Combined Clinical, Epidemiological, and Genome-Based Analysis Identified a Nationwide Outbreak of Burkholderia cepacia Complex Infections Caused by Contaminated Mouthwash Solutions

Abstract

Background In September 2018, Burkholderia cepacia complex (BCC) infections of three patients associated with exposure to a mouthwash solution (MWS) were notified to the Robert Koch Institute (RKI). As the product was still in the market and scale of the outbreak unclear a nation-wide investigation was initiated. Methods We aimed to investigate BCC infections/colonizations associated with MWS. Hospitals, laboratories and public health services were informed that BCC isolates should be sent to the RKI. These isolates were typed by pulsed-field gel electrophoresis (PFGE) and whole genome sequencing (WGS) including development of an ad hoc core genome MLST (cgMLST) scheme. Results In total, 36 patients from six hospitals met the case definition, the last patient in November 2018. Twenty-nine isolates from 26 of these patients were available for typing. WGS analysis revealed two distinct cgMLST clusters. Cluster 1 (Burkholderia arboris) contained isolates from patients and MWS obtained from four hospitals and isolates provided by the manufacturer. Patient and MWS isolates from another hospital were assigned to cluster 2 (B. cepacia). Conclusion The combined clinical, epidemiological and microbiological investigation, including whole genome analysis, allowed for uncovering a supraregional BCC outbreak in healthcare settings. Strains of B. arboris and B. cepacia were identified as contaminating species of MWS bottles and subsequent colonization and putative infection of patients in several hospitals. Despite a recall of the product by the manufacturer in August 2018 the outbreak lasted until December 2018. Reporting of contaminated medical products and recalls should be optimized to protect patients.

Burkholderia cepacia complex in cystic fibrosis: critical gaps in diagnosis and therapy

“…In Germany between August and September 2018, by means of whole-genome sequencing (WGS), lung infections caused by the same strain of Bcc were identified, which coincided with isolated specimens of two closed oral rinse vials (MWS) containing octenidine [ 13 ], a substance recommended in that country to prevent ventilator-associated pneumonia [ 14 ], that were of a lot used from three weeks before the outbreak. Two of the three infected patients died nine to 10 days after the identification of the microorganism, despite being treated with antimicrobials [ 13 ].…”

“…(2018). In parallel, 11 isolates from 10 patients treated in another hospital coincided with a different batch of MWS, while the isolates from the other 14 patients treated in other hospitals did not show molecular coincidence with the microorganisms isolated from the batches of MWS analysed, suggesting the likelihood that these batches have not been sampled [ 14 ].…”

“…The microbiological diagnosis of Bcc infection in individuals with CF has been recognized as complex [ 13 , 14 , 46 ]. Therefore, early diagnosis [ 14 , 45 , 47 , 48 ] is a difficult goal to achieve due to various factors, such as the slow growth of Bcc even in selective media (48 to 72 h) [ 7 , 39 ].…”

“…The microbiological diagnosis of Bcc infection in individuals with CF has been recognized as complex [ 13 , 14 , 46 ]. Therefore, early diagnosis [ 14 , 45 , 47 , 48 ] is a difficult goal to achieve due to various factors, such as the slow growth of Bcc even in selective media (48 to 72 h) [ 7 , 39 ]. These media include the selective agar for B. cepacia (BCSA) ( Figure 1 ) [ 49 ], Pseudomonas cepacia agar (PCA), and the oxidation medium fermentation of polymyxin, bacitracin, lactose (OFPBL), and there is no consensus on the optimal conditions for their isolation [ 39 , 50 ].…”

Taking hospital pathogen surveillance to the next level

“…Hospital pathogen surveillance goes far beyond simple outbreak analyses and has a much broader longitudinal dimension, building on patient networks and patient-to-patient transmission chains. Pathogen or AMR dissemination could go on for years if unnoticed or if the implemented infection prevention and control measures are less effective [50][51][52].…”