Phase II, randomized, double-blind, multicenter study comparing the safety and pharmacokinetics of tefibazumab to placebo for treatment of Staphylococcus aureus bacteremia.

Tefibazumab (Aurexis), a humanized monoclonal antibody that binds to the surface-expressed adhesion protein clumping factor A, is under development as adjunctive therapy for serious Staphylococcus aureus infections. Sixty patients with documented S. aureus bacteremia (SAB) were randomized and received either tefibazumab at 20 mg/kg of body weight as a single infusion or a placebo in addition to an antibiotic(s). The primary objective of the study was determining safety and pharmacokinetics. An additional objective was to assess activity by a composite clinical end point (CCE). Baseline characteristics were evenly matched between groups. Seventy percent of infections were healthcare associated, and 57% had an SAB-related complication at baseline. There were no differences between the treatment groups in overall adverse clinical events or alterations in laboratory values. Two patients developed serious adverse events that were at least possibly related to tefibazumab; one hypersensitivity reaction was considered definitely related. The tefibazumab plasma half-life was 18 days. Mean plasma levels were <100 microg/ml by day 14. A CCE occurred in six patients (four placebo and two tefibazumab patients) and included five deaths (four placebo and one tefibazumab patient). Progression in the severity of sepsis occurred in four placebo and no tefibazumab patients. Tefibazumab was well tolerated, with a safety profile similar to those of other monoclonal antibodies. Additional trials are warranted to address the dosing range and efficacy of tefibazumab.

Lack of seronegative hepatitis C virus infections in patients with chronic renal failure.

BACKGROUND: Recent reports have indicated that serologic testing for hepatitis C virus (HCV) in patients with chronic renal failure may be inadequate to detect infections in this patient population. METHODS: We prospectively tested 258 patients with end-stage renal disease who were referred for evaluation for renal transplantation for anti-HCV using a second-generation enzyme immunoassay (EIA) and a second-generation qualitative reverse-transcriptase polymerase chain reaction (RT-PCR). We confirmed all positive EIAs with a third-generation recombinant immunoblot assay and genotyped RT-PCR-positive specimens. RESULTS: We found that 22 patients (8.5%) had serological evidence of HCV infection. Nineteen (86%) of the antibody-positive patients were viremic (HCV RNA positive). All but 1 of the patients was infected with HCV genotype 1. None of the 233 HCV antibody-negative patients were shown to be viremic by RT-PCR. CONCLUSIONS: No additional HCV cases were detected by screening all patients for HCV RNA by RT-PCR. However, RT-PCR is a valuable adjunct to serology in antibody-positive patients to distinguish resolved from active infections.