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 at 200 mg/kg of
body weight in each of two infusions 24 h apart or placebo. During the 42-day observation period, antibody pharmacokinetics and safety were the primary characteristics studied. Information regarding the resolution of
bacteremia and
fever was also analyzed. Anti-type-5 and anti-type-8 capsular antibody levels peaked after the second infusion at 550 mug/ml and 419 mug/ml, respectively, and remained above 100 mug/ml at day 28. A total of 316 adverse events were noted in 39 of 40 subjects. Infusion-related adverse events in
Altastaph recipients were infrequent and similar to those among recipients of commercial intravenously administered
immunoglobulin G products. Five of 21 (23%) subjects in the
Altastaph group died, whereas 2 of 18 (11%) subjects in the placebo group died (P = 0.42). Compared to the control patients, the
Altastaph recipients had a shorter median time to the resolution of
fever (2 days and 7 days, respectively; P = 0.09) and a shorter length of
hospital stay (9 days and 14 days, respectively; P = 0.03). However, these findings are exploratory, and there were few differences in the other variables measured. High levels of opsonizing
antibodies were maintained for the initial 4 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).