Ceftazidime/Avibactam Shows Promise in Patients With Complicated Intra-Abdominal Infections
Combo therapy noninferior to merepenem in phase III trials
Positive results have been reported from pivotal phase III studies evaluating the investigational antibiotic ceftazidime/avibactam (Actavis/Forest Laboratories/Astra Zeneca) as a treatment for adult hospitalized patients with complicated intra-abdominal infections (IAIs).
Ceftazidime/avibactam consists of a cephalosporin (ceftazidime), an established treatment for serious bacterial infections, and a next-generation non–beta-lactam beta-lactamase inhibitor (avibactam). The compound is being developed to treat a range of Gram-negative bacterial infections, which are becoming resistant to antibiotics and pose an increasing threat to public health. The addition of avibactam protects ceftazidime from being broken down by beta-lactamases produced by resistant bacteria.
The global RECLAIM-1 and RECLAIM-2 trials evaluated the safety and efficacy of ceftazidime/avibactam, administered intravenously as a 2-hour infusion (2,000 mg/500 mg q8h), plus metronidazole compared with meropenem (Merrem I.V., AstraZeneca), administered intravenously as a 30-minute infusion (1 g q8h), in a total of 1,066 hospitalized adult patients with complicated IAIs in 30 countries. The data from both trials were analyzed as a single pooled dataset with the agreement of the FDA.
In both studies, ceftazidime/avibactam met the objective of statistical non-inferiority compared with meropenem. The primary endpoint was the clinical cure rate 28 to 35 days after randomization (the “test of cure” visit). In addition, ceftazidime/avibactam was effective in treating complicated IAI patients infected with ceftazidime-resistant bacteria.
The most commonly reported adverse events for ceftazidime/avibactam in combination with metronidazole were diarrhea, nausea, vomiting, and fever.
Ceftazidime/avibactam is an investigational antibiotic being developed to treat serious Gram-negative bacterial infections. It consists of ceftazidime, a third-generation, antipseudomonal cephalosporin, which is an established treatment for serious Gram-negative bacterial infections, and avibactam, a next generation, non–beta-lactam beta-lactamase inhibitor.
The addition of avibactam to ceftazidime protects ceftazidime from breakdown by beta-lactamases. Ceftazidime/avibactam was designed to offer a differentiated profile compared with that of existing treatment options in serious Gram-negative infections through its coverage of a broad range of species of carbapenem-resistant Enterobacteriaceae together with difficult-to-treat Pseudomonas aeruginosa combined with coverage of extended-spectrum beta–lactamase–expressing pathogens.
Most IAIs are a result of processes involving inflammation and perforation of the gastrointestinal tract, such as appendicitis, peptic ulcer disease, and diverticulitis. IAI is an important cause of morbidity and mortality, and is the second most commonly identified cause of severe sepsis in intensive-care units.
Complicated IAIs extend beyond the source organ into the peritoneal space. They cause peritoneal inflammation, and are associated with localized or diffuse peritonitis.
Antimicrobial therapy is an important part of the clinical management of IAIs, especially in critically ill patients requiring immediate empiric antibiotic therapy. The threat of antimicrobial resistance, however, is one of the major challenges associated with the antimicrobial management of complicated IAIs.
Source: Actavis; August 19, 2014.