Antibiotics beta-lactam

Interaction between Beta-Lactam Antibiotics and Aminoglycoside Antibiotics 

The beta-lactam antibiotics are anionic, unstable to hydrolysis, and act by inhibiting the synthesis of the bacterial cell wall. 

FIGURE 13. Cyclic voltammogram of the phenytoin Na CPZ-HCl system. Both reagents were in aqueous solution at 37 °C, Pt/Pt electrodes. Potentials vs. SCE. Sweep rate lOOmV/sec. The peaks at about —300 mV and at about +250 mV do not occur in the voltammograms of the components. The peak at about +700 mV is due to the chlor-promazine free radical. 

FIGURE 14. Structures of beta-lactam antibiotics examples. A benzyl penicillin sodium. B carbenicillin. C cephalotin. 

Strategies for Organic Drug Synthesis and Design, Second Edition. By Daniel Lednicer Copyright 2009 John Wiley Sons, Inc. 

---

Michael reactions and, 895 Beta-keto ester, 851 alkylation of, 859-860 cyclic, 892-893 decarboxylation of, 857, 860 Michael reactions and. 895 pKd of, 852 synthesis of, 892-893 Beta-lactam antibiotics, 824-825 Beta oxidation pathway, 1133-1137 mechanism of, 1133-1136 Beta-pleated sheet (protein), 1038 molecular model of, 1039 secondary protein structure and, 1038-1039 Betaine, 720 Bextra. structure of, 544 BHA, synthesis of, 629 BHT, synthesis of. 629 Bicycloalkane. 129 Bijvoet. J. M., 299 Bimolecular, 363... 

Torii, S., Tanaka, H., and Inokuchi, T. Role of the Electrochemical Method in the Transformatic of beta-Lactam Antibiotics and Terpenoids. 148, 153-193 (1988). 

MJ Pikal, AL Lukes, JE Lang, K. Gaines. Quantitative crystallinity determinations for beta-lactam antibiotics by solution calorimetry Correlations with stability. J Pharm Sci 67(6) 767-773, 1978. 

Boll, M., et al. Expression cloning of a cDNA from rabbit small intestine related to proton-coupled transport of peptides, beta-lactam antibiotics and ACE-inhibitors. Pflugers Arch. 1994, 429, 146-149. 

Saito, H., et al. Cloning and characterization of a rat H+/peptide cotransporter mediating absorption of beta-lactam antibiotics in the intestine and... 

Wenzel, U., D. T. Thwaites, and H. Daniel. Stereoselective uptake of beta-lactam antibiotics by the intestinal peptide transporter. Br. ]. Pharmacol. 1995, 116, 3021-3027. 

Bretschneider, B., M. Brandsch, and R. Neubert. Intestinal transport of beta-lactam antibiotics analysis of the affinity at the H+/peptide symporter (PEPT1), the uptake into Caco-2 cell monolayers and the transepithelial flux. Pharm. Res. 1999, 16, 55-61. 

Terada, T., et al. Recognition of beta-lactam antibiotics by rat peptide transporters, PEPT1 and PEPT2, in LLC-PK1 cells. Am. J. Physiol. 1997, 273, F706-F711. 

Ganapathy, M. E., et al. Differential recognition of beta-lactam antibiotics by intestinal and renal peptide transporters, PEPT 1 and PEPT 2. 

Kramer, W., et al. Interaction of renin inhibitors with the intestinal uptake system for oligopeptides and beta-lactam antibiotics. Biochim. Biophys. Acta 1990, 1027, 25-30. 

Cefadroxyl and cefaclor are beta-lactam antibiotics which show high affinity for the PepTl carrier system, whereas the other two beta-lactams, cephalotin and cef-metazole, are not recognized by PepTl protein and are not actively transported in the intestine. However, as the VolSurf Caco-2 model predicts that all the beta-lactams are nonpenetrating compounds, it is very probable that, as they rely only the diffusion mechanism, cefadroxyl and cefaclor will not cross the cell monolayer. 

Winston DJ, Winston GH, Bruckner DA, Champlin RE Beta-lactam antibiotic therapy in febrile granulocytopenic patietns. Ann Intern Med 1991 115 849-859. 

Rothstein, J. D., Patel, S., Regan, M. R. etal. Beta-lactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Nature 433 73-77,2005. 

Penicillin G 24 million units/24 h IV in four to six equally divided doses may be used in place of nafcillin or oxacillin if strain is penicillin susceptible (minimum inhibitory concentration 0,1 mcg/mL) and does not produce /5-lactamase vancomycin should be used in patients with immediate-type hypersensitivity reactions to beta-lactam antibiotics (see Table 37-3 for dosing guidelines) cefazolin may be substituted for nafcillin or oxacillin in patients with non-immediate-type hypersensitivity reactions to penicillins... 

The sodium salt of the phenylglycine derivative (33) was investigated as an absorption promoter for the rectal absorption of beta-lactam antibiotics and insulin [80JAP(K)31040 81CPB1998, 81CPB2012], (Naphthothiazol-2-ylidene)malonates (1661 and 1662) were applied in silver halide photographic emulsions as sensitizer dyes [82JAP(K)54936]. 

Later in his career, Nagata s group made notable and useful synthetic contributions to the beta lactam field. This included developing an economically feasible synthetic method for the industrial manufacture of 1-oxacephems from penicillin G. These efforts led to the worldwide introduction in the 1980s of several clinically prominent and effective beta lactam antibiotics of the 1-oxacephem class including moxalactam. 

A. L. Demain, R. R Elander, The beta-Lactam Antibiotics Past, Present, and Future , Antonie van Leeuwenhoek 1999, 75, 5-19. 

K. E. Price, D. N. McGregor, Basic Design of beta-Lactam Antibiotics - Cephalosporins , Scan. J. Infect. Dis. -Suppl. 1984, 42, 50-63. 

J. M. Frere, B. Joris, B. Granier, A. Matagne, F. Jacob, C. Bourguignon-Bellefroid, Diversity of the Mechanisms of Resistance to beta-Lactam Antibiotics , Res. Microbiol. 1991, 142, 705-710. 

E. Nakashima, A. Tsuji, M. Nakamura, T. Yamana, Physicochemical Properties of Amphoteric beta-Lactam Antibiotics. IV. First- and Second-Order Degradations of Cefaclor and Cefatrizine in Aqueous Solution and Kinetic Interpretation of the Intestinal Absorption and Degradation of the Concentrated Antibiotics , Chetn. Pharrn. Bull. 1985, 33, 2098-2106. 

A. G. De Oliveira, M. V. Scarpa, H. Chaimovich, Effect of Hexadecyltrimethyl-ammo-nium Bromide-Based Microemulsions on the Rate of Decomposition of the beta-Lactam Antibiotic Cephaclor , J. Pharm. Sci. 1997, 86, 616-620. 

Beta-lactam antibiotics are a second great class of antibacterials penicillins, cephalosporins, carbapenems, and monobactams. They act by inhibiting bacterial cell wall synthesis. 

Beta-lactam antibiotic one of several classes of antibacterials possessing the P-lactam nucleus. 

Kahan JS, Kahan EM, Goegelman R, Currie SA, Jackson M, Stapley EO, Miller TW, Miller AK, Hendlin D, Mochales S, Hernandez S, Woodruff HB, Bimbaum J. (1979) Thienamycin, a new beta-lactam antibiotic. I. Discovery, taxonomy, isolation and physical properties. JAntibiot 32 1-12. 

Cephalosporins. These beta-lactam antibiotics share many features with the penicillins including mechanism, spectrum of action, distribution ans toxicity potential. At the present time, the cephalosporins are classified into three groups, designated as generations. 

Inhibition of cell membranes synthesis in microorganisms (beta-lactam antibiotics, vancomycin, cycloserine). 

The primary mechanism of the action of beta-lactam antibiotics is the inhibition of synthesis of cell membranes of bacteria, which causes them to quickly die. Their initial action is to initiate the work of autolytic enzymes, which destroy cell membranes and cause lysis of the bacteria. 

As already noted, beta-lactam antibiotics interfere with biosynthesis of the primary component of cell membranes—pepfidoglycan. Because of the fact that this process does not take place in human and other mammalian cells, beta-lactam antibiotics are relatively non-toxic to humans. 

Beta-lactam antibiotics specifically bind with a number of proteins of cytoplasmic membranes known as penicillin-binding proteins (PBP). These proteins are enzymes involved in the reaction of transpeptidafion during the break up of cell membranes during growth and division. 

For example, Escherichia coli have six PBP. PBP-la and -lb, which are transpepfidases, are involved in the synthesis of peptidoglycan. PBP-2 is necessary for supporting the rodshaped form of bacteria. Selective inhibition of this enzyme causes production of other non-rod-shaped forms of bacteria, which eventually undergo lysis. PBP-3 is necessary to form the partition during division. Selective inhibition of this enzyme leads to the formation of a fibrous form of bacteria containing many units of rod-shaped bacteria unable to separate one from another, which results in their death. Various beta-lactam antibiotics have a selective affinity to one or a few PBP. Inactivation of certain PBP (PBP-la, -lb, -2, or -3) causes cell death. Unlike these, inactivaition of low-molecular PBP (PBP-4, -5, and -6) is not lethal to bacteria. 

Resistance of pathogenic microorganisms to beta-lactam antibiotics can result from one or a few of the mechanisms listed below inability of the drug to directly find an active site a change in PBP function, which is expressed in the reduction of affinity to the drag or inactivation of the drug by bacterial enzymes. 

Beta-lactam antibiotics must pass through the outer layer of the cell in order to get the desired PBP to the surface of the membrane. In Gram-positive bacteria, the cell membrane is the only layer covering the cytoplasmic membrane. In a few types of this bacteria, there is a polysaccharide capsule on the outer side of the cell membrane. However, not one of the described structures can serve as a barrier for the diffusion of small molecules such as beta-lactams. Therefore, the idea that the cause of possible resistance is the inability of beta-lactam antibiotics to get the desired PBP is not likely to be a possible mechanism of resistance for Gram-positive bacteria. 

---