Screening for Beta-Lactam Allergy in Joint Arthroplasty Patients to Improve Surgical Prophylaxis Practice.

BACKGROUND: The reliability of patient-reported penicillin allergies has been disputed. A Drug Allergy Clinic (DAC) was established at our institution in combination with an electronic best practice alert (BPA) in the Orthopedic Clinic. Joint arthroplasty patients with a reported history of beta-lactam allergy (HOBA) were preoperatively referred via the BPA to the DAC. The purpose of this study was to determine the effectiveness of beta-lactam allergy screening in enabling the surgical team to optimize antimicrobial prophylaxis. METHODS: Between February 2013 and May 2015, 161 patients with a HOBA were referred to the DAC where they underwent penicillin skin testing (PST), a drug challenge to a beta-lactam antibiotic, and/or had no intervention depending on the history obtained. RESULTS: PST was performed on 140 of 161 (87%) patients. A negative PST was noted in 139 (99%) patients, indicating no penicillin allergy. Cefazolin was safe to use in 145 (90%) patients evaluated. Significantly more patients evaluated in the DAC vs those not seen got cefazolin in any surgical prophylaxis regimen (90% vs 77%) without any adverse perioperative reactions. Concurrently, the use of non-beta-lactam antibiotics was significantly less in the patients evaluated vs not evaluated (16% vs 27%). The overall use of cefazolin in orthopedic surgeries in patients with HOBA was >84% over the course of the study period. CONCLUSION: Beta-lactam allergy screening using a BPA and a DAC promotes the use of standard surgical prophylaxis with cefazolin. Joint arthroplasty surgeons should consider implementing allergy screening programs to promote antimicrobial stewardship.

HOXB4 but not BMP4 confers self-renewal properties to ES-derived hematopoietic progenitor cells.

BACKGROUND: Achieving transplantation tolerance remains an unresolved clinical challenge. Although bone marrow transplantation (BMT) induces mixed chimerism that establishes transplantation tolerance, the preconditioning regimens required for BMT to succeed are too prohibitive for routine use. Recently, embryonic stem (ES) cells have emerged as a potential alternative cell source to bone marrow cells. However, it remains difficult to efficiently differentiate these cells into hematopoietic cells. Here, we tested whether bone morphogenetic protein-4 (BMP-4)-treated or HOXB4-transduced ES-derived hematopoietic cells engraft permanently inducing long-term mixed chimerism. METHODS: Initially, 129 SvJ R1 ES cells (H-2) were treated with BMP-4 for 36 hr. The cells were phenotyped and polymerase chain reaction studies were performed. The robustness of mixed chimerism was tested using mixed lymphocyte cultures and skin grafts. Chimeric MRL (H-2) animals received grafts from 129SvJ (H-2), Balb/c (H-2) or class II (H-2) donor mice, and graft survival was monitored. Additionally, HOXB4-transduced ES cells were shown to more efficiently differentiate into hematopoietic progenitor cells that engrafted in allogenic and syngeneic recipient mice. RESULTS: BMP-4 treatment induced Sca-1 expression and up-regulated HOXB4, BMP-4, and BMP receptor gene expressions. The cells induced transient mixed chimerism, whereas cells derived from HOXB4-transduced ES cells engrafted long term (>100 days). CONCLUSIONS: Although BMP-4 promotes hematopoiesis of ES cells, its impact is only transient, whereas permanent ectopic expression of HOXB4 significantly confers self-renewal and long-term engraftment of ES-derived hematopoietic cells. This strategy could facilitate the establishment of an alternative source of hematopoietic cells that could induce transplantation tolerance.