title: Laboratory replication of filtration procedures associated with Serratia marcescens bloodstream infections in patients receiving compounded amino acid solutions.
abstract: OBJECTIVE
  Specific deviations from United States Pharmacopeia standards were analyzed to investigate the factors allowing an outbreak of Serratia marcescens bloodstream infections in patients receiving compounded amino acid solutions.
  
  
  METHODS
  Filter challenge experiments using the outbreak strain of S. marcescens were compared with those that used the filter challenge organism recommended by ASTM International (Brevundimonas diminuta ATCC 19162) to determine the frequency and degree of organism breakthrough. Disk and capsule filters (0.22- and 0.2-μm nominal pore size, respectively) were challenged with either the outbreak strain of S. marcescens or B. diminuta ATCC 19162. The following variables were compared: culture conditions in which organisms were grown overnight or cultured in sterile water (starved), solution type (15% amino acid solution or sterile water), and filtration with or without a 0.5-μm prefilter.
  
  
  RESULTS
  Small-scale, syringe-driven, disk-filtration experiments of starved bacterial cultures indicated that approximately 1 in every 1,000 starved S. marcescens cells (0.12%) was able to pass through a 0.22-μm nominal pore-size filter, and about 1 in every 1,000,000 cells was able to pass through a 0.1-μm nominal pore-size filter. No passage of the B. diminuta ATCC 19162 cells was observed with either filter. In full-scale experiments, breakthrough was observed only when 0.2-μm capsule filters were challenged with starved S. marcescens in 15% amino acid solution without a 0.5-μm prefiltration step.
  
  
  CONCLUSIONS
  Laboratory simulation testing revealed that under certain conditions, bacteria can pass through 0.22- and 0.2-μm filters intended for sterilization of an amino acid solution. Bacteria did not pass through 0.2-μm filters when a 0.5-μm prefilter was used.
authors.affiliation: Heather Moulton-Meissner, Ph.D., is Associate Service Fellow, Division of Healthcare Quality Promotion (DHQP); Judith Noble-Wang, Ph.D., is Supervisory Microbiologist, DHQP; LCDR Neil Gupta, USPHS, M.D., is Medical Officer, DHQP; LCDR Susan Hocevar, USPHS, M.D., is Medical Officer, DHQP; CDR Alex Kallen, USPHS, M.D., is Medical Officer, DHQP; and Matthew Arduino, Dr.P.H., is Branch Chief, Clinical Environmental Microbiology, DHQP, Centers for Disease Control and Prevention, Atlanta, GA. ftw2@cdc.gov.
authors.forename: Heather
authors.initials: H
authors.lastname: Moulton-Meissner
authors.affiliation: Heather Moulton-Meissner, Ph.D., is Associate Service Fellow, Division of Healthcare Quality Promotion (DHQP); Judith Noble-Wang, Ph.D., is Supervisory Microbiologist, DHQP; LCDR Neil Gupta, USPHS, M.D., is Medical Officer, DHQP; LCDR Susan Hocevar, USPHS, M.D., is Medical Officer, DHQP; CDR Alex Kallen, USPHS, M.D., is Medical Officer, DHQP; and Matthew Arduino, Dr.P.H., is Branch Chief, Clinical Environmental Microbiology, DHQP, Centers for Disease Control and Prevention, Atlanta, GA.
authors.forename: Judith
authors.initials: J
authors.lastname: Noble-Wang
authors.affiliation: Heather Moulton-Meissner, Ph.D., is Associate Service Fellow, Division of Healthcare Quality Promotion (DHQP); Judith Noble-Wang, Ph.D., is Supervisory Microbiologist, DHQP; LCDR Neil Gupta, USPHS, M.D., is Medical Officer, DHQP; LCDR Susan Hocevar, USPHS, M.D., is Medical Officer, DHQP; CDR Alex Kallen, USPHS, M.D., is Medical Officer, DHQP; and Matthew Arduino, Dr.P.H., is Branch Chief, Clinical Environmental Microbiology, DHQP, Centers for Disease Control and Prevention, Atlanta, GA.
authors.forename: Neil
authors.initials: N
authors.lastname: Gupta
authors.affiliation: Heather Moulton-Meissner, Ph.D., is Associate Service Fellow, Division of Healthcare Quality Promotion (DHQP); Judith Noble-Wang, Ph.D., is Supervisory Microbiologist, DHQP; LCDR Neil Gupta, USPHS, M.D., is Medical Officer, DHQP; LCDR Susan Hocevar, USPHS, M.D., is Medical Officer, DHQP; CDR Alex Kallen, USPHS, M.D., is Medical Officer, DHQP; and Matthew Arduino, Dr.P.H., is Branch Chief, Clinical Environmental Microbiology, DHQP, Centers for Disease Control and Prevention, Atlanta, GA.
authors.forename: Susan
authors.initials: S
authors.lastname: Hocevar
authors.affiliation: Heather Moulton-Meissner, Ph.D., is Associate Service Fellow, Division of Healthcare Quality Promotion (DHQP); Judith Noble-Wang, Ph.D., is Supervisory Microbiologist, DHQP; LCDR Neil Gupta, USPHS, M.D., is Medical Officer, DHQP; LCDR Susan Hocevar, USPHS, M.D., is Medical Officer, DHQP; CDR Alex Kallen, USPHS, M.D., is Medical Officer, DHQP; and Matthew Arduino, Dr.P.H., is Branch Chief, Clinical Environmental Microbiology, DHQP, Centers for Disease Control and Prevention, Atlanta, GA.
authors.forename: Alex
authors.initials: A
authors.lastname: Kallen
authors.affiliation: Heather Moulton-Meissner, Ph.D., is Associate Service Fellow, Division of Healthcare Quality Promotion (DHQP); Judith Noble-Wang, Ph.D., is Supervisory Microbiologist, DHQP; LCDR Neil Gupta, USPHS, M.D., is Medical Officer, DHQP; LCDR Susan Hocevar, USPHS, M.D., is Medical Officer, DHQP; CDR Alex Kallen, USPHS, M.D., is Medical Officer, DHQP; and Matthew Arduino, Dr.P.H., is Branch Chief, Clinical Environmental Microbiology, DHQP, Centers for Disease Control and Prevention, Atlanta, GA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Arduino
mesh_terms: D016470:Bacteremia / Q000453:epidemiology*; D004196:Disease Outbreaks; D004339:Drug Compounding / Q000592:standards*; D005374:Filtration / Q000379:methods*; D006801:Humans; D010288:Parenteral Nutrition; D010607:Pharmacy Service, Hospital; D016868:Serratia Infections / Q000453:epidemiology*; D012706:Serratia marcescens; D014481:United States / Q000453:epidemiology