Some Adverse Drug Reactions Common in the Postoperative Period
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Benzylpenicillin
Benzylpenicillin
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Cross antigenicity of cephalosporins with penicillin has been studied experimentally and also by using serum from penicillin sensitive individuals. Definite hypersensitivity reaction was observed in all the animals sensitised with cephalosporins and challenged with penicillin except in rats. Cephalosporins could elicit reaction in tissues sensitised passively with serum obtained from penicillin sensitive individuals.
Antigenicity
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Several recent surveys of clinical isolates have indicated that substantial fractions of naturally occurring populations of Streptococcus pneumoniae have undergone a distinct upward move in the required minimal inhibitory concentration (MIC) of benzylpenicillin (from a range of 0.006–0.008 to 0.03–0.05 µg/ml). Evidence is presented that in clinical pneumococcal isolates, penicillin-binding proteins (PBPs) groups 1 and 2 have a decreased affinity for radioactive benzylpenicillin as compared with penicillin-sensitive isolates from the same locale. Exposure of a penicillin-sensitive type 2 strain (MIC, 0.006 µg/ml) to sequentially increasing concentrations of penicillin allowed the isolation of spontaneous resistant mutants with stepwise increases in the MIC of penicillin required (0.01–0.02, 0.025–0.05, and 0.1 µg/ml), and in these laboratory isolates too, PBP groups 1 and 2 showed decreased affinity for labeled benzylpenicillin. DNA from the low-level resistant clinical or laboratory isolates could be used to transform the appropriate levels of penicillin resistance into penicillin-sensitive laboratory isolates. These findings suggest that significant fractions of natural pneumococcal populations may have acquired one or two of the low-level penicillin resistance genes.
Benzylpenicillin
Penicillin binding proteins
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SUMMARY Tube sensitivity tests show that, of twelve penicillins, ampicillin, benzylpenicillin and 6-aminopenicillanic acid were the most active when tested against medium-sized inocula (106 organisms) of twelve strains of penicillinase-producing Klebsiella (11 Klebsiella aerogenes and 1 K. ozaenae), which had been isolated from clinical material and were resistant to both ampicillin and tetracycline. An inoculum size effect was consistently noted when ampicillin and benzylpenicillin were tested against different inocula; the effect was significantly greater with ampicillin. The following parameters were measured for the strains, using both benzylpenicillin and ampicillin: magnitude of the inoculum size effect; inherent sensitivity (sensitivity of a small inoculum); rate of penicillin destruction; ability of penicillins to pass bacterial permeability barriers. From considerations of the relationships between these values, it has been concluded that penicillinase is primarily responsible for the observed resistance of only two of the twelve strains; although penicillinase and the lack of ability of penicillins to obtain free access into the bacterial cells add to the over-all penicillin resistance of the other ten strains, the primary reason for their penicillin resistance is neither their possession of penicillinase nor their permeability barrier: such resistance presumably reflects an innate lack of sensitivity of the cell wall synthesizing complex to inhibition by penicillins.
Benzylpenicillin
Klebsiella
Amp resistance
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Cephalosporin Antibiotic
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The response to benzylpenicillin of 2 strains of Staphylococcus aureus was investigated in vitro using 3 techniques in parallel: continuous turbidimetric monitoring, continuous microscopic monitoring, and thin-section electron microscopy. Cultures of staphylococci were exposed to several concentrations of penicillin for various intervals of time before terminating the antibiotic activity with penicillinase. Bacterial lysis by penicillin was concentration-dependent and showed an optimal dosage effect which was very marked for one of the strains. The growth and division of cells continued for up to 1 h in the presence of penicillin. A variety of morphological responses was observed at each penicillin concentration. These changes ranged from complete bacterial lysis to apparently normal cells, and included several different types of aberrant morphological forms. On addition of penicillinase to cultures exposed to penicillin, there was a time interval before survivors began to divide. This period was increased by raising the concentration of penicillin or by increasing the period of exposure to penicillin. Bacteria resuming growth after surviving penicillin action exhibited markedly aberrant septation. Most of the survivors were found to originate from clumps of cocci rather than from individual cells or small groups.
Benzylpenicillin
Penicillin resistance
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Two groups of 49 patients each with generalized forms of meningococcal infection were observed. The patients of the 1st group were treated with ampicillin in a dose of 200-400 Units/kg and the patients of the 2nd group were treated with benzylpenicillin in a dose of 200000-300000 Units/kg of the body weight daily. Comparison of the ampicillin and benzylpenicillin liquor levels showed that benzylpenicillin was more persistent during the whole period between the injections. The indices of the patients' recovery in the groups observed did not differ significantly, which provided a conclusion that ampicillin was clinically effective and may be recommended as an independent etiotropic drug for treatment of generalized forms of meningococcal infection.
Benzylpenicillin
Meningococcal meningitis
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The bactericidal activity of benzylpenicillin and ampicillin on 21 strains of enterococci was evaluated and compared to the activity of these drugs in combination with streptomycin (20 μg/ml). On a weight basis, ampicillin was about twice as effective as benzylpenicillin. Neither of the drugs was rapidly and completely bactericidal for any of the 21 strains of enterococci when used alone. The addition of streptomycin greatly enhanced the early bactericidal rate achieved with any given amount of either penicillin and permitted the elimination of viable organisms in vitro. These results suggest that, for the time being, combined antibiotic therapy might be desirable in enterococcus endocarditis and that ampicillin, although more effective than benzylpenicillin, should not be relied upon as a single drug in that disease.
Benzylpenicillin
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1. Antisera have been produced in rabbits to benzylpenicillin and four members of the cephalosporin C family and to conjugates of these substances with bovine gamma-globulin. 2. Deacetoxycephalosporin C reacted less readily and deacetylcephalosporin C lactone more readily with bovine gamma-globulin than did benzylpenicillin, cephalosporin C or deacetylcephalosporin C. 3. Antisera to free or conjugated benzylpenicillin agglutinated red cells sensitized with a variety of penicillins, but only reacted to a significant extent with cells sensitized with the cephalosporins tested when the latter contained an N-phenylacetyl or chemically related side chain. 4. Antisera to members of the cephalosporin C family agglutinated cells sensitized with these cephalosporins or with penicillin N, but did not react with cephalosporins whose side chains were chemically unrelated to alpha-aminoadipic acid. 5. Members of the cephalosporin C family and products of hydrolysis of cephalosporin C behaved as hapten inhibitors of antisera to cephalosporin C, but 7-aminocephalosporanic acid was relatively ineffective. 6. These findings are discussed in relation to differences in the chemical properties of penicillins and cephalosporins.
Benzylpenicillin
Cephalosporin C
Cephaloridine
Hapten
Cephalosporin Antibiotic
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