In this large phase III trial, the efficacy of DaunoXome was comparable to that of ABV. Response rates, time to treatment failure, and overall survival were similar on both treatment arms. DaunoXome is a safe and effective primary therapy for advanced AIDS-related KS.

A 41-year-old man with acute lymphoblastic leukemia developed multiple Scedosporium apiospermum brain abscesses. The infection progressed despite neurosurgical drainage and treatment with itraconazole, amphotericin B, and ketoconazole, but the brain abscesses completely resolved after treatment with posaconazole alone.

TPV/r demonstrated superior antiviral activity, compared with investigator-selected, ritonavir-boosted protease inhibitors, at week 24 in treatment-experienced patients with multidrug-resistant HIV-1 infection.

Pseudomonas gladioli was isolated from 11 patients with cystic fibrosis. It resembled Pseudomonas cepacia on the selective and differential medium OFPBL, producing yellow colonies after 48 to 72 h of incubation. Isolates were characterized biochemically, by DNA hybridization, and by cellular fatty acid analysis. A review of the clinical status of selected patients colonized by P. gladioli did not reveal any apparent association of this organism with infections complications of cystic fibrosis. Thus, the clinical implications may differ depending on which of these two closely related species is reported by laboratories. Determination of the fatty acid profile of isolates by gas chromatography may be a useful adjunct to biochemical characterization as a means of identification. In contrast to P. cepacia, most isolates of P. gladioli contained 3-OH Clo0o fatty acid under the growth conditions used.

Loperamide (LOP) is a peripherally acting opioid receptor agonist used for the management of chronic diarrhea through the reduction of gut motility. The lack of central opioid effects is partly due to the efflux activity of the multidrug resistance transporter P-glycoprotein (P-gp) at the blood-brain barrier. The protease inhibitors are substrates for P-gp and have the potential to cause increased LOP levels in the brain. Because protease inhibitors, including tipranavir (TPV), are often associated with diarrhea, they are commonly used in combination with LOP. The level of respiratory depression, the level of pupil constriction, the pharmacokinetics, and the safety of LOP alone compared with those of LOP-ritonavir (RTV), LOP-TPV, and LOP-TPV-RTV were evaluated in a randomized, open-label, parallel-group study with 24 healthy human immunodeficiency virus type 1-negative adults. Respiratory depression was assessed by determination of the ventilatory response to carbon dioxide. Tipranavir-containing regimens (LOP-TPV and LOP-TPV-RTV) caused decreases in the area under the concentration-time curve from time zero to infinity for LOP (51% and 63% decreases, respectively) and its metabolite (72% and 77% decreases, respectively), whereas RTV caused increases in the levels of exposure of LOP (121% increase) and its metabolite (44% increase). In vitro and in vivo data suggest that TPV is a substrate for and an inducer of P-gp activity. The respiratory response to LOP in combination with TPV and/or RTV was not different from that to LOP alone. There was no evidence that LOP had opioid effects in the central nervous system, as measured indirectly by CO 2 response curves and pupillary response in the presence of TPV and/or RTV.Loperamide (LOP; Imodium, McNeil-PPC, Inc.) is a peripherally acting opioid receptor agonist that reduces gut motility and that is used for the management of chronic diarrhea (8,25). The principal metabolic fate of loperamide in humans involves oxidative N-dealkylation to N-demethyl-loperamide as the principal metabolite. In human liver microsomes, cytochrome P450 3A4 (CYP3A4) appears to be the major isozyme responsible for loperamide metabolism, with minor contributions from CYP2B6 (9). At the doses used to control diarrhea, LOP has very poor penetration of the blood-brain barrier and produces no central opioid effects, such as respiratory depression, pupillary constrictions, analgesia, or changes in alertness (26). The poor central nervous system (CNS) penetration is attributed both to LOP active cellular efflux via the multidrug resistance transporter P-glycoprotein (P-gp) in the blood-brain barrier and to low systemic oral bioavailability (24). When P-gp is inhibited, LOP and its metabolites may potentially enter the brain and cause opioid-induced central neurological adverse events (AEs) (23, 24).Current treatment for human immunodeficiency virus type 1 (HIV-1) infection consists of a combination of antiretroviral agents of different classes. Tipranavir (TPV) is a potent nonpeptidic HIV-1 and HIV-...