Outbreak of Serratia marcescens bloodstream infections in patients receiving parenteral nutrition prepared by a compounding pharmacy

Parenteral nutrition (PN) is widely used in healthcare settings to deliver critical nutrients to patients unable to tolerate enteral feeding. The intravenous formulation is intended to provide all daily nutritional requirements, such as electrolytes, amino acids, dextrose, and lipids, and is considered to be one of the most complex pharmaceuticals to prepare because of the need for careful titration and combination of multiple components [1, 2]. Preparation under rigorous sterile conditions is especially crucial as the nutrient-rich formulation can act as favorable growth media for microorganisms [3, 4] and because the process requires the multistep transfer of several ingredients into a single container, providing opportunities for microbial contamination during the compounding process [5]. In the United States, PN can be compounded in a healthcare facility, outsourced to a compounding pharmacy, or purchased as manufactured, premixed formulations [5]. Healthcare facilities that administer PN to patients often lack the time, expertise, and technology to produce these solutions in their own facilities. As a result, the preparation of PN is frequently outsourced to compounding pharmacies specializing in these practices. In 2011, approximately 43% of 556 US hospitals with >600 beds randomly surveyed reported outsourcing their nutrition support preparations [6]. Compounding pharmacies are expected to adhere to current standards for preparation and handling of compounded sterile preparations (CSPs). One such standard is the United States Pharmacopeia's (USP) General Chapter “Pharmaceutical Compounding—Sterile Preparations,” which details conditions and practices that minimize risks of contamination of CSPs, including PN [7]. Additional standards for compounding PN solutions also exist [8, 9]. The adoption of strict standards for sterile compounding have contributed to a decline in the burden of contaminated PN preparations, and US outbreaks related to mishandling of PN during compounding are rare [2]. However, compounding CSPs, especially using nonsterile active pharmaceutical ingredients (APIs), involves challenging and complex processes, and outbreaks associated with improperly compounded preparations are being increasingly reported [10–20]. In March 2011, the Centers for Disease Control and Prevention (CDC) was notified of 5 patients with Serratia marcescens bloodstream infection (BSI) in one hospital in Alabama. Receipt of PN from a single compounding pharmacy was identified as a potential common source. The pharmacy was an independent, state-licensed compounding pharmacy in Birmingham that was registered with the Alabama State Board of Pharmacy and subject to the state laws and regulations pertaining to the compounding of parenteral therapy [21]. During the outbreak period, the pharmacy supplied PN to 6 healthcare facilities (5 acute care hospitals and 1 long-term acute care hospital), all located within Alabama. Prescriptions for PN were received daily by the pharmacy, and compounded PN preparations were delivered to hospitals each night. On 15 March 2011, after being notified of these S. marcescens BSIs, the pharmacy voluntarily ceased all compounding activities and subsequently recalled all CSPs as a precautionary measure. An investigation was conducted by the Alabama Department of Public Health and CDC to determine the extent of the outbreak, identify risk factors for infection among PN recipients, and review PN compounding practices to identify potential sources of contamination.