Penicillins: PENICILLINS MECHANISM OF ACTION AND ANTIMICROBIAL SPECTRUM

MECHANISM OF ACTION OF PENICILLIN:

All penicillins produce their bactericidal effect by inhibition of bacterial cell wall synthesis. The mechanism of action of penicillin is as follows:

(1) PENICILLIN BINDING PROTEINS:

Penicillins inactivate numerous proteins on the bacterial cell membrane. The penicillin binding proteins are the bacterial enymes involved in the synthesis of cell wall and in the maintenance of morphologic features of bacterium. Exposure to these antibiotics can therefore not only prevent cell wall synthesis but also lead to lysis of bacteria.

(2) INHIBITION OF TRANSPEPTIDASE:

Some penicillin binding proteins catalyze formation of the cross linkages between peptidoglycan chains. Penicillins inhibit this transpeptidase catalyzed reaction, thus inhibiting the formation of cross linkages essential for cell wall integrity.

(3) PRODUCTION OF AUTOLYSINS:

Many bacteria, particularly gram positive cocci produce autolysins that pariticpate in normal remodeling of bacterial cell wall. In the presence of a penicillin, the degradative action of the autolysins proceeds in the absence of cell wall synthesis.

Thus, the antibacterial effect of the penicillin is the result of both inhibition of cell wall synthesis and destruction of existing cell wall by autolysins.

ANTIMICROBIAL SPECTRUM OF PENICILLINS:

(1) PENICILLIN G:

Penicillin G is a basis for therapy of infections caused by number of gram positive and gram negative cocci, gram positive bacilli and spirochetes.

GRAM POSITIVE AND GRAM NEGATIVE COCCI

GRAM POSITIVE BACILLI

SPIROCHETES

(2) PENICILLIN V:

Penicillin V has a spectrum similar to Penicillin G.

(3) METHICILLIN, NAFICILLIN, OXACILLIN, CLOXACILLIN AND DICLOXACILLIN:

These are penicillinase-resistant penicillins. Their use is restricted to treatment of infections caused by penicillinase-producing staphylococci.

(4) AMPLICILLIN AND AMOXICILLIN:

They have an antibacterial spectrum similar to Penicillin G but are more effective against gram negative bacilli (Escherichia coli, Haemophilus influenzae, Proteus mirabilis and Salmonella typhi). Ampicillin is the drug of choice for gram positve bacillus (Listeria monocytogenes).