Expert Insight: Reliable and rapid antimicrobial resistance identification for appropriate therapy: Your questions answered

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Dr. Jose Alexander, AdventHealth Orlando

In this on-demand SelectScience webinar, Dr. Jose Alexander discusses the vital role a clinical microbiology lab can take in integrating rapid sample-to-result technology for the identification of antimicrobial resistance patterns.

Dr. Alexander, clinical microbiologist and director of microbiology, virology and immunology at AdventHealth Orlando, highlights how rapidly identifying resistance mechanisms is critical in directing appropriate and effective therapy to support positive patient outcomes and prevent further spread of antimicrobial resistance to help support local stewardship and infection control programs.

Read on for more insights from the live Q&A session or register to watch the webinar at any time that suits you.

Q: Why are ampC beta-lactamases (amp-C) epidemiologically as important as extended-spectrum beta-lactamase (ESBL)?

JA: Amp-C is epidemiologically as important as ESBL especially in the family of Enterobacteriaceae which includes E. coli, Klebsiella, Pneumoniae and Proteus. These four organisms usually do not carry any resistance against third-generation cephalosporins.

All resistance against third-generation is an acquired resistant mechanism, just like ESBL. So, an amp-C on an ESBL behaves similarly to an amp-C and a SPICE organism to an ESBL. This is a plasmid-mediated mechanism that can be transferred from multiple organisms from the same or different species.

From the epidemiological criteria and concern that ESBL has in these four groups of organisms, amp-C is an acquired mechanism by plasmid that can have the same significant impact from an epidemiological perspective.

Q: Why should ESBL/amp-C screening be included routinely on antimicrobial susceptibility testing (AST) panels?

JA: One of the ways that a laboratory is able to identify ESBL and amp-C is by performing confirmatory testing. Suspicion of these mechanisms arises when the susceptibility panel is resistant or intermediate to some of the third or fourth-generation cephalosporins. Confirmatory testing normally takes 24 hours.

If you want to be able to do a rapid screening and confirmation, we need to make sure that we have tools during the first process to perform susceptibility testing. One of the best ways is creating algorithm systems on the AST automated platform. They are able to evaluate the MIC distribution and quickly present the possible resistant mechanism present.

The other way is by using some of the wells, the microdilution automated method has a panel that contains a combination of antimicrobials and its inhibitors, for example, third-generation cephalosporins and fourth generation with clavulanic acid or organist antimicrobials with cloxacillin, which is a powerful inhibitor of amp-C.

So those are some of the options the antimicrobial susceptibility panel can lead to rapid identification. Amp-C and ESBL can be identified by a combination of inhibitors and MIC distribution.

Q: How could AST manufacturers include ESBL/amp-C screening routinely?

JA: When ESBL presents the lowest breakpoint for cephalosporins, especially on Enterobacteriales, the indication was that if you are validating the lowest breakpoint, there is no need to perform routine ESBL screening and there is also no need to change the interpretation of the antimicrobial.

You can have an organism with ceftriaxone resistance/ceftazidime susceptible in all breakpoints from the CLSI. You perform an ESBL screening or confirmatory testing. If this confirmatory testing was positive, ceftazidime needs to be changed to resistant. In the new breakpoint, you can do ESBL screening for epidemiological purposes, such as for isolation, or for data collection.

The importance of this is that some of the changes are that you are using the lowest breakpoint, so you are using a more sensitive method, but also you are adjusting treatment based on those MICs. So technically you can have an organism resistant to ceftriaxone, susceptible to ceftazidime. In that case, you don't do ESBL, you can go ahead and use ceftazidime as a therapeutic option for this patient.

In all facilities, with the clinical data we've been collecting, and in our antimicrobial stewardship program, we adopt the new lowest breakpoint. We don't have a need to do confirmatory testing, but we still need to have the ESBL screening and to be able to isolate those patients. The clinical data also shows that for some of the patients that we treat, some of the physicians don't feel comfortable treating a patient with a third-generation or fourth-generation ceftazidime or cefepime when the organism was only resistant to ceftriaxone because they know that there was an ESBL present.

For the CLSI, the reason to not do screening is that the breakpoints are lower. That means that if they are susceptible, those antimicrobials can still be used for a therapeutic option, but the screening was still considered important for epidemiological purposes.

Q: Can we use cefepime to treat ESBL-producing isolates?

JA: Yes, but that would not be a good therapeutic option. The reason is that ESBL enzymes CTX-M or even SHV-TEM have an activity that reaches cefepime.

If you have data, or if you can track the MIC from all your ESBL-producing organisms, you can see that multiple strains can actually be susceptible to cefepime and still be ESBL positive. In our facility, 44% of all our ESBLs are cefepime susceptible.

Even with that characteristic, we normally don't recommend using cefepime as a possible therapeutic option. In the case of amp-C, it's a different story because those enzymes don't have the same affinity against cefepime as the third generation.

In the SPICE-M organism that naturally produces amp-C, cefepime is the best therapeutic option. This is because in the narrow spectrum antimicrobials, amp-C is repressed and it's not going to be able to hydrolyze. If the ESBL is susceptible to cefepime and depending on the source, for instance, if it is a urinary tract infection where we know beta-lactam concentrate better, it could be an option. I would just be careful with the use of cefepime on an organism that is confirmed to be an ESBL.

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