Topic
Penicillin
About: Penicillin is a research topic. Over the lifetime, 17916 publications have been published within this topic receiving 368480 citations. The topic is also known as: penicillin antibiotic & PCN.
Papers published on a yearly basis
Papers
More filters
TL;DR: It is suggested that a likely explanation for the survival of phagocytized bacteria in the presence of high concentrations of most antibiotics is the inability of the antibiotic to enter the phagocyte.
Abstract: Bacteria that survive inside polymorphonuclear neutrophils (PMN) following phagocytosis are protected from the bactericidal action of most antibiotics. Two possible explanations are altered metabolism by intraleukocytic bacteria or failure of antibiotics to enter the phagosome. The oxygen consumption of intraleukocytic and extraleukocytic bacteria was measured as an index of bacterial metabolism. PMN respiration and bactericidal activity were suppressed with large doses of hydrocortisone and extraleukocytic bacterial oxygen consumption was abolished by the addition of lysostaphin. Intraleukocytic bacterial continued to consume oxygen suggesting that surviving ingested micro-organisms are metabolically active. Neither penicillin (which cannot kill intraleukocytic bacteria) nor rifampin (which can kill intraleukocytic bacteria) was bactericidal for staphylococci at 5 degrees C. Thus, rifampin is not uniquely able to kill "resting" bacteria.Intraleukocytic or extraleukocytic Staphylococcus aurens were incubated with [benzyl-(14)C]penicillin for 2 h at 37 degrees C. Live intraleukocytic bacteria bound only 13% as much penicillin as live bacteria incubated with killed PMN. To measure the penetration of antibiotics into PMN, [(14)C]rifampin and [(14)C]penicillin were measured in leukocyte pellets and in the supernatant fluid. The total water space in the pellets was quantitated using tritium water and the extracellular water space was measured using Na(235)SO(4). All penicillin associated with the cell pellet could be accounted for in extracellular water. Thus penicillin was completely excluded from the leukocytes. Rifampin was concentrated in the cell pellet 2.2 times when compared with the supernatant concentration. These studies suggest that a likely explanation for the survival of phagocytized bacteria in the presence of high concentrations of most antibiotics is the inability of the antibiotic to enter the phagocyte. Rifampin, which is highly lipid soluble, can enter leukocytes and kill intracellular bacteria.
217 citations
TL;DR: It is suggested that inhibition of cell wall synthesis by any means triggers bacterial autolytic enzymes by destabilizing the endogenous complex of an autolysin inhibitor (lipoteichoic acid) and Autolytic enzyme.
Abstract: During penicillin treatment of an autolysin defective mutant pneumococcus we have observed three novel phenomena: (i) Growth of the mutant cultures is inhibited by the same concentrations of penicillin that induce lysis in the wild type. (ii) Mutant bacteria treated with the minimum growth inhibitory concentration of penicillin will lyse upon the addition of wild-type autolysin to the growth medium. Chloramphenicol and other inhibitors of protein synthesis protect the cells against lysis by exogenous enzyme. Sensitivity of the cells to exogenous autolysin requires treatment with penicillin or other inhibitors of cell wall synthesis (e.g., D-cycloserine or fosfonomycin) since exogenous autolysin alone has no effect on bacterial growth. (iii) Treatment with penicillin (or other inhibitors of cell wall synthesis) causes the escape into the medium of a choline-containing macromolecule that has properties suggesting that it contains pneumococcal lipoteichoic acid (Forssman antigen). Each one of these three phenomena (growth inhibition, sensitization to exogenous autolysin, and leakage of lipoteichoic acid) shows the same dose response as that of the penicillin-induced lysis of wild-type pneumococci. On the basis of these findings we propose a new hypothesis for the mechanism of penicillin-induced lysis of bacteria. It is suggested that inhibition of cell wall synthesis by any means triggers bacterial autolytic enzymes by destabilizing the endogenous complex of an autolysin inhibitor (lipoteichoic acid) and autolytic enzyme. Escape of lipoteichoic acid-like material to the growth medium is a consequence of this labilization. Chloramphenicol protects bacteria against penicillin-induced lysis by interfering with the activity of the autolytic enzyme, rather than by depleting the concentration of the enzyme at the cell surface.
215 citations
TL;DR: Clinically significant IgE-mediated penicillin allergy can be safely confirmed or refuted using skin testing with penicilloyl-poly-lysine and nativePenicillin G and, if skin test is negative, an oral amoxicillin challenge.
Abstract: Penicillin is the most common beta-lactam antibiotic allergy and the most common drug class allergy, reported in about 8 % of individuals using health care in the USA. Only about 1 % of individuals using health care in the USA have a cephalosporin allergy noted in their medical record, and other specific non-penicillin, non-cephalosporin beta-lactam allergies are even rarer. Most reported penicillin allergy is not associated with clinically significant IgE-mediated reactions after penicillin rechallenge. Un-verified penicillin allergy is a significant and growing public health problem. Clinically significant IgE-mediated penicillin allergy can be safely confirmed or refuted using skin testing with penicilloyl-poly-lysine and native penicillin G and, if skin test is negative, an oral amoxicillin challenge. Acute tolerance of an oral therapeutic dose of a penicillin class antibiotic is the current gold standard test for a lack of clinically significant IgE-mediated penicillin allergy. Cephalosporins and other non-penicillin beta-lactams are widely, safely, and appropriately used in individuals, even with confirmed penicillin allergy. There is little, if any, clinically significant immunologic cross-reactivity between penicillins and other beta-lactams. Routine cephalosporin skin testing should be restricted to research settings. It is rarely needed clinically to safely manage patients and has unclear predictive value at this time. The use of alternative cephalosporins, with different side chains, is acceptable in the setting of a specific cephalosporin allergy. Carbapenems and monobactams are also safely used in individuals with confirmed penicillin allergy. A certain predictable, but low, rate of adverse reactions will occur with all beta-lactam antibiotic use both pre- and post-beta-lactam allergy evaluations.
214 citations
TL;DR: Significant similarity found by x-ray crystallography in the spatial arrangement of the elements of secondary structure provides strong support for earlier hypotheses that beta-lactamases arose from penicillin-sensitive D-alanyl-D-alanine-peptidases involved in bacterial wall peptidoglycan metabolism.
Abstract: Structural data are now available for comparing a penicillin target enzyme, the D-alanyl-D-alanine-peptidase from Streptomyces R61, with a penicillin-hydrolyzing enzyme, the beta-lactamase from Bacillus licheniformis 749/C. Although the two enzymes have distinct catalytic properties and lack relatedness in their overall amino acid sequences except near the active-site serine, the significant similarity found by x-ray crystallography in the spatial arrangement of the elements of secondary structure provides strong support for earlier hypotheses that beta-lactamases arose from penicillin-sensitive D-alanyl-D-alanine-peptidases involved in bacterial wall peptidoglycan metabolism.
213 citations
TL;DR: When aureomycin became available and was shown to be effective in therapy of isolated cases of pneumococcic meningitis, it was decided to test its efficacy by treating alternate patients with either penicillin or Aureomycin.
Abstract: PNEUMOCOCCIC meningitis is well known as one of the most serious forms of bacterial meningitis. Before the sulfonamides were used pneumococcic meningitis was almost always fatal. With the advent of penicillin an era of more successful therapy was started. Originally it was established that when small systemic doses of penicillin were given the result could be greatly improved by administering the antibiotic intrathecally. It was later shown1that the administration of large doses of penicillin systemically gave still better results and that intrathecal penicillin therapy was unnecessary when this regimen was employed. In spite of these advances, however, approximately one of three persons with pneumococcic meningitis still died, as shown on analysis of series of unselected cases. Consequently, when aureomycin became available and was shown to be effective in therapy of isolated cases of pneumococcic meningitis, we decided to test its efficacy by treating alternate patients with either penicillin
213 citations