News of a bacterial strain resistant to the most powerful antibiotics recently grabbed headlines and produced dire warnings of an imminent threat to public safety. But in fact the bacterial attack has come not by blitzkrieg but in steady waves. It is in large measure the product of many years of indiscriminate use of medications once hailed as miracle drugs: antibiotics.

University of Colorado Hospital is among a growing number of health care facilities in Colorado and around the nation now fighting back by tightening its scrutiny of antibiotic use. Among the aims: narrow the bacterial targets, thereby decreasing collateral damage to other flora in the gut; and limit the duration of treatment to trim the opportunities for bacteria to develop resistant mutations.

Of course, patients must be protected all the while. But keeping a closer eye on antibiotic prescribing is no longer just an option for health care providers. It’s a necessity, said Norihiro Yogo, MD, an infectious disease specialist and director of antimicrobial stewardship at UCH. He notes that a study published this spring in JAMA concluded that a whopping 30 percent of antibiotic prescriptions were unnecessary. That translates to some 46 million prescriptions in the ambulatory setting alone during the 2010-2011 study period.

The issue gained prominence in 2015 when the White House hosted a forum on antibiotic resistance and released a “National Action Plan” for combating it. Last month, the Centers for Medicare and Medicaid Services (CMS) proposed a rule with twin mandates for hospitals: develop programs to prevent infections and establish antimicrobial stewardship initiatives to manage the antibiotics used to treat them.

While monitoring antibiotics requires increased surveillance of their use, the goal is not to punish but to protect, Yogo said.

“There is a perception that stewardship means assigning antibiotic police,” he said. “We’re sometimes seen as disciplinarians and enforcers. But our core mission is to make sure that we prescribe the right antibiotic, at the proper individual dose, duration and route. There is so much misuse that it becomes a patient safety issue by default.”

Prime targets

The primary targets of the hospital’s stewardship program are pneumonia and infections of the skin and the urinary tract, which together account for roughly 55 percent of antibiotics prescribed at UCH; and perioperative infections, which account for another 15 percent, Yogo said. The hospital is part of a statewide Antimicrobial Stewardship Collaborative launched a year ago to more closely manage prescribing of antibiotics for these conditions.

“We’re working toward developing and improving standard practice for antibiotic treatment of common infections,” Yogo said.

The benefits could be substantial, he noted. Shortening the initial prescribed duration of an antibiotic from 10 days to seven represents a 30 percent reduction in the amount of drugs used. Such a change, if sustained, could cut the risk of resistance and the spread of dangerous infections such as Clostridium difficile, or C. diff, that have been on the rise in recent years.

A sustained change needs sustained attention to clinical practice and decisions, said Matt Miller, PharmD, an infectious disease pharmacy specialist with UCH. Miller works with Yogo and other infectious disease specialists and inpatient pharmacists to review patients on antibiotics. They look for flags that point to the possibility of “de-escalating” antibiotic treatment, such as missing labs or mismatches between lab cultures and the prescribed drug, Miller said.

“Day-to-day reviews are the most efficient method,” Miller said. “They give us an opportunity to focus on the site of the infection.”

By the book

Miller and colleagues follow treatment guidelines contained in an antimicrobial stewardship booklet and on laminated cards. The resources specify recommended antibiotic treatment pathways for common conditions, such as catheter-associated urinary tract infections, as well as complicated infections like meningitis. They also list restricted antibiotics, which can only be administered without prior approval if they meet exception criteria, such as administration to lung or blood and marrow transplant patients.

In addition, Pharmacy collaborates with the hospital’s Microbiology team to measure the antibiotic sensitivities of organisms treated in the past year and the average number of medications used to treat them, Miller said. A resistance pattern of, say, e. coli to a particular antibiotic might lead to a change in the treatment guidelines, he said.

Yogo noted that all inpatient pharmacists have copies of the treatment guidelines and use them to help spread the antimicrobial stewardship message and the evidence behind the recommendations for specific treatments, doses, and duration. Pharmacy is also collaborating with perioperative and Internal Medicine teams to manage treatment of surgical site and urinary tract infections, respectively.

But even as the urgency to control antibiotic use increases, the need to protect patients remains paramount. That can create challenging treatment decisions for providers who care for patients at high risk for infections, such as blood and marrow transplant recipients.

“Our population is the most vulnerable there is and among the most complex medically,” said Jonathan Gutman, MD, associate professor with the Division of Hematology in the University of Colorado School of Medicine’s Department of Medicine.

Risk and reward

Gutman practices in the Blood and Marrow Transplant/Hematologic Malignancies program at UCH. Because of the challenges of treating BMT patients, Gutman said, the program has grown up independently of the school’s Infectious Disease Division and developed its own protocols for fighting life-threatening infections.

With the rapid growth of the BMT program at UCH, however, transplant providers are increasingly interested in working with infectious disease colleagues to gather more data about the effects of antibiotic medications and the safest and most effective treatment regimens, Gutman said.

He noted that he and other physicians and the program’s clinical pharmacists, Jeff Kaiser, PharmD, and Jenny Tobin, PharmD, are working with Miller to review the protocols for administering antibiotics to BMT patients.

“This is a nice opportunity to work together and develop best practices,” Gutman said. “There are many questions about optimizing the use of antibiotics that don’t have clear answers.”

One big question, for example, is how aggressively to treat infections in patients who are physically weak and immunocompromised. On the one hand, they are poorly equipped physically to ride out infections. At the same time, launching an all-out antibiotic assault without a clearly defined bacterial target can worsen the resistance problem. Gutman said he’s seen examples of BMT patients with infections that are resistant to multiple antibiotics.

“We have a tendency to look at using the big-gun antibiotics aggressively and right away,” Gutman said. “We are trying to give careful thought to that issue. We could stand to improve on it.”

He stressed, however, that the answers aren’t clear-cut. For example, a common enemy of BMT patients is neutropenic fever, which is brought on by a decrease in the number of neutrophils, a type of white blood cell that protects against infection. “It’s ubiquitous,” Gutman said, and needs to be treated quickly or it becomes “a time bomb.”

Yet a fair number of these patients have bacteria that are stubbornly resistant to antibiotics, Gutman said. Moreover, exposing patients to intensive antibiotic treatment can make them “rife for resistance issues” down the road, he added.

“That is more cost-efficient and least concerning in terms of resistance,” Gutman said.

Managing antibiotics while protecting patients requires a delicate balance, and the pressure to find that balance is great, Yogo said. The rise of highly resistant bacteria only serves to underscore their age-old ability to evolve and adapt to their environment. What is new today is the specter of bacteria immune from any antibiotic weapon, and at a time when there are few new ones in the drug-development pipeline.

“It’s not surprising that they are resistant,” Yogo said. “Resistance is inevitable, but we don’t want to speed it up. Antibiotic stewardship is of the utmost importance to our safety and our quality of life.”