Carbapenemase-Producing vs. AmpC-Producing Bacteria: Key Clinical Differences
Fundamental Mechanism Distinction
Carbapenemase producers hydrolyze carbapenems and nearly all beta-lactams, while AmpC producers remain susceptible to carbapenems despite resistance to cephalosporins. 1, 2
The critical difference lies in substrate specificity:
- Carbapenemases (Classes A, B, and D) actively destroy carbapenems, rendering them ineffective 3, 1
- AmpC beta-lactamases (Class C) hydrolyze cephalosporins and penicillins but carbapenems remain stable against these enzymes 4, 2
Resistance Spectrum
Carbapenemase Producers
- Confer resistance to virtually all beta-lactams including carbapenems, broad-spectrum cephalosporins, penicillins, and beta-lactamase inhibitor combinations 3, 1
- Three main enzyme classes with distinct profiles:
AmpC Producers
- Confer resistance to cephalothin, cefazolin, cefoxitin, most penicillins, and beta-lactamase inhibitor combinations 2
- Mediate resistance to third-generation cephalosporins (cefotaxime, ceftazidime, ceftriaxone) when overexpressed 2
- Critically, remain susceptible to carbapenems 3, 4, 2
- Can be chromosomal (cAmpC) in Enterobacter, Citrobacter, Serratia species or plasmid-mediated (pAmpC) in E. coli, Klebsiella, Proteus 6, 2
Clinical Expression Patterns
Carbapenemase Producers
- Constitutively expressed resistance that is immediately apparent on susceptibility testing 3
- Require rapid molecular testing to identify specific carbapenemase family for optimal treatment selection 3
AmpC Producers
- Inducible expression (chromosomal AmpC): Strains initially appear susceptible to third-generation cephalosporins but develop resistance during therapy through mutation 6, 2
- Constitutive expression (plasmid-mediated AmpC): Resistance is immediately apparent 6
- This inducibility creates a major pitfall: Enterobacter species may test susceptible to ceftriaxone initially but develop resistance mid-treatment, causing clinical failure 3, 2
Treatment Implications
Carbapenemase Producers
Treatment depends entirely on enzyme class 3, 5:
- KPC producers: Ceftazidime/avibactam or meropenem/vaborbactam as first-line (STRONG recommendation) 5
- MBL producers: Ceftazidime/avibactam PLUS aztreonam or cefiderocol (STRONG recommendation) 5
- OXA-48 producers: Ceftazidime/avibactam (CONDITIONAL recommendation) 5
AmpC Producers
- Carbapenems remain the preferred option, especially for severe infections 6, 7
- Cefepime is a carbapenem-sparing alternative supported by clinical evidence 6
- Avoid third-generation cephalosporins in species with inducible AmpC (Enterobacter, Citrobacter, Serratia) even if initially susceptible 3, 2
Epidemiological Context
Carbapenemase Producers
- Predominantly healthcare-associated infections 3
- Carbapenem resistance increased seven-fold since 2006 in Europe 3, 5
- Some countries report >50% carbapenem resistance in K. pneumoniae 3
AmpC Producers
- Plasmid-mediated AmpC common in community-acquired infections 6
- Chromosomal AmpC producers mainly healthcare-associated 6
Critical Pitfalls to Avoid
Never use third-generation cephalosporins for serious infections caused by Enterobacter, Citrobacter, or Serratia species, even when susceptibility testing shows sensitivity 3, 2. These organisms have inducible chromosomal AmpC that will develop resistance during therapy.
Do not assume carbapenem resistance means carbapenemase production 3. Some strains achieve carbapenem resistance through porin loss combined with AmpC or ESBL production, not carbapenemase enzymes 3, 8.
Recognize that 5-10% of cephalosporin-resistant K. pneumoniae produce plasmid-mediated AmpC rather than ESBL 3. These strains remain carbapenem-susceptible unless porin loss occurs 3, 8.