Biomedical subjects

John H Rex

Publications and source records attributed to John H Rex.

41 records · Page 3Linked to original sources

PubMed2002

Effect of the echinocandin caspofungin on expression of Candida albicans secretory aspartyl proteinases and phospholipase in vitro.

Although the echinocandin caspofungin primarily inhibits the synthesis of cell wall 1,3-beta-D-glucan, its fungicidal activity could also potentially perturb the expression of virulence factors involved in the ability of Candida albicans to cause infection. Expression of the C. albicans secretory aspartyl proteinase (SAP) and phospholipase B (PLB) virulence genes was determined by reverse transcription-PCR after the addition of caspofungin to cells grown for 15 h in Sabouraud dextrose broth. In cells that remained viable, expression of SAP1 to SAP3, SAP7 to SAP9, and PLB1 was unaltered after exposure to fungicidal concentrations (4 to 16 micro g/ml) of caspofungin over a period of 7 h. However, expression of SAP5 increased steadily beginning 1 h after exposure to caspofungin. These results indicate that caspofungin is rapidly fungicidal against C. albicans, before any suppression of SAP or PLB1 gene expression can occur.

Anti-Bacterial Agents↗

PubMed2002

In vitro activity of nystatin compared with those of liposomal nystatin, amphotericin B, and fluconazole against clinical Candida isolates.

We investigated the in vitro activity of nystatin and liposomal nystatin against 103 Candida isolates to determine the effect of both time and medium on MICs. We also compared the nystatin MICs with those of amphotericin B and fluconazole. Testing was performed in accordance with the National Committee for Clinical Laboratory Standards M27-A microdilution methodology with RPMI 1640, RPMI 1640 supplemented with glucose to 2% (RPMI-2), and antibiotic medium 3 supplemented with glucose to 2% (AM3). While nystatin MICs were similar to or slightly lower than liposomal nystatin MICs in RPMI 1640 and RPMI-2, they were markedly higher than liposomal nystatin MICs in AM3. Use of AM3 and determination of the MIC after 24 h of incubation provided a slightly wider range of liposomal nystatin MICs (0.06 to >16 microg/ml). Under these conditions, the MICs at which 90% of isolates were inhibited of nystatin and liposomal nystatin were 2 and 1 microg/ml, respectively. Nystatin and liposomal nystatin in general showed good activity against all Candida spp. tested. Although the MICs of nystatin and liposomal nystatin tended to rise in parallel with the amphotericin B MICs, nystatin and liposomal nystatin MICs of 1 to 2 and 0.5 to 1 microg/ml, respectively, were obtained for seven and six, respectively, of nine isolates for which amphotericin B MICs were >or=0.25 microg/ml. No correlation between fluconazole and nystatin or liposomal nystatin MICs was observed. As amphotericin B MICs of >or=0.25 microg/ml correlate with in vitro resistance, these results suggest that liposomal nystatin might have activity against some amphotericin B-resistant isolates. In vivo testing in animal models is required for clarification of this issue.

Amphotericin B↗

PubMed2002

New agents for the treatment of systemic fungal infections--current status.

Systemic antifungal chemotherapy is enjoying its most dynamic era. More antifungal agents are under development than ever before, including agents in entirely new classes. Major goals of current investigations are to identify compounds with a wide spectrum of activity, minimal toxicity and a high degree of target specificity. The antifungal drugs in development include new azoles {voriconazole, posaconazole (formerly SCH-56592), ravuconazole (formerly BMS-207147)}, lipid formulations of amphotericin B, a lipid formulation of nystatin, echinocandins {anidulafungin (formerly, LY-303366, VER-002), caspofungin (formerly MK-991), micafungin (formerly FK-463)}, antifungal peptides other than echinocandins, and sordarin derivatives. This discussion reviews the currently available antifungal agents and summarises the developmental issues that surround these new systemic antifungal drugs.

Journal Article↗

PubMed2002

Ravuconazole Eisai/Bristol-Myers Squibb.

Eisai and Bristol-Myers Squibb (BMS) are developing the triazole, ravuconazole, as a potential treatment for fungal infection [187888]. Eisai selected the compound for further development on the basis of its good safety profile and well-balanced antifungal activity [187888]. Ravuconazole has a broader antifungal spectrum than fluconazole and itraconazole, particularly against strains of Candida krusei and Cryptococcus neoformans [271854], [342757], [370312]. By June 1999, the compound was undergoing phase II trials [327113]. In November 2001, it was reported that BMS was seeking a co-development partner for the compound [430011]. In October 2001, analysts at ABN Amro predicted sales of US $50 million in 2003 [444020].

Administration, Oral↗

PubMedDate not supplied

Invasive candidiasis in immunocompromised hospitalized patients.

The frequency of infections by Candida species is increasing worldwide, with candidemia representing the fourth most common bloodstream infection in the U.S. The risk of infection is especially high in the immunocompromised, hospitalized patient. The treatment of and prophylaxis for Candida infection have led to the emergence of resistant species and the acquisition of resistance in previously susceptible species. Current therapeutic options include amphotericin B and its lipid compounds, fluconazole, itraconazole, voriconazole, and caspofungin. Research is focusing on better diagnostics and the evaluation of strategies such as prophylaxis in high-risk hosts and pre-emptive therapy.

Antibiotic Prophylaxis↗