What is Extended-Spectrum Beta-Lactamase (ESBL)?

From the Guidelines

For the treatment of ESBL-producing bacterial infections, carbapenems are the preferred choice, with meropenem, imipenem, or ertapenem being typical first-line treatments for serious infections. When considering the management of infections caused by multidrug-resistant bacteria, including those producing ESBLs, it's crucial to prioritize treatments that have shown efficacy against these resistant organisms. According to the guideline endorsed by the Italian Society of Infection and Tropical Diseases (SIMIT), among others, published in the International Journal of Antimicrobial Agents 1, the focus is on managing infections caused by metallo-β-lactamase (MBL)-producing carbapenem-resistant Enterobacterales (CRE), but the principles of using effective antibiotics against resistant bacteria can be applied broadly.

Key points to consider in the treatment of ESBL-producing infections include:

• The use of carbapenems as first-line therapy for serious infections due to their broad-spectrum activity and stability against beta-lactamases, including ESBLs.
• For less severe infections, such as uncomplicated urinary tract infections, alternatives like fosfomycin or nitrofurantoin may be considered based on local resistance patterns and patient factors.
• The importance of infection control measures to prevent the spread of ESBL-producing organisms, including strict adherence to contact precautions, hand hygiene, and thorough environmental cleaning.
• The role of antibiotic stewardship in minimizing the development and spread of antibiotic resistance, including the judicious use of broad-spectrum antibiotics and the implementation of antimicrobial stewardship programs.

In the context of managing ESBL-producing infections, while the provided guideline focuses on MBL-producing CRE, the principles of using effective, evidence-based treatments and prioritizing infection control and antibiotic stewardship are broadly applicable. Therefore, the treatment approach should always prioritize the use of antibiotics with known efficacy against the specific resistant organism, guided by local epidemiology and resistance patterns, and supported by high-quality clinical evidence 1.

From the FDA Drug Label

AVYCAZ demonstrated in vitro activity against Enterobacteriaceae in the presence of some beta-lactamases and extended-spectrum beta-lactamases (ESBLs) of the following groups: TEM, SHV, CTX-M, Klebsiella pneumoniae carbapenemase (KPCs), AmpC, and certain oxacillinases (OXA). ZERBAXA demonstrated in vitro activity against Enterobacteriaceae in the presence of some extended-spectrum beta-lactamases (ESBLs) and other beta-lactamases of the following groups: TEM, SHV, CTX-M, and OXA.

ESBL (Extended-Spectrum Beta-Lactamase) producing bacteria are susceptible to AVYCAZ and ZERBAXA, as both drugs have shown in vitro activity against ESBL-producing Enterobacteriaceae.

• AVYCAZ is active against ESBLs of the following groups: TEM, SHV, CTX-M, KPCs, AmpC, and certain OXA.
• ZERBAXA is active against ESBLs of the following groups: TEM, SHV, CTX-M, and OXA. 2 3

From the Research

ESBL Infections

• ESBL (Extended-Spectrum Beta-Lactamase) producing bacteria are a major threat to public health, causing infections that are difficult to treat 4, 5.
• Infections due to ESBL-producing Enterobacteriaceae (ESBL-E) are increasing worldwide, with carbapenems being the usual treatment of choice for serious ESBL infections 4.

Treatment Options

• Carbapenems, such as meropenem and imipenem, are recommended for the treatment of ESBL bloodstream infections (BSIs) in critically ill patients 4.
• Ertapenem should be reserved for patients with less severe presentations and used at high doses 4.
• Alternative carbapenem-sparing options, such as cephamycins, fluoroquinolones, and β-lactam/β-lactam inhibitor combinations (e.g., piperacillin/tazobactam), can be considered for milder presentations or BSIs from low-risk sources 4, 5.
• Oral treatment options, such as pivmecillinam, fosfomycin, and nitrofurantoin, may be effective for uncomplicated urinary tract infections (UTIs) caused by ESBL-producing Enterobacteriaceae 6, 7.

Carbapenem-Sparing Strategies

• Carbapenem-sparing strategies have been implemented due to the overuse of carbapenems and the emergence of resistance 5.
• Piperacillin-tazobactam is a debated agent for carbapenem-sparing, with conflicting results 5.
• New antibiotics, such as ceftolozane-tazobactam and ceftazidime-avibactam, appear to be effective carbapenem-sparing therapies 5, 8.
• The definitive role of new drugs should be assessed based on clinical data, local epidemiology, and microbiology 8.