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Fighting resistance in the ICU

Ongoing growth in antibiotic resistance has highlighted both the importance and the challenge of frontline stewardship.


While medicine as a whole is advancing, physicians have lost some ground against bacteria, particularly in the ICU.

“For a lot of patients, we've entered the preantibiotic era, where we're essentially practicing 19th-century medicine and having to do surgery and debride because there are no antibiotics. . . . We see those cases now, and that's the reality of 2019,” said Michael Stevens, MD, MPH, FACP, director of the antimicrobial stewardship program at VCU Health in Richmond, Va.

Growth in antibiotic resistance has highlighted both the importance and the challenge of frontline stewardship in the ICU. Early appropriate antibiotics have been proven to save lives, but overuse carries increasingly serious consequences.

Even a dose or two of very broad-spectrum antibiotics cause dramatic changes in the human microbiome, which can have a host of downstream effects, noted John A. Sellick, DO, MS, FACP, professor of medicine in the division of infectious diseases at the University at Buffalo in New York. “We're at the point now where, even in the first culture out, we're seeing resistant organisms,” he said. “In the past, we would rarely see that in those early cultures.”

To help hospitalists bring their best to this battle, antimicrobial stewardship experts offered tips on antibiotic selection, de-escalation, and stewardship interventions.

Starting broadly

For better or for worse, there tends to be a “better safe than sorry” mentality with antibiotics in the ICU, said Daniel J. Morgan, MD, MS, chief hospital epidemiologist at the Veterans Affairs Maryland Healthcare System in Baltimore. “It's often unclear what's making these patients sick, so the decision is often made to give them antibiotics—even if it seems unlikely that an infection is clearly part of what's making them sick,” he said.

That can be the correct choice, experts said. “If a patient's really sick and you're not sure what's going on, it is always OK to start broad. That's not usually the time to be judicious,” said Sarah Doernberg, MD, MAS, associate professor of clinical medicine and medical director of adult antimicrobial stewardship at the University of California, San Francisco (UCSF).

How broad to go is less clear, and it depends on the patient and setting. “It's important for everybody to know what organisms are in their community and what their empiric, up-front antibiotics should be,” said Gail Scully, MD, an assistant professor at the University of Massachusetts Medical School in Worcester, Mass.

Once broad-spectrum therapy is started, it's time to start thinking about narrowing it down to target the right pathogens. Since ICU patients are often intubated and unable to speak, the electronic health record (EHR) and family members can provide useful information on where the patient has recently been and other potential risk factors for drug-resistant bacteria, Dr. Doernberg said.

However, the EHR doesn't show the whole picture, especially if the patient was in a different hospital unconnected to the system, and documentation about other health care exposure risks can be poor, she noted. “So I think taking a good history with the family, if you're able to get them, can be very helpful” to get information on patients and their first symptoms, said Dr. Doernberg.

Hospital antibiograms can also be a useful tool to help determine the resistance patterns of organisms in the community, said Dr. Scully, who was coauthor of a recent review article on antibiotic use in the ICU, published in March 2018 by the Journal of Intensive Care Medicine. “If they can, [hospitals] should separate that by ward, so the ICU should have a separate antibiogram from patients on an acute care floor, if possible,” she said.

But even if an antibiogram suggests little or no resistance, physicians may still be wary of undertreatment in the ICU. “I think if a nervous person reads [an antibiogram], they would say, ‘Let's find the drug that always covers the most bacteria,’ and then reach for the broadest spectrum or multiple antibiotics,” said Dr. Morgan, also an associate professor of medicine and epidemiology and public health at the University of Maryland School of Medicine in Baltimore.

Dr. Doernberg agreed. “There's something about the [intensive care] setting that just makes people nervous, even if you have all the information about what to do,” she said.

But the tendency of clinicians to reach for powerful antibiotics isn't restricted to the ICU, according to a study published in the March 2018 Infection Control & Hospital Epidemiology. In the survey of 402 antimicrobial prescribers at five U.S. hospitals, 32% of prescribers “usually” or “always” preferred using the most broad-spectrum empiric antimicrobials possible.

Best practices

While there is no magic bullet for antibiotic decision making, some tools and practices may help.

For instance, newer nucleic acid testing of positive blood cultures can provide results within two hours, said Megan Mack, MD, a hospitalist and assistant professor at the University of Michigan School of Medicine in Ann Arbor. The test can determine, for instance, if a gram-positive coccus that was identified is either a true pathogen or just a skin contaminant, she said. “If I can find that out in two hours, I can potentially spare somebody an extra two days of antibiotics.”

Procalcitonin is another tool that may help clinicians make the decision to stop antibiotic treatment in some patients, although its use is hotly debated. “It is not something that we commonly use in the ICU to decide whether or not we're going to start antibiotics, but I think it can be useful for deciding when to stop,” Dr. Scully said.

Proper EHR documentation, whether in the ICU or on the wards, can also help get physicians, consultants, and nurses on the same page, Dr. Mack said. To engage hospitalists in antimicrobial stewardship, she led an intervention that targeted clinician documentation and communication during handoffs.

After the intervention, complete antimicrobial documentation (which includes the indication for antibiotics, the current day of therapy, and the expected duration of therapy) increased from 4% to 51% and 8% to 65% at two hospitals, according to results published in the August 2016 Journal of Hospital Medicine.

One impact of this improved documentation is that physicians don't need to round with a pharmacist to make informed decisions about de-escalating antibiotics on weekends or holidays, Dr. Mack said.

For example, take a patient admitted from the ED with sepsis and started on vancomycin and piperacillin/tazobactam. If urine cultures come back with pan-sensitive Escherichia coli, the covering physician can de-escalate, based on the hospital antibiogram, to a narrower agent like cefazolin, she said. “Making those changes takes active thought, mindfulness, and management, even within a shift. But I will say that is very rewarding.”

In addition to stopping antibiotics, shortening courses, and switching to oral drugs when possible, hospitalists should also make sure patients are receiving the correct doses, Dr. Scully said. “I think most hospitals have gone to prolonged infusion of many beta-lactam antibiotics,” she said.

It can often be difficult to optimize beta-lactam doses in ICU patients because many have unstable renal function or obesity, Dr. Stevens added. “It's probably more of an issue than is recognized,” he said. “The problem with intermittent dosing is that it drops too low to be effective periodically, and if it's doing that multiple times a day, then you're losing ground on that infection.”

Team feedback

To implement as many of these best practices as possible and meet The Joint Commission's requirement for antimicrobial stewardship programs, some hospitals have applied multidisciplinary approaches that are safe and effective in critically ill patients.

Since the ICU is such a high-risk setting, some medical centers use “handshake stewardship,” where a stewardship team member rounds face-to-face with the ICU team to help optimize therapy, Dr. Doernberg said. While this approach can be effective, it's also very resource intensive, she said. “You have to have a person who's able to round with the team, and it also relies on having a closed ICU.” At UCSF, this strategy doesn't work because hospitalists follow patients from the floor into the ICU, so there are multiple teams at any time with critically ill patients.

Instead, the hospital uses prospective audit and feedback, where a stewardship pharmacist electronically reviews all ICU and floor patients on broad-spectrum antibiotics and provides feedback to teams. However, “The ability to do that effectively in the ICU is probably lower than on the floor because the stakes are higher, those patients are more complex, and it's less likely that he or she will find something that's just so obvious to be able to [recommend] a change,” Dr. Doernberg said.

At VCU Health, the stewardship team reviews about 30 to 80 antibiotics orders per day, Monday through Friday, for opportunities to optimize antibiotic use, Dr. Stevens said. The program benefits from having pharmacists embedded in different units, such as the ICU, so the stewardship pharmacist often reaches out to the embedded pharmacist, whose team already trusts his or her recommendations, he said.

Formulary restriction or preapproval of certain broad-spectrum antibiotics may be easier to implement than audit-and-feedback protocols, Dr. Stevens noted. Many hospitals limit ordering of certain antibiotics, such as carbapenems, by requiring prescribers to call in the order, he said. “We're trying to reduce the emergence of resistance to that class of antibiotics because they're almost last-line antibiotics.”

Another intervention is an antibiotic timeout at 48 to 72 hours, which prompts clinicians to re-evaluate the treatment plan and consider antibiotic de-escalation and discontinuation. At Sharp Memorial Hospital in San Diego, a pharmacist-driven antibiotic timeout with physician support during daily multidisciplinary rounds reduced antibiotic use in the ICU, according to results published in October 2017 by Open Forum Infectious Diseases.

“If you involve the pharmacists, the nurses, the physicians all at the same time and make sure everyone's on the same page, I think you can make significant improvements in your antibiotic prescribing,” said Norihiro Yogo, MD, an infectious diseases subspecialist with Sharp Rees-Stealy Medical Group and director for antibiotic stewardship at Sharp Memorial Hospital.

As with audit and feedback, doing the timeouts and making sure patients are on the right antibiotic are less difficult with a closed ICU, he added. “I think it's easier to do that when you have a regular rounding schedule with familiar team members and an expectation to review the antibiotics. Once you lose these components, it's oftentimes harder to make the same improvements,” Dr. Yogo said.

Guidelines and culture

Institution-specific guidelines are a simple way to help frontline clinicians steward their antibiotics, even in hospitals with limited access to subspecialists.

At VCU Health, the stewardship team released more than 40 treatment guidelines and clinical pearls for common infectious diseases in mobile application format so that clinicians can download them directly to their devices, Dr. Stevens said. “Especially in resource-limited settings, where you don't necessarily have three pharmacists working in the stewardship program, those local guidelines can be incredibly valuable,” he said.

Building practical decision support into clinicians' workflow has been one of the most effective stewardship interventions at the University of Michigan, Dr. Mack said. For example, members of the hospital medicine group created pocket cards for clinicians that provide guidance for treating cellulitis, pneumonia, and Clostridium difficile infection, she noted.

In a separate and more recent effort, the stewardship team partnered with the information technology department to place institutional guidelines on the hospital website and embed them into order sets, Dr. Mack said. When entering orders for a patient with pneumonia, for example, the pneumonia order set will describe clinical definitions of community-acquired and health care-associated pneumonia, as well as diagnostic testing information and second- and third-line treatment options. “When you're on a clinical shift and you're that frontline provider, you need to know that [information] in real time at the point of care,” she said.

Infectious disease experts may create the guidelines, but hospitalists play the critical role of building a culture that implements them, the experts said. “That's the real way for stewardship to work, is to change the culture of the primary providers, not have some outside group make recommendations to them on a case-by-case basis,” said Dr. Morgan.

Dr. Yogo agreed, saying that the more hospitalists are involved in stewardship, the better patient outcomes will be. “To me, stewardship is a never-ending quality improvement project,” he said. “It really doesn't work if you have a top-down approach.”