Improving Survival Rates in Septic PatientsJune 11, 2020
Sepsis in Dogs and Cats
Sepsis is a common reason for dogs and cats to present to the emergency room. Sepsis is the result of an infection that enters the bloodstream and causes a severe inflammatory reaction, leading to negative effects all over the body. The mortality rate for sepsis can be over 50%, and even though it has been heavily researched over the last several decades, there have not been significant improvements in patient survival.
There are several possible ways to improve survival in septic patients. One way is to create tests that allow for the faster and easier diagnosis of sepsis. Multiple studies have shown that patient survival is improved the sooner that sepsis is diagnosed and antibiotics are started. Sepsis can be difficult to diagnose, which has the consequence of delaying the start of antibiotics. Having a reliable way to diagnose sepsis rapidly and accurately would allow for antibiotics to be administered earlier and therefore could improve patient survival. Previous studies have focused on the use of blood-based markers of inflammation to diagnose sepsis. These tests have been successful at diagnosing sepsis; however, they also have a high potential of being positive for other non-septic causes of inflammation.
Another approach to diagnosing sepsis is through the use of tests that can detect genetic material (i.e. DNA). In this scenario, the test would be detecting the genetic material of the bacteria that is causing sepsis. As the field of genetic diagnostics advances, analyzer machines are now becoming smaller and able to deliver results faster. Their smaller size allows for them to be installed directly in emergency rooms, resulting in doctors being able to analyze a sample faster than if they had to send it off to a lab. The faster results will allow for antibiotics to be started sooner, with some analyzers able to deliver a result in as little as one hour.
Current Treatment Options and Limitations
Another challenge in the treatment of sepsis is the high level of antibiotic resistance that is seen in the bacteria that commonly cause sepsis. Some bacteria are so strongly resistant that there are very few antibiotic options to treat them. Starting a patient on an antibiotic that turns out to not be effective against the infecting bacteria delays those patients in getting started on appropriate antibiotics and can greatly increase their chance of mortality.
There are currently tests available that can show what antibiotics a given bacterium is susceptible and resistant to, however it can take 3-5 days to get the results of these tests. This turnaround time is minimally helpful for the initial selection of the antibiotics in the first few hours of sepsis diagnosis, the most crucial time period to select an effective antibiotic. Previous studies have shown decreased survival when the initial antibiotic chosen is later shown to be one that the infecting bacteria are resistant to.
New Hope for Quicker Diagnosis and Treatment
Genetic diagnostics, as discussed above, are also able to detect bacterial genetic material that can indicate whether the bacteria are resistant to any antibiotics. This would allow for the time to diagnose antibiotic resistance to be reduced from 3-5 days to as little as one hour.
Appropriate antibiotics could then be started at the onset of treatment and there would be a significantly reduced risk of patients being started on a non-effective antibiotic during the most crucial period of their treatment. Ethos Discovery is currently collaborating with several genetic diagnostic companies to develop a diagnostic test that is able to rapidly diagnose sepsis and underlying antibiotic resistance directly in an emergency room setting.
Measuring and Managing Therapeutic Antibiotic Levels
While in the hospital, septic patients are treated with intravenous antibiotics. As they improve, these antibiotics are switched to oral formulations. There is ongoing debate on the appropriate duration for antibiotic therapy when treating sepsis. If they are stopped too soon, the infection could return. If they are continued for too long, studies have shown that patients are at an increased risk for developing antibiotic-resistant infections. Several blood-based markers have been demonstrated to be possible means to monitor sepsis and its response to treatment. A veterinarian could use the results of these tests to determine the most effective time to discontinue a patient’s antibiotics. Ethos Discovery is currently looking into the use of a blood marker called procalcitonin for this use.
One of the major consequences of sepsis is that it can compromise the circulatory system, making it less effective at circulating administered antibiotics and delivering them to the site of the infection. This means that standardly used antibiotic doses (calculated for heathier patients) might not be sufficient to fully clear the underlying infection in a septic patient. It has been shown that the effectiveness of an antibiotic is significantly correlated to the amount of time that the antibiotic level in the blood stream is kept above a certain level, called the therapeutic level. When using standard antibiotic doses, therapeutic levels cannot be maintained as effectively, and the infection might not resolve. Antibiotic doses can be increased to account for this issue, however these higher doses can come with increased side effects. To further complicate the issue, there is a limited pool of antibiotics to select from, with little research going into the development of new antibiotics. Ethos Discovery is pursuing studies looking into ways to improve antibiotic delivery, with the goal of making the antibiotics that are currently available more effective in the treatment of severe infections.
Sepsis can lead to many alterations around the body that can cause significant difficulty in the diagnosis and treatment of the underlying infection. Even though there has been little advancement in sepsis over the last several decades, the field is rapidly progressing, and it can be expected that we will soon start to see patient survival rates improve. Ethos Discovery hopes that its research will contribute to this improvement, which would not only be beneficial to veterinary patients, but to human patients as well.