• Publications
  • Influence
In Vitro and In Vivo Properties of Ro 63-9141, a Novel Broad-Spectrum Cephalosporin with Activity against Methicillin-Resistant Staphylococci
TLDR
The potential utility of Ro 63-9141 for the therapy of infections caused by susceptible pathogens, including MRSA, is suggested and a water-soluble prodrug, Ro 65-5788, is considered for development. Expand
A single amino acid substitution in Staphylococcus aureus dihydrofolate reductase determines trimethoprim resistance.
TLDR
Critical evidence concerning the resistance mechanism has been provided by NMR spectral analyses of 15N-labelled TMP in the ternary complexes of both wild-type and mutant enzyme, and studies show that the mutation results in loss of a hydrogen bond between the 4-amino group of TMP and the carbonyl oxygen of Leu5. Expand
Structure and function of the dihydropteroate synthase from Staphylococcus aureus.
TLDR
The three-dimensional structure of the substrate analogue binary complex could give important insight into the molecular mechanism of this enzyme, which defies a simple interpretation of their roles in resistance. Expand
Trapping of nonhydrolyzable cephalosporins by cephalosporinases in Enterobacter cloacae and Pseudomonas aeruginosa as a possible resistance mechanism
TLDR
Findings corroborate the assumption that binding of nonhydrolyzable cephalosporins, rather than hydrolysis by cep Halosporinases, may play an important role in resistance to these agents and other newer cep HALsporins in Enterobacteriaceae, as well as in other gram-negative bacteria. Expand
Mechanisms of resistance to trimethoprim, the sulfonamides, and trimethoprim-sulfamethoxazole.
  • R. Then
  • Biology, Medicine
  • Reviews of infectious diseases
  • 1 March 1982
TLDR
Several mechanisms of resistance that have rarely been discussed in the past are discussed, including metabolic alteration of trimethoprim or the sulfonamides and hyperproduction of p-aminobenzoic acid, and on the simultaneous presence of more than one mechanism. Expand
DNA and RNA synthesis: antifolates.
History and future of antimicrobial diaminopyrimidines.
  • R. Then
  • Biology, Medicine
  • Journal of chemotherapy
  • 1 December 1993
TLDR
Key milestones in the application of antimicrobial DHFR inhibitors were the introduction of TMP alone in 1972, the launch of a new combination of tetroxoprim, a close TMP-analog, with sulfadiazine, and the successful clinical trials with brodimopim, which proved clinically efficacious and safe with once-daily low dose monotherapy. Expand
Nature of trimethoprim-induced death in Escherichia coli.
Antimicrobial Dihydrofolate Reductase Inhibitors - Achievements and Future Options: Review
  • R. Then
  • Medicine, Biology
  • Journal of chemotherapy
  • 1 February 2004
TLDR
There are excellent chances for new drugs in this field, and they are thought to increase by limiting the spectrum of activity, whereas trimethoprim seems to present the optimum which can be achieved for a broad spectrum antibacterial agent. Expand
Mechanisms of trimethoprim resistance in enterobacteria isolated in Finland.
TLDR
Three different basic mechanisms were found to be responsible for TMP resistance in Enterobacteria from Finland and these were seen to occur not only independently but also simultaneously in the same strain. Expand
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