Colleen M. Lowry

Reactivity of (1→3)-β-d-Glucan Assay with Commonly Used Intravenous Antimicrobials

ABSTRACT Forty-four intravenous antimicrobials were tested for the presence of (1→3)-β-d-glucan (BG). Colistin, ertapenem, cefazolin, trimethoprim-sulfamethoxazole, cefotaxime, cefepime, and ampicillin-sulbactam tested positive for BG at reconstituted-vial concentrations but not when diluted to usual maximum plasma concentrations. False-positive BG assays may occur when some antimicrobials are administered; however, this needs to be confirmed.

Treatment of Human Disseminated Strongyloidiasis with a Parenteral Veterinary Formulation of Ivermectin

There are no parenteral antihelminthic drugs licensed for use in humans. We report the successful treatment of disseminated strongyloidiasis with a parenteral veterinary formulation of ivermectin in a patient presenting with severe malabsorption and paralytic ileus. To our knowledge, ivermectin levels are reported for the first time in this situation.

Both IgM and IgG anti-VSG antibodies initiate a cycle of aggregation–disaggregation of bloodstream forms of Trypanosoma brucei without damage to the parasite

Bloodstream forms of Trypanosoma brucei, when aggregated in the presence of either acute immune plasma, acute immune serum, purified IgM anti-VSG antibodies or purified IgG anti-VSG antibodies, subsequently disaggregated with a t1/2 for disaggregation of 15 min at 37 degrees C as long as the trypanosomes were metabolically active at the beginning of the experiment and maintained during the experiment in a suitable supporting medium. The t1/2 for disaggregation was found to be directly dependent upon temperature and inversely proportional to the antibody concentration. The trypanosomes were always motile and metabolically active during aggregation and after disaggregation and were fully infective for a mammalian host following disaggregation as well as able to grow and divide normally during axenic culture. The disaggregation was strictly energy dependent and was inhibited when intracellular ATP levels were reduced by salicylhydroxamic acid or following addition of oligomycin while respiring glucose. In addition the process of disaggregation was dependent upon normal endosomal activity as evidenced by its sensitivity to a wide variety of inhibitors of various endosomal functions. Disaggregation was not due to separation of immunoglobulin chains by either disulphide reduction or disulphide exchange reactions and gross proteolytic cleavage of the immunoglobulins attached to the surface of the parasite was not detected. In addition, gross cleavage or release of the VSG from the surface of the cell did not occur during disaggregation but proteolytic cleavage of a small proportion of either the VSG or the immunoglobulins could not be eliminated from consideration. Finally the mechanism of disaggregation was found to be a regulated process, independent of Ca2+ movements but dependent upon the activity of protein kinase C or related kinases and inhibited by the activity of protein kinase A as evidenced by the effects of a panel of inhibitors and cAMP analogues on the process of disaggregation. The mechanism of disaggregation displayed by trypanosomes aggregated by anti-VSG antibody is proposed to form part of the parasites defence against the host immune system and functions to aid survival of trypanosomes in the presence of antibody in the host prior to the occurrence of a VSG switching event.

Pharmacist-Driven Aminoglycoside Quality Improvement Program

Abstract Our objective was to determine the impact of a pharmacist-driven aminoglycoside quality improvement program on the dosing methods of aminoglycosides at our institution. We assessed our current quality through retrospective review of all patients receiving aminoglycosides during a 5-month period. We then developed and implemented a pharmacist-driven aminoglycoside dosing program and prospectively assessed patients during a matched 5-month period. Two hundred and sixteen patients were evaluated, 87 pre-program and 129 post-program. Prior to standardized pharmacist intervention, 44% of patients achieved optimal therapy. Post implementation, patients achieving optimal therapy increased to 80% (p < 0.001). Patients in the pre-program group had a higher rate of acute changes in renal function compared to the post-pro-gram group (14.9% versus 6.2% [p <0.05]). This pharmacist-driven aminoglycoside dosing quality improvement program increased the frequency of optimal dosing of aminoglycosides and reduced the incidence of nephrotoxicity at our institution.