Antibiotic prescribing dilemmas in the face of increasing resistance: How do diagnostics help?

There are a diminishing number of antibiotics in use today and very few drugs on the horizon. This, combined with the negative impact of the COVID-19 pandemic on infection control practices, has caused an increased need for antibiotic stewardship. The next pandemic could be even worse with secondary bacterial infections. Are we prepared?

In this SelectScience® webinar, now available on demand, experts in antibiotic prescribing, Jean Patel, Principal Scientific Affairs, Beckman Coulter Microbiology, Eric Myers, System Pharmacy Specialist, Infectious Diseases, Adventist Health, and Navaneeth Narayanan, Clinical Associate Professor, Infectious Diseases, Rutgers University, discuss their current practices for gram-negative and gram-positive bacteria, as well as the most effective antibiotic stewardship practices at their institutions.

Read on for highlights of the Q&A session and register now to watch the webinar on demand.

Why has antimicrobial resistance (AMR) become a global threat?

JP: I've spent a career watching the epidemiology of AMR, and it just spreads easily. It can amplify within a patient, and then it can spread from one patient to another. So now we have hard-to-treat infections all over the world.

EM: I think a lot can be attributed to travel. Global travel is a lot more prevalent now than it used to be. So, when we get some of these novel resistance mechanisms that can be passed via plasmid, they're able to spread all over the place a lot more quickly than maybe 40, 50 years ago.

NN: A lot of our antibiotics are derivative of natural compounds and bacteria have been exposed to that for millions of years. So, they have a pretty good head start on developing resistance. Plus, as Eric said, the world is very globalized, so infection can spread around the globe very quickly before we know it.

As fosfomycin is effective on some gram-negative bacteria, such as carbapenem-resistant Enterobacterales (CRE) isolates from uncomplicated urinary tract infections (UTIs), why do you not recommend this drug for CRE side treatment?

NN: Fosfomycin is a good drug. However, there is a discrepancy amongst the Enterobacterales in terms of its effectiveness, such as for E. coli, there's good effectiveness. It is also not as accessible in some parts of the United States, not every pharmacy carries it.

The dosing is difficult to figure out depending on the type of UTI you're dealing with. Also, you often don't know the etiology when you're treating a UTI upfront. It's empiric and then you figure it out after afterwards. Unfortunately, for Klebsiella species, it's not as reliable. And then the testing is even less reliable. So, it's hard to know if it is susceptible or not. So, I do think it is a good drug in certain cases, but in other cases, it might not be as reliable as we would hope.

EM: I agree. Susceptibility testing is a big limitation. When providers are dealing with an organism that's already very resistant, they want to make sure that the antibiotic they're using is going to be effective. My organization does not have fosfomycin on any of our automated susceptibility testing cards, so we don't really know that.

I do think it's a good point, though, about using agents that spare some of these newer antibiotics or even carbapenems for extended-spectrum beta-lactamase (ESBL) in UTIs. We do try to promote nitrofurantoin heavily for cystitis. We also try to promote single-dose aminoglycosides heavily for cystitis, even though a lot of people shy away from aminoglycosides because of the nephrotoxicity. But with a one-time dose, you can tend to avoid a lot of that and still spare some of these novel antibiotics.

JP: I think that susceptibility testing has been a challenge for this organism. There is a difference of opinion about whether this drug is appropriate just for E. coli or for other species of Enterobacterales. I think that difference has impacted different breakpoints around the world. There are differences between the Clinical & Laboratory Standards Institute (CLSI) breakpoints and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, and which breakpoints should occur on panels. So, there is no consensus on which are the right ones.

Could you address the intrinsic link between diagnostics stewardship and antimicrobial stewardship?

EM: Diagnostic stewardship is one of those things that, historically, antibiotic stewardship programs have not paid nearly enough attention to, but thankfully that’s changing today. We're starting to emphasize it a lot more. But you really cannot have an effective antibiotic stewardship program without diagnostic stewardship.

Providers will often reflexively treat a positive culture. Even if the patient doesn't necessarily have symptoms consistent with infection, once they're staring that positive culture in the face it becomes almost impossible to convince them not to treat it. Especially if it's a very resistant organism as the fear level goes up. The most effective way to prevent some of that is just to not get the culture to begin with. We classically think of urine cultures in this, treatment of asymptomatic bacteriuria. But even other culture sites such as sputum cultures and blood cultures are contaminated fairly often. That leads to more vancomycin use, and so on. Being good stewards of our cultures and of our diagnostics is extremely important for antibiotic stewardship.

NN: I'll add that getting the right specimens is important. Is it a tissue specimen from the operating room that might tell you something more about the pathogen, or is it a swab of the skin around the wound site where several organisms will be picked up whether there's an infection or not? This might not help you, but just cloud the picture. So, using diagnostics in the appropriate way is key. Then on the flip side, making sure that you try to access novel, helpful diagnostics for the right patient populations. All of this mitigates upstream issues rather than letting the issues get out and having to deal with it on the backend with trying to limit how much antibiotics are being overused in an appropriate way.

JP: There are some examples of healthcare settings which have written treatment guidelines based upon the diagnostics used in their institution. And this can be very specific. They know what kind of results a doctor would get, and you can teach doctors to use the antibiotics based upon a very specific test result. I think those kinds of treatment guidelines are really helpful.

NN: We've done that for some of our rapid diagnostics from blood cultures, depending on the resistance that's found and what we would recommend in general. Then we even provide decision support as a stewardship team to help support those general guidelines that we provide.

How can you suppress antibiotics resistance in a patient?

EM: I think, sadly, the only way to completely prevent antibiotic resistance is to not use antibiotics. Obviously, we know that's not really an option, because there are a lot of patients who need them. So, we're left with, how can we minimize antibiotic resistance as much as possible?

Essentially, it comes down to using as little antibiotics as we possibly can. My institution is focusing on the duration of therapy because it can be very difficult for a stewardship team to swoop in and convince a physician that they shouldn't be using antibiotics at all. But once they have come up with a diagnosis and have given an antibiotic, we can at least try to use the minimally effective duration and there's a lot of good literature there showing how that reduces some of these antibiotic-associated adverse events without impacting efficacy.

NN: Also, infection prevention. So, limiting the spread in healthcare facilities. That's not an intrinsic thing, but it's an important thing to think about. Obviously, there's a lot of overlap when we think about infection prevention in healthcare epidemiology and antibiotic stewardship.

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