Introduction {#S0001}
============

Antimicrobial resistance (AMR) has emerged as one of the most important challenges of public health care during the last 10 years and is considered to be one of the primary risks to human health.[@CIT0001],[@CIT0002] AMR is defined as the ability of a microorganism to survive or grow in the presence of a concentration of antibiotics that should be enough to restrain or kill that organism.[@CIT0003] In the coming 20 years, health care systems may be unable to treat bacterial diseases efficiently.[@CIT0004] Infections caused by multidrug-resistant microorganisms result in increased mortality, morbidity, and higher hospitalization rates as well as increased complications and health care costs.[@CIT0005]

Exacerbating factors responsible for the development of AMR include poor knowledge, misconceptions, views on infectious diseases, inappropriate prescription and medication use and patient demand.[@CIT0006]--[@CIT0010]

Misconceptions regarding the therapeutic effects of antibiotics have shown that people consider antibiotics to be extraordinary medications that can be used to treat any infection caused by viruses, bacteria or fungi.[@CIT0011] Thus, the problem of AMR can be minimized if the general population possesses good knowledge of the appropriate use of antibiotics.[@CIT0012]

In the Middle East region, the Kingdom of Saudi Arabia is among the richest developing countries, and its population is multiethnic.[@CIT0013] In most of the government hospitals in Saudi Arabia, medication provision and doctor consultation are free, and self-medication with antibiotics and nondoctor prescriptions are very common in the community. There are many reasons for self-medication with antibiotics: if patients use particular antibiotics for specific signs and symptoms in the past, he may use the same antibiotics if he feels his current illness is similar to the one the past. Other reasons such as friend advice based on similar experience or if the pharmacy is near to the patients' resistance and the hospital is far from patients may encourage self-prescription with antibiotics. A bad doctor--patient relationship may also discourage doctor consultations and encourage self-medication with antibiotics, such as the distance to the hospital being too far or advice from friends with regards to self-medication with antibiotics leading to no other information being obtained.[@CIT0013]

Internationally, the KSA has been recognized as a country with escalating AMR, which is a concern for the Kingdom health authorities.[@CIT0014] According to the results of a previous study, the use of antibiotics without any prescriptions is quite frequent in the community, and antibiotics are used to treat inappropriate conditions.[@CIT0015]

The public has easy access to antibiotics, and the availability of antibiotics is uncontrolled in the KSA. This frequent and easy access to antibiotics changes the perspective of interventions initiated by the health authorities to control the irrational use of antibiotics that leads to AMR.[@CIT0016],[@CIT0017] To date, very few studies have been reported on AMR in the KSA. However, the results of available studies have shown that there is very poor knowledge regarding antibiotic use and AMR among the general population.[@CIT0013],[@CIT0017]

To tackle the urgent issues surrounding AMR in Saudi Arabia, it is of vital importance to raise public awareness regarding this issue. A better understanding regarding the spread of AMR can encourage the general population to avoid practices and behaviors that spread antibiotic resistance.[@CIT0018]

In the KSA, there is no national surveillance system of AMR and health care-acquired infections. To date, no study has been conducted in Tabuk (North Western region) to assess the knowledge and awareness of people regarding antibiotic resistance. Therefore, the results of this study will provide data concerning the knowledge regarding AMR in Tabuk. In addition, this study will help the medical service division in planning and formulating new educational strategies and interventions to promote the appropriate use of antibiotics among the general population to minimize the escalating rate of AMR in this region. Therefore, we designed this study to determine the level of knowledge regarding AMR in the general population in Tabuk city. The locality of the study is shown in [Figure 1](#F0001){ref-type="fig"}. Figure 1Study area location.

Materials and methods {#S0002}
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Study design, sample size calculation and sampling {#S0002-S2001}
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This was a hospital-based cross-sectional study that was conducted in King Salman Armed Forces Hospital and King Khalid Armed Forces Hospital in Tabuk City between November 2016 and October 2017. The inclusion criteria for the study participants were that they be adults (either sex, male or female) and Saudi nationals who willingly agreed to participate in the study. Those who refused to participate, could not read the study questionnaire, were below 18 years of age or refused to participate were excluded from the study. Verbal consent to participate in the study was obtained prior to the start of the study, and parents or legal guardian of any participant under the age of 18 years provided this consent. The sample size was collected from the two hospitals mentioned above which are the main hospitals in the city of Tabuk. The outpatient departments in the two hospitals are the main areas where most of the patients are seen for treatment and follow-up. The sample size was based on a single proportion using the following formula adopted from Cochran (1977). $$\documentclass[12pt]{minimal}
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$${\rm{n}} = {{{Z^2}p(1 - p)} \over {{{\rm{d}}^2}}}$$
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n: the sample size=1,066

p: the probability of success (ie, AMR knowledge) =47.9%

Z: the standardized variable that corresponds to a 95% level of confidence=95%

d: the desired marginal error=3%

According to this formula, knowledge regarding AMR in Saudi Arabia was reported as 47.9%.[@CIT0017] Using this percentage and other parameters in the formula, the calculated sample size was 1,066. Additionally, it is important to consider the nonresponse rate, which we suggest was 20% of the total recruitment number (1,066), yielding a value of 213. The total sample size was 1,279 participants.

The study participants were selected from a range of different outpatient departments from King Salman Armed Forces Hospital and King Khaled Armed Forces Hospital which are now one hospital under the same administration using a simple random sampling technique by a trained research assistant. This is done through a computer-generated process in which each of the patients is assigned a number, after which the requested sample would be chosen at random. The dependent variable (AMR knowledge among study participants) and independent variables (sociodemographic characteristics, factors leading to antibiotic resistance, different diseases that can be treated with antibiotics and problems of antibiotic resistance) were recorded.

Study instrument and data collection {#S0002-S2002}
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The self-reported study questionnaire was developed following an extensive literature review of similar studies, and the AMR report published by the WHO was also used. The questionnaire consisted of two parts. The first part included sociodemographic characteristics and the second part consisted of three sections: the use of antibiotics, participants' general knowledge about antibiotics and participants' knowledge about antibiotic resistance. All of the questions were close-ended. The study questionnaire was forward and backward translated from English into Arabic with the help of a bilingual translator. The pretested and validated study instrument was first pilot-tested on 20 participants and then administered to the study participants who fulfilled the inclusion criteria by research assistants. Before analysis, the data were entered into SPSS IBM version 22 for Windows, cleaned and preprocessed, which involved accuracy checking, treatment of missing values and categorization of study variables.

Data analysis and modeling {#S0002-S2003}
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Data analysis was performed using SPSS version 22. Quantitative variables are presented as means ± SDs. Qualitative variables are presented using frequency tables and percentages. Multiple logistic regression was used to identify the factors associated with antibiotic resistance. All of the statistical values were considered significant at *P*≤0.05. Only the results of multivariate logistic analyses are reported, showing ORs and 95% CI.

Ethical approval {#S0002-S2004}
----------------

Ethical approval was obtained from the Research Ethical Committee of King Salam Armed Forces Hospital under project number RREC2016-145. The Research Ethical Committee also covers King Khalid Armed Forces Hospital. Verbal informed consent was acceptable and approved by the approving research ethics committee.

Results {#S0003}
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Of the 1,279 participants, 1,188 completed questionnaires without any missing values after data cleaning and management. The response rate was 93%.

[Table 1](#T0001){ref-type="table"} shows the sociodemographic characteristics of the study participants, while [Figure 2](#F0002){ref-type="fig"} shows the responses of participants regarding the use of antibiotics for treating certain conditions. The top 5 common conditions for which antibiotics were used were urinary tract infection (UTI), diarrhea, sore throat, gonorrhea and skin or wound infection, whereas the least common conditions were headache, HIV/AIDS, cold and flu and measles. [Figure 3](#F0003){ref-type="fig"} shows the knowledge of participants regarding AMR terminology, while [Table 2](#T0002){ref-type="table"} shows the knowledge of participants regarding antibiotic resistance. Only 10.2% of participants knew that AMR develops when bacteria become resistant to antibiotics, 17.6% of participants knew that it is difficult to cure an infection in the presence of antibiotic resistant bacteria and 25% of respondents knew that surgical procedures are dangerous during an AMR infection. Furthermore, 32.4% of respondents told us that they used antibiotics for the duration prescribed by the doctor, while 24.1% of respondents reported that they stopped taking antibiotics before the end of the treatment.Table 1Demographic characteristics of the study participants (n=1,188)CharacteristicsnPercentage (%)Age (years)16--2429725.025--3338932.734--4238532.443--51595.052--60584.9Total1,188100SexMale91376.9Female27523.1Total1,188100ResidenceTabuk city93578.7Rural side of Tabuk city25321.3Total1,188100EducationNo formal schooling786.612th grade or less16614.0High school graduate with diploma36630.8Technical/vocational training or associate degree19816.7University graduate with bachelor's degree25321.3Postgraduate degree12610.7Total1,188100Monthly income (SR)≤5,00014312.05,001--1,00024220.410,001--15,00033027.8≥15,00047339.8Total1,188100%NationalitySaudi1,07890.7Non-Saudi1109.3Total1,188100Job statusNot employed92477.8Employed998.3Retired16513.9Total1,188100 Table 2Factors related to antibiotic use by study participants (n=1,188)When did you last use antibiotics?In the last month86973.1%In the last 6 months1109.3%In the last year998.3%More than a year ago776.5%Never332.8%Total1.188100%From where did you get the antibiotics?Medical store or pharmacy89175.0%Stall or hawker15413.0%From the internet998.3%Friend or family member443.7%Total1,188100%When did you stop taking these antibiotic?When I felt better25421.4%When I had taken all of the antibiotics as directed37831.8%I don't know55646.8%Total1,188100%"Using antibiotics that were given to a friend or family member, as long as they were used to treat the same illness, is a correct practice."True48040.4%False29925.2%Don't know40934.4%Total1,188100%It's okay to use the same antibiotics which were used to treat the same symptoms in the pastTrue64954.6%False53945.4%Total1,188100% Table 3Knowledge regarding AMR (n=1,188)No.QuestionsYesNoI don't knowTotal1It occurs when antibiotic treatments do not work in the body121 (10.2%)792 (66.7%)275 (23.1%)1,1882When antibiotics do not treat infection209 (17.6%)880 (74.1%)99 (8.3%)1,1883Bacteria resistant to antibiotics are difficult to treat99 (8.3%)1,056 (88.9%)33 (2.8%)1,1884AMR can affect me and my family44 (3.7%)1,023 (86.1%)121 (10.2%)1,1885AMR is an issue in other countries but not here704 (59.3%)451 (38%)33 (2.8%)1,1886A problem for people who take antibiotics regularly385 (32.4%)770 (64.8%)33 (2.8%)1,1887Bacteria resistant to antibiotics can spread person to person198 (16.7%)924 (77.8%)66 (5.6%)1,1888AMR infections could make medical procedures more dangerous297 (25%)803 (67.6%)88 (7.4%)1,1889People should use antibiotics only when prescribed by doctors319 (26.9%)638 (53.7%)231 (19.4%)1,18810.People should not keep antibiotics and use them later for other illnesses946 (79.6%)66 (5.6%)176 (14.8%)1,18811AMR is one of the biggest problems the world faces671 (56.5%)418 (35.2%)99 (8.3%)1,18812There is not much people like me can do to stop AMR0 (0%)924 (77.8%)264 (22.2%)1,18813Governments should reward the development of new antibiotics1,078 (90.7%)99 (8.3%)11 (0.9%)1,18814Pharmaceutical companies should develop new antibiotics231 (19.4%)913 (76.9%)44 (3.7%)1,18815Patients should use antibiotics for the entire period described by the doctor198 (16.7%)913 (76.9%)77 (6.5%)1,18816Do you stop the antibiotic before the prescribed period?385 (32.4%)748 (63%)55 (4.6%)1,18817Failure to comply with the prescribed duration of treatment (antibiotics) can result in AMR286 (24.1%)825 (69.4%)77 (6.5%)1,18818Do you think that you should tell your doctor all the antibiotics that have already been taken previously?429 (36.1%)704 (59.3%)55 (4.6%)1,18819Have you ever used a particular antibiotic and then the use of the same antibiotic in a subsequent period did not improve symptoms?374 (31.5%)759 (63.9%)55 (4.6%)1,188[^1] Table 4Demographic characteristics, knowledge and practice of participants regarding antibiotics in relation to antimicrobial resistance (AMR) knowledgePredictorsDV: Knowledge of AMROR95% CI*p*-valueYesNoTotal**Sex**Male2536609130.7420.421.300.302Female662092751\-\--**Total**3198691188**Age group (years)**16-18772202976.4052.3317.550.00019-24823073892.7301.037.230.04325-341432423859.2993.3425.860.00035-441049592.7850.839.340.09745-54751581\-\--**Total**3198691188**Region**Tabuk city2536829350.4560.260.780.004Rural side of Tabuk city661872531\-\--**Total**3198691188**Education**Not educated22567831.0458.24116.910.000Primary778916614.0254.4244.450.000Middle1082583666.1982.0618.590.001Secondary551431983.1621.019.880.048Diploma222312530.2650.070.910.035Bachelor's degree2952815.0481.7214.790.003Master's degree640461\-\--**Total**3198691188**Monthly Income (Saudi riyals)**[\<]{.ul} 500044991430.0850.0230.3060.0005001-1000661762420.0280.0070.1090.00010001-15000882423300.3270.1770.6050.000[\>]{.ul}150001213524731\-\--**Total**3198691188**NationalitySaudi**26481410780.1050.0460.2360.000**NonSaudi**55551101\-\--**Total**3198691188**Job Status**Not employed2426829245.6932.99710.8160.000Employed3366993.2901.3887.7970.007Retired441211651\-\--**Total**3198691188**When did you use antibiotics the last time?**In the last month2316388690.3140.1160.8460.022In the last 6 months33771000.4380.1361.4070.165In the last year3366992.1020.6546.7540.212More than a year ago1166770.1280.0300.5410.005Never1122331\-\--**Total**3198691188**Where did you get the antibiotics from?**Medical store/ Pharmacy2536388910.2180.0700.6760.008Stall or hawker331211540.0230.0060.0830.000The internet2277990.0140.0030.0670.000Friend or family member1133441\-\--**Total**3198691188**Stop taking antibiotics once you've begun treatment**When I feel better941602548.2853.91817.5230.000When taken all antibiotics as directed832953782.6481.2265.7210.013Don't know1424145561\-\--**Total**3198691188**"Use antibiotics that were given to a friend or family member, as long as they were used to treat the same illness"**True1193614800.400.160.960.042False108191299108.9629.98395.930.000Don't Know923174091\-\--**Total**3198691188**It's okay to buy the same antibiotics from a doctor, if you're sick and they helped you get better when you had the same symptoms before**True1634866499.3143.68423.5500.000False1563835391\-\--**Total**3198691188[^2] Figure 2Participants\' knowledge of conditions that can be treated with antibiotics.Figure 3Participants\' knowledge regarding antimicrobial resistance.**Abbreviations: **AMR, antimicrobial resistance; DR, drug resistance; ARB, antibiotic resistant bacteria; SB, superbugs (multidrug resistance bacteria).

The results of the multiple logistic regression analysis ([Table 4](#T0004){ref-type="table"}) revealed that several factors showed a significant association with the knowledge of the participants regarding antibiotic resistance ([Table 3](#T0003){ref-type="table"}): age; region; education; monthly income; nationality; job status; use of antibiotics (in the last 6 months and more than a year ago); time of prescription; time during the antibiotic course when participants stopped taking antibiotics; giving antibiotics to a friend or family member as long as the antibiotics were used to treat the same illness; and buying the same antibiotics from a doctor if the participant was sick and the same antibiotics had helped the participant recover from the same symptoms. Before multiple logistic regression analysis, all possible confounding variables were considered.

Discussion {#S0004}
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The primary objective of this study was to determine the level of knowledge regarding AMR among study participants in two major hospitals in Tabuk city. One of the most important steps in combating AMR is augmenting the knowledge of the general public.

In this study, only 26.85% of the respondents had knowledge regarding antibiotic resistance, which is very low compared to the results of a similar study conducted in other parts of the kingdom. In contrast to this study, a higher percentage of knowledge regarding AMR was reported from South Korea,[@CIT0019] Kuwait (45.4%),[@CIT0020] and Saudi Arabia and Jordan (60.7%).[@CIT0021] Compared to these studies, studies from Hong Kong (91%) and Indonesia (85%) showed a greater knowledge of respondents for the term antibiotic resistance.[@CIT0011],[@CIT0022] In contrast, an Italian study showed a lower level of knowledge among study participants (ie, 9.8% knew the definition of antibiotic resistance).[@CIT0023] The above-discussed studies showed inconsistencies in the knowledge of populations regarding the AMR in different regions.

In this study, the knowledge of the study participants was good regarding the use of antibiotics for treating bacterial infection, but when queried regarding viral infection, the study population exhibited confusion and misconception. Over 60% of the respondents knew that antibiotics can be effectively used to treat bacterial infections. However, only one-fourth of the study population reported that antibiotics cannot be used to treat viral infections, showing that the respondents were not well aware that antibiotics have no therapeutic effect toward viral diseases. The same findings were reported in studies from Kuwait and Malaysia.[@CIT0020],[@CIT0024],[@CIT0025] In contrast to the findings of this study, a higher level of awareness regarding the appropriate use of antibiotics was reported in studies from the UK, Sweden, Jordan and European countries.[@CIT0007],[@CIT0021],[@CIT0026] The results of studies from Sweden and Kuwait confirm the confusion among the public regarding whether antibiotics are effective against bacteria or viruses.[@CIT0007],[@CIT0020]

In this study, 22--46% of the study participants used antibiotics to treat cold/flu (22%), fever (36%) and sore throats (46%). These findings are comparable with those reported in studies from the USA[@CIT0027] and Poland[@CIT0028] In contrast, a higher proportion of participants used antibiotics to treat a cold, flu, fever and sore throat in studies from Namibia, Nigeria and Jordan.[@CIT0021],[@CIT0029],[@CIT0030]

As discussed above, it is evident that the general population lacks proper knowledge regarding the appropriate use of antibiotics and the meaning of antibiotic resistance.

Females were 0.74 times (95% CI 0.42--1.30) more likely to be aware of AMR than were the male participants. Participants in the 16- to 18- and 25- to 34-year-old age groups had the highest awareness regarding antibiotic resistance. Literature reported that knowledge of AMR increased with age,[@CIT0031] a trend that was observed in this study.

Various studies around the world have concluded that a lack of knowledge regarding AMR is associated with lower education.[@CIT0007],[@CIT0009],[@CIT0024],[@CIT0032]

In his study, Francesco Napolitano identified a lower educational level and unemployment as being significantly associated with not knowing the definition of antibiotic resistance.[@CIT0023] In contrast to this study, participants with a lower education and an unemployed status were more likely to be aware of antibiotic resistance. The finding of Tatyana Belkina regarding education and knowledge concerning AMR is consistent with the findings of this study, as he has shown that more educated respondents were less knowledgeable regarding bacterial resistance in Yemen[@CIT0031]

Various studies across the globe have reported that age, gender and educational level are recognized as potential factors that influence attitudes toward antibiotics.[@CIT0009],[@CIT0018],[@CIT0023],[@CIT0033]

The following factors were significantly associated with AMR knowledge among participants: participants who used antibiotics in the last year (OR: 2.102, CI: 0.654--6.754), discontinued antibiotics upon feeling better (OR: 8.285, CI: 3.918--17.523), gave antibiotics to friends or family members to treat the same illness (\[False\]: OR: 108.96, CI: 29.98--395.93) and participants who asked their doctors to prescribe previously administered antibiotics for the same symptoms (OR:9.314, CI: 3.684--23.550).

Social factors, such as misconceptions regarding antibiotics, poor knowledge regarding infectious diseases, improper prescribing and use of antibiotics, overprescription of antibiotics at patient demand, nonadherence and self-medication, escalate the development of antibiotic resistance. Therefore, it is of vital importance that public health specialists and health care providers offer instruction to the community regarding the understanding and appropriate use of antibiotics.

Our study had serval limitations such as recall bias which was minimized by adapting a well-formatted, simple and easy-to-understand questionnaire and selection bias which was minimized by using appropriate sampling technique. One of the limitations is the study population is limited to the two major hospitals and not all the populations of the city. Using multicenter for data collection is strength of this study.

It is important for the benefit of society that the general public and individuals can understand the AMR phenomenon and minimize/control activities that result in the spread of antibiotic resistance. Behavioral interventions are of core importance to minimize the phenomenon of antibiotic resistance.

To correct the extensive misconceptions regarding antibiotic use, reliable and multifaceted interventions are needed to promote the appropriate use of antibiotics and deal with problems regarding antibiotic resistance. To effectively control and prevent antibiotic resistance, public health interventions are considered to be one of the most successful strategies that can promote the appropriate use of antibiotics.

Conclusions {#S0005}
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The results of this study demonstrated that the people of Tabuk are not well informed regarding AMR and its contributing factors. Furthermore, the study participants had many misconceptions regarding the use of antibiotics. Thus, this situation requires urgent educational intervention campaigns that can provide assistance to promote an awareness of the appropriate use of antibiotics in both king Salman and King Khalid Hospital in Tabuk. The Ministry of Health in Tabuk city should take strong action and enforce strict policies regarding dispensation of medications without prescription. In addition, physicians in both hospitals must also play a role in providing information to their patients so that they can adopt positive behaviors regarding the cautious use of antibiotics.

The authors are very grateful for the generous support provided by the Department of Academic Affairs, King Salman Armed Forces Hospital North Western Region, Tabuk city, Saudi Arabia. The authors appreciate the dedicated efforts made by Mr. Marwan Manajreh during the data collection and entry processes. The authors would also like to thank Ms. Sunu Krishnan for her administrative assistance support during the study. This study was fully sponsored by the Department of Academic Affairs of the King Salman Armed Forces Hospital North Western Region, Tabuk, KSA.

Informed consent {#S0006}
================

Informed consent was obtained from all the participants included in the study.

Disclosure {#S0007}
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The authors have no conﬂicts of interests to declare in this work.

[^1]: **Abbreviation:** AMR, antimicrobial resistance.

[^2]: **Note:** A *p*-value ≤0.05 was considered significant.
