From the Guidelines
The prevalence of Extended-Spectrum Beta-Lactamase (ESBL) and AmpC beta-lactamase producing organisms is a significant concern, with ESBL prevalence ranging from 10-40% of Enterobacteriaceae isolates globally, and AmpC prevalence typically lower, around 2-10% of isolates, as reported in the most recent study 1. The geographic distribution of these resistance mechanisms varies, with higher rates in Asia, Latin America, and parts of Southern Europe compared to North America and Northern Europe.
- The use of carbapenems, such as ertapenem, meropenem, or imipenem, is recommended for empiric treatment of suspected ESBL or AmpC infections, due to their reliable activity against these resistant organisms 1.
- Alternative agents, including piperacillin-tazobactam, ceftazidime-avibactam, or ceftolozane-tazobactam, may be considered, but their efficacy depends on the specific resistance mechanisms present, and should be guided by local epidemiology and antimicrobial stewardship principles 1.
- The increasing prevalence of these resistance mechanisms is driven by antibiotic selection pressure, poor infection control practices, and global travel, highlighting the need for ongoing surveillance and antimicrobial stewardship to manage these challenging infections 1.
- Carbapenem-sparing strategies, such as the use of beta-lactam/beta-lactamase inhibitor combinations, are desirable to reduce the spread of antibiotic resistance, and novel beta-lactams with anti-carbapenemase activity should be reserved for patients with specific resistance profiles, as identified by rapid molecular tests 1.
From the Research
ESBL Prevalence
- ESBL-producing bacteria are prevalent worldwide and correlated with hospital infections, but they have been evolving as an increasing cause of community-acquired infections 2
- The spread of ESBL constitutes a major threat for public health, and infections with ESBL-producing organisms have been associated with poor outcomes 2
- Established therapeutic options for severe infections caused by ESBL-producing organisms are considered the carbapenems, but carbapenem-sparing strategies have been implemented due to the pressure of carbapenem overuse and the emergence of resistance 2, 3
AmpC Prevalence
- AmpC β-lactamase-producing 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 4
- 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 4
- Production of AmpCs can be either inducible or constitutive, resulting in different resistance phenotypes, and strains producing cAmpCs in an inducible manner can easily yield mutants constitutively producing the enzyme which are resistant to these drugs 4
Treatment Options
- Carbapenems are often the preferred option for treating AmpC-producing Enterobacterales, especially for severe infections in which adequate source control is not achieved, but cefepime is also supported by substantial clinical evidence as an effective carbapenem-sparing option 5, 3, 4
- New antibiotics such as ceftazidime-avibactam and ceftolozane-tazobactam are carbapenem-sparing agents that appear to be interesting alternatives for the treatment of serious Gram-negative infections 6
- Other new β-lactams/β-lactamase inhibitors and non-β-lactam agents are also promising for the treatment of ESBL- and AmpC-infections, but further clinical data are needed to establish their efficacy in comparison to carbapenems 6