Anthony C.F. Chan, Ph.D. (Cantab)

Microbial contamination of hematopoietic progenitor cell (HPC) products is primarily caused by nonpathogenic contaminants, mostly from human normal skin flora such as Coagulase-negative Staphylococci and Propionibacterium acnes. Patients who received contaminated products were treated with antibiotics appropriate for the specific organisms identified, in addition to the standard antibiotic prophylaxis, generally levafloxacin (3rd generation of fluoroquinolone), acyclovir and fluconazole or itraconazole. Prophylactic administration of acyclovir helps limit CMV and other herpesvirus (herpes simplex virus, varicella-zoster virus) infections. Antibiotics were started before transplant, for patient who had a positive culture obtained before cryopreservation or as soon as a positive culture was reported after infusion [1].

Contaminated HPCs have been conclusively linked with iatrogenic infection in only 3 of 5046 patients so far. None of these patients subsequently developed clinical sepsis or major sequelae. An extensive search of literature failed to reveal a single death directly associated with contamination of HPC grafts [2]. Importantly, bacterial contamination of grafts does not affect engraftment kinetics in transplant patients. Schwella and colleagues compared time to engraftment, duration of fever, and days on antibiotics in patients who received contaminated grafts compared to those who received noncontaminated grafts [3]. No significant differences were found between the two groups. Some critical steps in HPC processing may also help decrease microbial contamination. Gram-positive bacteria (most common contaminant) survive cryopreservation poorly, and the preservative DMSO has some antibacterial properties [4]

In conclusion, it is the general experience of the transplant community that positive cultures are not associated with adverse events.

[1] Patah PA, Parmar S, McMannis J, et al., Microbial contamination of hematopoietic progenitor cell products: clinical outcome. Bone Marrow Transplantation 2007;40:365-8.
[2] Webb IJ, Coral FS, Andersen JW, et al., Sources and sequelae of bacterial contamination of hematopoietic stem cell components: implications for the safety of hematotherapy and graft engineering. Transfusion 1996;36:782-8.
[3] Schwella N, Rick O, Heuft HG, et al., Bacterial contamination of autologus bone marrow: reinfusion of culture positive grafts does not result in clinical sequelae during the posttransplantation course. Vox Sang 1998;74:388-94.
[4] Rowley SD, Davis J, Dick J, et al., Bacterial contamination of bone marrow grafts intended for autologous and allogeneic bone marrow transplantation: incidence and clinical significance. Transfusion 1988;28:109-12.