Spectra benzylpenicillin

Penicillinacylase is used industrially to catalyze the hydrolytic removal of the side chain in naturally occurring penicillins such as benzylpenicillin (4.49) and phenoxymethylpenicillin (4.50). The nucleus 6-aminopenicillic acid (4.48) is then used as the starting material for the preparation of semisynthetic penicillins. Appropriate acylation of the 6-NH2 group leads to )3-lactamase-stable and broad-spectrum penicillins. 

Benzylpenicillin or penicillin G has a narrow antimicrobial spectrum. It is active with respect to Gram-positive bacteria (staphylococcus, streptococcus, and pneumococci), causative agent of diphtheria, and anthrax bacillus. Gram-negative bacteria are resistant to it. Benzylpenicillin is broken down by stomach acid and destroyed by staphylococcus penicillinase. 

In terms of the spectrum of antimicrobial action, oxacillin is analogous to benzylpenicillin. However, it combines the resistance to penicillinase with durability in an acidic medium, which allows it to be used not only intramuscularly, but also orally. It is used for infections caused by... 

When culture results of CSE and/or blood are available therapy should always be streamlined. If the meningococcus, pneumococcus, group B streptococcus or Listeria are penicillin sensitive, this small spectrum agent (benzylpenicillin 6x3 million units/day i.v.) would be the therapy of choice. 

Penicillin V is a narrow-spectrum penicillin and has similar antibacterial activity to benzylpenicillin. It is active against many streptococcal infections, but it is inactivated by penicillinases. Flucloxacillin is a penicillinase-resistant antibiotic and is effective against infections caused by penicillin-resistant staphylococci. In comparison to penicillin V, attachment of carbocyclic/heterocyclic ring directly to the C6 carbonyl group confers resistance to beta-lactamases due to steric hindrance around the amide group. 

Infra-red Spectrum. Principal peaks at wavenumbers 1620,1777, 1500, 1310,1700, 703 (benzylpenicillin sodium, KBr disk). 

Benzylpenicillin (1942) is produced by growing one of the penicillium moulds in deep tanks. In 1957 the penicillin nucleus (6-amino-penicillanic acid) was synthesised and it became possible to add various side-chains and so to make semisynthetic penicillins with different properties. It is important to recognise that not all penicillins have the same antibacterial spectrum and that it is necessary to choose between a number of penicillins just as it is between antimicrobials of different structural groups, as is shown below. 

Narrow spectrum (natural penicillins) benzylpenicillin. phenoxymethylpenicillin... 

Penicillin G (benzylpenicillin) 23 Aminopenicillins amoxicillin and ampicillin 24 Extended-spectrum penicillins 25 Cephalosporins 25 Imipenem 28... 

In the spectrum of benzylpenicillin...a large peak at 7.9 ppm (relative to tetramethylsilane at 10.0 ppm) was due to the gem-dimethyl group. The spectrum of cephalosporin C showed no such peak. A peak of the intensity required (for one methyl group) was present at 7.4 ppm... a peak due to the (other) single methyl was in a position expected for the methyl of a CH3.CO.O group. 

Further studies of a-substituted benzylpenicillins led to the independent discovery by Pfizer and Beecham chemists of carbenicillin (< -car-boxybenzylpenicillin) (Figure 19) (89, 90), in which the gram-negative spectrum is extended still further (to Pseudomonas aeruginosa and the ampicillin-insensitive indole-positive Proteus species). 

Penicillin is an organic acid that is commonly supplied as sodium and potassinm salts. Penicillin V (Pen-Vee K and V-cillin K) and phenethicillin (Syncillin and Maxipen) are different from penicillin G (benzylpenicillin) in that they are more acid resistant. In addition to the broad-spectrum penicillins snch as ampicillin and amoxicillin, there is a... 

The penioillins usually are discussed under various groups based on spectrum of activity and sensitivity or resistanoe toward (3-lactamase. One of the earliest and still most commonly used penicillin is benzylpenicillin. 

Not understood. The interaction between nafcillin and warfarin is possibly due to increases in the metabolism of warfarin by the liver. Dicloxacillin also possibly reduces serum warfarin levels. Other penicillins (ampicillin, benzylpenicillin, carbenicillin, methicillin, ticarcillin ) have caused increased bleeding times when given alone, principally due to platelet inhibition, which might be additive with the effects of oral anticoagulants. Broad-spectrum antibacterials may decrease the gut flora and thereby possibly decrease production of vitamin K. Other factors relating to the disease may be important, see Coumarins -i- Antibacterials p.365. 

Holt and Stewart (1965) have studied the breakdown of ) -lactam antibiotics by infrared spectroscopy. The method is based on observation of the rupture of the integral lactam ring by penicillinase, )S-lactamase, with the production of penicilloic acid derivatives totally lacking in antibiotic activity. Figure 15.18 is the spectrum of benzylpenicillin before hydrolysis by a staphylococcal suspension, and Fig. 15.19 is the spectrum after rupture of the lactam ring by )3-lactamase of the bacteria. Figure 15.20 is the spectrum of 6-APA before hydrolysis, and Fig. 15.21 after lactam ring... 

The macrolide antibiotics are a group of compounds which have as a nucleus a ma-crocyclic lactone ring to which one or more sugars are attached. These sugars are essential for the antibiotic activity. Only three of the macrolides, i.e., erythromycin, oleandomycin, and spiramycin are used in human clinical practice, while a fourth, tylosin, is used in veterinary medicine and as a food preservative in industrial canning. These are all weakly alkaline and only slightly soluble in water. Erythromycin is the most active antibiotic of this group (Fig. 7). All of them are able to inhibit bacterial protein synthesis and are characterized by their bacteriostatic qualities. The antibacterial spectrum is similar to that of benzylpenicillin. 

Aminopenicillanic acid (6 APS) is an important precursor for the organic synthesis of new P. The compound itself has no antibiotic activity it is isolated as a fermentation product from cultures of Pen-cillium chrysogenum, or prepared by the enzymatic hydrolysis of benzylpenicillin. Thousands of new P. have been prepared by the acylation of 6 APS, but only a few of these are therapeutically useful, e.g Penicillin V is relatively stable to acid and is not hydrolysed in the stomach, so that it may be administered in tablet form Ampicillin (the aminophenyl-acetyl derivative of 6 APS), has a wider spectrum of activity than most other R, including activity against various Gram-negative bacteria (Typhus, E. coli, etc.). 

---