Correspondence
Treatment of Neonatal Sepsis with Immune Globulin
N Engl J Med 2012; 366:91January 5, 2012
- Article
To the Editor:
The International Neonatal Immunotherapy Study (INIS) Collaborative Group (Sept. 29 issue)1 reports that therapy with intravenous immune globulin was not associated with decreased mortality in neonatal sepsis. However, many patients who were included in this study had cultures growing coagulase-negative staphylococci, which are usually less pathogenic and are associated with a better outcome than are coagulase-positive staphylococci. In addition, such cultures often contain contaminants from skin. Since severe sepsis was not strictly defined in this study, many patients could have conditions that were falsely diagnosed as sepsis, with relatively mild symptoms and a false positive blood culture. The predominance of coagulase-negative staphylococci may have decreased the clinical effect of immune globulin, which might be the reason for the lack of statistical significance.
Yuichiro Oba, M.D.
Kentaro Iwata, M.D.
Kobe University Hospital, Kobe, Japan
oobau@mbj.ocn. ne. jp No potential conflict of interest relevant to this letter was reported.
1 References1
The INIS Collaborative Group
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Author/Editor Response
Oba and Iwata comment that coagulase-negative staphylococci are less pathogenic and may be skin contaminants. They hypothesize that a predominance of cases with cultures positive for coagulase-negative staphylococci may be a reason why our study did not show significant effects for intravenous immune globulin. We think that this is unlikely. More than 75% of the infants in our study had a very low birth weight. In this group, bloodstream sepsis with coagulase-negative staphylococci is associated with a markedly independent increase in the risk of cerebral palsy and adverse neurodevelopmental outcome and does not differ substantially from sepsis with other pathogens in these respects.1 In our study, 293 infants had gram-negative sepsis at enrollment (148 in the group assigned to receive intravenous immune globulin and 145 in the placebo group). In this subgroup, among the patients who were assigned to receive intravenous immune globulin, the relative risk of the primary outcome of death or major disability at 2 years was 0.92 (95% confidence interval, 0.71 to 1.19; P=0.39). There was no significant evidence of benefit. We plan a wider subgroup analysis to evaluate the effects of intravenous immune globulin in other groups of infants who may be identifiable at the time of presentation with illness, when a benefit of such therapy might still be possible. We have not yet identified any subgroup with evidence of benefit.
Ben Stenson, M.D.
Simpson Centre for Reproductive Health, Edinburgh, United KingdomPeter Brocklehurst, M.B., Ch.B.
Andrew King, B.A.
National Perinatal Epidemiology Unit, Oxford, United Kingdom
peter.brocklehurst@npeu. ox. ac. uk Since publication of their article, the authors report no further potential conflict of interest.
1 References1
Stoll BJ ,Hansen NI ,Adams-Chapman I , et al. Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection. JAMA 2004;292:2357-2365
CrossRef | Web of Science | Medline
