Several species of the genus Pleurotus have been found in this laboratory to form substances inhibitory for Staphylococcus aureus. Among these were two species, Pleurotus mutilus (Fr.) Sacc. and P. Passeckerianus Pilat, obtained from the Centraalbureau voor Schimmelcultures at Baarn. An antibacterial substance formed by these fungi was isolated in crystalline form from culture liquids; it was named pleuromutilin. P. mutilus grown on corn-steep, thiamine-peptone, or potato-dextrose agars for two days and tested by the streak-method, markedly inhibited Staphylococcus aureus, inhibited incompletely Mycobacterium smegma, and had no effect on Escherichia coli. Agar disks cut from colonies 10 days old formed inhibition zones 20 mm. in diameter with S. aureus and a small zone of incomplete inhibition with M. smegma. P. Passeckerianus produced similar zones of inhibition. Still Cultures.-P. mutilus was grown at 25°C. in 2800 ml. Fernbach flasks containing beech-wood shavings and a corn-steep medium.' About four weeks after inoculation the mycelium covered the surface of the liquid and the activity against S. aureus was about 512 dilution units per ml. Reflooding the mats with fresh corn steep medium resulted in as high activity in about one week after reflooding. The reflooding was repeated at about 10-day intervals until the mat became so thick that the operation was difficult. The flasks inoculated with P. Passeckerianus reached an activity of 256 dilution units per ml. in about one month.
Bone marrow suppression and anemia are frequent side effects of treatment of the acquired immunodeficiency syndrome (AIDS) with zidovudine (formerly azidothymidine [AZT]). We conducted a randomized, double-blind, placebo-controlled clinical trial of recombinant human erythropoietin (100 U per kilogram of body weight thrice weekly by intravenous bolus) in 63 patients with AIDS treated with zidovudine (29 in the erythropoietin group and 34 in the placebo group). Reductions in the number of units of red cells transfused and the number of patients given transfusions per month became apparent in the second and third months of the trial. The reductions were observed in patients with endogenous erythropoietin levels less than or equal to 500 IU per liter at base line, but not in patients whose levels were greater than 500 IU per liter at the beginning of the study. Although the hematocrit and hemoglobin level were not used as the primary criteria of efficacy because the patients received transfusions when their physicians decided that they needed them, a significantly higher rate of increase in the hematocrit was observed in the patients treated with recombinant human erythropoietin whose levels of endogenous erythropoietin were less than or equal to 500 IU per liter (0.00353 points per week) than in the patients given placebo (0.00116 points per week). This effect was not seen in patients with higher levels of endogenous erythropoietin. Serious side effects did not occur more often in the group treated with erythropoietin than in the placebo group. We conclude that recombinant human erythropoietin may be useful in patients with AIDS treated with zidovudine, although the indicators for its use remain to be clarified.
Therapy with r-HuEPO can increase the mean hematocrit and decrease the mean transfusion requirement in anemic patients with AIDS who are receiving zidovudine and have endogenous low erythropoietin levels (< or equal to 500 IU/L). Such therapy is of no apparent benefit in patients whose endogenous erythropoietin levels are higher than 500 IU/L.
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