• Penicillin is one of the most commonly used antibiotics globally; it has a wide range of clinical indications. Penicillin is effective against many different infections involving gram-positive cocci, gram-positive rods (e.g., Listeria), most anaerobes, and gram-negative cocci (e.g., Neisseria).

• Penicillin is one of the most commonly used antibiotics globally; it has a wide range of clinical indications. Penicillin is effective against many different infections involving gram-positive cocci, gram-positive rods (e.g., Listeria), most anaerobes, and gram-negative cocci (e.g., Neisseria).Importantly, certain bacterial species have obtained penicillin resistance, including enterococci. Enterococci infections now receive treatment with a combination of penicillin and streptomycin or gentamicin.

• Certain gram-negative rods are also resistant to penicillin due to penicillin’s poor ability to penetrate the porin channel.However, later generations of broad-spectrum penicillins are effective against gram-negative rods. Second-generation penicillins (ampicillin and amoxicillin) can also penetrate the porin channel, making these drugs effective against Proteus mirabilis, Shigella, H. influenzae, Salmonella, and E. coli. 

• Third-generation penicillin such as carbenicillin is also able to penetrate gram-negative bacterial porin channels. Fourth-generation penicillins such as piperacillin are effective against the same bacterial strains as third-generation penicillins and Klebsiella, enterococci, Pseudomonas aeruginosa, and Bacteroides fragilis.

• Penetration of penicillin G, dihydrostreptomycin, oxytetracycline, and chloramphenicol into interstitial fluid of calves was estimated using subcutaneously implanted, multiple perforated spherical polypropylene capsules as a model. Antibiotic concentrations were determined in simultaneously withdrawn serum and capsular fluid (CF) samples at intervals after single and multiple intramuscular injections of antibiotics at recommended dose schedules. 

• Peak concentrations of penicillin G in CF were 57% of those in serum, and the drug was eliminated from CF at a slower rate than from serum. Dihydrostreptomycin diffused into CF to a limited degree and was eliminated from CF much more slowly than from serum leading to gradual drug accumulation in CF upon repeated dosing. 

• Multiple injections of oxytetracycline resulted in CF drug levels comparable with those in serum. Concentrations of chloramphenicol in CF were generally similar to free (non-protein bound) serum drug levels. CF concentrations of penicillin G were within the range of the minimal inhibitory concentrations of the drug for pathogenic gram positive micro-organisms and CF levels of dihydrostreptomycin, oxytetracycline, and chloramphenicol were apparently sufficient to inhibit the majority of gram negative pathogens involved in bovine injections.

•  Advantages and limitations of the tissue cage model are briefly discussed.

• Penicillins can be metabolized to penicilloic acids in man, the extent being dependent on the penicillin structure. In the phenoxy penicillin series, phenoxymethyl penicillin was found to be particularly unstable, but the higher homologues were more stable. In the isoxazolyl series, oxacillin was unstable, and progressive insertion of halogen in the phenyl ring increased stability. Ampicillin and amoxycillin showed some instability, ampicillin possibly being the more stable. 

• After intramuscular administration, carbenicillin was very stable in the body, ampicillin was fairly stable, and benzyl penicillin was unstable. It is important to take into account the penicilloic acid content of urine when estimating total absorption of a penicillin. 

• Increased stability in the body as well as slower renal clearance can lead to high concentrations in the serum. Penicilloic acids seemed to be more slowly cleared from the body than penicillins. The liver is probably the site of inactivation.

• All of the penicillins are readily and actively secreted by the renal tubules and most are eliminated, almost completely unchanged, in the urine. The majority are excreted in small quantities in the bile, but this is a major route for elimination of nafcillin from the body.

• elimination of the penicillins from the body takes place largely via renal excretion, penicillin V and oxacillin are extensively degraded as well. In contrast to the situation with respect to ‘natural’ and ‘broad-spectrum’ penicillins, the serum half-life of the isoxazolyl congeners and nafcillin is only minimally prolonged in the presence of renal failure. These agents are only weakly haemodialyzable, while the other penicillins are rapidly removed from the circulation by this procedure.

1. Inhibition of cell wall synthesis by blocking transpeptidation :

•  Penicillin is one of the beta-lactam family that contain a characteristic four-membered beta-lactum ring that binds to penicillin binding protein (PBP) receptor on the surface of bacterial cell wall. PBP is the receptor for substrate peptidoglycan precursor in bacteria. Penicillin acts as alternative substrate and binds to PBP receptor and then inhibits transpeptidase which results in inhibition of cell wall synthesis. Without a cell wall, a bacterial cell is vulnerable to outside water and molecular pressures, which causes the cell to quickly die. Since human cells don't contain a cell wall, penicillin treatment results in bacterial cell death without affecting human cells.

• Gram-positive bacteria have thick cell walls containing high levels of peptidoglycan, while gram-negative bacteria are characterized by thinner cell walls with low levels of peptidoglycan. The cell walls of gram-negative bacteria are surrounded by a lipopolysaccharide (LPS) layer that prevents antibiotic entry into the cell. Therefore, penicillin is most effective against gram- positive bacteria where DD-transpeptidase activity is highest.

2. Activation of autolytic enzymes :

• Penicillin causes activation of autolytic enzymes of bacteria causing their death.

•  Autolysins are present in bacterial cell wall which maintains appropriate shape and size of cell and also helps in cell division. The activity of autolysin is regulated by components such as cell wall and teichoic acid. Use of antibiotics penicillin causes destruction of cell wall and disintegration of teichoic acid as a result of which autolysin is activated and cause cell lysis.