Antibiotic stewardship in sepsis

‘Treat only clinically significant infections,’ expert says



– When is it rational to consider de-escalating, or even stopping, antibiotics for septic patients, and how will patients’ future health be affected by antibiotic use during critical illnesses?

According to Jennifer Hanrahan, DO, of Case Western Reserve University, Cleveland, locating the tipping point between optimal care for the individual patient in sepsis, and the importance of antibiotic stewardship is a balancing act. It’s a process guided by laboratory findings, by knowledge of local pathogens and patterns of antimicrobial resistance, and also by clinical judgment, she said at the annual meeting of the Society of Hospital Medicine.

Dr. Jennifer Hanrahan MetroHealth Medical Center, Cleveland

Dr. Jennifer Hanrahan

By all means, begin antibiotics for patients with sepsis, Dr. Hanrahan, also medical director of infection prevention at MetroHealth Medical Center, Cleveland, told attendees at a pre-course at HM18. “Prompt initiation of antibiotics for sepsis is critical, and appropriate use of antibiotics decreases mortality.” However, she noted, de-escalation of antibiotics also decreases mortality.

“What is antibiotic stewardship? Most of us think of this as the microbial stewardship police calling to ask you, ‘Why are you using this antibiotic?’’ she said. “It’s really the right antibiotic, for the right diagnosis, for the appropriate duration.”

Of course, Dr. Hanrahan said, any medication is associated with potential adverse events, and antibiotics are no different. “Almost one-third of antibiotics given are either unnecessary or inappropriate,” she said.

Antimicrobial resistance is a very serious public health threat, Dr. Hanrahan affirmed. “Antibiotic use is the most important modifiable factor related to development of antibiotic resistance. With regard to multidrug resistant [MDR] gram negatives, we are running out of antibiotics” to treat these organisms, she said, noting that “Many antibiotics to treat MDRs are “astronomically expensive – and that’s a really big problem.”

It’s important to remember that, when antibiotics are prescribed, “You’re affecting the microbiome not just of that patient, but of those around them,” as resistance factors are potentially spread from one individual’s microbiome to their friends, family, and other contacts, Dr. Hanrahan said.

The later risk of sepsis has also shown to be elevated for individuals who have received high-risk antibiotics such as fluoroquinolones, third- and fourth-generation cephalosporins, beta-lactamase inhibitor formulations, vancomycin, and carbapenems – many of which are also used to treat sepsis. All of these antibiotics kill anaerobic bacteria, Dr. Hanrahan said, and “when you kill anaerobes you do a lot of bad things to people.”

Identifying the pathogens

There are already many frightening players in the antibiotic-resistant landscape. Among them are carbapenem-resistant Enterobacteriaceae, increasingly common in health care settings. Unfortunately, with methicillin-resistant Staphylococcus aureus (MRSA), “we’ve lost the battle,” Dr. Hanrahan said.

Acinetobacter is another increasing threat, she said, as is Candida auris, which has caused large outbreaks in Europe. Because it’s resistant to azole antifungals, once C. auris comes to U.S. hospitals, “You’re going to have a really big problem,” she said. Finally, multidrug resistant and extremely drug resistant Pseudomonas species are being encountered with increasing frequency.

And, of course, Clostridium difficile infections continue to ravage older populations. “One in 11 people aged 65 or older will die from C. diff infections,” said Dr. Hanrahan.

For all of these bacteria, she said, “I can’t tell you what antibiotics to use because you have to know what the organisms are in your hospital.” A good resource for tracking local resistance patterns is the information provided by the Centers for Disease Control and Prevention, including interactive maps showing health care–associated infections, as well as HealthMap ResistanceOpen, which maps antibiotic resistance alerts across the United States. The CDC also offers training on antibiotic stewardship; Dr. Hanrahan said the several hours she spent completing the training were well spent.

After a broad-spectrum antibiotic is initiated for sepsis, Dr. Hanrahan said that the next infectious disease–related steps should focus on identifying pathogens so antimicrobial therapy can be tailored or scaled back appropriately. In many cases, this will mean obtaining blood cultures – ideally, two sets from two separate sites. It’s no longer thought necessary to separate the blood draws by 20 minutes, or to try to time the draw during a febrile episode, she said.

What is important is to make sure that you’re not treating contamination or colonization – “Treat only clinically significant infections,” Dr. Hanrahan said. A common red herring, especially among elderly individuals coming from assisted living or in patients with indwelling urinary catheters, is a positive urine culture in the absence of signs or symptoms of urinary tract infection. Think twice about whether this truly represents a source of infection, she said. “Don’t treat asymptomatic bacteriuria.”

In order to avoid “chasing contamination,” do not obtain the blood culture samples from a venipuncture site. “Contamination is twice as likely when drawing from a venipuncture site,” Dr. Hanrahan noted. “When possible you should avoid this.”

It’s also important to remember that 10% of fever in hospitalized individuals is from a noninfectious source. “Take a careful history, and do a physical exam to help distinguish infections from other causes of fever,” said Dr. Hanrahan.

Additional investigations to consider in highly immunocompromised patients might include both mycobacterial and fungal cultures, although these studies are otherwise generally low yield. And, she said, “Don’t send catheter-tip cultures – it’s pointless, and it really doesn’t add much information.”

Good clinical judgment still goes a long way toward guiding therapy. “If a patient is stable and it’s not clear whether an antibiotic is needed, consider waiting and re-evaluating later,” Dr. Hanrahan said.

Generally, duration of treatment should also be clinically based. “Stop antibiotics as soon as possible, and remove catheters as soon as possible,” Dr. Hanrahan said, adding that few infections really warrant treatment for a fixed amount of time. These include meningitis, endocarditis, tuberculosis, and many cases of osteomyelitis.

Similarly, when a patient who had been ill now looks well, feels well, and is stable or improving, there’s usually no need for repeat blood cultures, Dr. Hanrahan said. Still, a cautious balance is where most clinicians will wind up.

“I learned a long time ago that I have to do the things that let me go home and sleep at night,” she concluded.

Dr. Hanrahan reported having been a consultant for Gilead, Astellas, and Cempra.

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