MaryBeth Frosco

Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC).

Over 10,000 research scientists attended the ICAAC meeting in Toronto, Canada. The continued increase in the rate of resistance in bacteria and fungi and the underlying mechanisms of resistance were the focus of many presentations this year. So, too, were the attempts to combat this emerging resistance crisis. Many papers described new modifications to older antimicrobials, novel classes of antimicrobials and the potential use of new antibacterial and antifungal targets.

Importance of antifungal drug-resistance: clinical significance and need for novel therapy.

The incidence of fungal infections has increased dramatically over the past few decades due to the increase in the members of the population susceptible to such infections. This population includes individuals undergoing chemotherapy for cancer, those enduring long-term treatment with antibacterial agents, those receiving immunosuppressive drugs following transplantations, or those immunosuppressed due to diseases, such as AIDS, or malignancies. Newer antifungal agents, namely the triazoles, have aided in both the treatment of fungal infections and in the prevention of disease in susceptible individuals. However, resistance to the azoles, as well as to the polyenes, has resulted in clinical failures. Only a few potential antifungal targets have been exploited to date and there is a critical need for the discovery and development of novel antifungal agents that will result in improved therapy in this ever-expanding patient population. An increased intensity in the study of fungal pathogens at the molecular level holds the key to such advances.

Bactericidal Activities of BMS-284756, a Novel Des-F(6)-Quinolone, against Staphylococcus aureus Strains with Topoisomerase Mutations

ABSTRACT 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 μg/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 log10 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.

39th Interscience Conference on Antimicrobial Agents and Chemotherapyof the American Society for Microbiology

The 39th ASM ICAAC Meeting, attended by over 16,000 delegates, highlighted numerous late-stage development antibacterials. The presentation of over 600 reports (posters, symposia and oral presentations) regarding resistance emergence underscores the evolving landscape of antibiotic susceptibility worldwide. Although bacterial genomic efforts are slowly expanding the potential sources of novel targets, the established antibacterial classes, including quinolones, beta-lactams, protein synthesis inhibitors and carbapenems, were most prevalent among the presentations. Quinolones dominated this conference, with many presentations of moxifloxacin (> 72 presentations), gatifloxacin (> 66 presentations) and gemifloxacin (> 59 presentations). The new class of antibacterials, the oxazolidinones, represented by Linezolid, was also highlighted.

98th General Meeting of the American Society for Microbiology. May 17-21, 1998; Atlanta, GA.

The 98th General Meeting of the American Society for Microbiology was held from May 17-21, 1998, in Atlanta, Georgia and was attended by well over 10,000 scientists. The theme of antibiotic resistance dominated the meeting with numerous presentations on resistance mechanisms, new targets and potential antimicrobial agents. Many new insights into the understanding of microbial physiology were provided. Microbial genomics was shown to be revolutionizing the way in which scientists can probe and explore bacteria and fungi.

Meeting Highlights Anti-infectives: 96th General Meeting of the American Society for Microbiology New Orleans, Louisiana, USA, 19–23 May, 1996

The 96th Annual Meeting of the American Society for Microbiology covered an eclectic blend of presentations including: old therapeutic drugs looking for new recommendations, new drugs in the process of approval or in various phases of clinical trials, new developments in bacterial pathogenesis, protein secretion and immunomodulation.