Clinical perspectives in integrating whole-genome sequencing into the investigation of healthcare and public health outbreaks - hype or help?

Outbreaks pose a significant risk to patient safety as well as being costly and time consuming to investigate. The implementation of targeted infection prevention and control measures relies on infection prevention and control teams having access to rapid results that detect resistance accurately, and typing results that give clinically useful information on the relatedness of isolates. At present, determining whether transmission has occurred can be a major challenge. Conventional typing results do not always have sufficient granularity or robustness to define strains unequivocally, and sufficient epidemiological data are not always available to establish links between patients and the environment. Whole-genome sequencing (WGS) has emerged as the ultimate genotyping tool, but has not yet fully crossed the divide between research method and routine clinical diagnostic microbiological technique. A clinical WGS service was officially established in 2014 as part of the Scottish Healthcare Associated Infection Prevention Institute to confirm or refute outbreaks in hospital settings from across Scotland. This article describes the authors' experiences with the aim of providing new insights into practical application of the use of WGS to investigate healthcare and public health outbreaks. Solutions to overcome barriers to implementation of this technology in a clinical environment are proposed.

Point-of-care testing by healthcare workers for detection of meticillin-resistant Staphylococcus aureus, Clostridioides difficile, and norovirus.

BACKGROUND: The feasibility of introducing three separate Cepheid GeneXpert® assays was assessed: Xpert SA Nasal Complete, Xpert C. difficile, and Xpert Norovirus for point-of-care testing (POCT) on a ward in a district general hospital. AIM: To establish a seven-day/24 h POCT service for meticillin-resistant Staphylococcus aureus (MRSA), Clostridioides difficile, and norovirus operated solely by healthcare workers (HCWs). METHODS: The Cepheid GeneXpert assays performance characteristics were assessed by comparing the assays to traditional central laboratory methods in terms of clinical turnaround times, hands-on time, number of process steps, time to result and diagnostic accuracy. HCW feedback was collected to consider the potential added value of applying this technology to improve patient flow and clinical care. FINDINGS: In total 1170 tests were carried out over the 16-month study period. The assays significantly reduced hands-on time, process steps, and time to result for identification of all three micro-organisms. Overall agreement with central laboratory testing was >98% for all three assays. Staff members fed back that POCT had a positive impact in terms of clinical utility. CONCLUSION: Xpert SA Nasal Complete for MRSA detection, Xpert C. difficile, and Xpert Norovirus can be used as POCT solely by HCWs in a ward setting. Each assay was used throughout a seven-day/24 h period with potential positive impact on bed management and patient care.

Pseudomonas aeruginosa intensive care unit outbreak: winnowing of transmissions with molecular and genomic typing.

BACKGROUND: Pseudomonas aeruginosa healthcare outbreaks can be time consuming and difficult to investigate. Guidance does not specify which typing technique is most practical for decision-making. AIM: To explore the usefulness of whole-genome sequencing (WGS) in the investigation of a P. aeruginosa outbreak, describing how it compares with pulsed-field gel electrophoresis (PFGE) and variable number tandem repeat (VNTR) analysis. METHODS: Six patient isolates and six environmental samples from an intensive care unit (ICU) positive for P. aeruginosa over two years underwent VNTR, PFGE and WGS. FINDINGS: VNTR and PFGE were required to fully determine the potential source of infection and rule out others. WGS results unambiguously distinguished linked isolates, giving greater assurance of the transmission route between wash-hand basin water and two patients, supporting the control measures employed. CONCLUSION: WGS provided detailed information without the need for further typing. When allied to epidemiological information, WGS can be used to understand outbreak situations rapidly and with certainty. Implementation of WGS in real-time would be a major advance in day-to-day practice. It could become a standard of care as it becomes more widespread due to its reproducibility and lower costs.

Prison and community outbreak of severe respiratory infection due to adenovirus type 14p1 in Tayside, UK.

BACKGROUND: This report describes the investigation and public health management of a community-based outbreak of severe adenovirus serotype 14p1 respiratory infection affecting the Tayside area during 2011. It is the first report of an adenovirus outbreak involving prisons. METHODS: An outbreak-based/incident management approach was carried out. Alerts were sent out to local doctors, general practitioners, prison healthcare staff and consultants so that cases could be identified prospectively. Sequencing of hexon, fibre and E1A regions of adenovirus were carried out to genotype the viruses. RESULTS: Fifteen cases were identified in total, including 13 confirmed cases and 2 possible cases. There were 3 deaths amongst the 13 confirmed cases, with a case fatality rate of 23%. Eight of the cases had a direct association with one of the two prisons in the area. CONCLUSIONS: We advise that surveillance measures for adenovirus infection and guidelines for the management of critically ill patients should be developed in order to identify outbreaks at an early stage and allow patients to receive appropriate treatment. Adenovirus infection should be borne in mind as a cause of severe pneumonia in closed settings such as prisons.

Malignancy within a Tail Gut Cyst: A Case of Retrorectal Carcinoid Tumour.

Purpose. Tailgut cysts with malignant transformation are rare entities. We discuss the diagnostic strategy and treatment of a malignancy within a tailgut cyst. Methods. In this study we report on the case of a 61-year-old man with a malignant neuroendocrine tumour arising within a tailgut cyst and an overview of the literature emphasising the histopathological characteristics and differential diagnosis. Results. Our patient presented with lower back pain, rectal pain, and increased urgency of defecation. MRI scan and CT-guided biopsy on histological analysis revealed a diagnosis of carcinoid tumour of the presacral space. The patient subsequently underwent an abdominoperineal excision of the rectum. Conclusions. This case highlights the importance of tailgut cysts as a differential diagnosis of presacral masses. It is a rare congenital lesion developing from remnants of the embryonic postanal gut and is predominantly benign in nature. Approximately half of cases remain asymptomatic; therefore, diagnosis is often delayed. Magnetic resonance imaging is the investigation of choice and an awareness of the possibility of malignant potential is critical to avoiding missed diagnosis and subsequent morbidity. Complete surgical excision allows accurate diagnosis, confirmation of oncological clearance, and prevention of mortality.

Use of Xpert® MRSA PCR point-of-care testing beyond the laboratory.

A meticillin-resistant Staphylococcus aureus (MRSA) polymerase chain reaction assay (Xpert(®) MRSA, Cepheid) was assessed for point-of-care testing (POCT) used by healthcare assistants in an orthopaedic pre-admission clinic and on a vascular ward to reduce turnaround time. POCT results were compared with the routine swabs taken for culture. The POCT assay was easy to use, the turnaround time for negative results was greatly reduced, and sensitivity was 75.0% in the pre-admission clinic and 80.0% in the vascular ward. There were 27 POCT-positive/culture-negative results, but there was no evidence of MRSA infection or colonization in these patients for at least a year post procedure. POCT for MRSA colonization performed beyond the laboratory has important advantages over laboratory-based methods and should be explored further.

PNA-FISH assays for early targeted bacteraemia treatment.

PNA-FISH S. aureus/CNS and GNR Traffic Light assays were compared with standard culture methods for identifying bacteraemia in 156 blood cultures from 131 patients. Results correlated with final culture results in 153 cultures. Retrospective case note review revealed that earlier targeted treatment would have occurred in 10.7% of cases.