AmpC β-Lactamase-Producing Organisms
AmpC β-lactamases are produced by specific Enterobacterales species with chromosomal genes (Enterobacter spp., Citrobacter freundii, Serratia marcescens, Morganella morganii, and Providencia spp.) and can also be acquired on plasmids by organisms like E. coli, Klebsiella pneumoniae, and Proteus mirabilis. 1
Organisms with Chromosomal AmpC (Inducible)
These organisms naturally possess chromosomal AmpC genes that can be induced or derepressed during treatment:
Primary Inducible AmpC Producers
- Enterobacter species (E. cloacae complex, E. aerogenes) - the most clinically significant with highest risk of resistance emergence during therapy 1, 2, 3
- Klebsiella aerogenes (formerly Enterobacter aerogenes) 3
- Citrobacter freundii 1, 2, 4
- Serratia marcescens 1, 2, 4
- Morganella morganii 2, 4, 5
- Providencia species 2, 4, 5
These organisms are often grouped as "ESCPM" (Enterobacter, Serratia, Citrobacter, Providencia, Morganella) in clinical microbiology 5. They typically appear susceptible to third-generation cephalosporins initially but can develop resistance during treatment through selection of derepressed mutants 6, 2.
Organisms with Plasmid-Mediated AmpC
These organisms acquire AmpC genes on transferable plasmids and typically show constitutive (constant) expression:
- Escherichia coli - most common plasmid-mediated AmpC producer 6, 2
- Klebsiella pneumoniae 1, 6, 2
- Klebsiella oxytoca 6
- Proteus mirabilis 6, 2
- Salmonella enterica 6
Plasmid-mediated AmpC producers are more commonly encountered in community-acquired infections, while chromosomal AmpC producers predominate in healthcare-associated infections 6.
Clinical Significance by Organism
Enterobacter species pose the highest risk for treatment failure because they frequently develop high-level constitutive AmpC expression during therapy with third-generation cephalosporins, even when initially susceptible 1, 2. This phenomenon is well-documented in Enterobacter bacteremia and meningitis 5.
The risk of emergent resistance during treatment appears lower for Serratia marcescens and Morganella morganii compared to Enterobacter species, though they retain the capacity for AmpC overexpression 3, 5.
Resistance Pattern
All AmpC producers demonstrate resistance to:
- All penicillins
- First and second-generation cephalosporins (cephalothin, cefazolin, cefoxitin)
- Third-generation cephalosporins when overexpressed (ceftriaxone, cefotaxime, ceftazidime)
- Piperacillin/tazobactam (β-lactamase inhibitors do not inhibit AmpC)
- Aztreonam 6, 2
Carbapenems remain the safest option for severe infections caused by AmpC producers, with cefepime serving as an effective carbapenem-sparing alternative due to its stability against AmpC hydrolysis 7, 6.