CDC Says Drug Pooling Caused Infections
Despite instructions in the product labeling to discard any unused portion of single-dose Epogen, by Amgen Inc., the hemodialysis centers staff routinely withdrew and pooled residual epoetin alfa for later use. This practice, which involved repeated puncturing of the stopper on preservative-free vials, led to a rash of Serratia liquefaciens infections among hemodialysis patients. In all, 15 patients showed evidence of infection with S. liquefaciens, a gram-negative bacterium rarely found in humans, over a six-week period in 1999.
The source of the infections was traced by scientists at the Centers for Disease Control and Prevention (CDC) and the Colorado Department of Public Health and Environment, who reported their findings in the May 17 New England Journal of Medicine (NEJM).
The CDC-led investigation focused on 208 hemodialysis sessions involving 48 patients treated on days during which the hemodialysis centers staff reported bloodstream S. liquefaciens infections. Twelve hemodialysis sessions were associated with bloodstream S. liquefaciens infection, and eight with fever indicating a possible infection. Five patients had a bloodstream infection or fever during two hemodialysis sessions.
Nearly two thirds of the 97 empty epoetin alfa vials kept by the hemodialysis center during the investigation were found to be contaminated with S. liquefaciens. In addition, a bacterial reservoir was discovered in a liquid-soap dispenser that had been repeatedly topped off with new soap instead of discarded or cleaned between fillings. The bacterium was also detected in a bottle of hand lotion located in the centers medication room.
At CDCs recommendation, the hemodialysis center ceased pooling preservative-free epoetin alfa and switched to disposable soap containers. These practices ended the S. liquefaciens outbreak.
The Colorado centers policy of repeatedly puncturing epoetin alfa vials and pooling residual medication, said the report, seemed to be a cost-saving measure suggested to the nursing and technical staff. The investigative team was unable to pinpoint the origin of the suggestion.
The team found, through use of a survey mailed to 103 hemodialysis facilities, that lapses in infection-control procedures are common during preparation of epoetin alfa doses. Of the 71 centers that returned the anonymous survey, 82 percent used the preservative-free, single-dose formulation of epoetin alfa. Seventy-eight percent of these centers reported routinely puncturing the vials more than once to remove additional doses of medication. Sixteen percent of these centers routinely pooled residual epoetin alfa into a common container for later use.
The report estimated that a hemodialysis center serving 150 patients each year could recover up to $180,000 over the annual Medicare payment for epoetin alfa doses if the entire volume in each vial were dispensed. Discarding unused medication, in contrast, could lead to the "waste" of $1.1 million worth of drug each year. These estimates were based on the 1997 Medicare reimbursement rate of $10 per 1,000 units of epoetin alfa.
A 1997 report by the Department of Health and Human Services' Office of Inspector General (OIG) stated that Amgen places an extra 25 percent volume of Epogen in each vial to compensate for material that cannot be withdrawn from the container. According to OIG, which communicated its findings to the Health Care Financing Administration, "there are indications that some free-standing dialysis facilities use, on average, one half of the overfill which would materially affect each provider's cost."
The OIG report did not address whether facilities using the overfill had purchased multiple-dose vials, which contain a preservative.