Resistant Phenotypes of Gram Negative Bacteria

We have a series of short cases & questions (5) on resistant phenotypes of gram-negative bacteria. There are a four major types of gram-negative resistance mechanisms:

  1. Enzymatic degradation
  2. Change in binding site (e.g. MecA)
  3. Loss of porin channels
  4. Efflux pumps.

Today we are focusing mostly on #1 and #3. Our first 4 cases will illustrate common patterns related to enzymatic degradation.

Enzymatic Degradation

β-lactam antibiotics are inactivated by a large number of enzymes known as β-lactamases. The most widely used classification of β-lactamases is the Ambler classification. This classification breaks up β-lactamases into 4 classes A, B, C, and D based on the type of enzyme (serine β-lactamases versus metallo β-lactamases). See this brief commentary on the classification from the Journal of Antimicrobial Chemotherapy, 2005.

While the Ambler classification is helpful, it helps to be able to identify different phenotypes in clinical practice based on susceptibility patterns, organism, and epidemiology. This awesome infographic was prepared by @sukritibanthiya.

Case 1

AmpC β-lactamases (Class C); Case 1

Historically, the mnemonic for remembering AmpC produces was the “SPACE” organisms mnemonic.

We like another mnemonic too: AMPCHES (pronounced “Amp- Cheese”)

(Credit to Dr. Arias @SuperBugDoc). Add A: Aeromonas/Acinetobacter

Key identifiers:

Case 2

ESBL-producing; Case 2

Key identifiers:

Molecular dx: CTX-M (most frequent US), TEM, SHV

Case 3

What is the mechanism of resistance of this K. pneumoniae?

Serine carbapenemases: KPC (class-A), OXA-48 (class-D); Case 3

Key identifiers:

Molecular diagnosis: KPC, OXA-48

Case 4

Extended panel: Cefiderocol-S.
Exploratory: In vitro synergy of ceftazidime/avibactam and Aztreonam using Agar-Etest methods-S.

What is the mechanism of resistance of this K.pneumoniae?

Metallo-β-lactamases: (NDM, VIM, IMP); Case 4

Key identifiers:

Molecular dx: NDM, VIM, IMP

Case 5

Which mechanism of resistance is likely expressed in this PSAR isolate?

OprD-mediated; Case 5

Organisms: Pseudomonas aeruginosa
OprD is porin that facilitates diffusion of carbapenems into the cell. Decreased expression results in resistance.

Key identifiers:

That is it! Hope you enjoy it. Thanks for the feedback and for sharing!

Authors: @LeMiguelChavez @InfectiousDan
Infographic: @sukritibanthiya

Originally tweeted by Infectious Diseases Fellows Network (@ID_fellows) on 11 May, 2021.