AmpC β-lactamase-producing Enterobacterales: what a clinician should know
Enterobacterales are among the most common causes of bacterial infections in the community and among hospitalized patients, and multidrug-resistant (MDR) strains have emerged as a major threat to human health. Resistance to third-generation cephalosporins is typical of MDRs, being mainly due to the production of extended spectrum β-lactamases or AmpC-type β-lactamases.
The objective of this paper is to review the epidemiological impact, diagnostic issues and treatment options with AmpC producers.
AmpC enzymes encoded by resident chromosomal genes (cAmpCs) are produced by some species (e.g., Enterobacter spp., Citrobacter freundii, Serratia marcescens), while plasmid-encoded AmpCs (pAmpCs) can be encountered also in species that normally do not produce cAmpCs (e.g., Salmonella enterica, Proteus mirabilis, Klebsiella pneumoniae and Klebsiella oxytoca) or produce them at negligible levels (e.g., Escherichia coli). Production of AmpCs can be either inducible or constitutive, resulting in different resistance phenotypes. Strains producing cAmpCs in an inducible manner (e.g., Enterobacter spp.) usually appear susceptible to third-generation cephalosporins, which are poor inducers, but can easily yield mutants constitutively producing the enzyme which are resistant to these drugs (which are good substrates), resulting in treatment failures. pAmpCs are usually constitutively expressed. Production of pAmpCs is common in community-acquired infections, while cAmpC producers are mainly involved in healthcare-associated infections.
To date, there is no conclusive evidence about the most appropriate treatment for AmpC-producing Enterobacterales. Carbapenems are often the preferred option, especially for severe infections in which adequate source control is not achieved, but cefepime is also supported by substantial clinical evidences as an effective carbapenem-sparing option.
KeywordsBeta-lactamases AmpC Enterobacterales Enterobacter Gram negative Antibiotic resistance
This work was performed as part of our routine work. No external funding was required for the project.
Compliance with ethical standards
Conflict of interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
In the past 2 years, C.T. has been paid for lectures on behalf of Pfizer, Novartis, Merck, Angelini, Gilead, and Astellas. G.M.R. has received research grants from Angelini, Basilea, Menarini, Merck, Nordic Pharma, Pfizer, Rempex, Shionogi, VenatorX, Zambon; has received congress lecture fees from Angelini, Basilea, Merck, Pfizer, Zambon; has received consultancy fees from Angelini, Menarini, Merck, Nordic Pharma, Pfizer, Rempex, Shionogi, Zambon. The other authors have nothing to declare. All authors read and approved the final manuscript.
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