What is the recommended treatment for complicated Gram-negative bacterial infections, including those producing beta-lactamases?

From the Guidelines

Ceftazidime-avibactam is recommended as a treatment option for complicated Gram-negative bacterial infections, including those producing beta-lactamases, particularly for infections caused by metallo-β-lactamase (MBL)-producing carbapenem-resistant Enterobacterales (CRE) in combination with aztreonam 1. The choice of empiric antibiotic regimens in patients with intra-abdominal infections (IAIs) should be based on the clinical condition of the patients, the individual risk for infection by resistant pathogens, and the local resistance epidemiology 1.

• In patients with community-acquired IAIs, agents with a narrower spectrum of activity are preferred, while in patients with healthcare-associated infections, antibiotic regimens with broader spectra of activity are preferred 1.
• The major pathogens involved in community-acquired IAIs are usual residents of gastrointestinal flora, including Enterobacteriaceae, streptococci, and certain anaerobes 1.
• For patients with severe infections with suspected or confirmed extended-spectrum beta-lactamase (ESBL) producers, combination therapy may be necessary, adding an aminoglycoside or a polymyxin 1.
• Ceftazidime-avibactam has in vitro activity against K. pneumoniae carbapenemase-producing bacteria and is a valuable option for treating infections caused by multidrug-resistant (MDR) gram-negative bacteria 1.
• The combination of ceftazidime-avibactam plus aztreonam has shown in vitro synergy and has been associated with lower 30-day mortality in patients with bloodstream infections caused by MBL-producing CRE 1.
• Treatment duration generally ranges from 7-14 days depending on infection site, severity, and clinical response, and susceptibility testing is crucial for guiding definitive therapy 1.
• Source control through drainage of abscesses or removal of infected devices is equally important for successful treatment outcomes 1.

From the FDA Drug Label

AVYCAZ is a combination of ceftazidime, a cephalosporin, and avibactam, a beta-lactamase inhibitor, indicated for the treatment of the following infections caused by designated susceptible Gram-negative microorganisms in adult and pediatric patients (at least 31 weeks gestational age): Complicated Intra-abdominal Infections (cIAI), used in combination with metronidazole, Complicated Urinary Tract Infections (cUTI), including Pyelonephritis, and Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP) DOSAGE AND ADMINISTRATION Dosage of AVYCAZ in Adult Patients with Creatinine Clearance (CrCl) greater than 50 mL/min: Infection Dose Frequency Infusion Time cIAI*, cUTI including Pyelonephritis, and HABP/VABP AVYCAZ 2.5 grams (ceftazidime 2 grams and avibactam 0.5 grams) Every 8 hours 2 hours

The recommended treatment for complicated Gram-negative bacterial infections, including those producing beta-lactamases, is AVYCAZ 2.5 grams (ceftazidime 2 grams and avibactam 0.5 grams) administered every 8 hours over 2 hours for:

• Complicated Intra-abdominal Infections (cIAI), used in combination with metronidazole
• Complicated Urinary Tract Infections (cUTI), including Pyelonephritis
• Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP) 2

From the Research

Recommended Treatment for Complicated Gram-Negative Bacterial Infections

The recommended treatment for complicated Gram-negative bacterial infections, including those producing beta-lactamases, is Ceftazidime-Avibactam 3, 4, 5, 6, 7.

Key Characteristics of Ceftazidime-Avibactam

• Ceftazidime-Avibactam is a combination of the third-generation cephalosporin ceftazidime and the novel non-β-lactam β-lactamase inhibitor avibactam 3, 4, 5, 6, 7.
• Avibactam has increased potency and expanded spectrum of inhibition of class A and C β-lactamases relative to available β-lactamase inhibitors 3.
• Ceftazidime-Avibactam is effective against many ceftazidime- and carbapenem-resistant Enterobacteriaceae and Pseudomonas aeruginosa 3, 4, 5, 6, 7.

Clinical Efficacy and Tolerability

• Clinical trials have demonstrated that Ceftazidime-Avibactam is effective and well-tolerated in patients with complicated urinary tract infections (cUTIs) and complicated intra-abdominal infections (cIAIs) 3, 4, 5, 6, 7.
• Ceftazidime-Avibactam has been shown to be non-inferior to carbapenem comparators in pivotal phase III non-inferiority trials 6.
• The safety and tolerability profile of Ceftazidime-Avibactam is consistent with that of ceftazidime alone and is generally typical of the injectable cephalosporins 6.

Approved Indications

• Ceftazidime-Avibactam is approved for the treatment of adults with complicated urinary tract infections (cUTIs), complicated intra-abdominal infections (cIAIs), hospital-acquired pneumonia (HAP), and other infections caused by aerobic Gram-negative organisms in patients with limited treatment options 6.

Dosage and Administration

• The approved dosage of Ceftazidime-Avibactam is ceftazidime 2 g-avibactam 0.5 g administered as a 2-hour infusion every 8 hours 3.