Credit: MRSA Survivors
All drugs – from the greatest medical treatments of the modern era to those that help only a small fraction of patients who take them – have benefits and risks, and researchers have to study both sides to quantify them and map out the best, safest uses. This balancing act is part of a constant quest within the medical community. In a perfect scenario, a drug will benefit the largest possible number of patients without causing side effects that outweigh those benefits.
It’s a calculation that’s different for each drug and each disease. Chemotherapy drugs, for instance, can cause severe side effects for individual cancer patients, but they may offer the best chance at beating the disease.
Antibiotic use represents a special challenge, in which too much of a good thing can be dangerous to public health as a whole, and the overuse of antibiotics over the past few decades has led to resistant strains of bacteria. In other words, the bugs are getting stronger, and smarter, and the antibiotics we have can potentially stop working if we’re not careful about how we use them.
The fight against a common, costly, hospital-acquired infection known as Clostridium difficile, or C. diff offers an illuminating case study in the area of so-called antibiotic stewardship. C. diff causes diarrhea and can lead to severe inflammation of the bowel and other complications. Patients with compromised immune systems – including those who undergo stem cell or bone marrow transplants to treat their cancers – are especially at risk. Even with a course of antibiotics, C. diff can lead to longer hospital stays and increased treatment cost. A study published in 2015 in the American Journal of Gastroenterology found the average cost of C. diff ranges from $8,911 to $30,049 per patient.
Doctors in the Abramson Cancer Center at the University of Pennsylvania have been giving some stem cell transplant patients oral vancomycin. It’s a standard antibiotic used to treat C. diff, only they’ve been giving it to patients before they even get the infection as a preemptive strike.
And it’s working. As of their presentation at the American Society of Hematology Meeting in December, they’ve tried this with 73 stem cell transplant patients, and none of them have developed C. diff. In a group of patients who did not get the drug in advance, 11 out of 55, or 20 percent, did develop the infection, which is in line with the national average of between 20 to 30 percent.
It’s important to note that this is a group of patients who are particularly at risk for C. diff. The transplant involves suppressing the patient’s immune system to make sure the body does not reject the new stem cells. Even after the procedure itself is over, the immune system still has a long way to go to build itself back up. During this period, patients are vulnerable to any number of infections, and even a simple one could be life-threatening.
So given the data about the drug’s impact so far and the risks to the patients involved, it stands to reason that now that we can simply give antibiotics to everyone who’s at risk and prevent C. diff altogether. Unfortunately, it’s not that simple.
“Over the past few years, this has become something that doctors are increasingly more aware of, and for us, it shows up in two areas,” said David Porter, MD, the director of Blood and Marrow Transplantation at Penn and the senior author on the C. diff study. “On the one hand, C. diff is increasingly common, and there’s an enormous initiative to try to minimize hospital-acquired infections. But antibiotic stewardship is increasingly a big issue. Not only can overuse of these drugs lead to more resistance, but many of these medications are extremely expensive so it also means the cost of treating patients will go up. That’s ok if they’re effective, but one needs to be certain they are having a positive effect.”
The C. diff example is a perfect case study. If just one out of every five patients would develop C. diff without this preventative approach, that means statistically, four out of every five patients are taking these antibiotics unnecessarily.
“We’ve had to be meticulous in expanding the use of these antibiotics,” said Alex Ganetsky, PharmD, a clinical pharmacist in the Blood and Marrow Transplantation Program in the Abramson Cancer Center and the study’s lead author. “We originally started with just eight patients and slowly increased the number of patients receiving preventative oral vancomycin. We looked for signs of resistance. We haven’t seen any yet. But we want to leave a longer time to follow up to make sure.”
Ganetsky and Porter say that’s the reason they have not tried to use oral vancomycin with patients other than stem cell transplant recipients.
“We’re more liberal in our antibiotic usage with stem cell transplant recipients simply because we’re working with a group of patients where you have to get it right the first time,” Porter said. “What we’re trying to do is maximize the appropriate use of antibiotics.”
But even with such a vulnerable patient population, there are still layers of oversight to prevent overuse. The Antibiotic Stewardship Program at Penn makes sure these drugs are being used appropriately, which can mean putting restrictions in place. My colleague recently reported on the program itself, and you can read more here. Currently, 22 different antibiotics are under restriction, which represents about 30 percent of the total available in the hospital system. When a medication is under restriction, a doctor can’t prescribe it without another independent physician or pharmacist reviewing the request.
While the system is designed to promote responsibility, it also creates an interesting dilemma. Even though Porter and Ganetsky seem to have found a way to prevent C. diff, can it ever really be used as a widespread method?
“We always try to do what’s right for the patient, but we also have to be sure we are learning from what we’re doing,” Porter said.
As to the question of more general usage, Porter said, “I think we’re still trying to learn if that will be appropriate, and we’re hoping our analysis can teach us the right strategy. But for right now, we want to identify and focus on the patients at the highest risk.”