Is ceftazidime (Ceftazidime)-avibactam effective against Extended-Spectrum Beta-Lactamase (ESBL)-producing Escherichia coli (E. coli) in bloodstream infections?

From the Guidelines

Yes, ceftazidime-avibactam is effective against Extended-Spectrum Beta-Lactamase (ESBL)-producing Escherichia coli in bloodstream infections. This combination antibiotic is specifically designed to overcome beta-lactamase resistance mechanisms. Ceftazidime is a third-generation cephalosporin that would normally be hydrolyzed by ESBLs, but avibactam is a non-beta-lactam beta-lactamase inhibitor that protects ceftazidime from degradation by binding to the ESBL enzymes, as noted in a study published in the Journal of Microbiology, Immunology and Infection 1.

The typical dosing for adults with normal renal function is 2.5 grams (2 g ceftazidime plus 0.5 g avibactam) administered intravenously every 8 hours. Treatment duration typically ranges from 5-14 days depending on the severity of infection and clinical response. Dose adjustments are necessary for patients with renal impairment. When treating ESBL-producing E. coli bloodstream infections, it's essential to:

• Obtain blood cultures before starting therapy
• Ensure source control if there's an identifiable focus of infection
• Monitor clinical response

Ceftazidime-avibactam provides a carbapenem-sparing option for treating these resistant infections, which is crucial for antimicrobial stewardship efforts to reduce carbapenem use and prevent further resistance development, as highlighted in guidelines endorsed by the Italian Society of Infection and Tropical Diseases 1 and the European Society of Clinical Microbiology and Infectious Diseases 1.

Key points to consider:

• Ceftazidime-avibactam is effective against ESBL-producing E. coli in bloodstream infections
• The combination is specifically designed to overcome beta-lactamase resistance mechanisms
• Dose adjustments are necessary for patients with renal impairment
• Ceftazidime-avibactam provides a carbapenem-sparing option for treating resistant infections, supporting antimicrobial stewardship efforts.

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). Avibactam restored activity of ceftazidime in animal models of infection (e.g. thigh infection, pyelonephritis, systemic infection induced by intraperitoneal injection) caused by ceftazidime non-susceptible beta-lactamase- producing (e.g., ESBL, KPC and AmpC) gram-negative bacteria. AVYCAZ has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections ... Escherichia coli

Ceftazidime-avibactam is effective against ESBL-producing E. coli. The drug label indicates that ceftazidime-avibactam has in vitro activity against ESBL-producing Enterobacteriaceae, including E. coli, and has restored the activity of ceftazidime in animal models of infection caused by ceftazidime non-susceptible beta-lactamase-producing gram-negative bacteria, including ESBL-producing E. coli 2.

• Key points:
  • Ceftazidime-avibactam has in vitro activity against ESBL-producing E. coli.
  • The combination has shown efficacy in animal models of infection caused by ESBL-producing gram-negative bacteria.
  • The drug label supports the use of ceftazidime-avibactam against ESBL-producing E. coli in clinical infections.

From the Research

Effectiveness of Ceftazidime-Avibactam Against ESBL-Producing E. coli in Bloodstream Infections

• Ceftazidime-avibactam is a combination antibiotic that has shown effectiveness against Extended-Spectrum Beta-Lactamase (ESBL)-producing Enterobacteriaceae, including E. coli, in various studies 3, 4, 5, 6.
• A systematic review and meta-analysis found that ceftazidime/avibactam may be a carbapenem-sparing option for the treatment of mild to moderate complicated urinary tract and intra-abdominal infections caused by ESBL-producing Enterobacterales species 5.
• In vitro studies have demonstrated the activity of ceftazidime/avibactam against ESBL-producing E. coli isolates, with avibactam restoring the activity of ceftazidime against these isolates 6.
• However, the use of ceftazidime-avibactam for the treatment of bloodstream infections due to ESBL-producing E. coli is not as well established, and more research is needed to determine its effectiveness in this setting.

Clinical Experience with Ceftazidime-Avibactam

• A retrospective multicenter study found that ceftazidime-avibactam was effective in treating serious infections due to gram-negative bacteria, including ESBL-producing Enterobacterales, with a clinical success rate of 90.5% 4.
• Another study found that ceftazidime-avibactam was associated with a significantly lower 30-day mortality rate compared to other regimens in the treatment of carbapenem-resistant Enterobacterales bloodstream infections 7.
• However, the study also noted that the use of ceftazidime-avibactam should be judicious and reserved for cases where other treatment options are limited or ineffective.

Considerations for Use

• Ceftazidime-avibactam is a costly drug and should be used judiciously to preserve its activity against carbapenem-resistant microorganisms 5.
• The use of ceftazidime-avibactam for the treatment of bloodstream infections due to ESBL-producing E. coli should be considered on a case-by-case basis, taking into account the severity of the infection, the susceptibility of the isolate, and the availability of other treatment options.