Diagnostic Tests for Gram-Negative Nosocomial Infections

Peter L. Salgo, MD: Run down some things you’d like. What are the tests that you want to confirm the pathogen and the tests that you then want to decide on treatment?

Debra Goff, PharmD, FCCP: So, I want a rapid diagnostic test.

Peter L. Salgo, MD: OK. Which ones for which bugs?

Debra Goff, PharmD, FCCP: Well, there are several out there. They are game-changing in the management of infectious diseases.

Peter L. Salgo, MD: What are they? Define them for everybody.

Debra Goff, PharmD, FCCP: One of the first that came to the market was an instrument by Cepheid that is a PCR-based and could tell you for bacteremic patients if you had MRSA (methicillin-resistant Staphylococcus aureus), MSSA (methicillin-sensitive Staphylococcus aureus), or coagulase-negative Staphylococcus. Now, we implemented that at Ohio State. It was game-changing in the management of Staphylococcus bacteremia. We could get patients on appropriate Staphylococcus therapy faster, and we actually had a trend toward a lower mortality. Because, gee, guess what, if you treat them with the right antibiotic sooner, they get better faster.

Peter L. Salgo, MD: Really? Really?

Debra Goff, PharmD, FCCP: Not really surprising. But it’s nice to have evidence, and that was back in 2010. There have been a plethora of studies, by everybody here on the panel, that have confirmed that. Rapid diagnostic tests; Sandy has done work with a rapid fungal diagnostic test. So, imagine direct from blood. For some of the rapid diagnostic tests, you have to have growth and a blood culture. There’s 24 hours, and then you could do the test. But in one of the new T2 tests, it’s direct from blood, meaning, in case you’re not aware of this test, you draw the blood and you send it to the lab, and in 2 to 3 hours, you know Candida albicans, Candida glabrata. That’s game-changing for an intensivist to know which antifungal actually will work instead of the paradigm we used for decades, which was “Let me start with my best guess, and in 3 to 4 days, I’ll know whether I was right.” How crazy is that?

Sandy J. Estrada Lopez, PharmD, BCPS (AQID): If you have that intra-abdominal infection after 2 weeks in the hospital and an antifungal is being considered, these patients stay on them for 2 weeks because there might be something there and the cultures didn’t grow anything. These are areas where we are able to start. Getting back to your original point: Start anything you want to as long as you have a path to figure out where you’re going with it. And so some of these rapid diagnostics help us get on that path much faster.

Jason Pogue, PharmD, BCPS-AQID: I think one of the big issues with the rapid diagnostics, at least in my opinion, is there are actually 2 main ones. First, it requires bacteremia or concern for fungi or whatever it is in that situation, and we need to get beyond that from that sample. But the second thing is I think that people—and I know this because I’ve spoken with people, and I even know how we rolled it out at our institution—do a poor job of telling people what that information is that’s popping up in the chart. If you look at Verigene or any of the ones that give you information, like you can get gram-negative rod, it will tell you the bug, it will tell you certain resistance genes; there are like 4 paragraphs of information that pop up. And it’s hard to even know what is positive when you’re looking at that. So, there’s a huge education piece that—

Peter L. Salgo, MD: So, you understand this? Can we give everybody your cell phone so that they can call you? My point is, yes, it was a joke, but in fact, somebody’s got to distill this.

Sandy J. Estrada Lopez, PharmD, BCPS (AQID): Well, first you have to get the information to someone. You lose all the benefit of a rapid diagnostic if the test result comes at 9:30 and you rounded at 8:30 and you’re not going to look in the chart again until the next day. Now you’ve lost 23 hours versus those rapid results. We learned, when we implemented PNA FISH 10 years ago, they were coming to a fax on my desk. So, if I wasn’t at my desk, then they were not acted on unless someone else happened to see the information.

Peter L. Salgo, MD: Did you say fax?

Sandy J. Estrada Lopez, PharmD, BCPS (AQID): I did. I did. Now they come to an electronic in-basket that all pharmacists do 24 hours a day in our hospital. And so a provider will be called if there is an actionable result.

Andrew Shorr, MD: I think although the rapid diagnostics have lost the promise and there are lots of issues that still need to be sorted with them, there are simple first-order issues that need to come well before that. And that certainly comes down with just knowing your antibiogram.

Peter L. Salgo, MD: I was going to say, isn’t it at least one of the ABCs, the bedrocks, here: Know what bugs you get, know what bugs your hospital is prone to, the antibiograms?

Andrew Shorr, MD: Right, because the antibiogram, you can break it out by ICU versus floor versus different ICUs, your stem cell unit versus whatever, and you can see what your problem bugs are. So, you can actually create, and it doesn’t take a lot of math to sit there and ask, “Well, if I want to make sure that I’m getting 90% coverage empirically right from my gram-negatives, what’s that combination? What X-versus-Y combination gets me there?” And that’s the way you’re going to get to that. Because, again, for a lot of these MDR pathogens, MDR Pseudomonas is probably 20% to 25% of my Pseudomonas cases, and about 20% of all my gram-negatives are Pseudomonas. So, 20% of 20% is now 4. That’s 4 in 100, maybe 1 Acinetobacter, so now we’re talking about 5 or 6 of these super ugly pathogens in 100 patients. That’s not a rate at which most people are going to start empirically treating for all those things. So, I need to still come up with what’s going to get me to 90%, and then I’m going to worry about that 5% that I’m never going to figure out until my rapid diagnostic, the patient’s failure to respond to therapy, or the eventual cultural insensitivity to guide me to figure out what’s going on.

Debra Goff, PharmD, FCCP: But your thought process that you just described is not done in the majority of hospitals. At most hospitals, if you walk around and ask a physician, “Can you name your top 5 pathogens in your hospital?” “Um, no.”

Peter L. Salgo, MD: And 2 of them are not hospital administrators.

Debra Goff, PharmD, FCCP: Right. And so, most people do not even know how to access their antibiogram. We’ve been preaching this for decades, and you’re absolutely right in your thought process, but I just don’t see it being done in the majority of hospitals unless someone takes ownership of doing it. And in the microlab, there are fewer and fewer microbiologists and microtechs. They’re getting short staffed. We’re seeing pharmacists doing antibiograms. I just don’t think that’s right. That’s not our training. Sure, we can learn it, but you know what, it’s like if you want the data, you’ve got to do it yourself. People just don’t take the time, but it’s important.

Andrew Shorr, MD: We’ve required our unit directors, whether they’re ICUs or intermediate care units or floor unit directors, to actually take ownership of understanding and disseminating the people who practice there what their local specific antibiogram is.

Peter L. Salgo, MD: If I may, we have been rounding in our ICUs with PharmDs who know the antibiograms and know the antibiotics and know the bugs in the hospital. It has been a game changer.

Andrew Shorr, MD: Absolutely.

Peter L. Salgo, MD: We love PharmDs.