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Antimicrob. Agents Chemother. doi:10.1128/AAC.00570-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

A phase II, randomized, multicenter, double-blind, placebo-controlled, trial of a polyclonal anti-Staphylococcus aureus capsular polysaccharide immune globulin in the treatment of Staphylococcus aureus bacteremia

University of Nebraska Medical Center, Omaha NE; Nabi Biopharmaceuticals, Rockville MD; St. Agnes Medical Center, Fresno CA; Montefiore Medical Center, Bronx NY; Durham Veterans Affairs Medical Center, Durham NC; Wayne State University, Detroit MI; Duke University Medical Center, Durham, NC

^* To whom correspondence should be addressed. Email: merupp{at}unmc.edu.

	Abstract

New treatment modalities are needed for the treatment of infections due to multidrug-resistant Staphylococcus aureus. S. aureus capsular polysaccharide immune globulin (Altastaph^®) is a polyclonal immune globulin preparation that is being developed as adjunctive therapy for persons with S. aureus infections complicated by bacteremia. In a Phase II, multicenter, randomized, double-blind, placebo-controlled trial, 40 subjects with documented S. aureus bacteremia received standard therapy plus either Altastaph, 200 mg/kg in each of 2 infusions 24 hours apart, or placebo. During the 42 day observation period, antibody pharmacokinetics and safety were the primary characteristics studied. Information regarding resolution of bacteremia and fever was also analyzed. Anti-type-5 and anti-type-8 capsular antibody levels peaked after the 2nd infusion at 550 µg/mL and 419 µg/mL, respectively, and remained above 100 µg/mL at day 28. 316 adverse events were noted in 39 of 40 subjects. Infusion-related adverse events in Altastaph recipients were infrequent and similar to those of commercial IVIG products. 5 of 21 (23%) of subjects in the Altastaph group died compared to 2 of 18 (11%) in the placebo group (P = 0.42). Compared to control patients, Altastaph recipients had a shorter median time to resolution of fever (2d vs. 7d, P = 0.09) and a shorter length of hospital stay (9d vs. 14d, P = 0.03). However, these findings are exploratory and there were few differences in other measured variables. High levels of opsonizing antibodies were maintained for the initial four weeks. Although the study was not powered to show efficacy, these preliminary findings and safety profile suggest that Altastaph may be an effective adjunct to antibiotics and warrants further investigation (ClinicalTrials.gov number, NCT00063089).