Tag: Antibiotic resistance

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The Quest for Direct-from-Blood Pathogen Detection Technologies

The medical community continues to strive for advancements in diagnostic technologies, particularly those that can detect pathogens directly from blood samples. A recent session at ASM Microbe 2024 in Atlanta chaired by Linoj Samuel delved into the complexities and challenges that have hindered the integration of these technologies into clinical practice. Direct-from-blood pathogen detection technologies are designed to bypass traditional culture methods, which can be time-consuming and sometimes ineffective in identifying fastidious or non-culturable pathogens. By utilizing such tools, healthcare providers can obtain actionable information swiftly, allowing for the narrowing of therapy and de-escalation of antibiotics. This rapid turnaround is crucial in managing sepsis, where every hour counts in the race against mortality and morbidity.

The session highlighted a blend of technical and non-technical challenges, from the intricacies of sample preparation, pathogen detection to the broader implications for clinical decision-making. Dr. Valeria Fabre’s insightful presentation underscored the potential of these technologies to revolutionize patient care, offering a clinician’s perspective on their impact on treatment strategies.

Economically, the implementation of these technologies presents both challenges and opportunities. While initial costs may be higher due to equipment and workforce training, the potential for reducing the length of hospital stays, decreasing the use of broad-spectrum antibiotics, and preventing the spread of resistant pathogens lead to significant savings.

Key takeaways from the discussion emphasized the need for a deeper understanding of the goals behind direct-from-blood pathogen detection. What are the specific outcomes we aim to achieve? How can these technologies influence clinical decisions, patient outcomes, and the economic aspects of healthcare? The current absence of this information hinders assessment of the value such diagnostics bring and thus their adoption. While much of the current efforts are focused on nucleic acid technologies, the development of imaging and spectroscopy-based technologies adds to the diversity of diagnostic approaches, potentially offering complementary benefits to nucleic acid-based methods. These technologies may provide additional layers of information, that may not be available through nucleic acid testing, such as greater confidence in detecting the presence/absence of bacteremia and antimicrobial susceptibility information.

Overall, there is a palpable sense of optimism about the future. The next generation of pathogen detection technologies promises to address current technical limitations more effectively. However, the adoption of these technologies hinges on a much better understanding, and more importantly demonstration, of their value. Failure to take this into account during development and design of validation studies may inhibit their use in clinical settings, which would be a shame.

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Blood Culture Turnaround Times: a pathway for reduction by at least 24 hours

Isolating bacteria directly from blood or positive blood culture present a unique set of problems for clinical microbiologists and researchers. We are happy that multiple recent studies using our Separation Cartridge have performed very well in both applications. This post relates to the positive blood culture application.

One ongoing study at a local hospital has observed that traditional ID results could be obtained within a day (whereas without using the cartridge results have taken 2-5 days) and that the ID results obtained using the cartridge matches that obtained by subculturing. 

The shorter time-to-result using the cartridge was because it eliminated the need for subculturing decreasing the time to ID & AST by at least 24 hours. While it is generally accepted that that direct testing of positive blood culture broths is feasible, results have been variable (for instance better success with Gram-negative rods (GNR) than Gram-positive cocci (GPC)), workflow sub-optimal, or the method too expensive.

Preliminary experiences indicate that the cartridge does not have these limitations. The process takes ≤ 5 minutes, requires no new instrumentation, and uses one buffer that can be easily sourced. Results have been consistent regardless of whether it is GNR / GPC. More studies are taking place at other hospitals and microbiology labs that we will keep you updated on.

If this is an area of interest to you or your organization, please contact us (www.3idx.com). We are interested in setting up demos and additional studies to assess performance in different settings and applications. Thank you.

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Antimicrobial Resistance: Many reasons to act soon

We have a first-hand experience, thanks to COVID, of when infections become deadly. Now imagine if treatments for diseases like salmonella, tuberculosis, malaria, and other infections are ineffective because of antimicrobial resistance (AMR). This would undo almost a century of medical progress.

AMR is when microbes adapt to the antimicrobial drugs used to treat them, rendering the drugs ineffective. Every time microbes are exposed to a drug, susceptible strains die in the presence of the antibiotic, whereas resistant strains survive and then multiply without competition from the susceptible strains. Antibiotic use is on the rise, with a 40% increase in use over 10 years (2000-2010). However, around 50% of antibiotics prescribed in the US are unnecessarily or inappropriately prescribed.

Why unnecessarily? Because it takes a long time to get test results, doctors prescribe antimicrobials while they wait. Since this is basically a trial-and-error process, they may end up trying several different antimicrobials by the time they get the diagnostic result. After they get the results, they may have to prescribe something entirely new. This process basically trains the microbes how to become resistant to antibiotics.

There are two ways to address AMR. The first is creating new antimicrobial drugs that the microbes are susceptible to. While this is an important way we can combat AMR, developing new drugs is reactive, rather than proactive. As we expose microbes to these new drugs, they will begin to develop resistance. This puts us back in the same place we started, and requires continual drug development to stay ahead. Even then, there is no guarantee that researchers will be able to develop a new drug by the time a microbe becomes resistant to the old one.

The second method of addressing AMR is developing better diagnostics. Better diagnostics will allow medical professionals to know what they’re dealing with faster, which allows them to use specific and effective treatments. Since microbes are being exposed to fewer drugs, they have less opportunities to become resistant, ultimately slowing down the spread of AMR. Doctors can continue using existing antimicrobials, and it gives researchers more time to develop new ones. 

Patients with an antimicrobial resistant strain of infection can expect longer hospitalizations or stays in intensive care. They will also likely need more tests, more expensive treatments, and spend more time not working, which increases the financial impact of the infection. Additionally, major surgery and many cancer treatments will be more dangerous without effective treatments for an infection. Hospital visits will be more risky, as hospital-associated infections (HAIs) are often antimicrobial resistant.

AMR also has significant impacts at the global level. 50,000 people die every year just in Europe and the US because of AMR right now, and these impacts keep getting worse as time goes on. By 2050, some researchers estimate that AMR will cause 10 million deaths, which would be 1.8 million more deaths than cancer. Additionally, Gross Domestic Product (GDP) would be 2-3.5% lower and 100 trillion dollars would be lost. 

Addressing AMR promptly and decisively is imperative to lessen these catastrophic impacts. The United States government, the World Health Organization, and other organizations have urged more careful use of antibiotics in healthcare and agriculture. They have also increased their support for the discovery and development of new antibiotics and better diagnostics. In the end, it will take the government, physicians, and all of us to effectively combat the spread of AMR. At the individual level, we need to increase awareness of AMR, and do our part to avoid pressuring physicians to prescribe antibiotics, especially when they are not needed.

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For want of a nail…

For want of a nail, as the proverb tells us, a kingdom was lost. Would we lose the battle against the spread of antibiotic resistant bacteria for want of a better diagnostic?

The CDC notes that we are already in a “post-antibiotic” era.  “Untreatable infections are no longer a future threat – they are a reality.” More than 2.8 million antibiotic-resistant infections occur in the United States each year resulting in more than 35,000 deaths. 223,900 people required hospital care for C. difficile. At least 12,800 people died in 2017 from these infections.  

Relying only on new antibiotics as a solution is an ineffective strategy.  Bacteria change continuously and develop new ways to resist antibiotics. Even a new antibiotic is effective only for a while before resistance emerges (see chart). The national plan to combat antimicrobial resistance calls for action in five core areas. One area is to ensure appropriate use of antibiotics. Better and innovative diagnostic tools are needed to achieve this goal.

In an era where DNA-based testing is seen as a solution for all identification needs, why is this approach not yielding the desired outcome? There are many reasons. One main reason is the absence of effective sample preparation approaches. 

Components that interfere with DNA-recognition (e.g. human DNA) affect test accuracy. Current approaches do not eliminate these components effectively or rapidly. As a result, the test results are not dependable or timely. In other words, they do not ensure appropriate antibiotic use.

Test accuracy will improve if bacteria is isolated from the patient sample before analysis. The challenge is to do so efficiently and rapidly. Ideally, the procedure should isolate any bacteria and not just a small number.

This is where the recently introduced separation cartridge from 3i Diagnostics could be transformational. Intact and live bacteria is isolated easily, accurately, and rapidly (≤ 1 hour) directly from the patient sample using their cartridge and a syringe pump. The best part? It doesn’t matter what the bacteria is! The isolated intact and live bacteria can be easily identified using any technique. We will discuss the relative merits of the different bacteria tests in a future post.

Infection can be caused by a wide range of bacteria. One cannot identify the bacteria if it is not isolated in the first place. Hence, the ability to isolate any bacteria improves the dependability of the identification test. It also simplifies the test procedure and reduces cost per test. Many health research organizations are starting to evaluate the cartridge.  Is it compatible with current clinical workflow? Does it improve accuracy of current tests? Does it help obtain results quicker? These are some of the question being asked by these studies. We will report on these studies when results become available

While we definitely need new antibiotics, existing ones still work. We however need to ensure that only those who need them receive them. Improved diagnostics will help slow the spread of antibiotic resistant bacteria and help preserve current and future, drugs. Sample preparation may not be as “cool” discovering a new antibiotic. But, in the effort to combat antibiotic resistance, it is just as important.