Raltegravir: the first HIV-1 integrase strand transfer inhibitor in the HIV armamentarium.

Raltegravir is the first integrase strand transfer inhibitor approved for the treatment of HIV-1 infection. As the first agent in this new class of antiretroviral therapies, raltegravir has demonstrated safety and efficacy in treatment-naive as well as heavily pretreated HIV-infected patients failing therapy with multidrug-resistant virus. Raltegravir has a favorable drug interaction profile that permits both administration to a wide, demographically diverse patient population and coadministration with many other therapeutic agents, including antiretroviral agents and supportive medications, without restrictions or dose adjustment.

Advances in antifungal chemotherapy.

The American Society for Microbiology sponsored the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), a premier annual scientific conference, in San Diego, California, September 24-27, 1998. At the ICAAC several sessions were held which focused on the pathogenesis of fungal disease, the in vitro susceptibility testing of new azole (voriconazole, Syn-2869, SCH-56592, carbendazim), echinocandin-like (FK-463, LY-303366, MK-0991), polyene (patricins) and established antifungal agents (fluconazole, itraconazole, amphotericin B, nystatin, terbinafine), the experimental in vivo activity of these new antifungal drugs in various animal models of fungal disease, and the clinical activity of fluconazole, itraconazole and liposomal amphotericin B formulations.

Medical mycology and current trends in antifungal chemotherapy.

The Medical Mycological Society of the Americas (MMSA) and the American Society for Microbiology (ASM) are both premier scientific organizations which held their annual conferences in Atlanta, Georgia, May 17-21, 1998. The MMSA scientific session focused on the role of animal models in drug development and on the immunology and molecular biology of the medically important fungi. The use of current molecular tools in identifying new fungal targets for the development of antifungal agents and for the study of fungal epidemiology was reviewed.

Human mycoses and current antifungal therapy.

The Focus on Fungal Infections meeting has become a popular conference for specialists in medical mycology and antifungal chemotherapy. Highlights of the 8th meeting are reported, with a focus on infection and therapy. Although the incidence of mycoses has increased, the identification of these fungal etiologic agents remains difficult.

Progress in antibacterial and antifungal chemotherapy.

The European Society of Clinical Microbiology and Infectious Diseases sponsored the 10th European Congress on Clinical Microbiology and Infectious Diseases in Stockholm, Sweden, May 28-31, 2000. At the ECMID, well-attended sessions were held which focused on the pathogenesis and therapy of viral, bacterial and fungal diseases. This report focuses on new information on resistance to antibacterial agents, including data from recent surveillance studies, and the in vitro and investigational clinical activity of new antibacterial (moxifloxacin, telithromycin) and antifungal (fluconazole, itraconazole, voriconazole, amphotericin B, liposomal formulations of amphotericin B, terbinafine and the candins) drugs.

Human mycoses and advances in antifungal therapy.

The 11th Focus on Fungal Infections meeting was held in Washington, D.C., U.

Micafungin sodium (FK-463).

FK-463 (micafungin) represents the latest development candidate in a novel chemical class of echinocandin lipopeptide antifungal compounds. This agent has potent in vitro and experimental in vivo activity against a variety of pathogenic Candida species (yeasts) and Aspergillus fumigatus (filamentous fungus). This compound has favorable pharmacokinetics and a unique mode of action that makes it active against fungal isolates resistant to established antifungal agents, particularly the triazole agent fluconazole.

Yeasts and fluconazole susceptibility in the Philippines.

Identification and fluconazole susceptibility of 579 yeasts isolated from patients in 16 medical centers throughout the Philippines in 1997-98 is reported. Speciation revealed the following distribution of yeasts (with percent occurrence): Candida albicans (49.6%); C.

Multicenter evaluation of a broth macrodilution antifungal susceptibility test for yeasts.

Thirteen laboratories collaborated to optimize interlaboratory agreement of results of a broth macrodilution procedure for testing three classes of antifungal drugs against pathogenic yeasts. The activities of amphotericin B, flucytosine, and ketoconazole were tested against 100 coded isolates of Candida albicans, Candida tropicalis, Candida parapsilosis, Candida lusitaniae, Torulopsis (Candida) glabrata, and Cryptococcus neoformans. Two starting yeast inoculum sizes (5 x 10(4) and 2.

Collaborative comparison of broth macrodilution and microdilution antifungal susceptibility tests.

A collaborative comparison of macro- and microdilution antifungal susceptibility tests was performed in five laboratories. MICs of amphotericin B, fluconazole, flucytosine, and ketoconazole were determined in all five centers against 95 coded isolates of Candida spp., Cryptococcus neoformans, and Torulopsis glabrata.

Sphingofungins A, B, C, and D; a new family of antifungal agents. I. Fermentation, isolation, and biological activity.

In screening for antifungal inhibitors from fungi, four related antifungal agents have been isolated from the cultivation of Aspergillus fumigatus ATCC 20857. These agents were initially produced by the microorganism growing on a solid millet-based medium. A liquid medium containing both glucose and glycerol has also been developed in which these antibiotics are produced in two phases.

Restricticin, a novel glycine-containing antifungal agent.

Restricticin (1) is a naturally-occurring antifungal agent which contains triene, pyran and glycine ester functionalities and is unrelated to any previously known family of natural products. This unstable compound, as well as its corresponding N,N-dimethyl derivative (2), have been produced and isolated from both solid and liquid fermentations of Penicillium restrictum. The desglycyl hydrolysis product, restrictinol (3), was produced via the hydrolysis of pure restricticin and as an artifact of the isolation of restricticin.

L-687,781, a new member of the papulacandin family of beta-1,3-D-glucan synthesis inhibitors. I. Fermentation, isolation, and biological activity.

A new beta-1,3-D-glucan synthesis inhibitor, L-687,781 is produced by the cultivation of Dictyochaeta simplex ATCC 20960. L-687,781 exhibits potent in vitro antifungal activity as well as anti-Pneumocystis activity in a rat model.

(Acyloxy)alkyl carbamate prodrugs of norfloxacin.

As a new prodrug approach to norfloxacin (NFLX) we prepared the acetoxyalkyl carbamates of the type NFLX-CO-OCHR-OAc by the reaction of sodium or mercuric acetate on NFLX alpha-chloroalkyl carbamates. These produrgs did not have the bitter taste of NFLX. In vitro, the acetoxyethyl carbamate exhibited activity only against Staphylococcus spp.

Collaborative investigation of variables in susceptibility testing of yeasts.

A multicenter study was performed to evaluate the effect of medium, incubation time (24 and 48 h), and temperature (30 and 35 degrees C) on intra- and interlaboratory variations in MICs of flucytosine, amphotericin B, and ketoconazole for yeasts. Testing was performed on coded isolates of Candida species (11 strains) and Cryptococcus neoformans (2 strains) by using a standard macrodilution protocol 11 laboratories. Four chemically defined media buffered to pH 7.

Treatment of Pneumocystis carinii pneumonia with 1,3-beta-glucan synthesis inhibitors.

Pneumocystis carinii pneumonia is a major cause of death in AIDS patients in the United States. The presently available treatments have limited use due to a high incidence of adverse reactions. Therefore, there is an urgent need for a safer method for treatment and prevention of this disease.

Lack of cross-resistance between efrotomycin and antibacterial agents used in the therapy of human and animal infections.

Efrotomycin is an N-methylhydroxypyridone glycoside antibiotic with activity primarily against Gram-positive bacteria. It is intended for use as a feed additive for swine. Although efrotomycin is unrelated to any antibacterial drug used in human or veterinary medicine, the possibility of cross-resistance with other antibacterials is of concern.

Isolation of saprophytic Cryptococcus neoformans from Puerto Rico: distribution and variety.

Until the present decade, no studies had been conducted in Puerto Rico on the saprophytic distribution and variety of Cryptococcus neoformans. Samples (522) of pigeon droppings from 14 western towns were tested for the presence of C. neoformans.

Virulence and antifungal susceptibility of environmental and clinical isolates of Cryptococcus neoformans from Puerto Rico.

Studies on the distribution, epidemiology and pathogenesis of Cryptococcus neoformans on the island of Puerto Rico are few. We have studied mouse virulence and in vitro antifungal susceptibility of 133 isolates of C. neoformans: 121 environmental and 12 clinical (9 from AIDS patients), that were isolated in Puerto Rico.

L-658,310, a new injectable cephalosporin. III. Experimental chemotherapeutics and pharmacokinetics in laboratory animals.

The therapeutic activity of L-658,310 was demonstrated in experimental bacteremias in normal, diabetic and neutropenic mice. Especially potent activity was shown against the usually difficult to control pathogens, Enterobacter cloacae and Pseudomonas aeruginosa, that were resistant to ceftazidime and/or gentamicin. Pharmacokinetic studies in mice showed a linear dose response in serum after the 20 and 50 mg/kg subcutaneous dose and urinary recoveries of administered dose of about 60% in 6 hours.

L-658,310, a new injectable cephalosporin. I. In vitro antibacterial properties.

The in vitro antibacterial spectrum of L-658,310, a new semisynthetic cephalosporin, was compared with ceftazidime, aztreonam and piperacillin against a wide variety of randomly selected human clinical isolates. The compound was found to be a broad spectrum bactericidal agent that was more potent than any of the comparison drugs against glucose nonfermenting bacteria. It has especially potent activity against Pseudomonas aeruginosa including multiply-resistant strains.

L-671,329, a new antifungal agent. III. In vitro activity, toxicity and efficacy in comparison to aculeacin.

L-671,329 is a novel, echinocandin-like natural product that possesses potent anti-Candida activity, including activity against Candida parapsilosis. The in vitro MICs of L-671,329 were comparable to aculeacin against 18 yeasts and three filamentous fungi in an agar dilution assay. L-671,329 lysed mouse red blood cells (RBCs) at a concentration of 400 micrograms/ml, but not at 50 or 12.

L-657,398, a novel antifungal agent: fermentation, isolation, structural elucidation and biological properties.

L-657,398 is a broad spectrum antifungal agent isolated from solid fermentation or from the mycelium of the liquid fermentation of Aspergillus ochraceus. Structurally, the compound is a novel pyrollidine related to anisomycin.