From the Guidelines
AmpC beta-lactamases are indeed becoming more prevalent than Extended-Spectrum Beta-Lactamases (ESBLs) in many clinical settings today, as evidenced by recent studies 1. This shift is significant because AmpC-producing organisms are resistant to cephalosporins, penicillins, and beta-lactamase inhibitor combinations like piperacillin-tazobactam, while remaining susceptible to carbapenems (meropenem, imipenem, ertapenem) and cefepime in many cases. The increasing prevalence of AmpC is concerning because these enzymes are often plasmid-mediated, allowing for horizontal transfer between bacteria, and they can be induced by exposure to certain antibiotics. Common bacteria harboring AmpC include Enterobacter species, Citrobacter freundii, Serratia marcescens, and increasingly Escherichia coli and Klebsiella pneumoniae. For empiric treatment of suspected AmpC infections, carbapenems are typically the safest choice (e.g., meropenem 1g IV every 8 hours), though cefepime (2g IV every 8 hours) may be effective in some cases, as suggested by the World Journal of Emergency Surgery 1. This trend underscores the importance of antimicrobial stewardship and appropriate empiric therapy selection, particularly in healthcare settings where AmpC prevalence is high or in patients with recent antibiotic exposure, as inappropriate initial therapy is associated with increased mortality. Some key points to consider in the management of intra-abdominal infections include:
- The choice of empiric antibiotic regimens should be based on the clinical condition of the patients, the individual risk for infection by resistant pathogens, and the local resistance epidemiology 1.
- Hospital-acquired IAIs are associated with an increased likelihood of pathogens with reduced susceptibility to standard antibiotic regimens 1.
- A Carbapenem-sparing regimen is preferred, and the use of carbapenems should be limited to preserve their activity against multidrug-resistant infections 1. The recent emergence of carbapenem resistance among Enterobacteriaceae poses a considerable threat to hospitalized patients, and inappropriate use of carbapenems should be avoided to reduce their selective pressure and association with the increase in carbapenem-resistant Enterobacteriaceae (CRE) 1.
From the Research
Comparison of AmpC and ESBL Prevalence
- The prevalence of AmpC-producing Enterobacteriaceae has been increasing, with some studies suggesting that it may now be more common than ESBL-producing Enterobacteriaceae 2, 3.
- However, the epidemiology of AmpC and ESBL producers can vary depending on the region and the specific bacterial species involved 3, 4.
Treatment Options for AmpC-Producing Infections
- Carbapenems are often considered the drugs of choice for treating infections caused by AmpC-producing Enterobacteriaceae, but alternatives such as cefepime may be effective in certain situations 2, 5, 6.
- Cefepime has been shown to be a reasonable option for treating invasive infections caused by AmpC-producing organisms, particularly when adequate source control is achieved 5, 6.
- The use of cefepime as a carbapenem-sparing option is supported by substantial clinical evidence, and it may be a suitable alternative for treating AmpC-producing Enterobacterales bloodstream infections 3, 6.
Diagnostic Challenges and Resistance Mechanisms
- The diagnosis of AmpC-producing Enterobacteriaceae can be challenging, and techniques to identify these organisms are still evolving 4.
- Resistance to carbapenems can arise in AmpC-producing bacteria through mechanisms such as outer membrane porin loss or efflux pump activation 4.
- The production of AmpC enzymes can be either inducible or constitutive, resulting in different resistance phenotypes, and the expression of these enzymes can be influenced by various factors, including the use of certain antibiotics 3, 4.