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Biomedical subjects

John F Barrett

Publications and source records attributed to John F Barrett.

28 records · Page 2Linked to original sources
PubMed2004

MRSA: status and prospects for therapy? An evaluation of key papers on the topic of MRSA and antibiotic resistance.

Methicillin-resistant Staphylococcus aureus (MRSA) is a serious nosocomial pathogen, and a related community-sourced MRSA is emerging. MRSA has evolved to become the major S. aureus phenotype in the hospital, emerging from just 30 to over 60% of the S. aureus population over the past 15 years. Together with its beta-lactam resistance, MRSA possesses multi-drug resistance genotype, including quinolones, macrolides and sulfonamides. MRSA has now emerged as the predominant nosocomial Gram-positive pathogen, and it has a high rate of mortality. Action must be taken to contain and eradicate MRSA through a combination of infection control and the development of novel anti-MRSA agents and vaccines.

Attitude to Health↗
PubMed2004

Patent alert.

Explore the source record for details and available documents.

Drugs, Investigational↗
PubMed2003

Sordaricin antifungal agents.

Compounds based on sordaricin were prepared via organometallic addition onto a fully protected sordaricin aldehyde. The fungal growth inhibition profiles for these compounds were established and the results are presented here. The synthesis of homologated sordaricin as well as ether and ester derivatives is presented, and structural rearrangement products upon oxidation. These compounds were evaluated as agents to inhibit fungal growth.

Aldehydes↗
PubMed2003

Antibacterials: are the new entries enough to deal with the emerging resistance problems?

Fifty years of making analogs based on less than ten antibacterial scaffolds has resulted in the development and marketing of over 100 antibacterial agents but, with the exception of the oxazolidinone core, no new scaffolds have emerged in the past 30 years to address emerging resistance problems. As the support for antibacterial research shifts away from large pharmaceutical companies, a wave of biotechnology companies have pursued a diverse choice of targets resulting in several novel classes of agent in late-stage development. Although critical for certain resistance niche needs, these agents are unlikely to provide the solution to the requirement for a major novel scaffold class of antibacterials.

Anti-Bacterial Agents↗
PubMed2003

Antibiotics and pharmacogenomics.

The widespread use of antibiotics impacts both the bacterial ecology and the host at multiple levels, both advantageously and deleteriously. Since serious bacterial infection can lead to death in the absence of antibiotic therapy, antibiotics remain a necessary weapon in the clinician's arsenal for maintaining good health. It is thus critical that the placement and usage of these crucial antibiotics be constantly improved, and that emerging antibiotic resistance is vigorously assessed. To realize both these ends, it may be valuable to turn to the discipline of pharmacogenomics and develop it for use in a fairly novel way, that is, as the means by which to determine and analyze the impact of antibiotic therapy on both the pathogen and host.

Anti-Bacterial Agents↗
PubMed2002

Oxime derivatives of sordaricin as potent antifungal agents.

Oxime derivatives of the sordarin aglycone have been identified as potent antifungal agents. The in vitro spectrum of activity includes coverage against Candida albicans and Candida glabrata with MICs as low as 0.06 microg/mL. The antifungal activity was established to be exquisitely sensitive to the spatial orientation of the lipophilic side chains.

Antifungal Agents↗
PubMed2002

Bactericidal activities of BMS-284756, a novel Des-F(6)-quinolone, against Staphylococcus aureus strains with topoisomerase mutations.

The antistaphylococcal activities of BMS-284756 (T-3811ME), levofloxacin, moxifloxacin, and ciprofloxacin were compared against wild-type and grlA and grlA/gyrA mutant strains of Staphylococcus aureus. BMS-284756 was the most active quinolone tested, with MICs and minimal bactericidal concentrations against S. aureus wild-type strain MT5, grlA mutant MT5224c4, and grlA/gyrA mutant EN8 of 0.03 and 0.06, 0.125 and 0.125, and 4 and 4 microg/ml, respectively. In the time-kill studies, BMS-284756 and levofloxacin exhibited rapid killing against all strains. Ciprofloxacin, however, was not bactericidal for the double mutant, EN8. BMS-284756 and levofloxacin were bactericidal (3 log(10) decrease in CFU/ml) against the MT5 and MT5224c4 strains at two and four times the MIC within 2 to 4 h. Against EN8, BMS-284756 was bactericidal within 4 h at two and four times the MIC, and levofloxacin achieved similar results within 4 to 6 h. Both the wild-type strain MT5 and grlA mutant MT5224c4 should be considered susceptible to both BMS-284756 and levofloxacin, and both quinolones are predicted to have clinical efficacy. The in vivo efficacy of BMS-284756, levofloxacin, and moxifloxacin against S. aureus strain ISP794 and its single mutant 2C6(1)-1 directly reflected the in vitro activity: increased MICs correlated with decreased in vivo efficacy. The 50% protective doses of BMS-284756 against wild-type and mutant strains were 2.2 and 1.6 mg/kg of body weight/day, respectively, compared to the levofloxacin values of 16 and 71 mg/kg/day and moxifloxacin values of 4.7 and 61.6 mg/kg/day. BMS-284756 was more potent than levofloxacin and equipotent with moxifloxacin against ISP794 both in vitro and in vivo, while BMS-284756 was more potent than levofloxacin and moxifloxacin against 2C6(1)-1.

Anti-Infective Agents↗
PubMed2002

Microbial genomics and novel antibiotic discovery: new technology to search for new drugs.

The process of prokaryotic drug discovery has been a model of success for over fifty years, yet the number of exploited bacterial targets is a mere fraction, less than 0.1% of the potential targets (based on total number of bacterial genes identified by gene sequence projects). To better understand the potential for drug intervention, multiple paradigms have been established in the pharmaceutical industry, all with some semblance of commonality and uniqueness to provide proprietary positioning, yet no company has been successful to date in taking a genomics approach to the finish line of having a genomics-based drug on the market. Within this overview, we provide a strategic overview of a sample process for the identification, validation and exploitation of novel antibacterial targets ascertained through a bioinformatics-based genomics drug discovery program.

Anti-Bacterial Agents↗
PubMed2001

Targeting DNA gyrase.

The discovery of the peptide DNA gyrase inhibitor microcin B17 (MccB17) in the early 1990s provided a new tool and hope for a novel peptide-based chemical starting point for a new generation of DNA gyrase inhibitors but the definitive mechanism-of-action of MccB17 has remained unknown. This research report [1], by one of the foremost laboratories in this discipline in the world, provides definitive data on the mode of inhibition of MccB17 and possibly opens the door for additional semisynthetic analogue synthesis based on the MccB17 chemotype. In addition, this unique peptide DNA gyrase inhibitor provides a contrast in activity versus quinolones, Ca(2+)-mediated inhibition/cleavage and the bacterial toxin/peptide CcdB.

Journal Article↗