X

Quality Statement

Pacific Biosciences is committed to providing high-quality products that meet customer expectations and comply with regulations. We will achieve these goals by adhering to and maintaining an effective quality-management system designed to ensure product quality, performance, and safety.

X

Image Use Agreement

By downloading, copying, or making any use of the images located on this website (“Site”) you acknowledge that you have read and understand, and agree to, the terms of this Image Usage Agreement, as well as the terms provided on the Legal Notices webpage, which together govern your use of the images as provided below. If you do not agree to such terms, do not download, copy or use the images in any way, unless you have written permission signed by an authorized Pacific Biosciences representative.

Subject to the terms of this Agreement and the terms provided on the Legal Notices webpage (to the extent they do not conflict with the terms of this Agreement), you may use the images on the Site solely for (a) editorial use by press and/or industry analysts, (b) in connection with a normal, peer-reviewed, scientific publication, book or presentation, or the like. You may not alter or modify any image, in whole or in part, for any reason. You may not use any image in a manner that misrepresents the associated Pacific Biosciences product, service or technology or any associated characteristics, data, or properties thereof. You also may not use any image in a manner that denotes some representation or warranty (express, implied or statutory) from Pacific Biosciences of the product, service or technology. The rights granted by this Agreement are personal to you and are not transferable by you to another party.

You, and not Pacific Biosciences, are responsible for your use of the images. You acknowledge and agree that any misuse of the images or breach of this Agreement will cause Pacific Biosciences irreparable harm. Pacific Biosciences is either an owner or licensee of the image, and not an agent for the owner. You agree to give Pacific Biosciences a credit line as follows: "Courtesy of Pacific Biosciences of California, Inc., Menlo Park, CA, USA" and also include any other credits or acknowledgments noted by Pacific Biosciences. You must include any copyright notice originally included with the images on all copies.

IMAGES ARE PROVIDED BY Pacific Biosciences ON AN "AS-IS" BASIS. Pacific Biosciences DISCLAIMS ALL REPRESENTATIONS AND WARRANTIES, EXPRESS, IMPLIED OR STATUTORY, INCLUDING, BUT NOT LIMITED TO, NON-INFRINGEMENT, OWNERSHIP, MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE. IN NO EVENT SHALL Pacific Biosciences BE LIABLE FOR ANY DIRECT, INDIRECT, INCIDENTAL, PUNITIVE, OR CONSEQUENTIAL DAMAGES OF ANY KIND WHATSOEVER WITH RESPECT TO THE IMAGES.

You agree that Pacific Biosciences may terminate your access to and use of the images located on the PacificBiosciences.com website at any time and without prior notice, if it considers you to have violated any of the terms of this Image Use Agreement. You agree to indemnify, defend and hold harmless Pacific Biosciences, its officers, directors, employees, agents, licensors, suppliers and any third party information providers to the Site from and against all losses, expenses, damages and costs, including reasonable attorneys' fees, resulting from any violation by you of the terms of this Image Use Agreement or Pacific Biosciences' termination of your access to or use of the Site. Termination will not affect Pacific Biosciences' rights or your obligations which accrued before the termination.

I have read and understand, and agree to, the Image Usage Agreement.

I disagree and would like to return to the Pacific Biosciences home page.

Pacific Biosciences
Contact:

Keeping a Close Eye on MRSA: Lessons Learned from PacBio Sequencing Surveillance 

Monday, October 7, 2019

Harm van Bakel

When MRSA hits your hospital, what do you do? 

If you’re located in Europe or other places where infection rates are still relatively low, you can take a seek-and-destroy approach, isolating an affected patient and working out in concentric circles to identify contacts and potential transmissions. 

If you’re in New York City, however, the strategy is not so simple. Hospital-associated infections with methicillin-resistant Staphylococcus aureus are endemic in the Big Apple, and this has required a fresh approach to treat and prevent the costly bacterial menace. 

At Mount Sinai Hospital, the strategy now involves SMRT Sequencing. Established in 2013, the Mount Sinai Pathogen Surveillance Program has sequenced more than 2,000 genomes, cataloging around 43,000 isolates from 22,000 patients. While its original role was in reactive outbreak investigation, it is now also used as a tool for proactive, continuous infection surveillance for common hospital pathogens.

As previously reported in this blog post and this webinar, adding SMRT Sequencing to routine surveillance of MRSA and C. difficile throughout the hospital has provided a more comprehensive view of drug resistance and revealed new pathogenic strains and unexpected transmission paths.

We recently caught up with Harm van Bakel, Assistant Professor of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, to learn more about how the program has evolved and some of the results published in this paper.

 

Why did you choose SMRT Sequencing?

MRSA is highly clonal. Traditional molecular strain typing methods, such as pulsed-field gel electrophoresis (PFGE), S. aureus protein A (spa) typing, and multilocus sequence typing (MLST), can  facilitate rapid screening, but their resolution is limited, and they are unable to capture genetic changes that lead to alteration or loss of typing elements. 

Asa  result, short-read whole genome sequencing has emerged as the gold standard for studying lineage evolution and nosocomial outbreaks. By comparing sequences of your clone of interest to a reference genome, you are able to profile changes in the core genome. However, you may still be missing crucial information contained in non-conserved ‘accessory’ genome elements, which harbor a lot of virulence and drug resistance determinants, and evolve more rapidly. 

These accessory elements, which include endogenous prophages, mobile genetic elements, and plasmids, are very repetitive in nature, so long-read sequencing that is able to resolve these was needed to help us determine what’s going on in both the core and accessory genome elements. It also gives us additional information to tease apart the evolution of an outbreak.

In the paper, we gave an example of a persistent outbreak in the hospital’s neonatal intensive care unit, which was eventually traced to adult hospital wards, with ventilators as a potential vector. Long-read sequencing enabled comparative genome and gene expression analyses of the outbreak clone to hospital background strains, in which we identified genetic and epigenetic changes, including acquisition of accessory genome elements that may have contributed to the persistence of the outbreak clone.

 

What lessons have you learned from continuous surveillance? 

Logistically, we have learned that integration and automation are key. In the beginning, we were a little naive. But we quickly realized that you can’t just analyze the genomes in a vacuum. Just identifying infection relatedness between two patients isn’t enough either. You have to understand how certain strains may have spread between patients. This requires detailed information about the patient’s condition, where they have been in the hospital, which staff and equipment they have come in contact with. We had to develop bioinformatics tools to layer genetic information on top of patient and hospital epidemiologic records to create a single, integrated map. We’ve found we need an entire support system in addition to the sequencing in order to make it work. We’re fortunate that our health system has the centralized testing and medical records systems to help us operate in an efficient manner. 

Scientifically, we have learned that there’s a lot more happening under the surface than we were aware of — in regards to strain types, evolution, frequency, virulence and transmission. We continue to see under-the-radar outbreaks that we wouldn’t be aware of without a sequencing-based surveillance program. And we’ve learned that MRSA can be colonized for a long time and re-emerge weeks, if not months later, when infected patients return to the hospital. 

The continuous surveillance has led to a much better understanding of how pathogens circulate throughout the hospital. It allows us to be more proactive. In some cases, it has led to interventions in certain wards. In the case of the NICU outbreak, if we had implemented continuous sequencing before it occurred, we may have been able to intervene much sooner. 

 

What’s next?

We want to continue to improve the program so that it’s fast and cost effective enough to inform infection prevention. Not only does this benefit patient care, but it can help avoid larger outbreaks, ward closures, and other costs associated with investigating and reacting to infections.

We also want to build a more comprehensive view of all pathogens, so we have started to track viral pathogens too, including influenza. 

And we have expanded the program beyond just Mount Sinai Hospital, into the entire Mount Sinai Health System, including other hospitals and community care facilities that cover most of the Manhattan area. We hope this will help us understand just how pathogens are moving throughout the system as patients travel from facility to facility, and to detect new pathogens emerging from the community.

We can’t make headway into reducing the MSRA endemic unless we understand it better. We need to better map the route of transmission of the pathogen between people, and in the environment. This is only possible through hospital-wide – and ideally region-wide – surveillance. 

 

Subscribe for blog updates:

Archives