Facilitation of penicillin haptenation to serum proteins.

Traditionally, penicillin binding to serum proteins was believed to be a passive chemical process; however, it appears to be facilitated by serum factors. The objectives of this in vitro investigation were to examine facilitated penicillin haptenation, to study the kinetics of haptenation, and to determine the nature of haptenation-facilitating factors. The model involved addition of [3H]benzylpenicillin to serum or albumin solutions (at pH 7.3 to 7.4) and incubation at 37 degrees C for up to 72 h. The extent of penicillin binding to proteins in serum was found to be four- to fivefold higher than with solutions having comparable concentrations of purified albumin, total protein, or total immunoglobulin. Ultrafiltration of serum reduced penicillin binding to serum proteinssubstantially. An ultrafiltrable haptenation-facilitating factor(s) was found to be less than 0.5 kDa but was not calcium or magnesium. Finally, the extent of penicillin binding was related to albumin purity, as binding substantially increased with albumin purity. These findings suggest that there is a factor(s) in serum that facilitates covalent binding of penicillin to serum proteins. The factor(s) can be removed and then restored to increase penicillin binding to albumin. It appears that at least one component of the facilitation factor is less than 0.5 kDa, which suggests that it is not a peptide and that it is some simple serum component other than calcium or magnesium

Lipopolysaccharide-reactive immunoglobulin E is associated with lower mortality and organ failure in traumatically injured patients

Antilipopolysaccharide (anti-LPS) immunoglobulin G (IgG) and IgM have been associated with protection from LPS effects in vivo. We investigated the presence of IgE and anti-LPS in 32 patients that had experienced severe traumatic injury and in 35 healthy volunteers; we also investigated whether IgE anti-LPS was associated with important clinical events. Plasma samples were collected daily from patients in the intensive care unit and on one occasion from volunteers; the samples were assayed for IgE anti-LPS. IgE anti-LPS was assayed by enzyme-linked immunosorbent assay with monoclonal anti-human IgE as the capture antibody. Detection was accomplished with biotin-labeled LPS (Escherichia coli J5 mutant) followed by streptavidin-peroxidase with 2,2\u27-azino(3-ethylbenzthiazoline)sulfonic acid as the substrate. The assay was demonstrated to be specific for IgE and LPS-biotin by nonreactivity of control sera with high-titer anti-LPS IgG and IgM and by inhibition with unlabeled LPS. IgE anti-LPS was detected in 1 of 35 healthy controls (2.9%o) and 25 of 32 traumatically injured patients (78%) (P \u3c 0.001). The presence of IgE anti-LPS was associated with a lower incidence of death (P = 0.026) and of renal failure (P = 0.0012). There was no apparent temporal relationship between detection of IgE anti-LPS and clinical events. IgG anti-LPS was detected more frequently in patients that were positive for IgE anti-LPS (P = 0.06) but was not associated with clinical events. The inability to detect IgE anti-LPS may be related to adverse clinical events through depletion of specific IgE due to LPS exposure after trauma or through saturation of the assay by IgE with other specificities. We have reported increased total IgE concentrations in these patients (J. T. DiPiro, R. G. Hamilton, T. R. Howdieshell, N. F. Adkinson, and A. R. Mansberger, Ann. Surg. 215:460-466, 1992)

Controversies in Drug Allergy: Beta-Lactam Hypersensitivity Testing

All beta-lactam use is associated with a certain rate of adverse reactions. Many of these adverse reactions result in an allergy to the beta-lactam being entered into the patient's medical record. Unfortunately, only a small minority of these recorded allergies are clinically significant immunologically mediated drug hypersensitivity. An unconfirmed allergy to beta-lactams is a significant public health risk, because patients so labeled typically do not receive narrow-spectrum penicillins and cephalosporins when clinically indicated. The alternative antibiotics they receive result in poorer clinical outcomes, increased incidence of serious antibiotic-resistant infections, prolonged hospitalizations, and greater health care utilization. There is a wide variation in beta-lactam allergy incidence and prevalence around the world, based in part on the specific beta-lactams used and overused. There is a wide variation in specific protocols used to confirm current tolerance of beta-lactams and remove these inaccurate allergy reports. Harmonizing testing protocols, when possible, may lead to more widespread use of narrow-spectrum beta-lactams, when clinically indicated, and improve patient safety worldwide. Further research is needed to better understand the regional differences in reporting beta-lactam allergy as this relates to regional differences in beta-lactam use and overuse, the frequency of clinically significant immunologically mediated beta-lactam hypersensitivity, and the optimal testing strategies to confirm current tolerance, based on presenting clinical symptoms