Antimicrobial and beta-lactamase inhibitory activities of carpetimycins A and B, new carbapenem antibiotics

Abstract

Carpetimycins A and B showed widely broad spectra and potent activity against gram-positive and gram-negative bacteria, including various species of anaerobic bacteria. The antimicrobial activity of carpetimycin A was 8 to 64 times greater than that of carpetimycin B and 4 to 128 times greater than that of cefoxitin. The inhibitory concentration of carpetimycin A required to inhibit more than 90% of clinical isolates was 0.39 ,ug/ml for Escherichia coli and Klebsiella and 1.56 ,ug/ml for Proteus and Staphylococcus aureus. At a concentration of 3.13 ,ug/ml, carpetimycin A inhibited almost all clinical isolates of Enterobacter and Citrobacter, which showed resistance to many clinically used ,B-lactam antibiotics. Carpetimycins A and B furthermore were shown to have potent inhibitory activities against several kinds of 1-lactamases produced by P-lactan-resistant strains; they inhibited not only penicillinase-type P-lactamases but also cephalosporinase-type P-lactamases, which were insensitive to clavulanic acid. In combination with P-lactam antibiotics such as ampicillin, carbenicillin, and cefazolin, carpetimycins A and B showed synergistic activities against P-lactam-resistant bacteria.

Carbapenems: Past, Present, and Future

“…Thienamycin was the first "carbapenem" and would eventually serve as the parent or model compound for all carbapenems. A series of other carbapenems were also identified (30,92,107,147,149,162,163,172,233); however, the discovery of thienamycin was paramount.…”

Discovery and development of new antibiotics: the problem of antibiotic resistance

“…When the molecular mechanism of resistance is characterized, it has been feasible to design specific therapeutic combinations on the basis of the antagonism of the major resistance determinants. This approach has been reviewed by Labia et al (29) and is exemplified by the introduction of amoxicillin-clavulanate combination therapy (5 (27), and the penem BRL-42715 (9), which can inhibit a variety of cephalosporinases (including clavulanate-resistant ones), have been reported to be useful in combination with broadspectrum cephalosporins.…”

“…Without the development and introduction of new or improved antibiotics to ensure coverage of resistant organisms, empirical treatment must often rely on combination therapy. In the future, the use of adjunctive therapy with immune modulators such as granulocyte macrophage colony-stimulating factor and granulocyte colony-stimulating factor will certainly increase (21 27,37,39,50), so we will not do so here. However, it is important to recognize the two overall types of antibiotic resistance which occur, i.e., "endogenous" resistance versus exogenous or "positive-function" resistance (3,22).…”

Review on a Potential of Antibiotics

“…[30] There have also been a number of other carbapenems discovered. [35,36] Figure 5. Structure of Carbapenem [30] Carbapenems play a critical role in our struggle against bacterial illnesses.…”