Cell Wall Inhibitors

A cell wall inhibitor is an antimicrobal drug that inhibits the growth or functionality of the cell wall of a pathogen. The more common cell wall inhibitors follow:

Penicillin

Penicillin is a group of antibiotics that have a fi-lactam ring the core structure of penicillins. This core structure is referred to as a "nucleus." Each member of the group has a different side chain that is attached to the b-lactam ring. Penicillin can be natural or semisynthetic.

• Natural penicillin. Natural penicillin is extracted from the Penicillium mold. The major disadvantage of natural penicillin, except for Penicillin V, is that it is negatively affected by stomach acid, meaning that the most effective way to administer natural penicillin is an intramuscular injection. Another problem is that penicillin itself can be attacked by the enzyme penicillinase. Penicillinases, also known as b-lactamases, are enzymes produced by many bacteria that attach to the b-lactam ring of the penicillin, rendering penicillin ineffective. The more common natural penicillins are:

• Penicillin G is the prototype compound for natural penicillin as is used in defense of staphylococci, streptococci, and several spirochetes. Natural penicillin has a narrow spectrum of activity. Penicillin G lasts up to six hours when injected intramuscularly.

• Procaine penicillin is a combination of the drugs procaine and penicillin G and lasts up to 24 hours, although the concentration of procaine penicillin diminishes after four hours.

• Benzathine penicillin is a combination of benzathine and penicillin G and can last for up to four months.

• Penicillin V is not inhibited by acid in the stomach and can be taken orally.

• Semisynthetic penicillin. Semisynthetic penicillins are chemically altered natural penicillins that are designed to overcome disadvantages of natural penicillins. There are two ways in which scientists modify natural penicillins. They stop the natural synthesis of a Penicillium molecule and use the penicillin nucleus. The other way is to modify the side chains from the natural penicillin and insert a new side chain that overcomes the disadvantage of the original side chain. This is the technique used to combat peni-cillinase. Common types of semisynthetic penicillin are:

• Methicillin was the first semisynthetic penicillin developed to resist penicillinase.

• Oxacillin is a newer semisynthetic penicillin that resists penicillinase and has replaced methicillin.

• Ampicillin is a semisynthetic penicillin that overcomes the narrow spectrum of activity of natural penicillin by attacking gram-negative and gram-positive bacteria. Ampicillin is not resistant to penicillinases.

• Amoxicillin is similar to ampicillin.

• Carbenicillin is a member of the carboxypenicillin group and has a broad spectrum of activity against gram-negative bacteria and is used to fight Pseudomonas aeruginosa.

• Ticarcillin is similar to carbenicillin.

• Mezlocillin is a member of the ureidopenicillins group of penicillins and is a modification of ampicillin, giving it a broader spectrum of activity against bacteria.

• Azlocillin is similar to mezlocillin.

• Augmentin (which is the trade name) is a combination of amoxicillin and potassium clavulanate, which is produced by streptomycete. Amoxi-cillin attacks gram-negative and gram-positive bacteria and potassium clavulanate resists penicillinase.

Monobactams

Monobactams are synthetic antibiotics that have a single lactam ring and resist penicilinase. Monobactams destroy only areobic gram-negative bacteria such as E. coli.

Cephalosporins

Cephalosporins are resistant to penicillinases and destroy gram-negative bacteria. The disadvantage of cephalosporins is they can be made ineffective by ^-lactamases.

Carbapenems

Carbapenems have a broad spectrum of activity that prevents the breakdown of the antibiotic by the kidneys. These antibiotics inhibit the synthesis of cell walls. An example is Primax (trade name). Primax has proved effective against 98 percent of all organisms that were isolated from patients in hospitals.

Bacitracin

Bacitracin is used against staphylococci and streptococci and other gram-positive bacteria and is used as a topical antibiotic for superficial infections.

Vancomycin

Vancomycin has a very narrow spectrum of activity and is the most effective antibiotic against staphylococci that produce penicillinase. Vancomycin is used in the treatment of endocarditis. However, vancomycin can be toxic to humans.

Isoniazid

Isoniazid (INH) inhibits mycolic acid, which is needed for synthesizing the cell wall of Mycobacteria tuberculosis. Isoniazid is only effective fighting mycobacteria tuberculosis.

Ethambutol

Ethambutol is similar to isoniazid and is used as a secondary treatment to avoid Mycobacteria tuberculosis becoming resistant to isoniazid.

CHAPTER 16 Antimicrobial Drugs PROTEIN INHIBITORS

A protein inhibitor drug interferes with the pathogen's capability to synthesize protein. The commonly used protein inhibitor drugs follow.

Aminoglycosides

Aminoglycosides are a group of antibiotics that were the first to attack gramnegative bacteria. Their disadvantage is that they can cause permanent damage to the auditory nerve and cause kidney damage. Commonly used members of this group of antibiotics are:

• Streptomycin is used as a secondary treatment to tuberculosis. It was discovered in 1944 and today is used sparingly because of its toxic effect on humans and the fact that bacteria quickly become resistant to it.

• Neomycin is a topical antibiotic used for superficial infections.

• Gentamicin is an antibiotic used to combat Pseudomonas aeruginosa infections.

Tetracyclines

Tetracycline is a broad-spectrum antibiotic that attacks both gram-positive and gram-negative bacteria. Tetracyclines are able to combat pathogens that invade cells because they can enter body tissues. They are used against urinary tract infections, rickettsial infection, and chlamydial infections. Tetra-cyclines are also used as the secondary treatment for gonorrhea and syphilis. The disadvantages of tetracyclines are discoloration of teeth in children and liver damage in pregnant women. Common members of the tetracycline group of antibiotics are:

• Oxytetracycline is a commonly used form of tetracycline that is also known as Terramycin.

• Chlortetracyline is another commonly used form of tetracycline that is also known as Aureomycin.

• Doxycycline is a semisynthetic form of tetracycline that has a longer-lasting effect than the natural form of tetracycline.

• Minocyline is a semisynthetic form of tetracycline.

Chloramphenicol

Chloramphenicol is a broad-spectrum antibiotic that is small enough to effect areas of the body that are too small for other antibiotics to enter. Chloramphenicol is an antibiotic of last resort because it inhibits formation of blood cells, causing aplastic anemia.

Macrolides

Macrolides are a group of antibiotics that have a similar effect as that of penicillin G. They affect the organism by inhibiting its ability to synthesize protein and are a secondary drug when penicillin G is unavailable or the organism has become resistant to penicillin G. Macrolide antibiotics can be administered orally, making them the choice for treating children who have streptococcal and staphylococcal infections. The most commonly used macrolide is Erythromycin, which is used to treat legionellosis, mycoplasmal pneumonia, and streptococcal and staphylococcal infections.

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