Antibiotics are a group of chemical compounds that either kill bacteria or inhibit their growth, they are used frequently in medicine to cure infections. They are the most frequent prescribed drugs (1). They are ineffective against viral infections and most other infections. Antibiotics either kill microorganisms or stop them from reproducing, allowing the body's natural defences to eliminate them.
There are four major sites in the bacterial cell that are sufficiently different from the human cell that they serve as the basis for the action of clinically effective drugs: cell wall, ribosomes, nucleic acids, and cell membrane(9).
Classes of antibiotics are:
- Aminoglycosides
- Carbapenems
- Cephalosporins
- Fluoroquinolones
- Glycopeptides and lipoglycopeptides (such as vancomycin)
- Macrolides (such as erythromycin and azithromycin)
- Monobactams (aztreonam)
- Oxazolidinones (such as linezolid and tedizolid)
- Penicillins
- Polypeptides
- Rifamycin
- Sulfonamides
- Streptogramins (such as quinupristin and dalfopristin)
- Tetracyclines(10).
Table 1. Mechanisms of action of important antibiotics:
Mechanism
|
Antibiotic class
|
Inhibition of cell wall synthesis
|
Penicillins, cephalosporins, imipenem, vancomycin, aztreonam
|
Inhibition of protein synthesis
|
Chloramphenicol, erythromycin, clindamycin, tetracycline, aminoglycosides
|
Inhibition of nucleic acid synthesis
|
Sulfonamides, trimethoprim, quinolones
|
Alteration of cell membrane synthesis
|
Polymyxin, daptomycin
|
this table summarizes the action of the most common antibiotics(9).
Antibiotics are classified according to its’ spectrum into:
- Narrow-spectrum antibiotics: are active against one or very few types (e.g., vancomycin is primarily used against certain gram-positive cocci, namely, staphylococci and enterococci).
- Broad-spectrum antibiotics: are active against several types of microorganisms (e.g., tetracyclines are active against many gram-negative rods, chlamydiae, mycoplasmas, and rickettsiae).
- Extended-spectrum antibiotics : are chemically modified to include additional types of bacteria (usually gram-negative bacteria) (11).
They are available in different preparations:
- Injectable intravenous.
- Injectable intramuscular.
- Injectable subcutaneous.
- Oral.
- Eye drops.
- Ointment.
- Creams.
Bactericidal and bacteriostatic activity:
Bactericidal antibiotics kills bacteria, whereas bacteriostatic antibiotics inhibit their growth, in some clinical situations (immediate life-threatening infections) it is essential to use bactericidal rather than bacteriostatic drugs.
Dis-advantages of bacteriostatic antibiotics:
- Bacteria can grow again when antibiotic is withdrawn.
- Host immune responses are needed in the elimination of bacteria(9).
Antibiotic resistance happens when bacteria develop the ability to resist the effects of antibiotics which means it continues to grow and multiply(12).
Infections caused by multi-drug resistant bacteria are hard, and sometimes impossible, to treat. In most cases it requires extended hospital stays, extensive monitoring and toxic alternatives with a wide range of unpleasant side effects(12).
Antibiotic
|
Resistant strains
|
Penicillin
|
Penicillin-resistant Staphylococcus aureus
Penicillin-resistant Streptococcus pneumoniae
Penicillinase-producing Neisseria gonorrhoeae
|
Vancomycin
|
Plasmid-mediated vancomycin-resistant Enterococcus faecium
Vancomycin-resistant Staphylococcus aureus
|
Amphotericin B
|
Amphotericin B-resistant Candida Auris
|
Methicillin
|
Methicillin-resistant Staphylococcus aureus
|
Extended-spectrum cephalosporins
|
Extended-spectrum- beta lactamase producing Escherichia coli
|
Azithromycin
|
Azithromycin-resistant Neisseria gonorrhoeae
|
Table2: example of commonly used antibiotics and strains resistant to it(12).
Mechanisms of antibiotic resistance:
- Modifications of the antibiotic molecule (produce enzymes that inactivate the drug by adding specific chemical moieties to the compound or that destroy the molecule itself).
- Decreased Antibiotic Penetration and Efflux, decreasing permeability of the cell membrane to the drug or production of complex pumps to efflux the antibiotic compound out of the cell, both ways prevent the antibiotic molecule from reaching its target inside the cell membrane.
- Changes in the target sites, either by target protection (e.g. proteins that dislodge the bacteria from its binding site) or modifications to the target site.
Modifications occur by mutation of the target site thus blocking antibiotic effect, enzymatic cleavage of the target site or complete replacement or bypass of the target site which means synthesizing new targets accomplishing the first ones’ functions but are not inhibited by the antibiotic molecule or simply getting rid of the target and compensate to live without its functions.
- Resistance due to global cell adaptations.
Resistance to one antibiotic class can be achieved by different mechanisms and one bacterial cell can be able to use multiple mechanisms of resistance to survive the effects of antibiotics. As an example, fluoroquinolone resistance can occur by three biochemical routes, all of which may coexist in the same bacteria at a given time (producing an additive effect and, often, increasing the levels of resistance):
1. mutations in genes encoding the target site of fluoroquinolones (DNA gyrase and topoisomerase IV). 2. overexpression of efflux pumps that extrude the drug from the cell.
3. protection of the fluoroquinolone target site by a protein(13).
Genetic basis of resistance:
- Chromosomal mediated resistance, due to a mutation in the gene that either the target of the drug or the transport system.
- Plasmid mediated resistance, extrachromosomal DNA that carries genes that encode enzymes able to degrade antibiotic molecules, plasmids frequently mediate resistance to multiple drugs and have high rate of transference.
- Transposon mediated resistance, genes that transport either within or between large pieces of DNA such as chromosomes and plasmids. Composed of three gene flanks:1. Transposase, which transport of the transposon,2. Repressor which regulate synthesis of transposase,3. The drug resistance gene(9).
Transfer of DNA between bacteria contribute largely to the spreading of antibiotic resistance.
Mechanisms of DNA transfer between bacteria:
- Transformation, direct absorption, incorporation and expression of exogenous DNA between closely related bacteria, and it is mediated chromosomally be encoded proteins(14).
- Transduction, DNA transfer is mediated by independently replicating bacteriophages, bacterial viruses that can package segments of host DNA in their capsid, and inject it into a new host when an environmental stimulus triggers cell lysis. When this happens, the new injected genetic material in the cell infected by the virus can be recombined with the chromosomal DNA, generating either a lytic or lysogenic cycle(15).
- Conjugation, transfer of genetic materials between two bacteria using plasmids(16).
Overuse and misuse of antibiotics can lead to selection of resistance strains and emergence of new multi drug resistance bacteria(9).
Antibiotic sensitivity testing:
Measure the sensitivity of the bacteria to each antibiotic. Its results are the most important factor to determine the choice of antibiotic or combination of antibiotics to treat the patient. It has two types of tests:
- The tube dilution test, which is used to determine the minimal inhibitory concentration.
- The disk diffusion (Kirby Bauer) test which defines the diameter of the zone of inhibition(9).
Antibiotic sensitivity tests are done frequently to define resistance pattern in different areas and to formulate guidelines of antibiotic prescription.
Previous studies:
- Knowledge, attitudes and practices relating to antibiotic use among community members of the Rupandehi District in Nepal, Anant Nepal1, Delia Hendrie, Suzanne Robinson and Linda A. Selvey.
A quantitative survey was conducted with 220 community members of the Rupandehi district of Nepal, with cluster sampling techniques applied to select households. Interviews were carried out face-to-face using a structured questionnaire. Responses were presented using descriptive analysis, with chi-squared tests and regression analysis applied to identify factors associated with KAP about antibiotic use and the Spearman’s rank order correlation coefficient calculated to examine the relationship between responses to the KAP questions.
The sample comprised more females (54%) than males, the average age of respondents was 38.5 years and almost 60% of respondents lived in rural areas. Respondents had relatively good knowledge about aspects of antibiotic use other than identifying antibiotics. The concept of antibiotic resistance was well known but imperfectly understood. Half of respondents (50.9%) were unsure whether skipping doses would contribute to the development of antibiotic resistance, 88.2% indicated they would go to another doctor if not prescribed an antibiotic when they thought one was needed and nearly half (47.7%) believed antibiotics helped them get better more quickly if they had a fever. Most respondents reported correct practices accessing and using antibiotics, however, 84.6% at least sometimes preferred an antibiotic when they have a cough and sore throat. Logistic regression showed respondents with higher levels of education tended to have better knowledge, more appropriate attitudes and better practices about antibiotic use. Rural respondents were less likely to have better knowledge about antibiotic use, while females were more likely to report better practices.
- Knowledge, Attitude and Practice towards Antibiotic Use among the Public in Kuwait Abdelmoneim Ismail Awad, Esraa Abdulwahid Aboud.
A cross-sectional survey was performed using a pretested self-administered questionnaire on a sample of 770 randomly selected Kuwaiti individuals. Descriptive and multivariate logistic regression analysis were used in data analysis.
The response rate was 88.3%. Nearly three-quarters (72.8%) of respondents had been prescribed antibiotics within 12 months prior to the study period, and 36% of them had not finished the course of treatment. Over one-quarter (27.5%) were self-medicated with antibiotics to treat mainly common cold, sore throat and cough. Self-medication was more prevalent among those who were prescribed antibiotics and those who had attitudes towards using and accessing antibiotic inappropriately. Almost 47% of participants had low knowledge regarding action, use, safety and resistance of antibiotics. Forty one percent of respondents had attitudes towards using and accessing antibiotic inappropriately. Better knowledge was found to be a predictor for positive attitude. Respondents level of agreement that doctors often prescribe antibiotics to meet the patient’s expectation, and that doctors often take time to consider carefully the need for an antibiotic were 52.7% and 35.3%, respectively.
- Community knowledge and practices regarding antibiotic use in rural Mozambique: where is the starting point for prevention of antibiotic resistance? Olga Cambaco, Yara Alonso Menendez, John Kinsman.
The study was conducted in Manhiça, a semi-rural district of Southern Mozambique. Sixteen in-depth interviews and four focus group discussions (FGDs) were conducted with community members to explore lay knowledge and practices regarding antibiotics and awareness of antibiotic resistance. The qualitative data was analyzed using a combination of content and thematic analysis. The SRQR guidelines for reporting qualitative studies was performed.
Although participants did not hold any consistent knowledge of antibiotics, their visual recognition of amoxicillin (distinct red yellow capsule) was acceptable, but less so for different types and brands of antibiotics. The majority of participants were aware of the term ‘antibiotic’, yet the definition they gave was rarely backed by biomedical knowledge. Participants associated antibiotics with certain colors, shapes and health conditions.
Participants reported common habits that may contribute to resistance: not buying the full course, self-medication, sharing medicines and interruption of treatment. Most had never heard of the term ‘antibiotic resistance’ but were familiar with the phenomenon. They often understood the term ‘resistance’ as treatment failure and likened ‘resistance’ to non-compliance, ineffective medication, disease resistance or to an inability of the physical body to respond to it.
There is a broad understanding of the importance of medication compliance but not specifically of antibiotic resistance. In addition, there is a recognized gap between knowledge of responsible drug compliance and actual behavior.