Acronymous organisms: ESCAPPM and HACEK

Or is "acronymic" the correct adjective? In any case, the college loves to repeat this question. Past iterations have included:

The ESCAPPM organisms with induceable cephalosporinase

The following is a list of Gram-negative organisms who might occasionally appear to be sensitive to β-lactam antibiotics, but who in fact develop a resistance rapidly, owing to the overexpression of induceable chromosomal AmpC cephalosporinase/β-lactamase enzymes.

  • Enterobacter
  • Serratia
  • Citrobacrter
  • Acinetobacter (and Aeromonas)
  • Proteus
  • Providencia
  • Morganella

The linked article on this topic also identifies Chromobacterium violaceum,  EnterobacterE. coliHafnia alvei, Lysobacter lactamgenusOchrobactrum anthropiProteus rettgeri,  Pseudomonas aeruginosaPsychrobacter immobilis, Rhodobacter sphaeroides and Yersinia enterocolitica as carriers of the AmpC cephalosporinase/β-lactamase.

An intelligent person would not be satisfied with a mere list, and would go on to ask the question,

What the hell is this AmpC β-lactamase?

George A. Jacoby puts it best in his excellent article, which is the primary resource for this topic:

"AmpC β-lactamases are clinically important cephalosporinases encoded on the chromosomes of many of the Enterobacteriaceae and a few other organisms, where they mediate resistance to cephalothin, cefazolin, cefoxitin, most penicillins, and β-lactamase inhibitor-β-lactam combinations"

In brief:

  • AmpC β-lactamase is a chromosomal-mediated enzyme (unlike ESBL β-lactamase which is non-induceable and plasmid-mediated)
  • In a given population of an ESCAPPM organism, there are mutants which express this β-lactamase. Within a short time during the course of treatment, this clone proliferates.
  • AmpC β-lactamase is not inhibited by clavulanic acid, but some may be inhibited by tazobactam (thus there is a variable sensitivity to Tazocin).

The ESKAPE group

In addition to the ESCAPPM bunch, in 2009 the Infectious Diseases Society of America launched another acronym to describe the group of pathogens which - over the coming decades - are going to pose the greatest threat to mankind by virtue of their antimicrobial resistance:

  • Enterococcus faecium
  • Staphylococcus aureus
  • Klebsiella pneumoniae
  • Acinetobacter baumanii
  • Pseudomonas aeruginosa
  • Enterobacter sp.

Panic regarding the "post-antibiotic era" is spread further by anxious reports of such nightmarish creatures as a pan-drug-resistant Acinetobacter, which apparently reproduces quite comfortably in a pot of boiling meropenem.

ESBL organisms

ESBL organisms carry extended spectrum β-lactamase which confers resistance to roughly the same selection of drugs as the AmpC enzyme.  However, ESBl organisms will demonstrate a good honest resistance to cephalosporins and β-lactams in a culture, as the enzyme is non-induceable and plasmid-mediated. Even though the patterns of resistance and sensitivities between ESCAPPM and ESBL organisms can be very similar, there are some broad differences. Specifically, they differ in their response to fourth generation cephalosporins (of which the only commercially available members right now are cefepime and cefpirome). ESCAPPM organisms are usually susceptible to fourth generation cephalosporins, whereas ESBL organisms can hydrolyse them (Paterson & Bonomo, 2005). This statement is something of an oversimplification because there are multiple different possible ESBL and AmpC enzyme variants and several classification systems exist, all of which are better than just labelling organisms as "ESCAPPM" or "ESBL", which leads to confusion. Even more confusing is the overlap between groups, as nothing stops these organisms from shamelessly expressing both enzymes at you.

Anyway: a list of common ESBLs:

  • E.coli
  • Enterobacter
  • Salmonella 
  • Citrobacter
  • K. pneumonia and oxytoca
  • Proteus
  • Providentia
  • Morganella morganii

The HACEK group of endocarditis organisms

These are a bunch of oropharyngeal Gram-negatives which had previously been thought to be frequently responsible for infective endocarditis, but are now known to be fairly rare, responsible for only about 3% of native valve endocarditis. Fortunately, most of them are sensitive to bog-standard ceftriaxone

  • Haemophilus species: H.aphrophilus, H.parainfluenzae and H.paraphrophilus
  • Actinobacillus and Aggregatobacter species
  • Cardiobacterium hominis
  • Eikenella corrodens
  • Kingella kingae

Why care about them, if they are such rare pathogens? Well. First of all, they were the subject of Question 28.2 from the first paper of 2022. Secondly, the slow growth of these organisms means the cultures are usually negative. Vegetations will be visible, and PCR testing will reveal the relevant pathogen, but the cultures will remain negative.

References

BOYLE, ROBERT J., et al. "Clinical implications of inducible beta-lactamase activity in Gram-negative bacteremia in children." The Pediatric infectious disease journal 21.10 (2002): 935-939.

Sfakinos, John. "Detecting the dual presence of AmpC and ESBL enzymes."Microbiology Australia 30.5 (2009): 208-209.

Philippon, Alain, Guillaume Arlet, and George A. Jacoby. "Plasmid-determined AmpC-type β-lactamases." Antimicrobial agents and chemotherapy 46.1 (2002): 1-11.

Das, MD, M., et al. "Infective endocarditis caused by HACEK microorganisms."Annual review of medicine 48.1 (1997): 25-33.

 

Chambers, Stephen T., et al. "HACEK infective endocarditis: characteristics and outcomes from a large, multi-national cohort." PloS one 8.5 (2013): e63181.

Habib, Gilbert, et al. "Value and limitations of the Duke criteria for the diagnosis of infective endocarditis." Journal of the American College of Cardiology 33.7 (1999): 2023-2029.

Durack, David T., et al. "New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings." The American journal of medicine 96.3 (1994): 200-209.

Jacoby, George A. "AmpC β-lactamases." Clinical microbiology reviews 22.1 (2009): 161-182.

Boucher, Helen W., et al. "Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America." Clinical Infectious Diseases 48.1 (2009): 1-12.

Pogue, Jason M., David A. Cohen, and Dror Marchaim. "Polymyxin-Resistant Acinetobacter baumannii: Urgent Action Needed." Clinical Infectious Diseases(2015): civ044.