Determination of slime-producing S-epidermidis specific antibodies in human immunoglobulin preparations and blood sera by an enzyme immunoassay - Correlation of antibody titers with opsonic activity and application to preterm neonates

Slime-producing Staphylococcus epidermidis is responsible for severe infect ions in immunocompromised patients and, particularly, in premature infants who are transiently deficient in IgG. A sulfated polysaccharide with molecu lar mass of 70-kDa (20-kDa PS) has been recognized as the major polysacchar ide component and antigenic determinant of S. epidermidis extracellular sli me layer. The presence of adequate amounts of antibodies to 20-kDa PS in pa tients' sera would be of importance to pr-event or treat slime-producing S. epidermidis bacteremia. Administration of intravenous immunoglobulin (IVIG ) is considered to be a reasonable IgG replacement therapy and has been wid ely used to prevent or treat neonatal sepsis. Clinical trials have shown co nflicting results on the efficacy of IVIGs and this phenomenon has been att ributed to the variability of IVIG preparations in the content and opsonic activity of IgG against microorganisms of clinical importance. Monitoring o f antibodies to distinct bacterial macromolecules, which are species-specif ic and responsible for bacterial infections, has not been performed previou sly. A highly precise and repeatable enzyme immunoassay was developed to de ter-mine quantitatively the levels of antibodies against the 20-kDa PS of S . epidermidis slime. The amount of 20-kDa PS specific antibodies found in 2 7 lots of an IVIG preparation (Sandoylobulin(R)) correlated well with their in vitro opsonic activity against slime-producing S, epidermidis. The majo rity of lots (75%) having titers higher than 200 units:ml showed significan t opsonic activity (50-75%) towards slime-producing S. epidermidis. Sandogl obulin(R) lots with titers higher than 200 units/ml of 20-kDa PS specific I gG were administered as a prophylactic agent to low-birth weight (lower tha n 1700 g) preterm neonates immediately after birth. The levels of total and 20-kDa PS specific IgG in neonates' blood sera were significantly higher t han those found in the control group, even 10 days after the last infusion. The rate of slime-producing S. epidermidis bacteremia in neonates who rece ived IVIG was also considerably lower than those in the control group. The results of this study suggest that specific IgG titers estimated by the dev eloped enzyme immunoassay may well be indicative of the IVIG opsonic activi ty against slime-producing S. epidermidis. Furthermore, administration of S andoglobulin(R) with titers higher than a cut-off value of 200 units:ml may significantly protect preterm neonates against slime-producing S. epidermi dis bacteremia. (C) 2000 Elsevier Science B.V. All rights reserved.