What are the definitions of Extended-Spectrum Beta-Lactamase (ESBL), Ampicillin (AMP) C, and Carbapenem resistance, and which drugs are resistant to these three types of resistance?

From the Guidelines

ESBL, AmpC, and carbapenem resistance are defined as the production of enzymes that can hydrolyze and inactivate beta-lactam antibiotics, including penicillins, cephalosporins, and carbapenems, and are typically resistant to most penicillins, cephalosporins, and aztreonam, but remain susceptible to carbapenems, beta-lactam/beta-lactamase inhibitor combinations, and cephamycins. The drugs resistant to these three types of resistance include:

• ESBL-producing organisms: resistant to most penicillins, cephalosporins (except cefoxitin and cefotetan), and aztreonam, but remain susceptible to carbapenems, beta-lactam/beta-lactamase inhibitor combinations, and cephamycins 1
• AmpC beta-lactamases: resistant to penicillins, cephalosporins (including cephamycins like cefoxitin), and beta-lactam/beta-lactamase inhibitor combinations (except newer ones like ceftazidime-avibactam), but remain susceptible to carbapenems, fourth-generation cephalosporins like cefepime, and newer beta-lactamase inhibitor combinations 1
• Carbapenem-resistant organisms: resistant to virtually all beta-lactams including carbapenems, with variable susceptibility to newer agents like ceftazidime-avibactam, meropenem-vaborbactam, or imipenem-relebactam depending on the specific carbapenemase 1 Some of the treatment options for these resistant infections include:
• Carbapenems (meropenem, imipenem, ertapenem) for ESBL-producing organisms
• Carbapenems or cefepime for AmpC-producing organisms
• Newer agents like ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, or non-beta-lactams like colistin, tigecycline, or aminoglycosides for carbapenem-resistant organisms, with therapy guided by susceptibility testing 1

From the FDA Drug Label

There are several mechanisms of resistance to carbapenems: 1) decreased permeability of the outer membrane of gram-negative bacteria (due to diminished production of porins) causing reduced bacterial uptake, 2) reduced affinity of the target PBPs, 3) increased expression of efflux pump components, and 4) production of antibacterial drug-destroying enzymes (carbapenemases, metallo-β-lactamases).

Cross-resistance is sometimes observed with isolates resistant to other carbapenems.

Definition of Resistance:

• ESBL (Extended-Spectrum Beta-Lactamase): Not directly defined in the label, but implies resistance to beta-lactam antibiotics.
• AMP C: Not directly defined in the label.
• Carbapenem Resistance: Defined as several mechanisms including decreased permeability, reduced affinity of target PBPs, increased expression of efflux pump components, and production of antibacterial drug-destroying enzymes.

Drugs Resistant to these Three:

• The label does not provide a list of drugs resistant to ESBL, AMP C, and carbapenem resistance.
• However, it mentions that meropenem is active against most isolates of certain microorganisms, but cross-resistance is sometimes observed with isolates resistant to other carbapenems 2.

From the Research

Definition of ESBL, AMP C, and Carbapenem Resistance

• ESBL (Extended-Spectrum Beta-Lactamase) refers to a type of enzyme produced by certain bacteria that confers resistance to most beta-lactam antibiotics, including penicillins, cephalosporins, and aztreonam 3.
• AMP C (AmpC beta-lactamase) is another type of enzyme that can hydrolyze and inactivate a wide range of beta-lactam antibiotics, including cephalosporins and penicillins 4.
• Carbapenem resistance refers to the ability of certain bacteria to resist the effects of carbapenem antibiotics, which are often considered the last line of defense against serious infections 5, 6.

Drugs Resistant to ESBL, AMP C, and Carbapenem

• ESBL-producing bacteria are often resistant to most beta-lactam antibiotics, but may be susceptible to carbapenems, such as meropenem and imipenem 5.
• AMP C-producing bacteria may be resistant to cephalosporins and penicillins, but may be susceptible to carbapenems and certain other antibiotics, such as cefepime 4.
• Carbapenem-resistant bacteria are often resistant to most antibiotics, but may be susceptible to certain newer antibiotics, such as ceftolozane/tazobactam, ceftazidime/avibactam, and cefiderocol 5, 7.
• Other antibiotics that may be effective against ESBL, AMP C, and carbapenem-resistant bacteria include beta-lactam/beta-lactamase inhibitor combinations, such as piperacillin/tazobactam, and certain fluoroquinolones and aminoglycosides 6, 4.

Treatment Options

• The choice of antibiotic for treating ESBL, AMP C, and carbapenem-resistant infections depends on various factors, including the severity of the infection, the susceptibility of the bacteria, and the patient's underlying health conditions 5, 6, 7.
• Carbapenems are often considered the first-line treatment for serious ESBL and carbapenem-resistant infections, but alternative antibiotics may be used in certain situations, such as in patients with milder infections or in those who are allergic to carbapenems 5, 6.
• Consultation with an infectious diseases specialist is recommended for the treatment of antimicrobial-resistant infections, as the field of antimicrobial resistance is highly dynamic and treatment options are constantly evolving 7.