Penicillins, composition

Peanut oil, composition of, 1062 Pedersen, Charles John, 666 Penicillin, discovery of, 824-825 Penicillin V, specific rotation of, 296 stereochemistry of, 321 Penicillium notation, penicillin from. 824... 

Filter aids are widely used in die fermentation industry to improve the efficiency of filtration. It is a pre-coated filter medium to prevent blockage or blinding of the filter by solids, which would otherwise wedge diemselves into the pores of the cloth. Filter aid can be added to the fermentation broth to increase the porosity of the cake as it formed. This is only recommended when fermentation product is extracellular. Filter aid adds to the cost of filtration. The minimum quantity needed to achieve the desired result must be established experimentally. Fermentation broths can be pretreated to improve filtration characteristics. Heating to denature proteins enhances the filterability of mycelial broths such as in penicillin production. Alternatively, electrolytes may be added to promote coagulation of colloids into larger, denser particles, which are easier to filter. The filtration process is affected by the viscosity and composition of the broth, and the cell cake.5... 

Cephalosporins consist of a six-membered dihydrothiazine ring fused to a /3-lactam ring. Thus, the cephalosporins (A -cephalosporins) are structurally related to the penicillins (section 2.1). The position of the double bond in A -cephalosporins is important, since A -cephalosporins (double bond between 2 and 3) are not antibacterial irrespective of the composition of the side-chains. 

In contrast, parenteral suspensions have relatively low solids contents, usually between 0.5 and 5%, with the exception of insoluble forms of penicillin in which concentrations of the antibiotic may exceed 30%. These sterile preparations are designed for intramuscular, intradermal, intralesional, intraarticular, or subcutaneous injection. Syringeability is an important factor to be taken into consideration with injectable dosage forms. The viscosity of a parenteral suspension should be sufficiently low to facilitate injection. Common suspending vehicles include preserved isotonic saline solution or a parenterally acceptable vegetable oil. Ophthalmic and optic suspensions that are instilled into the eye/ear must also be prepared in a sterile manner. The vehicles are essentially isotonic and aqueous in composition. The reader should refer to Chapter 12 for further discussion on parenteral products. 

Calcined [MgAl] LDH was also used to adsorb penicillin G acylase [121]. The calcined LDH phases have porous structures, large specific surface areas and abundant basic sites to bind the enzymes. The effect of varying the composition of the LDH precursor and calcination temperature on the activity of the immobilized enzyme has been reported. In this case, the percentage of immobilized proteins increases up to 88 %. 

The fermentation step to produce penicillin GA is the major cost element in the overall process to produce 6-APA. This is substantially due to the high cost of sterile engineering (Table 4.6 and 4.7). Clarification, extraction and solvent recovery steps are also significant, a reflection of the dilute and impure composition of fermentation broths. The concentration of 6-APA in the final broth has a big effect on total process costs. Thus increasing final 6-APA concentrations from 1.2-6.0% have been calculated to reduce production costs by over 50% (Table 4.8). By contrast the 6-APA production step cost is quite small, and is less that half the cost of the solvent recovery process (Table 4.6). The costs of the immobilized enzyme is not insignificant in a recent calculation it was estimated at 2.5 /kg 6-APA (Rasor and Tischer, 1998). 

Penicillin V or phenoxymetliylpenicillin is a -lactam antibiotic produced by Penicillium notatum. It is a biosynthetic penicillin that should be differentiated from the semisynthetic penicillins since it is produced by altering the composition of the medium where the mold is growing. 

B Korat, H Mottl, W Keck. Penicillin-binding protein 4 of Escherichia coli molecular cloning of the dacB gene, controlled overexpression, and alterations in murein composition. Mol Microbiol 5 675-684, 1991. 

A Severin, AM Figueiredo, A Tomasz. Separation of abnormal cell wall composition from penicillin-resistance through genetic transformation of Streptococcus pneumoniae. J Bacteriol 178 1788-1792, 1996. 

A Severin, MV Vaz Pato, AM Figureiredo, A Tomasz. Drastic changes in the peptidoglycan composition of penicillin-resistant laboratory mutants of Streptococcus pneumoniae. FEMS Microbiol Lett 130 31-35, 1995. 

Several natural penicillins can be produced, depending on the chemical composition of the fermentation medium used to culture penicillium. Penicillin G (benzylpenicillin) has the greatest antimicrobial activity of these natural penicillins and is the only natural penicillin used clinically. However, penicillin G is not stable it is extremely acid-labile. Only about one-third of an oral dose is absorbed under the most ideal conditions. Therefore, it is generally not given orally but is administered by intramuscular injection. Several newer derivatives of penicillin G have been developed that do have good to excellent oral absorption (e.g., cloxacillin, ampicillin, and amoxicillin). 

Absorption Most of the penicillins are incompletely absorbed after oral administration and reach the intestine in sufficient amounts to affect the composition of the intestinal flora. However, amoxicillin is almost completely absorbed. Consequently, it is not appropriate therapy for the treatment of shigella- or salmonella-derived enteritis, since therapeutically effective levels do not reach the organisms in the intestinal crypts. Absorption of penicillin G and all the penicillinase-resistant penicillins is decreased by food in the stomach since gastric emptying time is reduced and the drugs are destroyed in the acidic environment. Therefore, they must be administered 30-60 minutes before meals or 2-3 hours postprandially. Other penicillins are less affected by food. 

Recently, many batch operations have been transformed into fed-batch (semicontinuous) operations by the gradual introduction of nutrient into the reactor. The rationale is to control the feed optimally to maximize a composite performance index. For the case of penicillin fermentation, for example, for which the specific growth rate and the specific penicillin formation rate are mutually disposed, the optimal feed policy is carried out in two phases. During the first phase, cell biomass is quickly built up to the allowable maximum level. During the second product formation phase, the feed is controlled such that... 

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