Induction Potency of Various Beta-Lactam Derivatives in Gram-Negative Rods

Abstract

The induction potency of various (3-lactams as well as that of ‘nonspecific’ inducers such as the media employed or body fluids were studied in gram-negative clinical isolates and in their resistant corresponding counterparts. In all wild-type isolates quite a few (3-lactams (mainly cefoxitin and imipenem) shared the ability to induce the chromosomal ^-lactamase, whereas all (3-lactams – including 6-APS and 7-CPS clavu-lanic acid, and sulbactam (both (3-lactamase inhibitors), exhibited strong induction potency in their corresponding resistant counterparts. Moreover, all resistant counterparts exhibited the phenomenon of ‘nonspecific’ induction, whereas the wild-type strains did not. Interestingly, in both Proteus vulgaris 4917 W and Providencia rettgeri 862 W wild-type strains most P-lactam compounds were potent inducers, thus providing an explanation for resistance against P-lactamase-unstable compounds. The addition of subinhibitory concentrations of the quinolone compound enoxacin or chloramphenicol did not influence the phenotypic (3-lactamase expression, neither in wild-type strains nor in their resistant counterparts, whereas the addition of clindamycin or gentamicin resulted in a marked decrease of enzyme production in cephalosporinase overproducers, the P. vulgaris and the P. rettgeri isolates.

Drugs That Changed Society: History and Current Status of the Early Antibiotics: Salvarsan, Sulfonamides, and β-Lactams

“…β-Lactamases are widely distributed [ 70 , 71 , 74 , 75 ] and have been studied intensive because of their ability to neutralize the clinical effect of penicillins. In several pathogenic organisms, expression of β-lactamases is provoked by β-lactam antibiotics [ 76 ]. The β-lactamases are divided into three classes A (penicillin-hydrolyzing), C (cephalosporin-hydrolyzing) and D (oxacillin-hydrolyzing) and Class B the metallo-β-lactamases [ 44 , 70 , 72 , 77 ].…”

Variation in Induction of Chromosomal Beta-Lactamase Expression in Strains of <i>Enterobacter cloacae</i>

“…Class I P-lactamases can be in duced not only by P-lactam antibiotics but also by 'nonspecific' agents, like gly cine [2], thiamine, complex media and various body fluids [3]. Cefoxitin has proved to be a potent inducer in E. cloa cae strains [4], The molecular basis of P-lactamase induction is still not com pletely understood, but in E. cloacae and in C. freundii the induction of the ampC gene coding for this class I (1-lactamase is controlled by a least two genes, ampR and ampD [5]. AmpR is a regulatory pro tein, which represses the synthesis of AmpC in the absence, and stimulates the expression of ampC in the presence, of a (1-lactamase inducer [6,7].…”