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

Journal of Perinatology volume 26, pages 290–295 (2006)Cite this article

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. Altastaphâ„¢ 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

References

  1. Baker CJ, Melish ME, Hall RT et al. Intravenous immune globulin for the prevention of nosocomial infection in low-birth-weight neonates. N Eng J Med 1992; 327: 213–219.

    Article  CAS  Google Scholar 

  2. Stoll BJ, Hansen N, Fanaroff AA et al. Late-onset sepsis in very low birth weight neonates: the experience of the NICHD neonatal research network. J Pediatrics 2002; 110: 285–291.

    Article  Google Scholar 

  3. Healy CM, Palazzi DL, Edwards MS, Campbell JR, Baker CJ . Features of invasive staphylococcal disease in neonates. Pediatrics 2004; 114: 953–961.

    Article  Google Scholar 

  4. Fanaroff AA, Korones SB, Wright LL et al. A controlled trial of intravenous immune globulin to reduce nosocomial infections in very-low-birth-weight infants. N Eng J Med 1994; 330: 1107–1113.

    Article  CAS  Google Scholar 

  5. Essawi T, Na'was T, Hawwari A, Wadi S, Doudin A, Fattom AI . Molecular, antibiogram and serological typing of Staphylococcus aureus isolates recovered from Al-Makased Hospital in East Jerusalem. Trop Med Int Health 1998; 3: 576–583.

    Article  CAS  Google Scholar 

  6. Fattom AI, Sarwar J, Ortiz A, Naso R . A Staphylococcus aureus capsular polysaccharide (CP) vaccine and CP-specific antibodies protect mice against bacterial challenge. Infect Immun 1996; 64: 1659–1665.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Hill HR . Biochemical, structural, and functional abnormalities of polymorphonuclear leukocytes in the neonate. Pediatr Res 1987; 22: 375–382.

    Article  CAS  Google Scholar 

  8. Ballow M, Cates KL, Rowe JC, Goetz C, Desbonnet C . Development of the immune system in very low birth weight (less than 1500?g) premature infants: concentrations of plasma immunoglobulins and patterns of infections. Pediatr Res 1986; 20: 899–904.

    Article  CAS  Google Scholar 

  9. Schelonka RL, Infante AJ . Neonatal immunology. Semin Perinatol 1998; 22: 2–14.

    Article  CAS  Google Scholar 

  10. Walsh MC, Kliegman RM . Necrotizing enterocolitis: treatment based on staging criteria. Pediatr Clin North Am 1986; 33: 179–201.

    Article  CAS  Google Scholar 

  11. Papile L, Burstein J, Burstein R, Koffler H . Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1500. J Pediatr 1978; 92: 529–534.

    Article  CAS  Google Scholar 

  12. Lemons JA, Bauer CR, Oh W et al. Very low birth weight outcomes of the national institute of child health and human development neonatal research network, January 1995 through December 1996. Pediatrics 2001; 107: e1.

    Article  CAS  Google Scholar 

  13. Zaidi AK, Harrell LJ, Rost JR, Reller LB . Assessment of similarity among coagulase-negative staphylococci from sequential blood cultures of neonates and children by pulsed-field gel electrophoresis. J Infect Dis 1996; 174: 1010–1014.

    Article  CAS  Google Scholar 

  14. Benjamin Jr DK, Ross K, Benjamin DK, McKinney Jr RE, Auten R, Fisher RG . When to suspect fungal infections in neonates: a clinical comparison of Candida albicans and Candida parapsilosis fungemia with coagulase-negative staphylococcal bacteremia. Pediatrics 2000; 106: 712–718.

    Article  Google Scholar 

  15. Fattom AI, Sarwar J, Ortiz A, Naso R . A Staphylococcus aureus capsular polysaccharide (CP) vaccine and CP-specific antibodies protect mice against bacterial challenge. Infect Immun 1996; 64(5): 1659–1665.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Lee JC, Park JS, Shepherd SE, Carey V, Fattom A . Protective efficacy of antibodies to the Staphylococcus aureus type 5 capsular polysaccharide in a modified model of endocarditis in rats. Infect Immun 1997; 65(10): 4146–4151.

    CAS  PubMed  PubMed Central  Google Scholar 

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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

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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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