National epidemiology of mycoses survey: a multicenter study of strain variation and antifungal susceptibility among isolates of Candida species.

The National Epidemiology of Mycoses Survey (NEMIS) involves six academic centers studying fungal infections in surgical and neonatal intensive care unit (ICU) patients. We studied variation in species and strain distribution and anti-fungal susceptibility of 408 isolates of Candida spp. Candida spp. were isolated from blood, other normally sterile site cultures, abscesses, wounds, catheters, and tissue biopsies of 141 patients hospitalized in the surgical (107 patients) and neonatal (34 patients) ICUs of medical centers located in Oregon, Iowa, California, Texas, Georgia, and New York. Isolates were also obtained from selected colonized patients (16 patients) and the hands of health care workers (27 individuals). DNA typing was performed using pulsed field gel electrophoresis, and antifungal susceptibility to amphotericin B, 5-fluorocytosine, fluconazole, and itraconazole was determined using National Committee for Clinical Laboratory Standards (NCCLS) methods. Important variation in susceptibility to itraconazole and fluconazole was noted: MICs of itraconazole ranged from 0.25 microgram/mL (MIC90) in Texas to 2.0 micrograms/mL (MIC90) in New York. Similarly, the MIC90 for fluconazole was higher for isolates from New York (64 micrograms/mL) compared to the other sites (8-16 micrograms/mL). In general, DNA typing revealed patient-unique strains; however, there were 13 instances of possible cross-infection noted in 5 of the medical centers. Notably, 9 of the 13 clusters involved species of Candida other than C. albicans. Potential transmission from patient-to-patient (C. albicans, C. glabrata, C. tropicalis, C. parapsilosis) and health care worker-to-patient (C. albicans, C. parapsilosis, C. krusei) was noted in both surgical ICU and neonatal ICU settings. These data provide further insight into the epidemiology of nosocomial candidiasis in the ICU setting.

Antiviral action of 5-amino-2-(2-dimethyl-aminoethyl)benzo-[de]-isoquinolin-1,3-dion e.

A newly synthesized imide derivative of 3-nitro-1,8-naphthalic acid, 5-amino-2-(2-dimethylaminoethyl)benzo-[de]-isoquinolin-1,3-dione (designated M-FA-142), was tested on chick embryo cells against herpes simplex virus type 1 (HSV-1) and vaccinia virus (VV), and on Vero cells against African swine fever virus (ASFV). At a concentration of 4 micrograms/ml the drug inhibited VV replication by about one order of magnitude, and that of HSV-1 by about three orders of magnitude. A minor effect was shown against ASFV. Virus inhibition was found to depend on the amount of drug and multiplicity of infection. No virucidal effect was observed on the viruses tested, except for a slight effect on HSV-1. Inhibition of virus growth could be reversed when the drug was removed from the cell culture medium. Serial passages of HSV-1 and VV in the presence of the drug caused the appearance of drug-resistant viruses.

Estudio ultraestructural de la accion de dos derivados benzo (de) isoquinolil-1,3-diona sobre Trypanosoma cruzi "in vitro". / Ultrastructural study of the effect of 2 derivatives benzo (de) isoquinoline-1,3-dione on Trypanosoma cruzi in vitro

Fueron analizadas las alteraciones a nivel ultraestructural, producidas por dos derivados benzo (de) isoquinolil-1,3-dioma, en formas de cultivo de Trypanosoma cruzi.Estos compuestos, M-12210 y FA-142, son drogas intercalantes del DNA que tienen una gran afinidad por este. El DNA del kinetoplasto pierde su estructura regular de doble hilera, produciendose arqueamientos la cromatina aparece irregularmente condensada en los nucleos, en el citoplasma se observa gran cantidad de inclusiones lipidicas y vacuolas

In vitro action of three benzo (de) isoquinoline-1,3-dione derivatives against Trypanosoma cruzi

Investigou-se a acao "in vitro" contra Trypanosoma cruzi, forma epimastigota, de tres derivados benzo (de) isoquinolina 1,3 dionas, (5 nitro-2-(2 dimetilaminoetil); 5-nitro 2-(2-(1 pirrolidina) etil) e 5 amino-2-(2-dimetilaminoetil)). Os resultados obtidos neste trabalho, mostram que os tres compostos inibem o crescimento normal da forma de cultura de Trypanosoma cruzi

Imide derivatives of 3-nitro-1.8-naphthalic acid: their inhibitory activity against DNA viruses.

The antiviral action of a new drug, 5-amino-2-(dimethylaminoethyl)-benzo-[de]-isoquinolin-1.3-dione has been studied against herpes simplex type 2 (HSV-2) and adenovirus type 5 (Ad-5) grown in Vero cells. The concentration of the drug which gives a 5 log10 reduction in virus titer was 4 micrograms/ml (maximum tolerated concentration) for HSV-2. The anti-HSV-2 activity of this compound was one log. more powerful than that of iododeoxyuridine (IDU). At this concentration the drug shows virucidal activity against HSV-2. No inhibition was found when the drug was tested against Ad-5. The inhibition of virus production has been studied depending upon the amount of drug or virus, and drug addition-time after infection. Reversibility of inhibition after drug removal, and drug resistance in the presence of the drug have also been determined.

Synthesis and mode(s) of action of a new series of imide derivatives of 3-nitro-1,8 naphthalic acid.

Four new imide derivatives of 3-nitro-1,8-naphthalic acid have been synthesised. The compounds show strong cytostatic activity against both HeLa and KB cells and are moderately toxic towards both mice and rats (LD50 above 4 mg/kg IP). Two of the most active compounds, M-4212 and M-12210, prevented the development of mouse Ehrlich ascites and rat Yoshida carcinoma. All these drugs block cell growth by inhibiting the synthesis of both DNA and RNA. In particular, both M-4212 and M-12210 raise the melting point of double-stranded DNA.

Antiviral action of benzo[de]isoquinoline-1,3-diones: 5-nitro-2-(2-dimethylaminoethyl) and 5-nitro-2-[2-(1-pyrrolidine)-ethyl] derivatives.

Two benzo[de]isoquinoline-diones, namely 5-nitro-2-(2-dimethylaminoethyl)-benzo[de]isoquinoline-1,3-dione and 5-nitro-2-[2-(1-pyrrolidine)-ethyl]-benzo[de]isoquinoline-1,3-dione, caused inhibition of the viral replication, when assayed against herpes simplex and vaccinia viruses in chick embryo cell cultures. Influenza and Sindbis virus replication were unaffected by these chemicals. Virucidal effects were unobserved. The inhibitory activity is time-related. Ocular and dermal infections with vaccinia virus in rabbits were prevented or disease severity reduced whenever they were treated with either one of these two drugs.