidisciplinary team [53].Moreover, Antibiotic stewardship programs (ASPs) should address not only for doctors in practice but also students in medical school.Work on the program from the academic levels will give a positive impact reflected on awareness in the optimal use and dangerousness of resistant organisms [54].With this funding, CDC is fighting the antibiotic resistance by accelerating outbreak detection and prevention in every healthcare facility, supporting innovative research to address gaps in knowledge related to resistant bacteria, enhancing surveillance on proper use of antibiotics and antibiotics resistance, and informing providers and the general public about antibiotic resistance and optimal use of antibiotics [55].

OBJECTIVES
Study goals were to assess the knowledge, attitude towards optimal use of antibiotics, and awareness regarding the resistant bacteria among medical students at two universities, University A University B, and to determine if gender, age, education, and nationality affect antibiotic use and resistance knowledge, attitude, and awareness and to statistically compare University A and University B medical students' antibiotic use and resistance knowledge, attitude, and awareness.

MATERIALS AND METHODS
Cross sectional survey by using structured selfadministrative questionnaire.The questionnaire was adapted from the previous study to meet current goals [12].The previous study's author granted permission if the source article and author are credited.The prior study validates and reliability.Experts examined a questionnaire.Three medical student groups: The first year: medical knowledge is still raw.Third year: Students begin undergraduate clinical rotations and learn basic medical knowledge.The fifth-year: students should have the most antibiotic knowledge in their last year of undergraduate clinical rotation.This distribution will show student knowledge levels.This poll excludes the second and fourth years since their basic and clinical knowledge may be incomplete.The questionnaire has four sections.Demographics begin.The second section will test participants.The third portion will examine antibiotics attitudes.Finally, the fourth portion will determine antibiotic resistance awareness.

Questionnaire
Experts reviewed the questionnaire.

University A
Description of the sample according to the demographic variables.From the table (1) the number of males at university A and their percentage (144, 49%), while the number of females and their percentage (150, 51.1%).The age group (18-21) was the biggest number (169, 57.5%), while the percentage of the group aged between (22 -25) was (120, 40.8%), and the lowest percentage for group age more than 25 (2, 0.7%).The number and percentage of Saudis (137, 47.2%), while the number and percentage of non-Saudis (153, 52.8%).The number and percentage of students in the first year (104, 35.2%) and the number and percentage of students in the third year (107, 36.4%), while the number and percentage of students in the fifth year (83, 28.2%).The number and percentage of students with a family member working in the health sector were (188, 64.4%) and the percentage of students who do not have relatives working in the health sector (104, 35.6%).where the mean is (1.88) standard deviation (0.320), rate of awareness is (94%), and the lowest level in question 6 (Antibiotics used in animals can lead to antibiotic resistance), where the mean was (1.32), standard deviation (0.507), and awareness rate of (66%).Chi-square tests demonstrated statistical significance.There is a difference between those who answered a correct answer and those who responded incorrect answer and for those who answered correctly in all statements and statistical terms.6).The mean (1.7270), standard deviation (0.26168), and attitude ratio (86.35%) are positive.As indicated in the table and figure, positive attitudes regarding antibiotics ranged from medium to high, and the mean in all paragraphs was (1.55-1.93).Question 8 (do you think hand hygiene will prevent infection transmission) had the highest level of attitude with a mean (1.93), standard deviation (0.271), and estimated (96.5%).Question 7 (Have you ever started an antibiotic therapy after a simple doctor call, without a proper medical examination) had the lowest mean (1.55), standard deviation (0.499), and estimated positive attitude (77.5%).Chi-square tests demonstrated statistical significance.All statements except the seventh had a difference between those who answered correctly and those who answered incorrectly.

University B
Description of the sample according to the demographic variables.8) shown the level of awareness toward antibiotics among the medical students at University B is high with a mean (1.7425), a standard deviation (0.21366), and an awareness rate of (87.13%).As shown by the table(7)and figure(8) the level of awareness was low and high, the mean average in all the paragraphs ranged from (1.28 to 1.90), where the highest level of awareness found in question (2) (In particular, have you discussed the problem of antibiotic resistance during study courses), the mean was (1.90), with a standard deviation (0.298), and an awareness rate of (95%) , while the lowest expression measures the level of awareness (6) (Antibiotics used in animals can lead to antibiotic resistance) the mean was (1.28 ), standard deviation (0.449), and an awareness rate of (64%).The results of the chi-square test are statistically significant, there is a difference between those who answered correctly and those who answered incorrect answers and for those who answered correctly in all the statements except the question (6) where those who responded the wrong answer were more than the correct answer which means statistically significant.9), antibiotic positivity ranged from mild to high.All paragraphs averaged (1.65-1.89).Question 8 (Do you think hand hygiene will reduce the chance of infection transmission) had the greatest antibiotic attitude, with a mean of (1.89), a standard deviation of (0.319), and a positive attitude of (94.5%).The lowest level of attitude was question (3) (Do you stop taking antibiotics when you start feeling better), with a mean (1.65), standard deviation (0.479), and estimated positive attitude (82.5%).The chi-square test shows a difference between those who replied properly, those who answered incorrectly, and those who answered right in all statements.

Statistical significant and correlation between different independent variables related to: A. Knowledge
The difference in the average knowledge of antibiotics in the study sample by the gender differences at the level of statistical significance 0.05.

Figure (10) of the average of knowledge toward antibiotics by the gender variables.
According to the table (9) and figure (10), differences are found in the mean of knowledge toward antibiotics in the sample of the study based on the gender variable and for females.To determine the statistical significance of these differences, we used the Independent Samples T-test.According to the table (10), the Independent samples T-test shown that the value of T = -2.458 is a statistically significant value of ( P_ VALUE ) <0.05 so, the decision will be the acceptance of research hypothesis, the average knowledge of the sample of the study population varies by gender at the statistical significance level (0.05) for females in mathematical terms.So, the level of knowledge regarding antibiotics is higher among females (0.75) than males (0.70).The difference in the average knowledge of antibiotics in the study sample according to year of birth at the level of statistical significance 0.05.According to the table (11) and figure (11) there are differences in the mean of knowledge toward antibiotics in the study sample which is related to the year of birth variable (22-25).To determine the statistical significance of these differences, we used the Independent samples T-test.12), the Independent samples T-test shown that the value of T = 4.351 is statistically significant (P-value <0.05) so, the decision will be the acceptance of research hypothesis, the average of the knowledge in the study sample varies according to the year of birth at the statistical significance level (0.05) age group (22-25), mathematical terms.In this regard, the level of knowledge regarding antibiotics is higher among the age group (22-25) (0.77) than other age group.

T-test for Equality of Means
The difference in the average knowledge of antibiotics in the study sample according to year of study at the level of statistical significance 0.05.According to the table (13) and figure ( 12), there are differences in the average knowledge of medical students toward antibiotics in the sample of the study attributed to the year of study.To determine the statistical significance of these differences, we used the ANOVA Test.

Total
By used the ANOVA Test, we found the value of F = 44.414test is statistically significant (P-VALUE <0.05) and the this mean the acceptance of research hypothesis, the average of knowledge in the sample of the study differs according to the year of study at the statistical significance level of (0.05).To know which antibiotic knowledge averages have statistically significant differences depending on the year of study variable, we did the LSD test.From the LSD test, we found a statistical difference in the average knowledge regarding antibiotics between first-year students and third-year students and the positivity for thirdyear students, also a statistically significant difference in the average knowledge toward antibiotics between first and fifthyear students and the benefit for fifth-year students, and a statistically significant difference in the average knowledge of antibiotics between third and fifth-year students and the positivity for fifth year students.

B. Awareness
The difference in the average awareness of antibiotics in the study sample according to the year of birth at the level of statistical significance 0.05.According to table (16) and figure ( 13), there are differences in the mean of awareness about antibiotics among the study sample which based on the year of birth, and we found these differences appear on age (22)(23)(24)(25).To determine the statistical significance of these differences, we used the Independent samples T-test.Through the Independent Samples T-test, we found that the value of T = -4.751 is statistically significant (P-value <0.05) and this acceptance of research hypothesis, the average awareness of the study sample varies according to the year of birth at the statistical significance level (0.05), and the level of awareness toward antibiotics is higher among the age  According to the table (18) and figure ( 14), we found the differences in the mean of awareness regarding antibiotics among the study sample were attributed to the year of study variable.In order to determine the statistical significance of these differences, we used the ANOVA Test.

Table (17) Independent Samples T-test, the statistical differences of awareness toward antibiotics according to year of birth variable T-test for Equality of Means
.

Total
The study hypothesis will be accepted because the F = 35.810test is statistically significant (P-VALUE <0.05) in the ANOVA test table.We will use the LSD test to compare years of study statistically.From the LSD test, we found a statistical difference in the average awareness about antibiotics among first and thirdyear students and the positivity for third-year students, a statistical difference in the average awareness of antibiotics among first and fifth-year students and the positivityfor fifthyear students, and a statistical difference in the average awareness towards antibiotics among third and fifth-year students and the positivity for fifth-year students.

C. Attitude
The difference in the average attitude of antibiotics in the study sample according to the gender variable at the level of statistical significance 0.05 Table (21 According to the table (21) and figure (15), we found virtual differences in the average attitude regarding antibiotics in the sample of the study to be attributed to the gender variable and these virtual differences appeared for females.To determine the statistical significance of these differences, we used the Independent samples T-test.From the Independent samples T-test we found, that the T = -2.538test value is statistically significant (P-VALUE <0.05) so, the decision will be to accept research hypothesis, the average of the attitude toward antibiotics in the sample of the study varies by gender at the statistical significance level (0.05).So, the level of attitude toward antibiotics varies according to the gender of the student and the positivity appeared for the females.
The difference in the average attitude of antibiotics in the study sample according to the year of birth at the level of statistical significance (0.05).According to the table (23) and figure ( 16), there are simple differences in the mean of attitude regarding antibiotics in the study sample and it's attributed to the year of birth variable and for the age group (22-25).To determine the statistical significance of these differences, we used the Independent samples T-test.

Attitude
From the Independent samples T-test table, we found that the value of the T = -2.746test is statistically significant (P-VALUE <0.05) and this indicate the acceptance of the research hypothesis, the mean of attitude toward antibiotics in the study sample varies according to year of birth at the statistical significance level (0.05).The difference was in favor of the age group (22-25) in mathematical terms, which mean the attitude of antibiotics in the age group (22-25) is greater than group age (18-21).The difference in the average attitude of antibiotics in the study sample according to the year of study at the level of statistical significance (0.05).Table (25 According to table (25) and figure ( 17), the sample's average attitude toward antibiotics differs by the year.We used the ANOVA Test, to determine the statistical significance of these differences.

Total
From the ANOVA Test table, we found that the value of the F = 8.778 and it's a statistically significant where (P-VALUE <0.05) in this regard, the decision to accept the research hypothesis and there are statistically significant differences According to the LSD test results we found a statistical difference in the average attitude toward antibiotics between first-year students and third-year students and the positivity for third-year students, a statistically significant difference in the average attitude regarding antibiotics between first and fifth-year students and this significance for the fifth-year students, and no statistical significance difference in the average attitude of antibiotics between third and fifth-year students.

Correlation of dependent variables (knowledge, awareness, and attitude):
A) knowledge with awareness By using simple linear regression, a relationship between knowledge and awareness has been appeared.Also, we found a correlation and effect between the degree of knowledge and awareness toward antibiotics.A positive effect is shown on figure (18) with a significant correlation table (28), these results revealed that as the knowledge is increasing, the awareness level becomes high.According to table (28) and figure (18), the knowledge and awareness about antibiotics are positively correlated (R = -0.516)and statistically significant (α = 0.05).As seen in the table, the limiting factor (26.6% = R2) is antibiotic awareness, which is explained by the independent variable's effect on the dependent variable's antibiotic knowledge.The regression test of the analysis of the single variance (F = 151.66) is statistically significant at α = 0.05.Thus, the regression between knowledge and awareness toward antibiotic is statistically significant.Through the table, the regression constant B0 and regression factor B1 are statistically significant at α = 0.05.T-test values were significant at α = 0.05.Regression coefficients yield the linear regression equation.1.32 + 0.58X knowledge B0 = 1.32:Zero awareness is 1.32.As knowledge increases, awareness increases 0.58 degrees.

B) knowledge with attitude
Knowledge and attitude regarding antibiotics has been correlated, we found this correlation by using simple linear regression.Figure (19) shows a favorable effect and substantial connection (29).These findings showed that knowledge boosts attitude.From the table (29) and the previous figure ( 19), there is a positive correlation between knowledge and attitude (R = -0.21),which is statistically significant at (0.05 = α).As indicated in the table, the limiting factor (4.4% = R2) explains the effect of the independent variable (antibiotic knowledge) on the dependent variable (antibiotic attitude).The regression test's statistical test value (F = 18.97) is statistically significant at the statistical significance level (α = 0.05) in the table.The regression between antibiotic knowledge and attitude is statistically significant.
The regression constant, regression coefficient B1, and T-test values are all statistically significant at α = 0.05.Regression coefficients yield the linear regression equation.B0 (Constant) = 1.32:The degree of direction is 1.55 when the degree of direction is zero.B1 (knowledge) = 0.58: The degree of direction increases by 0.26 degrees as the degree of knowledge increases one degree.According to the statistical analysis in the study awareness and attitude were not correlated.

DISCUSSION
By continuous education through correct use of antibiotics and dangerousness of resistance germs the emergence of AMR will be reduced.Knowledge, awareness, and attitude must start at the bottom.Thus, testing education, awareness, and attitude is crucial to rational antibiotic use and antibiotic resistance reduction.This study compares medical students' knowledge, awareness, and attitudes on antibiotics and antibiotic resistance at two Universities to assess students' science understanding.Undergraduate medical education is the first step.Medical students will prescribe antibiotics in the future; thus, we need to know their antibiotic and antibiotic resistance teaching.At these stages, medical students' baseline knowledge, awareness, and attitude must be assessed.Medical education should emphasize practical experience to rationalize antimicrobial usage and minimize antibiotic resistance.Healthcare professionals must educate Saudis among the community to bridge the government-public gap.Thus, healthcare professionals must be well-informed about antibiotics and antibiotic resistance.Students' knowledge, awareness, and attitude can affect Saudi medicine overuse.Antibiotic resistance is largely caused by humans and animals overusing antibiotics.Overcrowding, poor cleanliness, and lack of infection control can spread resistant germs in hospitals and communities.Students should understand these key risk factors and AMR's onset [56].From this perspective, medical students who are knowledgeable and aware of antibiotic use can help prevent unnecessary antibiotic use.This study includes 419 people from two colleges, (53.2%) percent male (223) and (46.8%) female (196).This study compared two medical Universities with similar academic levels.In both Universities, participants had above-average antibiotic resistance knowledge.

Knowledge University A antibiotic knowledge
University A knows antibiotics from our perspective, antibiotic knowledge was high (71.81%)and the highest rate of responders was in question 3 (Antibiotics used for treatment of bacterial infections) with 97% correct answers, while the lowest rate was in item 8 (New antibiotics are usually better than old ones) with 22% correct answers.

University B antibiotic knowledge
We observed (74.3%) of University B students were knowledgeable about antibiotics.Question 1 (penicillin or amoxicillin are antibiotics) had the highest percentage of accurate responses (89%).The lowest degree of knowledge was in question 8 (New antibiotics are usually better than old ones) with an estimated 28%.Question 8 revealed the two Universities' students insufficient antibiotic knowledge.The considerable growth in knowledge shows that students in both Universities are keeping up with the modern scientific approach to antibiotics, which bodes well for their future understanding.
In this regard, a survey of 202 students at Northern Border University in Saudi Arabia found a high rate of antibiotic selfmedication and inappropriate antibiotic knowledge [57].A Riyadh survey found that dentistry students may prescribe antibiotics inappropriately to treat various diseases, indicating a gap in their antibiotic teaching and practice [58].A Jordanian study found that (55.6%) of antibiotics used as prevention against infections, (49.0%) utilized left-over drugs without physician consultation, and (51.8%) took antibiotics based on relative counsel [59].In Southern India, doctor of pharmacy students were better educated about antibiotic usage and resistance than compared to B Pharm students.Future treatments should be targeting students towards educating the B Pharm students so that they can implement the acquired knowledge in their practice knowledge [60].In a Chinese university study, undergraduate students had poor antibiotic knowledge, moderately accurate beliefs, inappropriate actions, and high rates of self-medication [61].A Kosovo pharmacy student study found good and intermediate antibiotics knowledge.Half of them selfprescribe antibiotics, although most would not serve them without a prescription [68].Awareness Antibiotic resistance awareness at University A Our study found that University A students are aware of antibiotics (87.16%), which is a good sign that the University is communicating the global threat of antibiotic resistance.In our antibiotic awareness study, we asked students six questions.This part covered the definition and exclusion of resistant bacteria and how humans and animals propagate antibiotic-resistant bacteria.Question 1 (Have you heard of antimicrobial resistance) had the highest awareness (94%).All students are aware of antibiotic resistance, although issue 6 (Antibiotics used in animals can contribute to antibiotic resistance) has the lowest awareness (66%).Antibiotic resistance awareness at University B As in University A, where the University B study shows high student awareness, this indicates a positive response to resistant bacteria.Our poll indicated 87% of pupils were aware of antibiotic resistance.Question 2 (In particular, have you discussed the problem of antibiotics resistance during study courses) had the greatest estimated awareness (95%).Question 6 (Antibiotics used in animals can cause antibiotic resistance) had the lowest awareness (64%).We observed that both colleges had the lowest degree of awareness in the same question, indicating that further research is needed to raise awareness of the relationship between humans and animals and resistant microorganisms.Compared to a local study at Northern Border University Saudi Arabia among students, 60% of respondents heard about resistance bacteria and how random antibiotic usage harms the body, indicating high awareness.40% don't understand antibiotic resistance [57].In a study of medical students in a southern Indian teaching hospital, more than 85% were aware of antibiotic resistance's effects.In research, 79% of respondents were aware of inadequate therapy, extension of sickness, bacterial resistance, and increased medical costs [63].A UK study found that almost all participants felt that overusing antibiotics makes them less effective and renders bacteria resistant [64].Attitude Attitude toward antibiotics at University A From this poll, University A students had a positive attitude regarding antibiotic use, which is a good sign.Eight attitude questions assessed pupils' levels.These questions allow us to examine how students utilize antibiotics, whether they consult a doctor or stop eating when they feel better.Its necessary knowledge reflects constant unjustifiable usage, and the correct scientific technique continues to using optimally.Antibiotic attitudes were 86.35% in our sample.Question 8 (Do you think hand hygiene will minimize virus transmission) had the greatest attitude (96.5%).Question 7 (Have you ever begun an antibiotic therapy following a simple doctor call, without proper medical assessment) had the lowest level of attitude (77.5%), but overall, it was good towards antibiotic use.Attitude toward antibiotics at University B As in the case of University A, the level of attitude in medical students towards antibiotics found high with an estimated rate (86.23%).Question 8 (Do you think hand hygiene will reduce the chance of infection transmission) had the highest attitude (94.5%), while question 3 (Do you usually stop taking antibiotics when you start feeling better) had the lowest (82.5%).From the present survey, we found the highest level of attitude in question 8 (Do you think hand hygiene will reduce the chance of infection transmission) with an estimated rate of 96.5% at University A and 94.5% at University B, indicating students' awareness of the importance of hand hygiene in healthcare settings.Compared with a national study managed in Riyadh among dental students which showed that's only 13.1% of dental students would administer antibiotics for two to three days, whereas 86.8% would prescribe antibiotics for more than three days [64].In another study, Aljouf research of nonmedical students, 62.6% stopped antibiotics after improvement, while 28.1% finished the course.The survey also found that 53.5% of students rely on previous prescriptions, 14.5% on experience, and 3.5% on pharmacist guidance [65].Medical students' knowledge, attitude, and behavior should start at the ground level in the first year and continue through the last year to apply antibiotics resistance awareness in practice.Knowledge and attitude from higher education promote reasonable antibiotic usage and give positive impact to create healthy environment.Finally, lawmakers, pharmaceutical companies, and medical professionals must encourage rational drug prescribing in medical colleges and hospitals.Antimicrobial agents should be dealing with an integrated approach involving all specialties.The poll showed that education increases knowledge, awareness, and attitude.We also observed that information affects awareness and attitude.This correlation shows how knowledge improves students' drug perception and attitude.

CONCLUSION
Antimicrobial agents have saved millions of lives and revolutionized medicine, but restricted resources are making them less effective.Misuse and overuse of antibiotics lead to increase the global health burden which is antibiotic resistance.A healthy society relies on good science.Effective education helps provide the community with a complete health strategy and instills information, awareness, and attitudes that influence behavior and habits.In the Gulf and Saudi Arabia, resistant germs pose a global issue.International organizations and centers fight resistance bacteria, as do local governments representing the health, educational, industrial, and agricultural sectors.Antibiotic use and distribution can only improve if everyone does their part.Resistance germs are fought at various levels, internationally represented in organizations and centers, in addition to the local representative of governments represented by the health sector, educational, industrial, and agricultural sector.Thus, antibiotic use and resistance education is needed for positive impact among public and health society.Knowledge is the first step to rational use and antibiotic resistance prevention.Several concepts must be understood, attitude and awareness and their correlation with knowledge.We found this relationship, suggesting that taking antibiotics without a doctor's prescription and stopping them after feeling better may increase AMR prevalence.Our exploratory study found that the medical students' in both Universities at different healthcare courses have a good knowledge and are aware of antibiotic resistance, but they need to focus more on practical application of experience to rationally use antimicrobial agents and reduce antibiotic resistance.We advocate continuing antibiotic-related activities that foster an enthusiastic academic generation pursuing high education.Moreover, adding a course highlighting the optimal use of antibiotics and the risk of antimicrobial agents.Through the program, we will help to maintain a level of knowledge and attitude on our health community.

CONFLICT OF INTEREST
We declare that there is no conflict of interest.

Figure ( 4
Figure (4): Statistical averages and standard deviations of knowledge toward antibiotics at University A.
Figure (11): Average knowledge toward antibiotics in the study sample according to the year of birth variable.
Figure (12): The average of knowledge toward antibiotics according to the year of study variable.
Figure (13):The average awareness toward antibiotics according to the year of birth variable.
25) (0.77) compared to the age group (18-21) (0.70).The difference in the average awareness of antibiotics in the study sample according to the year of study at the level of statistical significance 0.05.
Figure (15): The average of attitude toward antibiotics according to the gender variable.

Figure ( 16 )
Figure (16):The average of attitude toward antibiotics according to the year of birth variable.
Figure (17): The average of attitude toward antibiotics according to the year of study variable.
according to the year of study variable.For a comparison the years of study we used the LSD testTable (27):Multiple comparisons using the LSD test, the statistical differences according to the year of study.
Figurer :( 18): Simple linear regression for the effect and association of knowledge with awareness.

Figure( 19
Figure(19):Simple linear regression for the effect and association of knowledge with attitude.
Numerical averages, standard deviations, frequencies, and percentages have been used.Also, the chi-square test, independent samples T-test, the ANOVA test and the LSD test, and simple linear regression have been used.For statistical analysis: we used a statistical package for social science software (SPSS).
The prior study validates and reliability.Hardcopy questionnaire distribution.See appendix for full questionnaire.Site: University A and University B. Data collection: From the period May 2018 to January 2019.Study approval: The study was approved by IRB at University A and faculty of medicine at University B. University B sample size: 111 students.Three-group comparison.37 students per group assuming 0.5 effect size, α = 0.05, β = 0.2.Respond rate: 294 (73.5%) of 400 University A students completed a paper questionnaire.

Table ( 2
) and figure (4) show antibiotic knowledge is high.

): Statistical averages, mean, and standard deviations of awareness toward antibiotics at University A.
Antibiotic awareness is high, as shown in table (3) and figure(5).The level of awareness toward antibiotics, in general, is high.The level of the mean is (1.7432), with a standard deviation (0.24767).The table and figure illustrate low and high awareness.The mean average in all paragraphs ranged from (1.32 -1.88), with the highest level of awareness in question 1 (Have you ever heard about antibiotic resistance?),  Awareness: To classify the level of awareness from low (1-1.333),medium (1.334-1.666),and high (1.667-2).

): Statistical averages and standard deviations of attitude toward antibiotics at University A.  Attitude: To classify the level of attitude from low(1- 1.333), medium(1.334-1.666), and high(1.667-2).
The level of attitudes is high, according to the table (4) and figure (

Table ( 5): Distribution of the members of the sample at University B. Percent Frequency Demographic 63.4 78 Male Gender 36.6 45 Female 41.5 51 18-21 Year of birth
The first year had 44 students (35.8%), the third year 45 (36.6%), and the fifth year 34 (27.6%).61 students (53.5%) have family members in the health industry, whereas 53 students (46.5%) did not.

): Statistical averages and standard deviations of knowledge toward antibiotics at University B.  Knowledge: To classify the level of knowledge from low
28%).The results of the chi-square test are statistically significant, and there is a difference between those who responded correctly and those who answered the wrong answers in all of the statements except the question (8) where those who answered the wrong answer were more than the correct answer and statistical significance.
From the table (6) and figure(7)shown the level of knowledge about antibiotics among medical students at University B, in general, is high.The level of the mean is (0.7429) with a standard deviation of (0.211) and an estimated rate of (74.3%).As shown in the table (6) and figure (7) the level of knowledge ranged from low to high.The arithmetic mean in all the paragraphs ranged between (0.28 and 0.89).The highest level of knowledge was in the question 1 (Penicillin or Amoxicillin are antibiotics) where the mean is (0.89) with a standard deviation (0.309) and an estimated knowledge rate (89%), while the lowest level of the knowledge of medical students found in question (8) (New antibiotics are usually better than old ones) where the mean is (0.28), standard deviation (0.499), and an estimated

): Statistical averages and standard deviations of awareness about antibiotics at University B.  Awareness: To classify the level of awareness from low(1-1.333), medium(1.334-1.666), and high(1.667- 2).
According to the table (7) and figure (

Table ( 29): Results of simple linear regression for the effect and association of knowledge on attitude
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