Penicillin antimicrobial activity

Widespread clinical acceptance continues to be accorded to the cephalosporins, and the field is extremely active as firms search for the ultimate contender. Among the characteristics desired is retention of the useful features of the older members (relatively broad spectrum, less antigenicity than the penicillins, relative insensitivity toward 3-lactamases, and convenience of administration) while adding better oral activity and broader antimicrobial activity (particularly potency against Pseudomonas, anaerobes, meningococci, cephalosporinase-carrying organisms, and the like). To a considerable extent these objectives have been met, but the price to the patient has been dramatically increased. 

Tetracyclines are a family of antibiotics which display a characteristic 4-fused-core ring structure (Figure 1.16). They exhibit broad antimicrobial activity and induce their effect by inhibiting protein synthesis in sensitive microorganisms. Chlortetracycline was the first member of this family to be discovered (in 1948). Penicillin G and streptomycin were the only antibiotics in use at that time, and chlortetracycline was the first antibiotic employed therapeutically that retained its antimicrobial properties upon oral administration. Since then, a number of additional tetracyclines have been discovered (all produced by various strains of Streptomyces), and a variety of semi-synthetic derivatives have also been prepared (Table 1.18). 

The penicillins are a large group of bactericidal compounds. They can be subdivided and classified by their chemical structure and spectrum of activity. The structure common to all penicillins is a (3-lactam ring fused with a thiazolidine nucleus (Fig. 45.1).The antimicrobial activity of penicillin resides in the (3-lactam ring. Splitting of the (3-lactam ring by either acid hydrolysis or (3-lactamases results in the formation of penicilloic acid, a product without antibiotic activity. Addition of various side chains (R) to the basic penicillin molecule... 

The answer is b. (Hardman, p 1128.) Tetracycline is one of the drugs of choice in the treatment of Rickettsia, Mycoplasma, and Chlamydia infections. The antibiotics that act by inhibiting cell-wall synthesis have no effect on Mycoplasma because the organism does not possess a cell wall penicillin G, vancomycin, and bacitracin will be ineffective. Gentamicin has little or no antimicrobial activity with these organisms. 

In 1975, a United States Department of Agricultui e (USDA) survey showed that 5.3% of the 529 carcasses sampled were positive for antibiotic residues (2). Only 17 of the 5301 samples (0.3%) were positive for penicillin, whereas 12 of 728 samples (1.6%) were positive for sulfonamides. Nonspecific antimicrobial activity was found in 154 of the 5301 samples (2.9%) analyzed. 

Microbiological tests have indicated that penicillin G is stable to heat. Pasteurization temperatures and times commonly applied to milk and milk products are inadequate for inactivation of tlie antibiotic if it is present (26-29). At 71 C, a total of 1705 min was required to inactivate completely penicillin G in milk, whereas at boiling temperatures or above, all data indicated that a portion of tire penicillin activity in milk survived boiling for 60 min or autoclaving at 15 psi steam pressure for 15-30 min (26, 29). Milk from treated cows retained some of its antimicrobial activity even after conversion to dried skim milk powder (30). 

Lanolin has been used for many years as a vehicle for pharmacologically active substances in ophthalmic ointments and topical formulations.55-60 In addition to being a vehicle for penicillin and other antimicrobial substances, lanolin contains lipids such as 10-methyldodecanoic acid and 12-methyltridecanoic acid, which have antimicrobial activity.61,62... 

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). 

Like the penicillins, cephalosporins contain a P-lactam ring that is necessary for antimicrobial activity. However, a six-member dihydrothiazine ring replaces the five-member thiazoUdine ring characteristic of the penicillins. 

The appropriate energy content and reactivity of the /8-lactam 0=C-N bond (cf. the problem of 6(7)a-methyl and methoxy substitution and 2-substituted derivatives). Although the molecular orbital calculations on penicillins and cephalosporins [271,272,293] are not enough to yield exact conclusions, it is likely that a parabolic relationship exists between the electron population of the 0=C-N bond and the antimicrobial activity. 

Parenteral preparations with antimicrobial activity, which depends on the causative pathogenic microorganism, and pharmacokinetic properties that meet most of these criteria include procaine penicillin G (aqueous suspension), amoxicillin trihydrate-clavulanate potassium combination (aqueous suspension), and enro-floxacin (solution). Enrofloxacin is not approved for use... 

Polyoxyethylene stearates are unstable in hot alkaline solutions owing to hydrolysis, and will also saponify with strong acids or bases. Discoloration or precipitation can occur with salicylates, phenolic substances, iodine salts, and salts of bismuth, silver, and tannins.Complex formation with preservatives may also occur. The antimicrobial activity of some materials such as bacitracin, chloramphenicol, phenoxymethylpenicillin, sodium penicillin, and tetracycline may be reduced in the presence of polyoxyethylene stearate concentrations greater than 5% w/w. ... 

Miscellaneous Antibiotics. Because of the activity found in some of the materials in the early testing and that are discussed later under Bacitracin and Penicillin, a considerable number of antibiotics were screened with the hope that there would be a range of activity which might relate (a) to their antimicrobial activity, (b) to their mode of action as antibiotics, or (c) to some other biological relationship. The results of some of this work are shown in Table I (22). Our hopes were substantiated in that we have found a range of activity going from... 

The cephalosporins and tetracyclines are commonly used for treatment of UTIs in other species. However, in horses, the cephalosporins are rarely more advantageous than the penicillins or potentiated sulfonamides. However, ceftiofur has broad-spectrum antimicrobial activity and may be indicated when urinary pathogens are resistant to... 

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