Sunday 20 January 2019

ANTIBIOTICS

Antibiotics are the medicines which are used to treat infections. Infections may be due to bacteria, fungi or virsuses. Almost everyone suffers from infection someimes in his life time.

Being infected is a bad feeling and everybody dislikes it. Sometimes, these infections are so dreaded that it is better to get immunity against such bad infections. So, vaccines are used to present such bad infections, Commonly used vaccines are BCG ( to prevent Tuberculosis), DPT ( to prevent Diphtheria, Pertusis and Tetanus), Anti Hepatitis B Surface antigen Vaccine ( to prevent infection against hepatitis B), Polio vaccine, etc.

But, all infections are not so dangerous, like common cold, sore throat, and small furuncle or small reddish pimple. Such infections usually subside by themselves due to the immunity of our own body. This immunity is mainly provided by white blood cells (WBCs) and lymphocytes present in our body. These act like Policemen patrolling our internal security. These security personnel detect and kill the foreign microbials or microorgaisms like bacteria.

Sometimes, infecions may overwhelming and required to be treated with antibiotics. Like common cold not subsiding and persisting for longer duration with superadded bacterial infection or sinusitis. Or, sore throat associated with yellowish sputum with cough and fever. So, we need to take antibiotics to treat such infections.

Infections may be superficial or deep, local or systemic. The infection depends upon virulence or the microorganism, resistance of the person, and living conditions. Like persons with diabetes with uncontrolled blood sugar level and patients on long term steroids have low resistance or immunity against the infecive microrgansms. Person living in crowded places with other people infected with communicable diseases are prone to acquire infections of the airborne diseases like tuberculosis, influenza, etc.

Skin infections are commonly caused by Staphylococcus aureus and Streptococcus. Invention  of Penicillins in 1928 by Scottish researcher, Alexander Flemming, made a great difference to the outcome of patients with infecions.

Sir Alexander Fleming

Sir Alexander Fleming was a Scottish physician, microbiologist, and pharmacologist. His best-known discoveries are the enzyme lysozyme in 1923 and the world's first antibiotic substance benzylpenicillin from the mould Penicillium notatum in 1928. The simple discovery and use of the antibiotic agent has saved millions of lives, and earned Fleming – together with Howard Florey and Ernst Chain, who devised methods for the large-scale isolation and production of penicillin – the 1945 Nobel Prize in Physiology/Medicine.


Penicillin was effective against fatal infections caused by bacteria. But, over time, these bacteria outsmarted the drug and developed resistance to these drugs. But, consistent efforts by the physicians, microbiologists, pharmacologists, biotechnologists and other inventors led to the development of many anti-microbial drugs which are commonly known as antibiotics.

So, commonly uses antibiotics are penicillins, cephalosporins, tetracyclines, macrolides, quinolones, anti-viral drugs, anti-fungal drugs, etc.
Common bacteria are described as Gram positive or Gram- negative. Gram positive bacteria are stained positively by Gram stain. 
Some bacteria produce exotoxins and some produce endotoxins. 
Tbe bacteria which produce exotoxins are Cornyebacterium diphtheriae, Clostridium tetani, C.botulinum, C.perfringens, Bacillus anthracis, Staphylococcus aureus, Streptococcus pogens ( all are examples of Gram positive bacteria).
Gram negative bugs which produce exotoxins are E.coli, Vibrio cholerae, and Bordetella pertusis. 
Endotoxin is a polysaccharide and is found in the cell wall of Gram-negative bacteria. 
Some bacteria do not stain well with Gram-stain, like Treponema, Rickettsia, Mycoplasma, Legionella pneuophila, Mycobacteria and Chlamydia.
For treponemes-darkfield microscopy and fluorescent antibody staining is used. 
Mycobacteria are acid-fast bacilli. Legionella is stained with silver stain.

Gram positive bacteria are broadly classified in 2 groups; Cocci and Bacilli.
Gram positive cocci are classified into two; catalase positive clusters ( Staphylococcus) and catalase negative chains ( Streptococcus). 
Catalase postive staphylococci are further classified into two groups as Coagulase positive ( S.aureus) and coagulase negative [ Staphylococcus epidermidis ( Novobiocin sensitive) and Staphylococcus saprophyticus ( Novobiocin resistant ].
Gram postive and catalase negative chains of cocci are Strptococcus. On the basis of hemolysis Streptococci are divided into 3 categories: Green ( partial ) hemolysis; Sterptococcus pneumoniae, Clear hemolysis Streptococcus pyogens ( group A Bacitracin sensitive), S.agalactiae ( group B, Bacitracin resistant) and 3rd category of streptococci with no hemolysis examples are Enterococcus ( E.fecalis) and Peptostreptococcus( anaerobe).




Exapmple of Gram positive bacilli ( rods) are: Clostridium ( anaerobe), Cornyebacterium, Listeria and Bacillus.


Gram negative bacteria which appear pink are broadly classified into three groups : Cocci, C0ccoid rods and rods. 
Gram negative cocci are Neisseria mningitidis and N.gonorrhoeae. These two are differentiated on the basis of Maltose fermenter chacteristic. N. menigitidis is Malose fermenter and N. gonorrhoeae is Maltose noferenter.

The examples of cgram negative coccoid rods are Hemophlus influenzae, Pasteurella, Brucella and Bordetella pertusis.

Gram negative rods are further subdivided into two subtypes based Lactose fermenter characteristic. Lactose fermenter gram negative rods are Klebsiella, E,coli and Enterobacter which are Fast fermenter and Citrobacter, and Serratia Slow fermenters.
Lactose nonfermenter gram negative rods are subdivided into two groups, based on oxidase property. Oxidase positive are Pseudomonas and oxidase negative are Shigella, Salmonella and Proteus.






Penicillin C is for intravenous use and Penicillin V is for oral use. 
Penicillin binds penicillin-binding proreins , blocks transpeptidase cross-linking of cell wall and activates autolytic enzymes. It is bactericidal for gram positive cocci and rods, gram negative cocci and spirochetes.

Methicillin, nafcillin have narrow spectrum and used against penicillase resistant Staphyloccus aureus.

Ampicillin, Amoxicillin have wider spectrum, penicillanse sensitive, also combined with clavulanic acid ( penicillanase inhibitor) to enhance spectrum. Amoxicillin has greater oral bioavailability than ampicillin. These two extended-spectrum penicillin and are useful against certain gram positive bacteria and gram negative rods ( Hemophilus influenzae, E.coli, Listeria monocytogens, Proteus mirabilis, Salmonella and enterococci). 

Carbenicillin, Piperacillin and Ticarcillin are extended spectrum penicillin and useful against Pseudomonas  and gram negative rods , susceptible to penicillanase, used with clavulanic acid.

Cephalosporins are beta lactam drugs. It inhibits cell wall synthesis 


Imipenem
      Imipenem is a broad spectrum, beta lactamase-resistant carbapenem. It is always administered with cilastatin which is inhibitor of renal dihydropeptidase 1 to decrease inactivation in renal tubules. Ii is used against gram positive cocci, gram negative rods and anaerobes. It is drug of hoice against Enterobacter. Its toxicity includes GI distress, skin rash, and CNS oxicity ( seizures).

Vancomycin

Aminoglycosides

Tetracyclines 

Macrolides

Chloramphenicol

Clindamycin

Sulfonamides

Trimethoprim

Fluroquinolones

Metronidazole




References: 
Wikpedia

Alexander Fleming (1881–1955): Discoverer of penicillin, Siang Yong Tan, Yvonne Tatsumura

Singapore Med J. 2015 Jul; 56(7): 366–367. doi: 10.11622/smedj.2015105















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