21 AmpC beta-lactamases: epidemiology, infection control and treatment Introduction A well-known healthcare-related problem among patients in hospitals and nursing homes is the increasing antibiotic resistance in gram-negative bacteria (David M. Livermore et al. 2007). Extended spectrum beta-lactamase (ESBL)-producing gram-negative bacteria within the order Enterobacterales, such as Escherichia coli and Klebsiella pneumoniae, are increasingly found worldwide. Due to the resistance caused by the beta-lactamases, frequently used beta-lactam antibiotics are no longer effective. This limits the options for adequate treatment for the patient, because empirical therapy for bloodstream infections in most Dutch hospitals is based on the use of beta-lactam antibiotics. For example, second- and third-generation cephalosporins such as cefuroxime, ceftriaxone or ceftazidime occupy an important place in the Netherlands as the first-choice treatment for sepsis, as described in the SWAB guideline Sepsis 2020 (Sieswerda et al. 2020). Although to a lesser extent than ESBL, acquired AmpC beta-lactamases have emerged as a potential threat to the utility of broad-spectrum penicillins and thirdgeneration cephalosporins (Jacoby 2009). Acquired AmpC beta-lactamases are encoded on plasmids and are transferable between different bacteria species. Detecting AmpC production in Enterobacterales can be challenging and guidelines and protocols on the detection and infection prevention are still scarce. In this review, the background of the resistance mechanism and possible detection methods of plasmid-encoded AmpC are described. A summarized overview of the epidemiology of plasmid-encoded AmpC in the Netherlands is provided as well. Furthermore, some descriptions of outbreaks with plasmid AmpC are given with possible guidance on infection prevention regarding the spread of AmpC producing Enterobacterales. Finally, the treatment options for infections with AmpC producing Enterobacterales are summarized. Background of AmpC The existence of the AmpC beta-lactamase in E. coli has been known since the 1940s of the twentieth century (Jacoby 2009). In the 1960s, the name AmpC was first used in scientific literature for a specific mutant of a penicillinase regulated by the ampA (Jacoby 2009). This type of penicillinase was later found to be different from other known penicillinases such as blaTEM-1. In the Ambler classification, the AmpC betalactamases are classified in a separate class C (Bush and Jacoby 2010). The most notable feature of the AmpC beta-lactamases is that they can hydrolyse cephalosporins and cephamycins, such as cefoxitin and cefotetan. This last type of beta-lactam antibiotic cannot be hydrolysed by ESBLs, such as the SHV or CTX-M beta-lactamases (Jacoby 2
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