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What are antibiotics?

Antibiotics, or antimicrobials, are microorganisms (such as metabolites or synthetic analogues of actinomycetes) that are primarily used to hinder the growth of other microorganisms (bacteriostatic action) or to eliminate them (bactericidal action). This encompasses a wide range of antibiotics, including those that target bacteria, fungi, and other less significant pathogens. Nevertheless, in the context of medical treatment, antibiotics commonly pertain specifically to antibacterial medications. Antibiotics are drugs that can inhibit or kill other microorganisms (bacteria/fungi/virus/parasites, etc.) at low concentrations. They have low toxicity, high safety, and can be directly applied to the human body.

Antibiotic biosynthetic pathways.Antibiotic biosynthetic pathways. (Clardy J., et al., 2009)

Types of antibiotics and their functions

Beta-lactam antibiotics are a broad category of antibiotics that have a common chemical structure known as the beta-lactam ring. This structural characteristic is essential for their mode of operation. These antibiotics are highly used and efficient for treating bacterial illnesses. The main mechanism of action of beta-lactam antibiotics is the inhibition of bacterial cell wall production. Their mechanism of action involves binding to particular penicillin-binding proteins (PBPs) situated inside the bacterial cell wall. PBPs are enzymes that facilitate the creation of connections between peptidoglycan molecules, which are vital constituents of the bacterial cell wall. Beta-lactams hinder the activity of these enzymes, hence impeding the bacteria's ability to construct a functional cell wall. Consequently, the bacteria undergo cell lysis and perish, particularly during their attempts to proliferate and divide. β-Lactam antibiotics are a very significant category of antibacterial drugs that have global relevance. The discovery and commercialization of the first β-lactam antibiotic, Penicillin G, represents a significant milestone in the field of contemporary chemotherapy. This category include penicillins, cephalosporins, monobactams, and carbapenems. These antibiotics eradicate germs by disrupting the process of synthesising the bacterial cell wall. They attach to and disable enzymes responsible for the formation of cross-links in the peptidoglycan layer, resulting in the weakening of the cell wall and the destruction of bacteria.

Macrolide antibiotics are a broad category of antibiotics that are often used to treat various bacterial infections, especially those affecting the respiratory system, skin, and soft tissues. Their notable characteristic is their wide-ranging efficiency, including the ability to combat a multitude of gram-positive bacteria as well as some gram-negative bacteria. Macrolides have efficacy against atypical infections and some bacteria that show resistance to other classes of antibiotics. Macrolides generally exert their action by suppressing bacterial protein synthesis. They do this by attaching to the 50S component of the bacterial ribosome. This binding hinders the movement of protein synthesis, namely the addition of amino acids to developing peptide chains. As a result, it effectively stops bacteria from producing necessary proteins required for their development and reproduction. This category consists of erythromycin, azithromycin, and clarithromycin. Macrolides hinder bacterial protein synthesis by attaching to the bacterial 50S ribosomal subunit, impeding ribosome progression along the mRNA.

  • Fluoroquinolones

This category consists of ciprofloxacin, levofloxacin, and moxifloxacin. These substances function by suppressing the activity of DNA gyrase and topoisomerase IV, which are enzymes essential for the process of DNA replication and transcription in bacteria.

The tetracycline antibiotic family is famous for its potency against many different kinds of bacteria. As an example, these antibiotics work well against chlamydiae, mycoplasmas, rickettsiae, and even certain protozoans, in addition to Gram-positive and Gram-negative bacteria. By interacting with the 30S ribosomal subunit, tetracyclines prevent bacteria from producing new proteins. This binding stops aminoacyl-tRNA from attaching to the mRNA-ribosome complex, which stops amino acids from being added to developing peptide chains. So, tetracyclines prevent bacteria from making proteins that are essential for their development and reproduction. This category consists of tetracycline, doxycycline, and minocycline. Tetracyclines hinder protein synthesis by attaching to the 30S ribosomal subunit, which stops the aminoacyl-tRNA from binding to the RNA-ribosome complex.

Aminoglycosides are a class of antibiotics used to treat infections in children, especially those caused by Gram-negative bacteria. They are broad-spectrum and kill all types of bacteria. Among the aminoglycosides are streptomycin, gentamicin, tobramycin, and amikacin. No antibiotic is administered to neonates more often than gentamicin in the United Kingdom. It is necessary to administer aminoglycosides intravenously or intramuscularly since they are polar medicines and have low absorption in the gastrointestinal tract. We eliminate them via the kidneys. Since aminoglycosides' antibacterial activity and clinical effectiveness are best measured by the ratio of their peak concentration to the lowest inhibitory concentration of the pathogen, this pharmacokinetic-pharmacodynamic index is particularly applicable to these antibiotics. To prevent toxicity, it is necessary to monitor the patient's renal function, and therapeutic medication monitoring is often necessary, because of their narrow therapeutic index. This category include gentamicin, streptomycin, and amikacin. They form irreversible bonds with the 30S ribosomal subunit, leading to the incorrect interpretation of mRNA and the prevention of protein synthesis.

  • Sulfa antibiotics

Sulfa antibiotics, sometimes referred to as sulfonamides or sulphonamides, are a collection of man-made antibacterial medicines that include the sulfonamide group. These antibiotics were among the first systemic antibacterial drugs used in medicine and remain crucial for the treatment of many bacterial infections, especially those caused by gram-positive and some gram-negative bacteria. Sulfa antibiotics function by impeding the bacterial biosynthesis of folic acid, a vital vitamin necessary for the creation of nucleic acids and proteins. Sulfonamides specifically act as competitive inhibitors of the enzyme dihydropteroate synthase. This enzyme is responsible for converting para-aminobenzoic acid (PABA) into dihydrofolic acid, which is an initial stage in the manufacture of folic acid. Sulfa medicines inhibit bacterial synthesis of folic acid, a vital process for their growth and reproduction. Sulfonamides encompass sulfamethoxazole, frequently paired with trimethoprim, as seen in the formulation co-trimoxazole. They hinder the production of folic acid in bacteria by disrupting the activity of the enzyme dihydropteroate synthase in the pathway responsible for synthesizing folate.

  • Glycopeptides

Glycopeptides consist of vancomycin and teicoplanin. They hinder the formation of bacterial cell walls by attaching to the D-Ala-D-Ala end of cell wall building blocks, therefore blocking their integration into the cell wall.

  • Oxazolidinones

This category consists of linezolid. They hinder the process of protein synthesis by attaching to the bacterial 50S ribosomal subunit and obstructing the creation of a functioning 70S initiation complex.

  • Doxycycline antibiotic

Doxycycline, an antibiotic belonging to the tetracycline class, has been utilised in clinical settings for over five decades. It is a bacteriostatic medication that is well tolerated and functions by impeding the activity of bacterial ribosomes. It is typically administered once or twice daily at a dosage of 100 mg. It exhibits high tissue penetration and is readily assimilated. The serum half-life is between 18 and 22 hours, and renal or hepatic impairment does not necessitate a dosage adjustment. It demonstrates efficacy against a wide range of organisms, encompassing Gram-positive, Gram-negative, and atypical bacteria. In addition, it appears to possess anti-inflammatory properties that may be clinically applicable.

Cephalosporins are a kind of semi-synthetic beta-lactam antibiotics that are often utilized in both human and veterinary medicine. The World Health Organization has designated quinolones, macrolides, glycopeptides, and some cephalosporins as antimicrobials of utmost importance and top priority for human medicine. The fundamental structure of cephalosporin antibiotics was first obtained in 1945 from the fungus Cephalosporium acremonium. Like other beta-lactam antibiotics, it hinders the formation of cell walls by binding to penicillin binding proteins located inside the microbial membrane. This leads to the rupture and demise of the cells. Cephalosporins are broad-spectrum antibiotics that are less allergic and less vulnerable to beta-lactamases compared to penicillins. They are effective against both gram-negative and gram-positive bacteria, effectively halting the development of microbes.

  • Prophylactic antibiotics

Instead than treating illnesses, prophylactic antibiotics are used to avoid them. They are often given to patients in high-risk circumstances, such as before operations or certain medical procedures, to prevent infection. By halting the development and spread of infections, we hope to lessen the likelihood of surgical complications and the worsening of silent infections. Medicated to ward against infections at the surgical site before, during, and sometimes after the procedure. It is important to consider the kind of operation being performed as well as the common microorganisms that might be encountered when choosing an antibiotic. Orthopedic treatments and other sterile surgeries often employ cefazolin, although abdominal surgery may need a wider range antibiotic.

Reaction mechanism of antibiotics

Different antibiotics have different mechanisms of action on microorganisms. Generally speaking, antibiotics mainly have three mechanisms of action: inhibit the synthesis of cell walls, inhibit the synthesis of proteins, and inhibit the replication of genetic information.

Application of antibiotics

Antibiotics can control more than 95% of diseases caused by bacterial infections. Therefore, antibiotics are extensively used in the prevention and treatment of poultry, livestock, crops and other diseases, and have now become the main drugs for the treatment of infectious diseases. In addition to anti-bacterial infection treatment, antibiotics can also be used for anti-fungal, anti-tumor and immunosuppressive aspects. In addition, antibiotics are also used in food preservation, such as tetracycline used in meat preservation.

When were antibiotics invented?

Penicillin, the first effective antibiotic, was found in 1928 by Alexander Fleming. Penicillin was isolated and identified when Fleming noticed that a fungus called Penicillium notatum suppressed the growth of staphylococci on agar media. Mary Hunt of the Northern Regional Research Laboratory in Illinois identified a different type of fungus strain, Penicillium chrysogenum, from spoiled fruit. This strain produced significantly more penicillin than Fleming's strain, marking another important step in the development of penicillin.

The first real antibiotic, penicillin, entered clinical use in 1940; nevertheless, due to its exclusive activity against Gram-positive bacteria, it proved to be mostly ineffectual against a wide range of infectious disorders. When streptomycin was found in the lab of Selman Waksman at Rutgers University in 1943, it was the next big breakthrough in infectious disease control, but treating Gram-negative bacteria had to wait (see image below).

Antibiotic classes, their clinical introduction, and resistance identification.Antibiotic classes, their clinical introduction, and resistance identification. (Spagnolo F., et al., 2021)

Natural antibiotics

Natural antibiotics are bioactive compounds synthesised by diverse organisms, such as plants, fungi, and bacteria, which possess the capacity to impede the proliferation or exterminate other germs. Antibiotic drug development benefits greatly from natural compounds, particularly those classed as polyketides, non-ribosomal peptides, and aminoglycosides, which are the most clinically valuable scaffolds. Polyketides, which are synthesised by polyketide synthases (PKS), constitute a vast category of chemically varied natural compounds and are very significant secondary metabolites due to their wide-ranging applications in medicine, agriculture, and industry. Pikromycin, a polyketide antibiotic, was initially synthesised from S. venezuelae in 1950, making it the first of its kind. Pikromycin has demonstrated significant efficacy against respiratory pathogens that are resistant to many drugs. Erythromycin A, a notable polyketide antibiotic, with substantial clinical uses. It was initially identified in 1952 as a broad-spectrum antibiotic generated by S. erythraea. This antibiotic is used to treat a diverse range of bacterial illnesses, including respiratory and gastrointestinal infections, whooping cough, syphilis, and acne. It is particularly recommended for people who experience bad responses to penicillin. Although numerous natural antibiotics are ineffective against Gram-negative organisms, tetracyclines can inhibit both Gram-positive and Gram-negative bacteria (see images below).

Structures of natural products with antibiotic activity.Structures of natural products with antibiotic activity. (Pham J V, et al., 2019)

Common antibiotics

Among the antibiotics prescribed, penicillins such as Co-Amoxiclav (15.7%), Amoxicillin (4.2%), and penicillin (17.5%) were the most common. A group of antibiotics known as cephalosporins, which include the oral formulations Cefixime (16.2%), Cephalexin (6.7%), and Ceftriaxone (1.7%). Following this were the macrolides, which included azithromycin (12.8%), erythromycin (1.5%), and clarithromycin (1%). Ciprofloxacin, a quinolone, has seen dramatic growth in its use during the past several years.


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