Understanding antimicrobial resistance is crucial in microbiology, and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) provides vital guidance. One key concept is EUCAST Expected Resistant Phenotypes, which helps laboratories predict resistance patterns in various microorganisms. This article breaks down what these phenotypes are, why they matter, and how they guide effective antimicrobial testing and treatment decisions.

What are EUCAST Expected Resistant Phenotypes? A Detailed Overview

The EUCAST document "Expected Resistant Phenotypes" serves as an essential tool for microbiology laboratories. It aids in validating species identification, confirming susceptibility test results, and preventing unnecessary antimicrobial susceptibility testing (AST). Originally based on the "Intrinsic Resistance and Unusual Phenotypes" document, EUCAST updated its terminology, moving away from "intrinsic resistance" due to complexities in its definition.

Now, the guidelines are categorized into "Expected resistant phenotypes" and "Expected susceptible phenotypes," alongside "Expert rules."

Defining "Expected Phenotypes"

An Expected Phenotype refers to an agent (or group of agents) for which the vast majority of isolates of a specific microorganism are either resistant or susceptible. When an unexpected phenotype is observed, it signals that the laboratory should meticulously recheck the species identification, the susceptibility test results, or both.

Understanding Expected Resistant Phenotypes (Previously "Intrinsic Resistance")

An Expected Resistant phenotype applies when over 90% of all isolates of a species (regardless of origin) consistently exhibit a characteristic resistance mechanism or have Minimum Inhibitory Concentration (MIC) values above the PK/PD breakpoint listed in EUCAST tables. In these scenarios, a susceptible result should be regarded with strong suspicion.

Key implications for expected resistant phenotypes:

Testing Avoidance: Susceptibility testing for these agent-species combinations should normally be avoided.
Reporting: Laboratories are expected to either not report a result or, if a result is required, report the isolate as resistant without performing the test.
Clinical Advice: Clinicians should be advised against using the agent for the species in question.
Table Notation: In EUCAST tables, an "R" denotes an expected resistant phenotype, meaning any other result is unexpected.

Grasping Expected Susceptible Phenotypes

Conversely, an Expected Susceptible phenotype indicates that over 99% of all isolates of a species are universally expected to be susceptible. This is because significant acquired resistance mechanisms have not been reported, and/or MIC values are consistently below the EUCAST PK/PD breakpoint.

What to do when resistance is detected for an expected susceptible phenotype:

Suspicion: A resistant result in such a case should be viewed with suspicion.
Confirmation: If testing is performed and an unexpected resistant result occurs, it points to a potential issue with species identification and/or susceptibility testing. Such results must be confirmed using alternative methods.
Acquired Resistance: If the resistant result is suspected to be due to an acquired resistance mechanism, it requires confirmation by reference methodology and preferably by genome sequencing.

Specific Expected Resistant Phenotypes by Bacterial Group

EUCAST provides detailed tables outlining expected resistant phenotypes for various bacterial groups. These are crucial for guiding laboratory practices.

Expected Resistance in Enterobacterales and Aeromonas spp.

These bacteria are generally expected to be resistant to a broad range of antimicrobial agents, including:

Benzylpenicillin
Glycopeptides
Lipoglycopeptides
Fusidic acid
Macrolides (with exceptions like Azithromycin for typhoid/paratyphoid fever and Erythromycin for travelers' diarrhea)
Lincosamides
Streptogramins
Rifampicin
Oxazolidinones

Specific Enterobacterales and Aeromonas spp. also show expected resistance to other agents:

Citrobacter koseri, C. amalonaticus: Ampicillin/Amoxicillin, Amoxicilin-clavulanic acid, Ampicillin-sulbactam.
Citrobacter freundii, Enterobacter cloacae complex, Klebsiella aerogenes: Ampicillin/Amoxicillin, Amoxicilin-clavulanic acid, Ampicillin-sulbactam, Ticarcillin, Cefazolin, Cephalothin, Cefalexin, Cefadroxil, Cefoxitin, Cefuroxime.
Morganella morganii, Proteus mirabilis, P. penneri, P. vulgaris, Providencia rettgeri, P. stuartii, Serratia marcescens, Yersinia enterocolitica: Often resistant to a wide array of beta-lactams and other antibiotics like Tetracyclines, Tigecycline, Polymyxin B, Colistin, Fosfomycin, and Nitrofurantoin, depending on the species.

It's important to note that cefoxitin breakpoints are not defined for Enterobacterales due to chromosomal inducible AmpC β-lactamase, which leads to higher MICs.

Expected Resistance in Non-Fermentative Gram-Negative Bacteria

This group typically exhibits resistance to:

Benzylpenicillin
First- and second-generation cephalosporins
Glycopeptides
Lipoglycopeptides
Fusidic acid
Macrolides
Lincosamides
Streptogramins
Rifampicin
Oxazolidinones

Specific non-fermentative gram-negative bacteria with notable resistances include:

Acinetobacter baumannii complex (A. baumannii, A. pittii, A. nosocomialis): Resistant to many beta-lactams (e.g., Ampicillin/Amoxicillin, Ticarcillin, Cefotaxime/Ceftriaxone, Ceftazidime, Cefepime, Aztreonam) and typically to Tetracycline and Doxycycline, though Minocycline and Tigecycline may show varied susceptibility.
Burkholderia cepacia complex: Known for broad resistance including Ampicillin/Amoxicillin, Ticarcillin, Piperacillin, Ceftazidime, Cefepime, Aztreonam, Ertapenem, Imipenem, Meropenem, Ciprofloxacin, Chloramphenicol, Aminoglycosides, and Tigecycline.
Elizabethkingia meningoseptica, E. anophelis, Chryseobacterium spp.: Exhibit resistance to a very wide range of antibiotics including many beta-lactams, ciprofloxacin, and aminoglycosides.
Pseudomonas aeruginosa: Resistant to Ampicillin/Amoxicillin, Amoxicillin-clavulanic acid, Ampicillin-sulbactam, Ticarcillin, Cefotaxime/Ceftriaxone, Ertapenem, and specific aminoglycosides like kanamycin and neomycin due to low-level APH(3’)-IIb activity.
Stenotrophomonas maltophilia: Resistant to most beta-lactams (except Piperacillin-tazobactam), Ertapenem, Imipenem, Meropenem, and all aminoglycosides. It is typically susceptible to trimethoprim-sulfamethoxazole but resistant to trimethoprim alone. Resistance to tetracycline is constant, while doxycycline, minocycline, and tigecycline susceptibility varies.

Expected Resistance in Other Gram-Negative Bacteria

Gram-negative bacteria not listed above, specifically other than Enterobacterales and non-fermentative gram-negative bacteria, are generally resistant to:

Glycopeptides
Lipoglycopeptides
Lincosamides
Oxazolidinones

Notable specific examples include:

Haemophilus influenzae: Resistant to Fusidic acid, Streptogramins.
Campylobacter fetus, C. jejuni, C. coli: Often resistant to Fusidic acid, Streptogramins, Trimethoprim, and Nalidixic acid.

Expected Resistance in Gram-Positive Bacteria

Gram-positive bacteria are generally expected to be resistant to:

Aztreonam
Temocillin
Polymyxin B/Colistin
Nalidixic acid

Specific gram-positive organisms with expected resistances include:

Staphylococcus saprophyticus, S. cohnii, S. xylosus, S. capitis: Exhibit resistance to Fusidic acid, Ceftazidime, Cephalosporins (except ceftazidime), and Macrolides.
Other coagulase-negative staphylococci and S. aureus: Resistant to Fusidic acid.
Streptococcus spp.: Resistant to Aminoglycosides, Macrolides, Clindamycin, Quinupristin-dalfopristin.
Enterococcus faecalis: Resistant to Fusidic acid, Ceftazidime, Cephalosporins (except ceftazidime), Aminoglycosides (low-level resistance), Macrolides, Clindamycin, Quinupristin-dalfopristin, Vancomycin, Teicoplanin, Fosfomycin, Novobiocin, Sulfonamides.
Enterococcus gallinarum, E. casseliflavus: Resistant to Fusidic acid, Ceftazidime, Cephalosporins (except ceftazidime), Aminoglycosides (low-level resistance), Macrolides, Clindamycin, Quinupristin-dalfopristin, Vancomycin, Teicoplanin, Fosfomycin, Novobiocin, Sulfonamides.
Enterococcus faecium: Resistant to Fusidic acid, Ceftazidime, Cephalosporins (except ceftazidime), Aminoglycosides (low-level resistance and chromosomal AAC(6’)-I enzyme affecting synergism), Macrolides, Clindamycin, Quinupristin-dalfopristin, Vancomycin, Teicoplanin, Fosfomycin, Novobiocin, Sulfonamides.
Listeria monocytogenes: Resistant to Ceftazidime and all other Cephalosporins.
Leuconostoc spp., Pediococcus spp., Lactobacillus spp.: Resistant to Cephalosporins and Vancomycin.

Expected Resistance in Anaerobes

Anaerobic bacteria generally show resistance to:

Aztreonam
Aminoglycosides
Polymyxin B/Colistin
Nalidixic acid

A specific example is Clostridium ramosum, C. innocuum, which are expected to be resistant to Vancomycin.

Why is Understanding Expected Resistant Phenotypes Important for Students?

For students of microbiology, medical laboratory science, and related fields, a solid grasp of EUCAST Expected Resistant Phenotypes is fundamental. It underpins effective diagnostic strategies, helps prevent misinterpretation of AST results, and contributes to judicious antimicrobial stewardship. This knowledge ensures that when you encounter an unexpected susceptibility or resistance pattern, you know to investigate further rather than simply report a potentially erroneous result. It's a critical component of ensuring patient safety and combating antimicrobial resistance.

Frequently Asked Questions (FAQ) about EUCAST Expected Resistant Phenotypes

What is the main purpose of EUCAST Expected Resistant Phenotypes?

The main purpose is to serve as a validation tool for species identification, to aid in validating susceptibility test results, and to prevent unnecessary antimicrobial susceptibility testing. It helps microbiologists identify when a test result might be incorrect or unexpected.

How did the term "intrinsic resistance" evolve to "expected resistant phenotype"?

EUCAST decided to abandon the term "intrinsic resistance" because of identified difficulties in discussing and defining it. The concept was then re-categorized and clarified under the broader umbrella of "expected resistant phenotypes" to provide clearer guidance.

What should a laboratory do if a microorganism shows susceptibility to an agent for which it has an expected resistant phenotype?

If a species with an expected resistant phenotype appears susceptible, the laboratory should view this result with suspicion. They must recheck the species identification, review the susceptibility test procedure, or both. For expected resistant phenotypes, testing should ideally be avoided, and the isolate reported as resistant without testing, advising against the agent's use.

Where can I find the full EUCAST documents on Expected Phenotypes?

The full documents, including "Expected resistant phenotypes" and "Expected susceptible phenotypes" along with "Expert rules," are available on the official EUCAST website. Antimicrobial resistance is a significant global health challenge that these guidelines help address.

EUCAST Expected Resistant Phenotypes