Multi-Drug Resistant Gram-Negative Bacteria and Novel Treatment Approaches - Episode 5
Jason Gallagher, PharmD: Future direction in the treatment of resistant gram-negative bacteria is sort of multi-fold. One, obviously, is the development of further antibiotics, which we hope will continue. There have to be some questions ironed out in order to see that as we continue to go forward, though. One of the big ones is economic. As much as we’re concerned about increases in gram-negative resistance, it still isn’t high enough to justify some of the expenses that pharmaceutical companies pour into antibiotic development. Developing antibiotics is difficult, so hopefully we have found new ways to justify that going forward.
In the past several years, antibiotic resistance has been declared a national emergency, and that has allowed resources from the Department of Defense actually to go into grants that pharmaceutical companies receive in order to develop new antibiotics. So, some of the companies that might not have the resources to develop the antibiotics on their own have some support to do that. And that economic model will hopefully allow more companies to develop these agents. However, it can’t be all drug development.
One of the most important problems we have in infectious diseases is truly diagnostic. The delay from a person presenting with an infection to when we identify them with a particular type of resistant bacteria is too long. And at a typical institution, we’re talking 2 to 3 or more days from identification that someone is infected to finding the organism. And this is really intolerable, and it drives a lot of our antibiotic resistance because we’re treating them with broad-spectrum antibiotics, kind of our best guess. They’re not always the broadest spectrum ones because not everyone is starting with the biggest, baddest, most expensive agent up front, even when they sometimes should be, because we’re not very good at determining who the patient is who needs that. So, we’re starting with 1 type of broad-spectrum antibiotic, later finding out that it wasn’t the right choice. And this delay is really unacceptable, and we need a complete change in the way that our diagnosis of infectious diseases is done.
That is starting to happen. Labs are moving toward things that lead to rapid diagnostics. However, laboratories are really seen as an expense, and justifying the increased resources to make these diagnoses more quickly is something that can be challenging for institutions to do. But when you’re talking about institutional antimicrobial use, you’re really talking about a pretty small sliver of the overall picture—maybe 3% of antibiotics by weight given to inpatients in the United States compared to 17% to outpatients and then another 80% in agricultural. So, if we perfect 3%, we’re missing quite a bit.
That diagnostic revolution that I hope occurs really needs to be taking place in the outpatient setting as well, where we have to get good at something as absolutely simple as saying that this person has a viral infection versus a bacterial infection. Where, here, we may not be talking about the most resistant bacteria but we are talking about antibiotic use that puts antibiotic pressure on the organisms in the patient’s gut and around their body, allowing the more resistant ones to eventually flourish. And while in most people that won’t lead to any therapeutic concern, a percentage of them will then go on to develop resistant bacteria, which will then colonize others and sort of push this vicious circle forward.
My advice to anyone in the community seeing a patient with a multidrug-resistant bacterial infection is truthfully to call for help. If you are seeing somebody with a difficult-to-treat infection and you’re not used to seeing this type of organism, get an infectious disease clinician involved. The other thing I think is important is to think that a lot of these types of infections are going to be urinary tract infections. Then it’s always important to think about whether what is being found is a true cause in infection or an incidental finding.
If a patient has symptoms and this leads to a urine culture and a urinalysis, both of which are positive, and that patient has a urinary tract infection, that’s one thing. Talk to someone else for advice, especially since many of these infections are going to have to be treated intravenously since we have very few oral options for them. But if a person is not complaining of symptoms and it’s an incidental finding, that doesn’t require antibiotic use. And this is one of these things that everybody knows but it’s hard to practice because of a fear factor, truthfully, that goes into it, where it’s comforting to give antimicrobial therapy, comforting for the prescriber or the person recommending those antibiotics in the first place, even if it may not do anything for the patient themselves.
Transcript edited for clarity.