title: Reconstituted recombinant factor VIII can be safely infused continuously for at least three days: it is a poor microbial growth medium.
abstract: Reconstituted recombinant factor VIII (FVIIIrec) loses little biologic activity at room temperature for up to seven days and continuous infusion is convenient, effective hemostatically and requires less FVIIIrec concentrate than treatment by conventional bolus injections. However, the potential for bacterial contamination, with proliferation to high levels that can cause bacteremia, is a concern with continuous infusion. We studied the growth properties at 4, 25 and 35 degrees C in reconstituted FVIIIrec (Kogenate) and at 25 degrees C in 5% dextrose in water (D5%W) of three isolates each of Staphylococcus epidermidis, Staphylococcus aureus, Enterobacter cloacae, Klebsiella oxytoca, Serratia marcescens, Acinetobacter calcoaceticus, Stenotrophomonas maltophilia, Pseudomonas aeruginosa, Burkholderia cepacia, Flavobacterium spp. and Candida albicans, species most likely to contaminate infusate during preparation or administration and which have been implicated in more than 95% of all outbreaks and sporadic cases of nosocomial bloodstream infection traced to contaminated admixtures, biologic agents or medications administered parenterally. Reconstituted FVIIIrec allowed growth of only three species at 25 degrees C and 35 degrees C: S. marcescens, S. maltophilia and P. aeruginosa; logarithmic growth appeared only after 24-48 h. D5%W allowed growth of two gram-negative species, S. marcescens and B. cepacia. We conclude that reconstituted FVIIIrec (Kogenate) is a poor growth medium for most nosocomial pathogens, comparable with D5%W. If reconstituted aseptically, continuous infusion of reconstituted FVIIIrec should be safe, and it should not be necessary to replace the container or tubing more frequently than every 3 days, an administration schedule that can provide effective hemostasis at lower cost.
authors.affiliation: Department of Medicine, University of Wisconsin Medical School, Madison, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Didier
authors.forename: S
authors.initials: S
authors.lastname: Fischer
authors.forename: D G
authors.initials: DG
authors.lastname: Maki
mesh_terms: D016470:Bacteremia / Q000382:microbiology / Q000517:prevention & control / Q000635:transmission; D001419:Bacteria / Q000254:growth & development*; D002176:Candida albicans / Q000254:growth & development*; D003428:Cross Infection / Q000382:microbiology / Q000517:prevention & control; D004334:Drug Administration Schedule; D004340:Drug Contamination; D004355:Drug Stability; D005169:Factor VIII / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D011994:Recombinant Proteins / Q000008:administration & dosage; D012646:Self Administration; D012996:Solutions; D013997:Time Factors
chemical_list: D011994:Recombinant Proteins; D012996:Solutions; C078147:F8 protein, human; D005169:Factor VIII