B-Lactam antibiotics

Waxman, D.J. Strominger, J. L. (1983). Penicillin-binding proteins and the mechanism of action of B-lactam antibiotics. Annu. Rev. Biochem. 52, 825-869. 

Although many B-lactam antibiotics have been described, a relatively small number are used in food-producing animals and these are the only ones of concern as residues. Microbiological test procedures are ordinarily very sensitive to B-lactam antibiotics (49). 

Table II. Chromatographic Methods for Detection of B-lactam Antibiotic Residues in Foods...

Penicillins form several major metabolites which are excreted in the urine (83,84). These metabolites are usually inactive microbio-logically and they would not be detected by the usual microbiological tests. There are no analytical methods for these metabolites in tissues and, therefore, little is known as to their occurrence and persistence in tissues. There are no methods available for identifying residues of some commonly used B-lactam antibiotics including carbenicillin and ticarcillin. For cephapirin and ampicillin, except for one HPLC method for ampicillin in milk (79) only TLC procedures (72-74,76) with detection by bioautography are reported. 

Although some European countries still accept the results of the four plate test as confirming the presence of antibiotic residues in samples ( ), other work indicates that FPT test is not necessarily reliable. The occurrence of natural microbial inhibitors in tissues has frequently been noted (4,9,49,82), It has also been frequently observed that the results obtained by microbial and physicochemical procedures sometimes differ considerably (9,10,45,82,86), Results obtained in our laboratory suggest that even inactivation by penicillinase may not be totally specific for B-lactam antibiotics (W), The specificity of immunoassay procedures depends on the specificity of the antibody used in the test (95), Specific antisera are not widely available at present. Physicochemical procedures are therefore essential for identification and confirmation of suspect residues detected by microbiological tests. 

An important molecular target of the B-lactam antibiotics is an enzyme that acts as a transpeptidase in the stepwise polymerization leading to a thickened, strong bacterial cell wall. Several amino acids are present in addition to the terminal -alanyl- -alanyl unit which the Strominger hypothesis suggests has the same overall shape and reactivity as... 

Core structures of four B-lactam antibiotic families. The ring marked in each structure is the -lactam ring. The penicillins are susceptible to bacterial metabolism and inactivation by amidases and lactamases at the points shown. Note that the carbapenems have a different stereochemical configuration in the lactam ring that apparently imparts resistance to lactamases. Substituents for the penicillin and cephalosporin families are shown in Figures 43-2 and 43-6, respectively. 

Because of potential toxicity, bacterial resistance, and the availability of many other effective alternatives, chloramphenicol is rarely used. It may be considered for treatment of serious rickettsial infections such as typhus and Rocky Mountain spotted fever. It is an alternative to a B-lactam antibiotic for treatment of meningococcal meningitis occurring in patients who have major hypersensitivity reactions to penicillin or bacterial meningitis caused by penicillin-resistant strains of pneumococci. The dosage is 50-100 mg/kg/d in four divided doses. 

Pikal, M. J., Lukes, A. L., Lang, J. E., and Gaines, K. (1978), Quantitative crystalhne determinations for b-lactam antibiotics by solution calorimetry Correlation with stability, /. Pharm. Sci., 67,767-773. 

Grande s group has studied the titanocene-promoted intramolecular addition of epoxides to activated alkenes in both 5-exo and 6-endo cyclization modes as a new way of preparing polycyclic b-lactam antibiotics [ 110-112]. 

Antibiotic combinations EDTA and other agents Gentamicin and other agents Carbenicillin Other agents B-Lactam antibiotics Combinations of preservatives Sensitivity to antibacterial agents... 

SLC22A8) urate Drugs B-lactam antibiotics, diuretics, NSAIDs, quinidine... 

Ganapathy, M.E., Brandsch, M., Prasad, P.D., Ganapathy, V. and Leibach, F.H. (1995) Differential recognition of b-lactam antibiotics by intestinal and renal peptide transporters, PEPT1 and PEPT2. Journal of Biological Chemistry, 270, 25672-25677. 

B-Lactam Antibiotics. — Using cell-free preparations of eucaryotic organisms, e.g., Cephalosporium acremonium, it has very clearly been shown that the biosynthesis of penicillins involves the cyclisation of an intact molecule of the tripeptide (138) to give isopenicillin N (139) (cf. Vol. 12, p.25). Streptomyces clavuligerus is a procaryotic organism which produces 6-lactam antibiotics. A cell-free preparation of this organism has been obtained which would convert (138) into (139) ... 

B-Lactam antibiotic amoxycillin in therapy of infections 97MI14. 

Sheldon RA, van Reintwijk F, van Langen LM et al. (2001) Biocatalysts and biocattilysis in the synthesis of 3-lactam antibiotics. In Bruggink A (ed). Synthesis of B-lactam antibiotics. Kluwer Acad Publ, Dordrecht, pp 103-148... 

Morin, R. and Gorman, M. (eds) (1982) Chemistry and Biology of B-Lactam Antibiotics, York Academic Press. 

Our endeavours in peptide and 6-lactame chemistry concentrate on the use of four component condensations (4CC, Ugi reaction (refs. 1,2,5)) in the synthesis of peptides, B-lactam antibiotics and related compounds. 

Due to their excellent bactericidal and bacteriostatic properties and their general lack of serious side-effects (ref. 16) the B-lactam antibiotics still belong to the most favoured antibacterial drugs that are avaible. The research activities in the field of 6-lactam antibiotics including the chemical synthesis of 6-lactam antibiotics and related compounds, have increased up to now (ref. 16). 

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