Inducible AmpC β-lactamases in clinical isolates of Gram-negative bacteria

Inducible AmpC β-lactamases are chromosomally encoded enzymes found in several Gram-negative bacteria that provide resistance to a broad range of β-lactam antibiotics, including penicillins, most cephalosporins (including third-generation), and cephamycins (e.g., cefoxitin). Their expression is significantly increased (induced) in the presence of certain β-lactam antibiotics, which can lead to therapeutic failure.

Key CharacteristicsChromosomal Location: The genes (known as ampC genes) are typically located on the bacterial chromosome.
Inducible Expression: The enzyme is produced in high amounts only when the bacterium is exposed to specific inducing agents (e.g., cefoxitin, imipenem, or clavulanate).
Resistance Spectrum: AmpC enzymes can hydrolyze penicillins, first-, second-, and third-generation cephalosporins, and cephamycins. They are, however, generally not inhibited by commercially available β-lactamase inhibitors like clavulanic acid, sulbactam, and tazobactam.
Lack of Inhibition by Clavulanate: This feature helps distinguish them from Extended Spectrum β-Lactamases (ESBLs) in laboratory tests.

Common Clinical Isolates with Inducible AmpC
The ability for inducible AmpC production is intrinsic to several important opportunistic Gram-negative pathogens, often referred to by the acronym "ESCAPPM" organisms: Enterobacter spp. (E. cloacae, E. aerogenes)
Serratia spp. (S. marcescens)
Citrobacter spp. (C. freundii)
Acinetobacter spp.
Pseudomonas spp. (P. aeruginosa)
Providencia spp.
Morganella spp. (M. morganii)
Organisms like Escherichia coli and Klebsiella pneumoniae do not typically have an inducible chromosomal ampC gene; if they produce AmpC, it's usually due to a non-inducible mutation or acquisition of a plasmid-mediated AmpC gene, which presents a different clinical challenge.

Clinical Significance
The presence of inducible AmpC β-lactamases poses significant clinical challenges: Therapeutic Failure: Treatment with certain β-lactam antibiotics, even if the initial in vitro susceptibility test appears sensitive, can select for mutants that overexpress AmpC, leading to high-level resistance and treatment failure.
Misleading Lab Results: Standard susceptibility testing methods may not readily detect inducible resistance, making accurate laboratory detection critical for effective treatment and infection control.
Treatment Options: Infections caused by AmpC-producing bacteria usually require alternative antibiotics. Carbapenems (e.g., imipenem, meropenem) are often effective, but resistance can develop through other mechanisms like porin loss.
Due to the challenges in detection and the potential for clinical failure, the routine detection of AmpC β-lactamases in clinical laboratories is important for guiding appropriate antimicrobial therapy.

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