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

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 < or =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.     

Regulation and chance in the ontogeny of B and T cell antigen receptor repertoires

The adaptive immune system has to economically generate a large array of T and B cell antigen receptors (T cell receptors [TCRs], B cell receptors [BCRs]) that eliminate both longstanding and novel antigens from the host while preventing the production of deleterious (e.g., autoreactive) antigen receptors. Our studies focus on the mechanisms that shape the development of these antigen receptor repertoies during human ontogeny. The key to BCR and TCR diversity is the third complementarity determining region (CDR3) of the variable domain, which in the immunoglobulin heavy chain and TCR β chain, is created by the junction between the variable, diversity, and joining gene segments. The CDR3 diversity is constrained by overrepresentation of gene segments and lack of N regions during the first trimester of gestation and then increases exponentially during ontogeny until it reaches adult levels months after birth. This process parallels, and may contribute to, the stepwise acquisition of the ability to respond to specific antigens. Recent studies indicate that maturation of the CDR 3 repertoire is not accelerated by premature exposition to extrauterine antigen and thus appears to follow a strictly developmentally regulated program whose pacemaker(s) is still unknown.     

A porcine model predicts that a can-opener capsulotomy can be done safely in pediatric patients

PURPOSE: The purpose of this study was to compare the strength and safety of a continuous circular capsulorhexis (CCC) with a can-opener capsulotomy (COC) in a porcine model that closely resembles the high elasticity of the human pediatric lens capsule. METHODS: COCs (N = 47) and CCCs (N = 102) were performed inside the anterior chamber of fresh pig eyes, and any uncontrolled tears were noted. The circumference of the initial opening was measured in 18 COCs and 13 CCCs. After the opening was stretched to the point of rupture, the circumference was measured again. The ratio of the circumference at rupture to the initial circumference, minus one, was used as a measure of the maximal capsular strain. RESULTS: The can-opener technique produced a smooth round opening. One of the COCs (2.1%) and 23 of the CCCs (22.5%) had uncontrolled tears (chi2, P<.001). The mean maximal strain for COCs was 46.7% (SE, 8.3%) and for the CCCs, 47.7% (SE, 9.9%). This difference was statistically not significant (P = .93 by Student's t test). CONCLUSIONS: The porcine capsule is more reliably opened with fewer uncontrolled tears by a COC than by a CCC. The porcine model predicts that pediatric capsules can be opened safely with a COC.     

Multiple-locus variable-number tandem-repeat analysis of meticillin-resistant Staphylococcus aureus discriminates within USA pulsed-field gel electrophoresis types

Many isolates of meticillin-resistant Staphylococcus aureus (MRSA) are indistinguishable when compared using the standard pulsed-field gel electrophoresis (PFGE) typing method. This may present a problem when investigating local outbreaks of MRSA transmission in a healthcare setting. It also impedes investigation of the widely disseminated community-acquired MRSA (USA 300-0114) in the inpatient setting, which is displacing other traditional hospital-acquired PFGE types. Combination of methods, including multiple-locus sequence typing (MLST), spa typing and staphylococcal cassette chromosome mec (SCCmec) typing, have been used with, or in place of, PFGE to characterise MRSA for epidemiological purposes. These methods are technically challenging, time-consuming and expensive and are rarely feasible except in large laboratories in tertiary care medical centres. Another method, which is simpler and with faster turnaround time, is multiple-locus variable-number tandem-repeat analysis (MLVA). We investigated the utility of MLVA to distinguish common PFGE types. The results suggest that MLVA can be used to identify unrelated strains with identical PFGE patterns or confirm close genetic composition of linked isolates. MLVA could potentially be used in conjunction with PFGE to validate relationships, but further prospective evaluation of these relationships will be required in order to define the proper role, if any, for use of this method in hospital epidemiology.     

Interstitial Duplication of 7(q22→q34)

We report on a 3-year-old boy with an interstitial duplication of 7(q22→q34), confirmed with fluorescent in-situ hybridization. He had post-natal growth retardation, developmental delay, frontal and parietal bossing, deep-set eyes, strabismus, bilateral optic nerve hypoplasia, and mild dilatation of the cerebral ventricles. His Phenotype was not significantly different from that of the three previously reported patients with interstitial duplication of the smaller segment 7(q22→q31). © 1993 Wiley-Liss, Inc.     

Type V Aplasia Cutis Congenita: Case Report,Review of the Literature,and Proposed Treatment Algorithm

Abstract: Aplasia cutis congenita (ACC) is the congenital absence of skin. There are a number of different classifications based on distribution and associated findings. Type V ACC is unique in that the lesions are typically symmetric and found primarily on the trunk but can also include the upper and lower extremities. Type V is associated with the loss of a monozygotic co‐twin during the late first or early second trimester. Here we present an extensive case of type V ACC and a review of the literature, including a summary of treatment and outcomes. From the available literature, it appears that there is no benefit from early surgical intervention, and therefore we propose a treatment algorithm that starts with conservative management.     

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

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.     

Bacillus cereus bacteremia in a preterm neonate

Bacillus cereus is an uncommon but potentially serious bacterial pathogen causing infections of the bloodstream, lungs, and central nervous system of preterm neonates. A case of bacteremia caused by B. cereus in a 19-day-old preterm neonate who was successfully treated with vancomycin, tobramycin, meropenem, and clindamycin is described. Implications for the diagnostic laboratory and clinicians when Bacillus species are detected in normally sterile sites are discussed, and the small numbers of infant infections proven to be due to this organism that have been described previously are reviewed.