A substance producing cytotoxicity in tissue culture was detected in stool specimens from all of four patients with pseudomembranous colitis due to antibiotics and in one of 54 with antibiotic-associated diarrhea. These stools also caused enterocolitis when injected intracecally into hamsters. On each occasion, cytotoxicity in tissue culture and enterocolitis in hamsters were neutralized by pretreatment with gas-gangrene antitoxin. The toxicity in both tissue cultures and hamsters could be reproduced with broth cultures of clostridia strains isolated from four of the five stools. These results suggest that toxin-producing clostridia are responsible for antibiotic-associated pseudomembranous colitis.
Despite inducing a complex, robust immune response, the vaccine was unable to reduce the incidence of HIV-1. Two interpretations of the correlative results are that the levels of antibodies (i) caused both an increased (low responders) and decreased (high responders) risk of HIV-1 acquisition or (ii) represented a correlate of susceptibility to HIV-1 but had no causal effect on susceptibility. Although the data cannot definitively discriminate between these 2 explanations, (ii) appears to be more likely.
We report a randomized, double-blind, multicenter trial in which amphotericin B colloidal dispersion (ABCD [Amphotec]; 6 mg/kg/day) was compared with amphotericin B (AmB; 1.0-1.5 mg/kg/day) for the treatment of invasive aspergillosis in 174 patients. For evaluable patients in the ABCD and AmB treatment groups, respective rates of therapeutic response (52% vs. 51%; P=1.0), mortality (36% vs. 45%; P=.4), and death due to fungal infection (32% vs. 26%; P=.7) were similar. Renal toxicity was lower (25% vs. 49%; P=.002) and the median time to onset of nephrotoxicity was longer (301 vs. 22 days; P<.001) in patients treated with ABCD. Rates of drug-related toxicity in patients receiving ABCD and AmB, respectively, were 53% versus 30% (chills), 27% versus 16% (fever), 1% versus 4% (hypoxia) and 22% versus 24% (toxicity requiring study drug discontinuation). ABCD appears to have equivalent efficacy and superior renal safety, compared with AmB, in the treatment of invasive aspergillosis. However, infusion-related chills and fever occurred more frequently in patients receiving ABCD than in those receiving AmB.
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