Medicinal folklore was the primary treatment procedure for infections before the early 20th century. Over 2,000 years ago, a mixture of different antimicrobial properties was used to treat infections. 

The ancient Egyptians and ancient Greeks, and other ancient cultures used selected mold and plant materials for the treatment of infections. After the discovery of synthetic antibiotics, a new era in modern medicine begins.

The journey of antibacterials began in the late 1880s, with Paul Ehrlich. He discovered the first synthetic antibacterial organoarsenic compound salvarsan, now known as arsphenamine.

Antibiotics overview

• Antibiotics can inhibit the growth and replication of a bacterium or kill it outright.
• Antibiotics only used to target bacteria or bacterial infection. For fungal and viral infection the antifungals and antivirals drugs are used.
• Now, antibiotics are produced in industries on a large scale by the fermentation process. After the production of antibiotics in large tanks, they are extracted and purified through multiple physical processes and are converted into crystal form.
• Antibiotics are the Secondary Metabolites of microbes. The main production of the secondary metabolite occurs during the stationary phase of cell growth (idiophase).
• The antibiotic era began in 1929 with the penicillin discovery by Fleming.
• When an antibiotic functions to inhibit growth, it is called ‘antibiosis’.
• Antibiotics act against bacteria either by inhibiting their growth or killing them.

Antibiotics definition

Antibiotic is a Greek word, means against life, where anti means Against and biotic means life. 1942, Waksman first proposed the definition of antibiotics, according to him;

Antibiotics are chemical substances produced by various species of microorganisms that are capable, in low concentrations, of inhibiting the growth of or killing other microorganisms.

The modern definition of antibiotics are;

The substance produced by a microorganism or a similar product produced wholly (synthetic) or partially (semi-synthetic) by chemical synthesis and in low concentrations inhibits the growth of or kills microorganisms.

Some examples of antibiotics are Penicillin, phenoxymethylpenicillin, flucloxacillin, amoxicillin, Cephalosporins, Tetracyclines, etc.

Characteristics of an Ideal antimicrobial drug

An ideal antimicrobial therapeutic drug exhibits all of the following characteristics;

• The drug should be toxic or lethal to the microbes but nontoxic to host cells.
• It should not develop antimicrobial resistance.
• It should be microbicidal rather than microbistatic.
• It should be soluble- functions even when highly diluted in body fluids.
• The drug should be potent long enough to react, not broken down/excreted too early.
• It must assist the activities of the host’s defense.
• The drug will remain active in the host’s tissues/ body fluids.
• It doesn’t cause/result in allergies in the host body.
• It should be available for everyone at a reasonable price.
• It is readily delivered to the site of infection.

Source of Antibiotics 

• Bacteria, fungi, algae, corals, sponges, plants, and lower animals are among the common microorganisms that biosynthesize antibiotic compounds, but most secondary metabolites are actually biosynthesized by filamentous microorganisms like actinomycetes (about 75%) and molds (17%).
• The Streptomyces species alone produces about 180 different types of secondary metabolites.
• About 10,000 archived antibiotics are produced by Streptomycetes. All of them show a wide range of biological activities; e.g. antibacterial (streptomycin, tetracycline, chloramphenicol), antifungal (nystatin), antiviral (tunicamycin), antiparasitic (avermeetin), immunosuppressive (rapamycin), antitumor (actinomycin, mitomycin C, anthracyclines), enzyme inhibitor (clavulanic acid), and diabetogenic (bafilomycin, streptozotocin).
• Antibiotics are also produced by the different Bacillus strains, moenomycins, difficidims, bacillomycins and bacillaenes.

Classification of Antibiotic

Classification of antibiotics based on source

The antibiotic is divided into three categories based on their source such as;

1. Natural Antibiotics
2. Semi-synthetic Antibiotics
3. Synthetic Antibiotics

1. Natural Antibiotics

• These are also known as homeopathic remedies, which are produced by natural agents such as fungi.
• These are 100% natural without any artificial additives, some examples are honey and Echinacea.
• There are no devastating side effects of Natural Antibiotics.

Example of Natural Antibiotics

• An equal portion of honey and cinnamon can treat skin infections, insect bites, and eczema. 
• To treat viral, bacterial, parasites, and fungi infections, the olive leaf is a good choice as well.
• Moreover, its extract can treat colds, herpes, flu, sinusitis, and allergies.
• Wild indigo has also been used to treat bronchitis, sore throat, mouth sores, tonsillitis, and swollen glands.

2. Semi-synthetic Antibiotics

• These are chemically modified variants of natural antibiotics. These antibiotics are modified to increase their efficacy, to lower or nullify the side effects, or to change the microbe range that is sensitive to them.
• An example of Semi-synthetic Antibiotics is ampicillin.

3.  Synthetic Antibiotics

• Synthetic Antibiotics are designed and produced within the laboratories.
• Some examples of Synthetic Antibiotics are Linezolid and sulfonamides.
• Teh Synthetic Antibiotics are acted by inhibiting the protein synthesis process before its initiation, which is a crucial replication element that controls bacteria survival.

Classification of antibiotic based on bacterial spectrum

Based on the bacterial spectrum the antibiotics  are classified into two categories;

1. Broad Spectrum antibiotics 

• These types of antibiotics are act on the two different bacterial groups such as Gram-positive and Gram-negative or in a simple word when an antibiotic acts against a wide range of disease-causing bacteria are known as Broad-spectrum antibiotics.
• Some examples of broad-spectrum antibiotics are Doxycycline, Minocycline, Aminoglycosides (except for streptomycin), Ampicillin, Amoxicillin/clavulanic acid (Augmentin), Azithromycin, etc.

2. Narrow spectrum antibiotics 

• Narrow spectrum antibiotics definition: This type of antibiotic only acts on or only able to kill or inhibit limited species of bacteria.
• Some examples of Narrow spectrum antibiotics are vancomycin, fidaxomicin and sarecycline.
• Narrow spectrum antibiotics only kill or inhibit those bacterial species which are unwanted as a result it leaves most of the beneficial bacteria unaffected.
• There is a low propensity for bacterial resistance development against Narrow spectrum antibiotics.
• This type of antibiotic is only used when the disease-causing bacterial species are known.

Classification of antibiotic based on the administration route

Based on the administration route the antibiotics are classified into two groups such as;

• Injectable antibiotics: These types of antibiotics are injected intravenously. Penicillin G injection is an example of an injectable antibiotic.
• Oral or topical antibiotics: These types of antibiotics are taken by oral route. Some examples of topical antibiotics are bacitracin, neomycin, mupirocin, and polymyxin B.

Classification of antibiotic based on function

Based on function the antibiotics are classified into two classes such as;

• Bactericidal: These types of antibiotics act by inhibiting cell wall synthesis of bacterial cells. Some examples of Bactericidal are; beta-lactam antibiotics (penicillin derivatives (penams), cephalosporins (cephems), monobactams, and carbapenems),vancomycin, daptomycin, fluoroquinolones, metronidazole, nitrofurantoin, co-trimoxazole, telithromycin.
• Bacteriostatic: These types of antibiotics act by limiting the growth of bacteria by interfering with bacterial protein production, DNA replication, or other aspects of bacterial cellular metabolism. Some examples of Bacteriostatic antibiotics are tetracyclines, sulfonamides, spectinomycin, trimethoprim, chloramphenicol, macrolides and lincosamides.

Classification of antibiotic based on the mode of action

Based on mode of action antibiotics are classified into different classes;

1. Inhibit bacterial cell wall synthesis 
2. Alter the function and permeability of the cell membrane 
3. Inhibit protein synthesis (translation and transcription) 
4. Inhibit nucleic acid synthesis

Classification of antibiotic based on chemical structure

Based on the chemical structure the antibiotics are classified into the following categories;

Antibiotics	Chemical structure
Penicillins&Cephalosporins	β-lactam ring
Aminoglycosides (e.g Streptomycin, neomycin, amikacin)	Amino sugars in a glycosidie linkage
Macrolides (e.g.erythromycinand oleandomycin)	Macrooycliclocation
Chloramphenicol	Nitrobenzene,Derivative of dichlor acetic acid
Tetracyclines	Polycyclicnaphthone carboxide
Peptide antibiotics	Peptide linked D and L amino acids
Antifungalantibiotics	Polyens & nonpolyenes
Ansamacrolides (e.g.Streptovaricinsand rifamycins)	Naphto and benzoquinone nuclei derivatives
Anthracyclincantibiotics (e.g.adriamycin&duanomycin)	Anthracycline
Unclassified	Cycloserine, novobiocin and fusidic acid

Antibiotics and their mode of action

Antibiotic follows different mechanisms to inhibit the bacterial cell such as interfere with cell wall peptidoglycan biosynthesis, cell membrane integrity,and protein synthesis and inhibit DNA replication and repair, transcription, and intermediate metabolism (Inhibitors of Protein Synthesis).

The different Modes of Action of Antibiotics are discussed in below;

• The antibiotics inhibit the cell wall biosynthesis by inhibiting the enzymes which are responsible for the synthesis of different cell wall components.
• Antibiotics can disorganize the structure or inhibit the function of bacterial membranes.
• During the synthesis of protein, antibiotics can reduce the ribosomal subunits binding upon 50S to prevent the translation and further binding upon 30S. This binding is unfavorable as it may lead to false translation that produces toxic and mutated proteins. For DNA replication, there are antibiotics that affect DNA replication and repair inhibit enzymes like gyrase, topoisomerase, and N-methyltransferase
• Sometimes antibiotics also inhibit the bacterial RNA polymerase subunits by resisting the entry of the first nucleotide essential for polymerase activation.

Routes of Drug Administration

Drugs are introduced into the body by several routes such as. 

• They can be taken by mouth (orally).
• Given by injection into a vein(intravenously)
• Through the muscle (intramuscularly)
• Through the space around the spinal cord (intrathecally)
• Beneath the skin (subcutaneously)
• Placed under the tongue(sublingually)
• Through the rectum (rectally) or vagina(vaginally) 
• Instilled in the eye (by the ocular route); 
• Sprayed into the nose and absorbed through the nasal membranes(nasally)
• Breathed into the lungs, usually through the mouth(by inhalation); 
• Applied to the skin (cutaneously) for a local(topical) or bodywide (systemic) effect;
• Delivered through the skin by a patch (transdermally) for a systemic effect.

Generation of antibiotics

The term generation is only used for Penicillins and Cephalosporins (Beta lactam antibiotics) and depending on their activity on the cell wall of gram-positive and gram-negative bacteria they are sorted by accepting terms ‘ Broad spectrum’ and ‘Narrow spectrum’ antibiotics.

Due to the development of resistance properties against drugs it leads to the discovery of new antibiotic scaffolds and their subsequent chemical modification (when possible) to structures less susceptible to resistance. This has resulted in many cases in several “generations” of antibiotics

Each generation of antibiotics comes with improved properties including expanded bacterial spectrum, favorable pharmacology, and “resistance to resistance.”

There are five generations of antibiotics such as;

First Generation Antibiotics

• The first Generation Antibiotics have a narrow spectrum of clinical use which means there are only a few organisms that they are able to successfully treat with this class of penicillin.
• These are useful for common gram-positive bacteria which are responsible for ear and throat infections, venereal diseases of gonorrhea and syphilis, and staph infections due to Staphylococcus aureus that cause abscesses, endocarditis and pneumonia.
• A large number of the drugs in this group are resistant to organisms that produce penicillinase. Penicillinase is an enzyme that some bacteria are capable of producing. This enzyme is also known as beta-lactamase and it inactivates some of the penicillins.
• Examples of first Generation Antibiotics: Penicillin: Penicillin G and Penicillin V; Cephalosporins: Cephazolin, Cephalothin, Cephapirin, Cephalethin, Cephradin, Cephadroxin.

Second Generation Antibiotics

• The Second Generation Antibiotics have an extended or Intermediate spectrum of clinical use. These are used to treat Some gram +ve and gram-ve bacteria.
• These are functions equally as well as penicillin G class plus effective against Escherichia coli, Proteus mirabilis, and Haemophilus influenzae, these are associated with urinary, respiratory and ear infections
• Second Generation Antibiotics are not very effective against penicillinase- producing organisms.
• Examples of Second Generation Antibiotics: Penicillin: Amoxicillin, Ampicillin; Cephalosporin: Cefuroxime, Cephamandole, Cephoxitin, Cephaclor, Cephrozil, Loracarbef.

Third Generation Antibiotics

• Cephalosporin drugs of third generation are broad-spectrum and effective against both grams positive and gram negative bacteria. However, they are highly activity against gram-negative bacteria.
• They are used for the treatment of serious urinary, respiratory and bacteremic infections due to gram-negative Pseudomonas aeruginosa and Proteus vulgaris
• These are not resistant to penicillinase-producing organisms.
• Examples of Third Generation Antibiotics: Penicillin: carbenicillin and ticarcillin; Cephalosporins: Cephixime, Cephtriaxone, Cephotaxime, Cephtizoxime, Cephtazidime.

Fourth Generation Antibiotics

• These are extended-spectrum antibiotics. They are not resistant to Beta lactamase-producing microorganisms.
• These are used for serious infections due to Pseudomonas aeruginosa, Proteus vulgaris, Klebsiella pneumoniae and Bacteroides fragilis in combination with other antibiotics.
• Example of Fourth Generation Antibiotics: Penicillin: Mezlocillin and piperacillin, Cephalosporin: Cefepime.
• Mezlocillin and piperacillin are derivatives of ampicillin. These are more active in vitro on a weight basis. In addition, they have some activity against Klebsiella.
• Cefepime contains a positively charged quaternary ammonium attached to the dihydrothiazone ring. It can easily penetration through the outer membrane of gram-negative bacteria.
• Cefepime has a lower affinity than the third-generation cephalosporins for certain chromosomal – lactamases of gram-negative bacilli.

Fifth Generation Antibiotics

• These are rxtended spectrum Antibiotics. 
• Some examples of Fifth Generation Antibiotics are: Cephtaroline : Pneumonia, skin and soft tissue infection, Cephtobiprole: Methicillin-resistant Staphylococcus aureus.

How long does it take for antibiotics to work?

Once administered through one of several available routes, four pharmacokinetic properties determine the speed of onset of drug action, the intensity of the drug’s effect, and the duration of drug action:

• Absorption: First, drug absorption from the site of administration permits entry of the therapeutic agent (either directly or indirectly) into plasma.
• Distribution: Second, the drug may then reversibly leave the bloodstream and distribute into the interstitial and intracellular fluids.
• Metabolism: Third, the drug may be biotransformed by metabolism by the liver, or other tissues.
• Elimination: Finally, the drug and its metabolites are eliminated from the body in urine, bile, or feces. 

Pharmacokinetic parameters allow the clinician to design and optimize treatment regimens, including decisions as to the route of administration for a specific drug, the amount and frequency of each dose, and the duration of treatment.

Antibiotic Side Effects

The side effects of antibiotics occur due to the allergy to antibiotics, especially penicillin which can cause swelling of the tongue and face, rashes and difficulty in breathing. 

• The side effect of antibiotics can vary from simple to life-threatening reactions such as labored breathing and asthmatic attack.
• Most common side effects of antibiotics are Feeling sick, diarrhea and being sick. Sometimes digestive tract and infections of the mouth occur due to the destruction of good bacteria.
• There are other side effects of antibiotics such as; 
  • kidney stone formation with sulfonamides; 
  • Increased sun exposure sensitivity with tetracyclines; 
  • Blood clotting with cephalosporins; 
  • Deafness with erythromycin; 
  • Blood disorders with trimethoprim; and etc
• Penicillin, erythromycin, and cephalosporins are responsible for the colitisin older people and lead to severe diarrhea as well.

Antibiotic Uses

• Antibiotic Uses are used in veterinary medicine, poultry, cattle, fishes and in human medicine. 
• Antibiotics are needed in large quantities in animal farming to prevent and treat infections, but smaller quantities are also used to promote growth.
• Antibiotics also used to prevent Bacterial infections in fruits and vegetables such as streptomycin and oxytetracycline.

References

• Microbiology Society, What are antibiotics and how do they work? https://microbiologysociety.org/members-outreach-resources/outreach-resources/antibiotics-unearthed/antibiotics-and-antibiotic-resistance/what-are-antibiotics-and-how-do-they-work.html
• https://www.easynotecards.com/print_list/82983
• https://www.slideshare.net/fagooson/interpretation-of-prescription-or-medication-order