New data underscore the importance of following the recommended order of tasks within sepsis care bundles. Specifically, investigators found there are significant benefits from ensuring blood cultures are taken before broad-spectrum antibiotics are delivered to sepsis patients. While taking blood cultures should not significantly delay needed treatment, investigators noted their data prove that cultures taken post-treatment lose nearly half the clinical information needed to make subsequent treatment decisions.

The analysis involved seven medical centers in North America and took place between November 2013 and September 2018. The researchers enrolled adult patients who had presented to the ED with severe indications of sepsis.

Each participant underwent two blood culture draws: one before antibiotics were delivered and one within two hours of treatment initiation. Comparing the two samples, researchers found that the samples lose about 50% of their sensitivity if the blood cultures are drawn in a two-hour frame after starting antibiotics.

Investigators noted processes need to be developed to ensure blood cultures are taken prior to the delivery of antibiotics but in a way that does not delay treatment.

Experts who have led successful sepsis quality improvement efforts recommend hospitals and EDs establish a strict protocol for how and when care steps should be completed. That education should focus on ensuring clinicians understand how to use the protocol.

Important new data are prompting some hospitals and EDs to re-examine how they manage patients who present with sepsis. Specifically, the results of a study, led by investigators from Brigham and Women’s Hospital in Boston, underscores the importance of taking blood cultures before delivering antibiotics to patients with the condition.

The analysis involved seven medical centers in North America and took place between November 2013 and September 2018. Researchers enrolled adult patients who had presented to the ED with severe indications of sepsis. Participants were subjected to two blood culture draws: one before antibiotics were delivered and one within two hours of treatment initiation. When the results between the two samples were compared, investigators found that the post-treatment cultures were lacking a significant amount of clinical information, making it more difficult to pin down what organism to target in subsequent treatment decisions.1

With so much focus in recent years placed on making sure that sepsis patients receive antibiotics as quickly as possible, investigators noted these data are important because they demonstrate there is a cost to moving too quickly to treatment before the critical step of taking blood cultures.

Weigh the Benefits/Risks

Considering that sepsis guidelines already call for blood cultures to be taken before antibiotics are delivered, is it common for these tasks to take place in reverse order? David Sweet, MD, one of the authors of the new study and a clinical associate professor in critical care and emergency medicine at Vancouver General Hospital in Canada, believes this happens more often than many clinicians think.

“At most medical centers, the blood cultures are collected by a medical lab assistant ... and the person who gives the antibiotics is usually a nurse who places an IV and then hangs the antibiotics. It is two separate people,” he explains.

Under this arrangement, when a patient presents who is extremely sick, the nurse will want to administer powerful, broad-spectrum antibiotics immediately, Sweet observes. “The medical lab assistant who is responsible for taking the blood cultures may be somewhere else in the department or caught up with other tasks,” he says.

Consequently, rather than waiting for the lab assistant to finish his or her work elsewhere, the nurse often will administer the antibiotics.

While time-to-antibiotics is a critical factor in the care of sepsis patients, the study data show that if the blood cultures are not taken prior to this treatment, substantial information will be lost when the cultures are completed. “What we found is that you lose about 50% of your sensitivity if you do your blood cultures in that two-hour frame after starting your antibiotics,” Sweet explains. This loss of data jeopardizes the ability of the blood culture tests to accurately pinpoint what organism to target.

Typically, sepsis patients receive broad-spectrum antibiotics first until the blood culture test results return in a day or two. The resulting information enables clinicians to specifically target the affecting organism. “By knowing exactly what bug it is, you can narrow your antibiotic [choice] ... which will result in less resistant patterns to that antimicrobial ... in society as well as the individual,” Sweet shares.

Further, broad-spectrum antibiotics are much more expensive than antibiotics that are narrower in scope, so switching to an antibiotic that specifically targets the organism at issue is more cost-effective as well as better for the patient and society, Sweet argues. “The other issue is that these more aggressive, broad-spectrum antimicrobials have a tendency to kill off more of [a patient’s] natural gut flora because of their very nature,” he adds.

Thus, patients receiving broad-spectrum antibiotics for an extended period may be more vulnerable to a secondary infection such as Clostridioides difficile than if they received a simple, straightforward antibiotic like penicillin, Sweet observes. These are all reasons why it is important to gather all the diagnostic information from a blood culture test that has not lost half of its sensitivity, he explains.

“Our study shows that getting the blood cultures before [delivering] the various antimicrobials will give you significant benefits in determining the actual organism that is causing the infection,” Sweet says. “There is this push and pull going on right now. We know there is an increased mortality if you delay the antimicrobials, but also a benefit to getting the blood cultures done first.”

Consider Solutions

There are a few potential solutions to the problem, Sweet says. One obvious approach involves directing the nurse to place the IV and then draw the required blood samples from that IV poke before starting the antibiotics. However, Sweet notes that several centers that have tried this approach have discovered high levels of contamination into the blood cultures, most likely due to nurses using inconsistent or non-sterile techniques when conducting the blood draws.

“Most of the centers that I have seen try this have reverted back to having a medical lab assistant take the blood samples,” he says.

One way to eliminate this problem is to make sure nurses are trained on the proper techniques to conduct the blood draws under sterile conditions so that contamination does not occur, Sweet says. Alternatively, changes can be implemented so that medical lab assistants are ready and available to draw blood when patients with sepsis present.

“These people are very sick, so policies, techniques, and resources need to be in place to make sure the blood cultures are done quickly and before patients get their IV antibiotics,” he stresses.

Sweet envisions implementing a mechanism that works similarly to the way a STEMI code works for patients who are experiencing a heart attack, some sort of trigger that will alert medical lab assistants to immediately come to the bedside of a sepsis patient to take blood cultures. “I think that is probably the easiest way to do it,” Sweet says. “There has to be more emphasis on getting the medical lab assistants [to the patient] before the nurse gets the chance to administer antibiotics.”

Rethink Priorities

While the study data do not point to needed changes in sepsis guidelines, they do suggest a need for hospitals and EDs to perhaps re-think their priorities when caring for sepsis patients.

“A lot of our medical centers are very good at [sepsis] recognition, getting lactate measures, and delivering antibiotics and fluids,” Sweet explains. “But in a sicker subgroup of patients, we are not as good at getting our blood cultures done [before delivering antibiotics] because I don’t think the emphasis has been on that [requirement].”

For example, the Institute for Healthcare Improvement and the Society of Critical Care Medicine collaborated on the one-hour bundle for sepsis. This procedure calls on clinicians to measure a patient’s lactate levels and then repeat the measure if those levels are high, obtain blood cultures before antibiotics, deliver antibiotics, and then administer fluids. For patients with low blood pressure and high lactates, the bundle calls for vasopressors — all of this within the first hour, Sweet explains.

“Of all of those five things, which have been defined as the five most important things, the one that gets the least amount of emphasis is getting the blood cultures done,” he says.

Sweet notes the reason why blood cultures do not receive as much emphasis is because all the other measures relate to the immediate severity of illness, either providing important insight on the patient’s current condition or providing needed treatment.

“The blood cultures are part of the package, but [the results] are two days down the road,” he explains. “When you get the information back, you can narrow your antibiotics, which helps with [antimicrobial] resistance, helps with preventing Clostridioides difficile, and helps with costs. However, [taking blood cultures] is not a lifesaving measure up front, so I don’t think it has the same weight or emphasis as the other four aspects of the bundle.”

However, Sweet notes that the new study data prove that taking the blood cultures before antibiotics is important. One could lose about half the information in the test results if one waits to take the blood cultures until after the patient has received antibiotics. “What I hope is that [these study data] will emphasize that component a little bit more,” Sweet observes. “We have to have policies and procedures in place to get [the blood cultures] done before we deliver the antibiotics, but still not delay the antibiotics. We have to have more resources to get it done.”

Avoid Delays

Emily Gilbert, MD, medical director of the sepsis program at Loyola University Medical Center (LUMC) in Maywood, IL, agrees that obtaining blood cultures prior to the administration of antibiotics is important, but she stresses that this task should never delay the delivery of antibiotics.

“What we saw earlier, before we were emphasizing the sepsis bundle, is that people would delay the delivery of antibiotics because they couldn’t get the blood cultures,” she explains.

Typically, this would involve a patient from whom it was difficult to draw blood. “We were concerned that this delay was potentially leading to increased mortality. Now, we basically say to please try to get blood cultures prior to the delivery of antibiotics. If there is any sort of delay and you can’t get the blood, just give the antibiotics. That is a major part of the bundle that leads to decreased mortality,” Gilbert shares.

In the ED at LUMC, the same nurse who hangs the antibiotics for a sepsis patient also draws blood samples for any required tests. The process is somewhat simplified compared to an ED that uses two different people (a medical lab assistant and a nurse) to perform these tasks. However, Gilbert notes that nurses in the ED are highly skilled at drawing blood under sterile conditions, and there has been no problem with contamination of the blood samples.

“The nurses in the ED are who [the nurses on the upper floors] call when they can’t get an IV in or they can’t get blood,” Gilbert notes. “The [ED nurses] do this all the time, so there really hasn’t been an issue with contamination.”

Tap a Sepsis Coordinator

Further, LUMC’s sepsis care quality improvement program, implemented in advance of sepsis shock guidelines adopted by the Centers for Medicare & Medicaid Services (CMS) in 2015, has resulted in significant improvements, according to a recently published analysis. Researchers reviewed the records of nearly 14,000 adult patients with suspected infections, comparing the outcomes of those treated both before and after implementation of the quality improvement program.

For those patients treated following implementation of the program, the in-hospital death rate was 30% lower, and the time to discharge from the hospital was 25% faster than patients treated prior to implementation of the program, according to investigators. Also, the program was associated with $272,645 in savings.2

Among the key components of the sepsis program is a nurse who works full time as a sepsis coordinator, focusing on bundle requirements and pushing for continued quality improvement. Gilbert notes that in the early days of the program’s implementation, the sepsis coordinator organized regular meetings between core sepsis committee members and took charge of educating nurses on their role in managing sepsis.

“[The sepsis coordinator] would go to the nursing huddles in the morning and answer questions the nurses had about the new bundles,” she explains. “I was more responsible for educating the physicians and the residents.”

While the sepsis bundles are now ingrained into practice, the sepsis coordinator continues to provide education to the constant flow of new nurses joining LUMC and takes charge of collecting and reporting data to show how the hospital is performing with regard to carrying out the bundles as required and outcomes related to sepsis.

Push Ongoing Improvement

The sepsis program also includes a sepsis steering committee composed of Gilbert, the physician lead, a physician representative from the ED, a nurse from the ED, a floor nurse, the sepsis coordinator, and several administrators from quality improvement. “We meet once a month for one hour, and we review the data,” Gilbert shares. “We will talk about our metrics and what our goals are going forward.”

For instance, Gilbert notes that clinicians strive to put 95% of sepsis patients on antibiotics within the first hour. Also during this monthly meeting, committee members will respond to any questions that have emerged from clinicians on the floors or the ED, and they will discuss how to resolve any problems that have surfaced. For example, Gilbert recalls one discussion that revolved around floor nurses who said they did not always fully grasp what steps or treatment tasks were completed in the ED when sepsis patients were brought upstairs. “The ED nurses would start the sepsis bundle, but by the time the patients got to the floor the floor nurses weren’t sure what had been done,” Gilbert explains.

To resolve the problem, the sepsis committee created a bright green sepsis sheet that follows sepsis patients from the ED to the floors. “The sheet has all the components of the sepsis bundle. There are little boxes that the nurses in the ED check to say that blood cultures were drawn at noon, antibiotics were given at 12:30, when specifically the lactates were drawn, and what the value was,” Gilbert explains. “That form goes on the chart with the patient up to the floor so that the nurse on the floor can see exactly what has been done in the ED and what is still due within the bundle.”

Other aspects of the quality improvement program include a sepsis early warning system in the electronic medical record and other technologic features designed to enhance adherence to sepsis guidelines. There also is a mechanism in place to provide early feedback to physicians on their sepsis care decisions.

Establish a Protocol

Gilbert acknowledges that there has been some resistance to the continuing push for faster bundle times from frontline providers in the ED. She expresses some sympathy for their concerns.

“The issue with the one-hour bundle is that the ED does need some time to figure out what is going on,” Gilbert notes. “It is really hard to try to differentiate pneumonia from just flu, and you don’t want to throw a bunch of broad-spectrum antibiotics at the flu.”

Gilbert says that a too-hasty approach would mirror what happened several years ago with the ill-fated CMS bundle for the management of pneumonia. “We were throwing antibiotics at every single person who walked in with an upper respiratory infection because we needed to get antibiotics in ASAP for pneumonia,” she says. “Then, after a lot of outcry and a lot of overdosing on antibiotics, [CMS] pulled that bundle for pneumonia.”

While clinicians will always work hard to quickly deliver antibiotics to someone with a clear-cut case of bacterial sepsis, one hour is not always enough time to discern whether broad-spectrum antibiotics are the best course of action, Gilbert explains.

“Sometimes, people will come in with abdominal pain and diarrhea. It turns out that they have Clostridioides difficile,” she observes. “Antibiotics potentially worsen that situation. We really do need a little bit more time to work out what is going on with the patient rather than just [administering] antibiotics to them as soon as they hit the door.” Considering that LUMC has produced good results from its quality improvement approach with sepsis, Gilbert’s advice to colleagues pursuing similar goals is to establish a strict protocol that everyone needs to follow. For instance, create an order set with clearly defined steps. Make it accessible with the click of a button. This is particularly important for academic institutions like LUMC where new physicians and nurses are constantly arriving on the front lines.

“Education and a really easy-to-use order set are key,” Gilbert says. “People tend to get stuck in a routine in how they do things, so you really do need to continually educate people: This is how we do things now. Please use this order set. This is the bundle. This is how we manage sepsis.”


  1. Cheng M, Stenstrom R, Paquette K, et al. Blood culture results before and after antimicrobial administration in patients with severe manifestations of sepsis: A diagnostic study. Ann Intern Med 2019; Sep 17. doi: 10.7326/M19-1696. [Epub ahead of print].
  2. Afshar M, Arain E, Ye C, et al. Patient outcomes and cost-effectiveness of a sepsis care quality improvement program in a health system. Crit Care Med 2019;47:1371-1379.