MECHANISM OF DIFFERENT TYPES OF ANTIBIOTICS

Antibacterial Drugs are classified according to their site of action which are as follows :

CELL WALL SYNTHESIS INHIBITORS
There are 3 different mechanisms by which anti-cell wall drugs work and thus they are also classified as following:

  1. First classification involves the drugs that directly interact with Penicillin-Binding-Proteins (PBPs) and inhibit the transpeptidase activity which in turn inhibits the attachment of newly formed peptidoglycan subunit to the pre-existing one.
    This is the main mechanism of β-lactam antibiotics. These antibiotics include Penicillin (penams), cephalosporins, Penems, Carbapenems, and monobactams.
    These antibiotics bind to the penicillin-binding proteins which are enzymes present in the bacterial cell wall. Different β-lactam antibiotics bind in a different way. After the antibiotics bind to the enzyme, it changes the morphological response of the bacteria to the antibiotic.
  2. Second classification involves the drugs that bind to the peptidoglycan subunit, blocking different processes.
    The important class of compounds called as glycopeptides are mainly involved in this mechanism of anti-cell wall antibiotics.
    Vancomycin and Teicoplanin are the major examples of glycopeptide antibiotics.
    Vancomycin kills only gram-poitive bacteria whereas Teicoplanin is active against both. The overall mode of action of glycopeptides antibiotics is blocking transpeptidation i.e. similar to β-lactam antibiotics, they also inhibit the transpeptidase activity, and transglycosylation i.e. they being large in size attach to the peptidoglycan subunits thus creating a blockage which does not allow the cell wall subunits to attach to the growing peptidoglycan backbone.
  3. Third classification involves the drugs that block the transport of peptidoglycan subunits across cytoplasmic membrane.
    The main example of such type of drugs is bacitracin, which is a simple peptide antibiotic originally isolated from Bacillus subtilis.
    The mode of action of these class of drugs is blocking the activity of specific cell membrane lipid carriers which act as the attachment surface for peptidoglycan precursors and help in their movement from cell cytoplasm to exterior of the cell. This activity of lipid carriers is inhibited by bacitracin like drugs and they finally prevent the incoroporation of those precursors into cell wall thus inhibiting its biosynthesis.

Although, its route of administration is mostly oral or intramuscular, bacitracin is also known to show its effects when used as topical ointments like Neosporin.

INHIBITORS OF PROTEIN SYNTHESIS
Protein Inhibitors can be divided into 2 parts:

  1. Inhibitors binding to 30S subunits
    • Aminoglycosides bind to the bacterial ribosome, after which they cause tRNA mismatching and thus protein mistranslation.
    This occurs by mismatching between codons and anticodons, which synthesize proteins with incorrect amino acid. This mistranslated protein, along with correctly translated proteins move into move into the periplasm where most of the mistranslated proteins are degraded and some of them are inserted into cytoplasmic membrane. This causes disruption of the membrane, ultimately killing the bacterial cells.
    • Tetracyclines are bacteriostatic and block the binding of tRNAs with the ribosome during translation thus inhibiting protein synthesis. Most of the tetracycline class of drugs are broad spectrum and are active against wide range of bacteria.
  2. Inhibitors binding to the 50S subunit
    • Macrolides are the large class of naturally produced secondary antibiotics. They are basically broad spectrum, bacteriostatic antibiotics. Their main mode of action is blocking peptide chain elongation and they inhibit the formation of peptide bond.
    Patients allergic to penicillins are recommended erythromycin which is a macrolide.
    • Lincosamides include lincomycin and clindamycin. Though they are structurally different but functionally similar to macrolides. They are specifically known to inhibit streptococcal and staphylococcal infections.
    • Chloramphenicol also inhibits peptidyl transferase reaction inhibiting peptide bond formation. It was the first broad spectrum antibiotic and is very much active against a broad range of bacterial pathogens but is very toxic and can cause side.

INHIBITORS OF MEMBRANE FUNCTION
Biological cytoplasmic membranes are basically composed of lipids, proteins and lipoproteins. The cytoplasmic membrane acts as a selective barrier which allows the transport of materials between inside the cell and the environment.
A number of antibacterial agents work by targeting the bacterial cell membrane. They basically are involved in the disorganization of the membrane. Polymyxins and Lipopeptides are the main anti- cell membrane agents.

NUCLEIC ACID SYNTHESIS INHIBITORS
These drugs inhibit nucleic acid synthesis function by either of the following:

  1. Interfere with RNA of bacterial cell
    Antibacterial drugs of this mechanism are selective against bacterial pathogenic cells.
    For example: The drug rifampin, belonging to the drug class rifamycin blocks the bacterial RNA polymerase activity. It is also active against Mycobacterium tuberculosis and thus id used in the treatment of tuberculosis infection. It also shows side effects.
  2. Interfere with DNA of bacterial cell
    There are some antibacterial agents that interfere with the activity of DNA gyrase.
    The drug class fluoroquinolones show this mechanism. They are borad spectrum antibacterial agents. Some examples of drugs in fluoroquinolone family are Ciprofloxacin, Ofloxacin, Moxifloxacin, etc

INHIBITORS OF METABOLIC PATHWAYS
There are some antibacterial drugs which act as ANTIMETABOLITES and inhibits the metabolic pathways of bacteria.
• The sulfonamides block the production of dihydrofolic acid.
This blocks the production of purines and pyrimidines required for nucleic acid synthesis by blocking the biosynthesis of folic acid. Their mechanism of action is bacteriostatic and they are broad spectrum antibacterial agents. Though humans also obtain folic acid but these drugs are selective against bacteria.
Sulfones are also structurally and functionally similar to sulfonamides.
• Trimethoprim is used in the same folic acid synthesis pathway but at a different phase, in the production of tetrahydrofolic acid.
• There is another drug, Isoniazid which is an antimetabolite only selective against mycobacteria. It can also be used to treat tuberculosis when used in combination with rifampin and streptomycin.

INHIBITORS OF ATP SYNTHASE
There is a class of drug compounds called as Diarylquinolones that are specifically active against mycobacterial growth. They block the oxidative phosphorylation process and finally leading to reduced ATP production which either kill or inhibit the growth of mycobacterial species.

TYPHOID FEVER AND IT’S SYMPTOMS

Typhoid Fever or Typhoid is a systemic enteric infection caused by bacteria usually through ingestion of contaminated food or water. The disease is also referred by several other names such as Gastric Fever, Enteric Fever, Abdominal Typhus, Infantile Remittent Fever, Slow Fever, Nervous Fever, and Pythogenic Fever. The disease causes several symptoms causing mild to severe problems for the patients. The symptoms are generally seen from six to thirty days after exposure. Generally there is the gradual onset of high fever for several days, weakness, abdominal pain, constipation, headaches, and vomiting. Some people also develop a skin rash with red colored spots.
The cause of the disease is the bacterium Salmonella typhi which is also known as Salmonella enterica serotype typhi , mainly growing in the intestines and blood. Risk factors include poor sanitation and poor hygiene. Diagnosis of the disease is done by either culturing the bacteria or detecting the bacterium’s DNA in the blood, stool, or bone marrow. Culturing the bacterium is little bit difficult so Bone marrow testing is the mostly used method. It has been observed that a typhoid vaccine can prevent about 40-90% of the infection during the first 2-7 years. But this vaccine is always recommended for the people at high risk or travelling to the places where this disease is so common. Other efforts which can be done to prevent the disease are clean drinking water, good sanitation, and hand washing. The disease is usually treated with several antibiotics such as Azithromycin, Fluoroquinolones or third generation cephalosporins.

SIGNS AND SYMPTOMS
Usually, the complete course of untreated typhoid fever is divided into 4 different stages, where the each stage lasts for a week which makes the patient completely exhausted.
• In the first week, the body temperature of the patient rises slowly, and the fever fluctuations are generally seen with relative bradycardia, malaise, headache, and cough.
A bloody nose is also seen in this quarter of the disease and abdominal pain is also possible. There is also a decrease in the number of WBCs. Widal test is negative in the first week of the disease.

• In the second week, the person is often too tired to get up, with a very high fever and bradycardia is continued in this stage also with dicrotic pulse wave. In this stage, Delirium is frequent which gives the typhoid another name i.e. NERVOUS FEVER.
Rose spots also appear on the lower chest and abdomen. Rhonchi are heard in lung bases.
Diarrhea can occur in this stage : six to eight stools in a day, green, comparable to pea soup, with a characteristic foul smell. However, constipation is also frequent. The spleen and liver is enlarged and liver transaminases are elevated. Patients can still test positive.

The major symptoms of this fever is that the fever usually rises in the afternoon up to the first and second week.

• In the third week of the fever, a number of complications can occur like :
 Intestinal hemorrhage due to bleeding in congested Peyer’s patches: it can be very serious but is not usually fatal.
 Intestinal perforation in the distal ileum: this is a very serious complication and is usually fatal.
 Encephalitis.
 Respiratory diseases such as pneumonia and acute bronchitis.
 Neuropsychiatric symptoms with picking at bedclothes or imaginary objects.
 Metastatic abscesses, cholestasis, endocarditis, and osteitis.
 The fever is usually very high and oscillates very little over 24 hours. Dehydration is also caused.
 Platelet count goes down and risk of bleeding rises.