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A blinded, randomized, multicenter study of an intravenous Staphylococcus aureus immune globulin

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Abstract

Objectives:

Very low birth weight (VLBW) infants are vulnerable to nosocomial infections and subsequent morbidity; including infections caused by Staphylococcus aureus: 85% of nosocomial S. aureus infections are caused by capsular polysaccharide (CPS) types 5 and 8. Altastaph™ is a polyclonal investigational human immunoglobulin G (IgG) with high levels of opsonizing S. aureus CPS types 5 and 8 IgG.

Methods:

A Phase 2 clinical trial to assess the safety and kinetics of Altastaph in VLBW infants. Neonates in this multicenter study were randomized to receive two identical 20?ml/kg i.v. infusions of either 0.45% NaCl placebo or 1000?mg Altastaph/kg. Each infant was followed for 28 days after the second infusion or until discharge. Serum S. aureus CPS types 5 and 8 IgG levels were measured preinfusion and at various times after each infusion.

Results:

Of 206 neonates, 158 received both infusions. Adverse events were similar in the two treatment groups. Six subjects (3% in each group) discontinued owing to an adverse event. Geometric mean anti-type 5 IgG levels were 402 and 642?mcg/ml 1 day following infusion of the first (day 0) and Second (day 14) doses, respectively, in neonates ⩽1000?g and slightly higher in neonates 1001 to 1500?g. Trough levels before second infusion were 188?mcg/ml. Type 8 IgG levels were similar. Geometric mean IgG levels among placebo recipients were consistently <2 and <5?mcg/ml for types 5 and 8 in both weight groups. Three episodes of S. aureus bacteremia occurred in each arm.

Conclusions:

Infusion of Altastaph in VLBW neonates resulted in high levels of specific S. aureus types 5 and 8 CPS IgG. The administration of this anti-staphylococcal hyperimmune globulin was well tolerated in this population.

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Abbreviations

CoNS:

coagulase negative staphylococci

CPS:

capsular polysaccharide

ELBW:

extremely low birth weight

GM:

geometric mean

IgG:

immunoglobulin

IVIG:

intravenous immune globulin

VLBW:

very low birth weight

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Acknowledgements

This research was funded by NABI Biopharmaceuticals, Rockville Maryland. Dr Benjamin received support from 1U10-HD45962-02 and HD044799-01.

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Author notes

  1. D K Benjamin, R Schelonka, R White, H P Holley, E Bifano, J Cummings, K Adcock, D Kaufman, B Puppala, P Riedel, B Hall, J White and C M Cotton: For details regarding S. aureus prevention investigators. See Appendix A.

Authors and Affiliations

  1. Duke University Department of Pediatrics, Durham, NC, USA

    D K Benjamin Jr & C M Cotton

  2. University of Alabama Birmingham Department of Pediatrics, Birmingham, AL, USA

    R Schelonka

  3. Memorial Hospital of South Bend, South Bend, IN, USA

    R White

  4. NABI Biopharmaceuticals, Rockville, MD, USA

    H P Holley Jr

  5. Crouse Irving Memorial Hospital, Syracuse, NY, USA

    E Bifano

  6. East Carolina University The Brody School of Medicine Department of Pediatrics, Greenville, NC, USA

    J Cummings

  7. University of Mississippi Department of Pediatrics, Jackson, MS, USA

    K Adcock

  8. University of Virginia Department of Pediatrics, Charlottesville, VA, USA

    D Kaufman

  9. Lutheran General Children's Hospital, Park Ridge, IL, USA

    B Puppala

  10. Sunrise Hospital, Las Vegas, NV, USA

    P Riedel

  11. Wilford Hall, San Antonio, TX, USA

    B Hall

  12. Duke Clinical Research Institute, Durham, NC, USA

    D K Benjamin Jr & J White

Authors
  1. D K Benjamin Jr
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  2. R Schelonka
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  3. R White
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  5. E Bifano
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  6. J Cummings
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  7. K Adcock
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  8. D Kaufman
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  9. B Puppala
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  10. P Riedel
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  11. B Hall
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  12. J White
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  13. C M Cotton
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Consortia

on behalf of the S. aureus prevention investigators

Corresponding author

Correspondence to D K Benjamin Jr.

Appendix A

Appendix A

S. aureus prevention investigators Table A1

Table 3 Table a1
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Benjamin, D., Schelonka, R., White, R. et al. A blinded, randomized, multicenter study of an intravenous Staphylococcus aureus immune globulin. J Perinatol 26, 290–295 (2006). https://doi.org/10.1038/sj.jp.7211496

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  • DOI: https://doi.org/10.1038/sj.jp.7211496

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