Though antibiotics are crucial, concern about overuse in hospitals and inappropriate prescribing practices fuels debate about the complex relationship between antibiotic use and antimicrobial resistance.
Michael J. Brown, RPh
Antibiotics pose a conundrum: These drugs are crucial for destroying or slowing certain types of bacteria, but concern about overuse in hospitals and inappropriate prescribing practices fuels debate about the complex relationship between antibiotic use and antimicrobial resistance.
“Pharmacists play a pivotal role in antimicrobial stewardship in an organization, and it’s really around a multidisciplinary approach and a coordinated effort, with the goal to improve and measure appropriate use of antibiotics,” said Onisis Stefas, PharmD, MBA, vice president and chief pharmacy officer at Northwell Health in New York. “We look to promote high-quality care and positive clinical outcomes, we look to decrease length of stay where possible, and we also look to decrease microbial resistance.”
He explained that patients tend to first receive broad-spectrum antibiotics, which may then be replaced with a more appropriate narrow-spectrum antibiotic based on the subsequent lab results identifying the specific bacteria involved.
“We work hand in hand with providers,” Stefas said. “It is an interdisciplinary action to get the patient on the right drug at the right time.”
Antibiotics are generally overused, especially in patients in the emergency department, according to Michael J. Brown, RPh, BCPS, BCPP, a hospital pharmacist in Lake Oswego, Oregon, who specializes in psychiatry.
“There seems to be a tendency to use Zosyn [piperacillin and tazobactam] and vancomycin initially in patients who present with infectious symptoms,” he said. “This is what we call the shotgun approach and is effective in killing most bacteria. The downside is, this combination is hard on the kidneys, and overuse can lead to bacterial resistance.”
Sarah Jones, PharmD, BCPS-AQ ID, a clinical pharmacist in infectious diseases at Boston Children’s Hospital in Massachusetts, said the hospital is “a very antibiotic-using institution compared to many of its peers.”
“There is a lot of empiric antibiotic use in pediatrics still in all facets, though we have been trying over the last 2 to 3 years to chisel away antibiotic use,” she said. “There is a lot of movement in most centers to have antimicrobial stewardship programs up and running and trying to get to more of an appropriate antibiotic use.”
Surgeons are quick to add antibiotic therapy for patients looking unwell and then later question the drugs’ necessity, according to Jones.
“We are not a proactive stewardship program, but we look back retrospectively a day or 2 into therapy,” Jones said. “We try to explain why an antibiotic is not necessary in the setting that [it was started] for.”
Scaling Down Use
The good news: Many hospital pharmacists have become much more involved in antibiotic de-escalation. Hospital pharmacies have developed protocols for not only narrowing antibiotic therapy but also reducing costs by altering the route of the antibiotics used when appropriate. For instance, changing from an intravenous to an oral form can save a lot of money. Steps to reduce use involve better screening and lab testing, according to Brown.
“Broad-spectrum antibiotics should only be used initially if the infection is severe or life-threatening,” he said. “Clinical judgment is important, as well. Many antibiotics are used for urinary tract infections in elderly patients. This is often unnecessary unless the patient has symptoms such as altered mental status, pain with urination, or an increased urge to urinate.”
Pharmacists often act as gatekeepers to avoid misuse of antibiotics, Stefas noted, and are charged with reviewing antibiotics, providing recommendations on antimicrobial regimens, and reducing inappropriate or unnecessary use.
Boston Children’s Hospital practices “handshake stewardship,” in which pharmacists intervene with prescribing physicians and have a direct line of communication to residents, asking them to question their attending in a decision made by the team. According to Jones, the program has had lingering effects on future cases, with durations of antimicrobial therapy being more regularly followed.
J. Russell May, PharmD, FASHP, a clinical professor at the University of Georgia College of Pharmacy in Athens, practices at Augusta University Medical Center, where his students do amicrobial stewardship activities. He said that 53 of the antibiotics used in the hospital require a dose adjustment if the patient has decreased kidney function.
“Pharmacists can reduce the dosage of those antibiotics by protocol based on the level of kidney impairment,” he said. “That decreases the chance of a patient having an adverse reaction (and) prevents any toxicity from the drugs. And conversely, if the kidney function improves, we can go the other direction and increase dose to proper dosage.”
Becoming More Effective
Most progressive hospitals have pharmacy protocols regarding antibiotic therapy. For example, where Brown practices, staff follow all patients on antibiotics and monitor for appropriate agents, duration of therapy, and drug-drug interactions. “We also switch patients from intravenous therapy to oral as soon as possible,” he said.
“We may also suggest an infectious disease consult in certain circumstances,” Brown added. “We read progress notes from the physicians daily and review lab results. Our aim is to reduce cost, improve outcomes, and decrease drug resistance.”
An important part of the hospital pharmacist’s job involves looking at orders and ensuring that there are no duplicates, Stefas said. It’s also important to avoid dangerous drug-drug interactions, such as with warfarin and ciprofloxacin, which could increase bleeds.
“We look at food and drug allergies, as well, making sure a medication is used with food or without food and making sure the timing of that medication is not when patients are receiving their meals,” he added. “We’re also looking to make sure the right drug is used based on indication and the lab results.”
When a patient is discharged, a pharmacist on the floor should provide instructions, Stefas said.
“We let people know how important it is for a patient to continue that antibiotic, if necessary, out in the community,” he said. “We stress the importance to the patient and family because [otherwise] it can cause additional issues.” According to Stefas, early discontinuation of the regimen may contribute to the development of resistance to the antibiotic. This could result in the drug becoming less effective against that bacteria in the future.
A hospital pharmacist also does a lot of data analysis on prescribers and prescriptions and then passes that
information to providers to share what’s working, best practices with certain bacteria, and lab result trends.
Recent and in the Pipeline
The CDC reported that every year, Americans fight more than 2.8 million serious infections caused by antibiotic-resistant bacteria, with approximately 35,000 deaths. A sustained and robust pipeline of antibacterial drugs and novel therapies is critical to ensure that new interventions keep pace with evolving pathogens.
Brown noted that newer options include meropenem-vaborbactam (Vabomere), a newer agent to fight carbapenem-resistant Enterobacteriaceae (CRE).
“It is the first carbapenem Î²-lactamase inhibitor combination with activity against broad-spectrum Î²-lactamases,” he said. “We often use meropenem for patients who are sensitive to penicillin.”
In November 2019, the FDA approved cefiderocol, an antibacterial drug for patients aged 18 years or older with complicated urinary tract infections (cUTIs), including kidney infections caused by susceptible gram-negative microorganisms, who have limited or no treatment options.
Another newer addition: plazomicin (Zemdri), an aminoglycoside that received FDA approval in June 2018. Brown warns that this agent should be used only in patients with cUTIs, including pyelonephritis, who have limited or no options.
Eravacycline (Xerava), which is a tetracycline-class compound, was approved by the FDA in August 2018 to treat complicated intra-abdominal infections. Omadacycline (Nuzyra), another tetracycline, received approval in October 2018 and is indicated for community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections.