A multistate investigation of health care-associated Burkholderia cepacia complex infections related to liquid docusate sodium contamination, January-October 2016

Abstract

Background: Outbreaks of health care-associated infections (HAIs) caused by Burkholderia cepacia complex (Bcc) have been associated with medical devices and water-based products. Water is the most common raw ingredient in nonsterile liquid drugs, and the significance of organisms recovered from microbiologic testing during manufacturing is assessed using a risk-based approach. This incident demonstrates that lapses in manufacturing practices and quality control of nonsterile liquid drugs can have serious unintended consequences.

Methods: An epidemiologic and laboratory investigation of clusters of Bcc HAIs that occurred among critically ill, hospitalized, adult and pediatric patients was performed between January 1, 2016, and October 31, 2016.

Results: One hundred and eight case patients with Bcc infections at a variety of body sites were identified in 12 states. Two distinct strains of Bcc were obtained from patient clinical cultures. These strains were found to be indistinguishable or closely related to 2 strains of Bcc obtained from cultures of water used in the production of liquid docusate, and product that had been released to the market by manufacturer X.

Conclusions: This investigation highlights the ability of bacteria present in nonsterile, liquid drugs to cause infections or colonization among susceptible patients. Prompt reporting and thorough investigation of potentially related infections may assist public health officials in identifying and removing contaminated products from the market when lapses in manufacturing occur.

Keywords: Burkholderia cepacia complex; Drug manufacturing; Health care–associated infections; Nonsterile drugs.

Figure 1.

Epidemiologic Curve, January to September, 2016. Note: Epidemiologic curve by the date of the patient’s first culture yielding Bcc.

Figure 2:

Summary of Samples Analyzed by FDA Laboratories Note: Several products from multiple manufacturers were initially tested for contamination. As docusate samples from Manufacturer X began testing positive for Bcc, more docusate samples were collected and tested. This led to docusate forming a higher proportion of samples tested.

Figure 3.

Dendrogram: Percent Similarity of PFGE Patterns of Bcc isolates Note: Figure 3 includes a representative isolate from each of the affected states, that is indistinguishable or closely related by PFGE to Strain A or Strain B; the comment indicates the total number of isolates confirmed in that state. Products and environmental samples are indicated within strain clusters.

Figure 4:

Phylogenetic Tree Note: Phylogenetic tree based on Single Nucleotide Polymorphism (SNP) data of all sequenced isolates, displaying two distinct clusters of Burkholderia cepacia complex species. Average SNP count between both clusters, an ST102 and a novel MLST cluster, was 122355 SNPs. The genetic diversity of the novel Bcc strain cluster ranged between 0 and 11 SNPs, however a larger diversity range, from 0 to 49 SNPs, was observed for the B. contaminans clade. The first column to the right of the tree corresponds to Multilocus Sequence Typing (MLST) and Pulsed-Field Gel Electrophoresis (PFGE) data for each isolate. Columns in the gene matrix represent homologous gene clusters and are ordered by frequency of gene presence. Dark blue bars indicate gene presence and white gene absence.