Non-linear significant relationship between use of glycopeptides and isolation of vancomycin-resistant Enterococcus species in a university hospital setting.

BACKGROUND: Emergence of colonization and infection with vancomycin-resistant enterococci (VRE) has become a worldwide challenge. To investigate whether the increasing incidence of VRE isolation can be correlated with use of glycopeptides in the hospital setting, we conducted a hospital-wide two-year study in the university hospital of Vienna. METHODS: Within the period from January 2011 through December 2012 all patients with isolation of invasive or non-invasive VRE were retrospectively included. Specialty-specific data concerning the consumption of vancomycin and teicoplanin, fluoroquinolones and third generation cephalosporins in defined daily doses (DDDs) from June 2010 through May 2012 were extracted from the hospital pharmacy computer system. To assess the relationship between the usage of those antibiotics and the incidence of VRE (VRE-rate per 10 000 patients) a Poisson regression was performed. FINDINGS: In the study period 266 patients were colonized or infected with VRE. Specialty-specific VRE isolation was as follows: general surgical units (44 patients), bone marrow transplant unit (35 patients), general medical units (33 patients), cardiothoracic surgery (27 patients), nephrology (26 patients), haematooncology (22 patients), gastroenterology (17 patients), urology (17 patients), and the infectious diseases unit (11 patients). Hospital-wide consumption of glycopeptides was higher for teicoplanin than for vancomycin (26 242 versus 8677 DDDs). Specialty-specific VRE incidence significantly increased with the use of glycopeptides, fluoroquinolones or third generation cephalosporins (p < 0.001). The results of the Poisson regression for vancomycin (p = 0.0018) and teicoplanin (p < 0.0001) separately were both highly significant. Spearman's correlation coefficient indicated a strong correlation between the two variables (rho = 0.8). CONCLUSION: Overall usage of glycopeptides, fluoroquinolones or third generation cephalosporins contributed to the emergence of VRE in the hospital setting.

Surface disinfection of packed red blood cells with 70% ethanol.

No data or recommendations are available on feasibility of surface disinfection of blood bags, but some circumstances can make such procedures inevitable. Impact of immersion of blood bags in 70% ethanol for 30min was investigated with respect to alcohol penetration and changes of hemolysis parameters in the product, and bag material changes influencing material stability and composition. After immersion ethanol concentration in blood bags was below detection limit. Hemolysis parameters did not differ between blood products that had been exposed to ethanol and a control group. Inner surface of the bag material was unchanged according to our infrared spectrometry results. Also endurance testing showed no altered results. We conclude that immersion of blood bags in 70% ethanol for surface disinfection is a safe procedure for the quality of the blood product and the bag material.

Lack of impact of ABO blood group or corresponding isoantibodies on the immune response after rabies vaccination.

Demand for rabies hyperimmunoglobulin has increased recently, requiring optimization of vaccination schemes for immunized plasma donors. Possible resemblance of rabies vaccine to blood group antigens and consequential association of the immune response to rabies vaccine and blood group or corresponding isoantibodies has not yet been investigated. We analyzed antirabies antibodies after rabies vaccination and ABO blood group in 142 individuals, and isoantibody titers in 92 of those individuals. We did not find any correlation of the immune response with blood group or isoantibody levels. There was also no correlation with the sex of individuals, but there was a weak correlation between age and rabies-specific antibody level. Rabies vaccination schemes for immunized donors cannot be optimized on the basis of blood groups or isoantibody titers.

Biochemical characterization of autologous fibrin sealants produced by CryoSeal and Vivostat in comparison to the homologous fibrin sealant product Tissucol/Tisseel.

Different principles for production of "autologous fibrin sealant" have been established, and commercial devices employing these methods are nowadays available and used in clinical routine. Users might anticipate for these autologous fibrin sealants features comparable to commercial homologous fibrin sealants, used in surgical routine for many years. However, only little is known about biochemical properties, formation, cross-linking and stability of fibrin sealant clots produced for autologous use with the aid of commercially available devices. We have investigated protein composition, formation and stability of clots obtained from autologuous fibrin sealants produced with commercially available devices (CryoSeal and Vivostat) and compared these parameters to those of the industrially produced homologous fibrin sealant Tissucol/Tisseel. The CryoSeal product is a mixture of many plasma proteins; the Vivostat product and Tissucol/Tisseel appear as comparatively pure plasma derivatives. The products differ in their protein composition and concentrations, including their concentration in fibrin. Significant fibrin alpha and gamma-chain cross-linking by FXIIIa occurs only in Tissucol/Tisseel clots. In test tubes CryoSeal and Vivostat (tranexamic acid-free formulation) fibrin clots liquefy within 1-2 days, but Vivostat (tranexamic acid containing formulation) clots were stable for 4 days and showed partial liquefaction after 5 days. Tissucol/Tisseel clots, containing the protease inhibitor aprotinin, appeared unchanged over the observation period of 5 days. In an in vitro model mimicking in vivo conditions (diffusion of protease inhibitors and proteolytic digestion) clot liquefaction occurs at day 1 for all autologous fibrin sealants clots, with an observable delay for the tranexamic acid containing Vivostat, and day 5 for Tissucol/Tisseel clots. Characterization of the CryoSeal and Vivostat fibrin sealants and Tissucol/Tisseel and their performance show a clear difference in biochemical properties.

Transfusion-related exposure to the plasticizer di(2-ethylhexyl)phthalate in patients receiving plateletpheresis concentrates.

BACKGROUND: Di(2-ethylhexyl)phthalate (DEHP) is a plasticizer that can leach from medical devices including storage bags for plateletpheresis concentrates (PCs). In this study, the DEHP exposure to patients receiving PCs was determined and several variables were evaluated to reduce DEHP load to PC recipients. STUDY DESIGN AND METHODS: In 12 patients, serum DEHP was assessed before and after PC transfusion. For in vitro investigations, PCs were produced either with donor plasma or with 65 percent additive solution (AS; T-Sol) and stored for 5 days. Washing of PCs was performed according to AABB standards. DEHP levels were determined by gas chromatography-mass spectrometry. RESULTS: Transfusion of PCs led to a significant increase in serum DEHP. DEHP levels in the PCs continuously increased during storage, although the accumulation of DEHP was less in PCs stored in the AS, T-Sol, than when stored in plasma. Storage-related accumulation of DEHP contributed to a major part of the total DEHP load in PCs stored for 5 days. Washing of PCs led to a reduction of DEHP load. CONCLUSION: Recipients of PCs are exposed to DEHP, although the total amount represents only a small percentage of the defined tolerable intake. Reduction of storage time, the storage of PC in T-Sol, or the exchange of the storage medium before transfusion are practicable means to reduce the DEHP load in PC.

Potential approaches to prevent uncommon hemolytic side effects of AB0 antibodies in plasma derivatives.

Since hemolytic reactions in patients after administration of plasma derivatives like immunoglobulins or coagulation factor preparations have been described, titers of anti-A and anti-B-antibodies have to be below defined levels for batch release of these plasma-derived therapeutic products according to the European Pharmacopoeia. We have summarized clinical relevance of AB0 antibodies in plasma derivatives and related legal issues in the European Union, United States of America, and Japan. We have also discussed potential approaches for the prevention of hemolytic side effects with feasible steps in preparation of plasma derivatives, viz., (1) selection of donors, (2) exclusion of "dangerous donors", (3) optimizing ratio of the types of plasma, (4) removal of antibodies, (5) production of blood-group-specific plasma derivatives, (6) rejection of batches of plasma derivatives with high titers of antibodies, and (7) crossmatching before administration. For harmonization of standards for anti-A and anti-B in plasma-derived therapeutics the regulators and manufacturers will have to realistically deal with complex clinical, practical, and economic issues.

Quality of drainage blood: survival of red cells after re-transfusion and content of free hemoglobin and potassium.

Re-transfusion of drainage blood is widely used in orthopedic surgery, but objective evidence of the efficacy of re-transfusion of drainage blood in view of post-transfusion survival of RBC has not been given so far. With this study we wanted to evaluate the efficacy and safety of transfusion of drainage blood collected with HandyVac autotransfusion system. In 7 patients red cells in drainage blood were labeled with biotin and percentage of labeled red cells in circulation were determined immediately after re-transfusion, and during 10 days after surgery. To assess further unwanted side-effects of re-transfusion of drainage blood potassium and free hemoglobin were determined in the collected blood. Ten days after re-transfusion at mean 78.9% of drainage-blood derived RBC were found in circulation. Free hemoglobin in drainage blood ranged from 16.8 to 59.2 mg/dL; potassium in drainage blood ranged from 3.84 to 4.52 mmol/L. Our results suggest that re-transfusion of drainage blood collected with HandyVac autotransfusion system is an efficient procedure that seems to be safe in view of free hemoglobin and potassium in the product.

Impact of manufacturing, irradiation and filtration steps to bacterial contamination of autologous fibrin sealant.

BACKGROUND: Preoperative production of autologous fibrin sealant has become a routine procedure during the last years. As a certain percentage of blood products is contaminated with bacteria, contamination of plasma used for the production of fibrin sealant cannot be excluded. Especially in the orthopaedic setting, application of contaminated fibrin sealant can cause severe infections. MATERIALS AND METHODS: We contaminated plasma with Staphylococcus epidermidis, Corynebacterium striatum, Bacillus subtilis or Escherichia coli and produced fibrin sealant by cryoprecipitation and alcohol precipitation. Additionally, the products were gamma-irradiated at a dose of 30 Gy, frozen at -55 degrees C and filtered through a 0.2 microm filter after thawing. After each preparation step, samples were drawn and numbers of colony forming units were counted after incubation on agar plates. RESULTS: Cryoprecipitation, irradiation, freezing at -55 degrees C, and alcohol precipitation have only little impact on numbers of colony forming units. Filtration through a bacterial filter results in a sterile product. CONCLUSION: Bacteria in plasma as a starting material for production of fibrin sealant survive all routine steps of production, including gamma irradiation and freezing. Filtration of the product through a qualified bacterial filter is the only safe means to provide a sterile product.

Reduction of adverse citrate reactions during autologous large-volume PBPC apheresis by continuous infusion of calcium-gluconate.

BACKGROUND: Citrate-related side effects are common adverse reactions during PBPC apheresis. To reduce the incidence of citrate-related reactions, the effect of a continuous calcium-gluconate infusion on the appearance of hypocalcemic symptoms and on the subjective tolerance toward large-volume leukapheresis (LVL) was tested. STUDY DESIGN AND METHODS: A double-blinded, placebo-controlled trial was carried out in 50 patients undergoing standardized LVL at a median ACD-A ratio of 1.99 mg per kg and minute. Patients were randomly assigned to receive a continuous IV infusion of either saline or calcium-gluconate at a dose of 1.8 mmol calcium per hour. Subjective tolerance toward LVL was determined by standardized rating systems. Further, hormonal and electrolyte changes were monitored to assess the effect of continuous calcium infusion on calcium homeostasis. RESULTS: Continuous IV administration of calcium-gluconate throughout LVL reduced the incidence of citrate-related effects by 65 percent. In patients who developed signs of hypocalcemia, the symptoms were weaker, and less medical intervention was needed to resolve clinical symptoms. The subjective tolerance toward LVL was superior in patients receiving calcium support compared to control patients. Continuous calcium infusion attenuated changes in serum phosphorus compared to patients receiving saline. No differences were observed in the variation of serum potassium and serum magnesium between the control group and the treatment group. The administration of calcium was not associated with technical problems related to the apheresis procedure, neither was any effect of calcium support on the total number of CD34+ cells collected observed. CONCLUSION: These results indicate that continuous support of calcium-gluconate during LVL is an effective means of reducing the incidence of citrate-related symptoms and improving subjective tolerance toward LVL, without affecting the technical performance or the number of CD34+ cells collected.

Donor exposure to the plasticizer di(2-ethylhexyl)phthalate during plateletpheresis.

BACKGROUND: Di(2-ethylhexyl)phthalate (DEHP) is a plasticizer that is contained in most PVC devices, including apheresis disposables. Because DEHP can be extracted from apheresis disposables as the blood passes through the apheresis device, DEHP exposure was determined in healthy donors undergoing plateletpheresis performed with commercially available apheresis systems. STUDY DESIGN AND METHODS: The study population consisted of 36 healthy PLT donors undergoing plateletpheresis with either continuous or discontinuous apheresis devices. Serum concentrations of DEHP were determined from peripheral blood obtained before and after plateletpheresis, with gas chromatography-mass spectroscopy. RESULTS: Plateletpheresis performed with standard collection disposables resulted in a median increase of 232 percent of serum DEHP compared to levels before apheresis, corresponding to a total amount of DEHP exposed during a single apheresis of a median of 6.46 (range, 1.8-20.3) microg per kg of body weight. Endogenous levels of triglycerides showed a positive correlation with the amount of DEHP released. Increase in serum DEHP was short-term as serum DEHP rapidly returned to levels obtained before apheresis within 3 hours after completion of the apheresis course. Donor exposure to DEHP led to no variation in liver cell function within 48 hours after plateletpheresis. CONCLUSION: Commercial plateletpheresis disposables release considerable amounts of DEHP during the apheresis procedure, but the total dose of DEHP retained by the donor is within the normal range of DEHP exposure of the general population.