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Antimicrobial Agents and Chemotherapy, October 2005, p. 4121-4127, Vol. 49, No. 10
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.10.4121-4127.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Multicenter Study To Determine Antibody Concentrations and Assess the Safety of Administration of INH-A21, a Donor-Selected Human Staphylococcal Immune Globulin, in Low-Birth-Weight Infants

Trials-by-Design L.L.C., San Diego, California,¹ Wesley Medical Center, Wichita, Kansas,² Carolina's Medical Center, Charlotte, North Carolina,³ Eastern Virginia Medical School, Norfolk, Virginia,⁴ UMU—Syracuse, Syracuse, New York,⁵ Memorial Hospital, South Bend, Indiana,⁶ University of Alabama, Birmingham, Alabama,⁷ Christiana Care Health System, Newark, New Jersey,⁸ Inhibitex, Inc., Alpharetta, Georgia⁹

Received 31 March 2005/ Returned for modification 7 May 2005/ Accepted 8 July 2005

Nosocomial or late-onset sepsis is a common complication among premature infants, with a frequency inversely correlated with birth weight. Increased susceptibility to infection is due in part to an immature humoral (antibody-mediated) immune response. This study investigated the pharmacokinetics (PKs) and safety of a donor-selected specific intravenous immune globulin (IVIG) preparation, INH-A21 (Veronate), for prevention of sepsis in premature infants. Thirty-six infants weighing between 500 and 1,250 g during the first postnatal week were eligible to begin a series of up to four intravenous infusions of 500 or 750 mg/kg of body weight INH-A21. Blood samples were analyzed for antibodies against the Ser-Asp dipeptide repeat G (SdrG) and clumping factor A (ClfA) surface proteins of staphylococci. Sparse sampling and population PK analyses were performed to derive PK parameters. Following administration of the 500- and 750-mg/kg doses, the estimated average steady-state levels of anti-ClfA were 6.1 U/ml and 9.2 U/ml, respectively, and those of anti-SdrG were 5.2 U/ml and 7.7 U/ml, respectively. The elimination half-lives for anti-ClfA and anti-SdrG were 719 h and 701 h, respectively, and the clearances were 0.18 ml/h and 0.21 ml/h, respectively. In the final model, the values of the PK parameters were independent of gestational age. Both doses of INH-A21 were well tolerated, and the safety profile was similar to those of other IVIG preparations. These results suggest that a shorter dosing interval should be utilized between the first and second doses to achieve and maintain higher titers of anti-ClfA and anti-SdrG antibodies. Further studies examining INH-A21 for the prevention of late-onset sepsis in infants within the weight range studied are warranted.

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