Review of Related Literature

This part deals with the review of related literature conducted by both local and foreign

researchers closely related to the study. This encompasses some background information derived

from finished thesis, study, newspaper, articles, internet source, and other reading materials

about the materials used, which helps the researchers to support the study.

Conceptual Literature

Foreign

The discovery of antibiotics may be one of the greatest achievements in medicine.

According to WHO, 2020, antibiotics are medicines used to prevent and treat bacterial

infections. Antibiotic resistance occurs when bacteria change in response to the use of these

medicines. Bacteria, not humans or animals, become antibiotic-resistant. Antibiotic treatments

have improved clinical outcomes from infections, leading to the reduction of morbidity and

mortality in surgical, transplant, cancer, and critical care patients. Antibiotics can be bought for

human or animal use without a prescription, the emergence and spread of resistance is made

worse. Similarly, in countries without standard treatment guidelines, antibiotics are often over-

prescribed by health workers and veterinarians and over-used by the public. Antibiotic use has

been increasing globally - over the period 2000-2010 overall use is estimated to have increased

by 35%. This increase has been greater in low and middle-income countries. India, China and the

US used the most antibiotics over all. Five countries (Brazil, Russia. India, China and South

Africa) accounted for 76% of the increase in global consumption. This increase has been driven

by factors such as economic growth and increased access to antibiotics. High income countries
use more antibiotics on a per capita basis. In developed countries, the majority of the use of

antibiotics in the community is for respiratory infections (accounting for 90% of antibiotic sales

in Swedish children), urinary tract infections and soft tissue infections (Duguid et al., 2018)

As the consumption or usage of antibiotic continue to rise and people who lack knowledge

about antibiotics continue to consume even without proper prescription, condition results known

as antibiotic resistance which is a massive public health challenge currently. It refers specifically

to the resistance to antibiotics that occurs in common bacteria that cause infections.

Antimicrobial resistance is a broader term, encompassing resistance to drugs to treat infections

caused by other microbes as well, such as parasites (e.g. malaria), viruses (e.g. HIV) and fungi

(e.g. Candida). Antimicrobial resistance is resistance of a microorganism to an antimicrobial

drug that was originally effective for treatment of infections caused by it. Resistant

microorganisms (including bacteria, fungi, viruses and parasites) are able to withstand attack by

antimicrobial drugs, such as antibacterial drugs (e.g. antibiotics), antifungals, antivirals, and

antimalarials, so that standard treatments become ineffective and infections persist, increasing

the risk of spread to others (Nathwani et al., 2018). According to the Centers for Disease Control

and Prevention (CDC) in the United States, at least two million people get an antibiotic‐resistant

infection that causes at least 23000 deaths annually. When bacteria develop mechanisms to

survive and grow in the presence of the drugs that were designed to kill them, they are

considered resistant. If antibiotics and antifungals lose their effectiveness, then we lose the

ability to treat infections and control these public health threats. This leads to a high morbidity

and mortality, as well as a prolongation of hospitalization, which ultimately increases the

financial costs dispended for each patient (CDC, 2021).

 Antibiotic resistance is the result of improper consumption of antibiotics and the main cause

was and continues to be a lack of public knowledge about antibiotics, resulting in their overuse

despite recent stricter controls on their prescription and purchase worldwide. Unquestionably,

self-medication affects the quality of an effective therapy; the correct diagnosis by a medical

specialist often would avoid the use of last-line antimicrobials. Human use (and misuse) of

antibiotics has noticeably placed an unnatural selective pressure on bacteria, which has favored

their accelerated evolutionary process (Kon & Rai, 2016).

To directly counter the antibiotic resistance and address the urgent need for new antibiotics,

more rational approaches to modification and development of drug are clearly desired. It is a

long history of utilizing chemical modification approach to improve drug activity, inhibit the

growth of drug‐resistant bacteria, and treat infectious diseases. Without urgent action, we are

heading for a post-antibiotic era, in which common infections and minor injuries can once again

kill. The world urgently needs to change the way it prescribes and uses antibiotics. Even if new

medicines are developed, without behaviour change, antibiotic resistance will remain a major

threat. Behaviour changes must also include actions to reduce the spread of infections through

vaccination, hand washing, practising safer sex, and good food hygiene (WHO, 2020). Newer

antibiotics may not offer a solution on their own as they are likely to be expensive and

unaffordable in the developing world. More importantly, the newer drugs will also eventually

lose their potency. Educating public in correct use of antimicrobials could go a long way towards

curbing resistance (Brink et al., 2018).

Research Literature

Foreign

Inappropriate use of antimicrobial agents and the consequences of spread of

antimicrobial resistance is an increasing public health problem. In recent years, resistance to

antimicrobial agents that were previously effective has emerged or re-emerged in many regions

causing a global health threat and economic consequences. Among many other factors, behaviors

of community members and their limited knowledge associated with inappropriate antibiotics

use is contributing to antibiotic resistance. The increase in antibiotic resistance rates is mainly

attributed to inadequate prescriptions of antibiotics and their excessive use in the community,

mainly in primary care (Voidăzan et al., 2019). Antibiotic misuse not only leads to antibiotic

resistance but also treatment failure, increased hospitalization time, and economical burden.

Inappropriate use of antibiotics is driven by practices such as self-medication, poor compliance,

over-the-counter purchase, poor knowledge regarding the correct use of antibiotics, and

approaching informal sources for healthcare instead of a doctor (Bhardwaj et al., 2021).

The only sociodemographic factor found to be associated with each of knowledge, attitudes

and practices relating to antibiotics use was education. Respondents with higher education had

better knowledge and more appropriate attitudes and practices, a finding consistent with other

studies. The findings also suggest respondents in urban areas had better knowledge on antibiotic

use than those in rural areas. Area of residence was significantly associated with better

knowledge on antibiotics use, with rural respondents being less likely to have better knowledge

compared to urban residents. Other factors include patient perceptions of the patient–physician
interaction, including self-medication, knowledge regarding antibiotics, and the lack of adequate

policies for the restriction and control of prescribed antibiotic.

Educating the public on the roles of antibiotics and the ability to differentiate antibiotics

from other drugs could help to minimize antibiotic misuse. The concept of antibiotic resistance is

known but problems associated with antibiotic misuse were found to be imperfectly understood.

The findings of the study also indicated that the community has high expectations with regard to

being prescribed antibiotics, which increases the likelihood of non-prescription use of antibiotics.

Village doctors or health workers could provide education to community members, and mass

education campaigns conducted to emphasize the potential risks of resistance by using

nonprescription antibiotics and the inappropriateness of using antibiotic therapy for minor

ailments. Education of community members alone will not be enough to minimize any misuse of

antibiotics. A multifaceted approach involving policy makers, prescribers, and the general public

using both educational and regulatory measures is needed. Such measures should be embedded

in a general policy to change the culture of antibiotic use by improving awareness among the

general public and professionals about the risks associated with antibiotic use as well as reducing

public misconceptions about the benefit of taking antibiotics for minor illnesses.

The rationale for educating the public is that knowledge about antibiotic treatment and

awareness of antibiotic resistance are thought to influence patient and parent demand for

antibiotic prescribing. Because of wide cross-national differences in antibiotic use tailoring of

educational interventions requires determination of the needs of the audience in each country.
 The general public and patients should inform themselves and, if necessary, require health-

care providers to offer them information on the appropriate use of antimicrobials, antimicrobial

resistance and adverse reactions to antibiotics; use antimicrobials only if the medication was

been prescribed for them; not use antimicrobials that have not been prescribed for them (such as

left over antimicrobials, those prescribed for another person, or those obtained

without a prescription); return unused antibiotics to the pharmacies and local collection centres,

in accordance with local regulations for disposal (Voidăzan et al., 2019).

Alhomoud et al. (2017) reported that relatives, friends, and previous successful experience

with the same antibiotic are the major sources of information regarding antibiotics. Almost half

of the households in this study kept antibiotics and used leftovers. This malpractice of using

leftovers, can be attributed to patient’s unawareness of the indications for use, side effects, and

contraindications, which puts them at risk of using drugs inappropriately (Alhomoud et al., 2017;

Khalifeh, Moore and Salameh, 2017).

The study of Nepal et al., 2019 is an important step towards a better understanding of the

knowledge, attitudes and practices regarding antibiotic issues in the adult population in the

Rupandehi district of Nepal. The study also identified a relationship between respondents having

less knowledge, less appropriate attitudes and poor practices regarding the appropriate use of

antibiotics. Groups, such as those with lower formal education, who had less knowledge and less

appropriate attitudes and practices to antibiotic use and who could be targeted in education

campaigns. A positive finding was females having better practices in regard to antibiotic use. In

most developing countries, including Nepal, females hold the responsibility of taking care of
their children and other family members, thus their better practices should contribute to some

extent to the control of antimicrobial resistance.

In the analysis of the study of Voidăzan et al., 2019 results showed that among the basic

characteristics of the study population, the level of education, age, residence area and work

activity proved to be important indicators for the outcomes of interest. The lack of knowledge

regarding antibiotics among those with lower education has already been described. Respondents

with a low level of education (only primary school) have no comprehension of bacterial

resistance, whereas those with university studies showed knowledge regarding this phenomenon.

Levels of education also seem to play an important role in respondents classifying antimicrobial

resistance as a major issue. These findings indicate that it is necessary to strengthen the

knowledge regarding antibiotics and bacterial resistance among those with lower levels of

education, which could be accomplished through employing information campaigns, involving

the family doctor and even the occupational physician, as two pillars of the preventive health

systems in most of the countries.

Another finding in the study of Bhardwaj et al., 2021, is that more than half of the

respondents rightly identified bacteria becoming resistant to antibiotics while almost half of the

respondents were under the misconception that humans become resistant to antibiotics. These

results reflect that the general public does not have enough knowledge about the term antibiotic

resistance. The study also showed that females, respondents with high-school and intermediate

level education, and semi-professionals or those with clerical jobs were mostly ignorant about

bacteria become resistant to antibiotics.

 This study reflects the real situation of a southern community where people have several

misconceptions and misuses for antibiotics. More than half of the respondents think that

antibiotics treat viral infections, which justifies why almost 50% would take it to treat common

cold. These results highlight the mere fact that people still think that antibiotics are equivalent to

painkillers and antipyretics, which can be discontinued when symptoms improve. On another

front, pharmacists realize the harmfulness of selling antibiotics without a prescription and are

aware of the fines (Bin Nafisah et al., 2017). However, they continue to comply to patient’s

requests and sell antibiotics with no medical prescription to keep regular customers satisfied and

compete with other pharmacies (Bin Nafisah et al., 2017). Reinforcement and compliance to the

law concerning antibiotics dispensing is therefore crucial. For that, decision makers shall

improve practice concerning this topic (Hijazi et al., 2021).

The study of SA. Kristina et al., 2020, highlight that almost 70 % of participants reported

trusting internet as main information source regarding antibiotics use. In terms of practice, the

role of pharmacists as the source of information was mentioned by 58% respondents in this

study. Since more respondents in the study stated that they obtained information on antibiotic

usage from pharmacy personnel rather than from the other health professionals, pharmacists

seem to have a critical role to play in enhancing public understanding about appropriate

antibiotic treatment. Empowering the pharmacists’ role in raising public awareness through

digital media would increase the spread of information on antibiotic usage. The analysis on

factors associated with knowledge of antibiotics show that elderly individuals, male, lower level

of education than bachelor, relying on the internet as the source of information about antibiotic

usage had limited knowledge of antibiotic use. These categories should be the main targets for
future educational interventions. Since professional pharmacists play an important role in

educating the public about antibiotics, they must be involved as role models to improve

misperception and increase awareness both in the public and in clinical setting.

Local

Antimicrobial resistance is widespread in the Philippines as well and has emerged as a

public health concern. Self-medication is defined as the use of medicinal products by an

individual to treat self-diagnosed symptoms, or as the unsuitable administration of prescribed

medicinal products, including intermittent or prolonged use of antibiotics and sharing of

medication. Self-medication with antibiotics is particularly problematic, as it has been cited as a

major contributor to antibiotic resistance. Furthermore, self medication with antibiotics can

quadruple the odds of developing a drug resistant infection. Recent meta-analyses have estimated

that 38% of the world’s population engages in self-medication with antibiotics. According to the

World Health Organization (WHO), self-medication varies by location, with the highest

prevalence in Southeast Asia and the Western Pacific Region—from 58-64%. In these same

regions, the prevalence of resistance to many common antibiotics is on the rise. Southeast Asian

region more broadly has suggested that self-medication may be associated with cultural

misconceptions, premature termination of antibiotic courses, insufficient regulations and

enforcement of pharmaceutical law, and antibiotic knowledge and/or attitudes. Globally,

education, age, sex, household size, severity of illness, former medical use, and poverty have

been associated with antibiotic self-medication.

Of the 27 member states in the Western Pacific Region participating in the WHO’s 2015

evaluation of global antibiotic resistance, only one country, the Philippines, did not participate.
Thus, a critical gap exists in the present understanding of antibiotic misuse in the Philippines;

this gap is especially concerning as the Philippines has a documented history of prevalent

antibiotic misuse. Compared to other countries, the Philippines has had the smallest percentage

of prescriptions filled by doctors, with nonmedical sources being the most common source of

antibiotics. Furthermore, the Philippines has been reported to have one of the highest rates of

antibiotic sharing.

The study of Alexander, 2016 stated that a recent review by Radyowijati et al. (2003)

highlighted the deficit in antibiotic diversion research; it revealed that the majority of studies on

self-medication with antibiotics have examined antibiotic prescribing and the purchasing of

antibiotics without a prescription rather than informal antibiotic dispensing within a community.

Antibiotic self-medication literature has established that antibiotics are commonly available from

nonmedical sources in low income countries, including countries in Southeast Asia. Data from

the sari-sari stores revealed that antibiotics were readily available without prescription.n

Furthermore, a full course of antibiotics was rarely available for purchase. The descriptive,

observational data regarding antibiotic characteristics and availability in sari-sari stands

provide insight into the epidemiology of antibiotic misuse and adverse health consequences, such

as the development of an antibiotic-resistant infection. For example, beta-lactam antibiotics (i.e.,

amoxicillin, cephalexin, and penicillin) were the most common types of antibiotics found for

purchase in the sari-sari stores. Given the high prevalence of reported antibiotic self-medication

and diversion present in the Philippines. Additionally, data from sari-sari stores indicate that

antibiotics diverted throughout this community may present significant health concerns, as the

antibiotics were sold in ineffective dose sizes, often expired, or occasionally improperly stored.
 The Philippine Food and Drug Administration strictly prohibits the selling or dispensing of

antibiotics without a prescription from a licensed physician. However, patients can still purchase

antibiotics without a prescription in the Philippine. Patients perceive that they can easily buy

antibiotics even without a doctor's prescriptio. This high rate of antibiotic self-medication can be

attributed to Filipino’s limited understanding of proper antibiotic use. For instance, Filipino

mothers usually give antibiotics to their children with coughs even without a doctor’s

prescription. Patients also reuse their previous medical prescriptions to get antibiotics from

pharmacies. The lack of access to physicians and the high cost of medical consultation also

contribute to the rampant self-medication of antibiotics

The study of Crusis et al., 2019 implies that most of the people were unmindful of what

antimicrobials are used for. In addition, people considered antimicrobials as their first choice of

treatment. This shows that the respondent’s first line of treatment in terms curing diseases is the

use of antimicrobials and they use it even for pain. The role of the pharmacists plays very

important in the education the patients on drug use. A study in Jordan highlights the educational

intervention an effective tool in order to improve the knowledge of the people with regards to the

proper use of drugs. This include prevention of unnecessary use of antimicrobials. Pharmacists

as one of the healthcare providers are the one responsible in providing drug information in order

to improve the knowledge of people on antibiotics use and AMR. Pharmacists plays a key role

being more accessible educators than other healthcare professionals (Shehadeh et al., 2016).

Hence, physicians should be prudent in prescribing antibiotics to their patients. Health workers

should educate their patients to increase their knowledge of proper antibiotic use. Pharmacists

should also practice appropriate dispensing of antibiotics (Ornos et al., 2022).

 Results of the study of Crusis et al., 2019 have shown that people tend to practice using

antimicrobials as a treatment for skin wounds and injuries by wrong manner of administration. It

has been a norm before that the active ingredients inside the capsule were mistaken to be used as

a dusting powders for skin wounds which is considered as an antimicrobial misuse. Irrational use

of antimicrobials is one of the significant causes of AMR which is validated by the study of

Jones et al. (2005).

The study of Collantes & Germo in 2018, included educational attainment as a factor that

affects the knowledge on antibiotics among the residents of Sitio Nasipit in Cebu, Philippines

since most of the respondents attained a high school degree and some were even college

graduates. Residents have the basic knowledge and understanding about antibiotics. Moreover,

based on the results, the researchers found out that the respondents have high level of trust

towards their doctors. Proper counseling can be taken advantage of to impart knowledge to the

patient about rational antibiotic use and compliance since patients listen well to what their

healthcare provider says.

Antimicrobial resistance requires solutions tailored to its specific drivers and necessitates an

intersectoral approach. Government legislation is crucial to regulate antibiotic prescription and

dispensation and ensure accessibility and affordability of antimicrobials. Partnerships

between academic and private sectors are needed to understand local antimicrobial resistance

patterns and design culturally appropriate solutions. Public education on antimicrobial resistance
must involve health-care providers, public health experts, and community leaders, especially

from rural regions, to tackle the challenges of conveying medical information in lay language.

Finally, the creation of global health networks to share best practices in addressing antimicrobial

resistance in low-income and middle income countries (LMICs) like the Philippines will help

advance the global goal of eradication (Robredo et al., 2022).