Allergan’s researchers have presented data at IDWeek from the International Network for Optimal Resistance Monitoring (INFORM) program that monitors the prevalence of resistant bacteria and changing trends of resistance, as well as the in vitro activity of antibiotics against these pathogens.
Allergan’s Vice President, Clinical Development, Anti-Infectives, David Melnick, explained that the INFORM program represented Allergan’s significant commitment to investing in research that advances our understanding of the prevalence, impact and appropriate management of infections caused by resistant Gram-negative pathogens, such as carbapenem-resistant Enterobacteriaceae (CRE).
The company explained that Carbapenem-resistant Enterobacteriaceae (CRE) is one of the three most urgent public health threats identified by the U.S. Centers for Disease Control and Prevention (CDC).1 Klebsiella pneumoniae carbapenemase (KPC) producing bacteria are a common subset of CRE bacteria and account for approximately 85 percent of all CRE infections in the U.S.
The INFORM data presented at IDWeek reported that the antibiotic AVYCAZTM (ceftazidime and avibactam) demonstrated potent in vitro activity against certain common Enterobacteriaceae pathogens isolated from patients with complicated urinary tract infections (cUTI) in U.S. hospitals, including those caused by certain KPC-producing Gram-negative bacteria, meropenem non-susceptible Klebsiella pneumoniae and isolates demonstrating an extended-spectrum beta-lactamase (ESBL)-phenotype. These pathogens are often resistant to multiple antimicrobial agents, which may be important when limited alternative treatment options are available. This analysis also found AVYCAZ was highly active against certain Klebsiella species resistant to other beta-lactam antibiotics, as well as Pseudomonas aeruginosa, including the majority of isolates non-susceptible to meropenem.
Ceftazidime and avibactam was approved by the U.S. Food and Drug Administration (FDA) as AVYCAZ in February 2015 for the treatment of cUTI including pyelonephritis and complicated intra-abdominal infections (cIAI), in combination with metronidazole, caused by designated susceptible bacteria, including certain Enterobacteriaceae and Pseudomonas aeruginosa for patients 18 years of age and older. As only limited clinical safety and efficacy data for AVYCAZ are currently available, reserve AVYCAZ for use in patients who have limited or no alternative treatment options.
According to Allergan, this approval was based in part on data that found AVYCAZ demonstrated in vitro activity against Enterobacteriaceae in the presence of some beta-lactamases and ESBLs of the following groups: TEM, SHV, CTX-M, Klebsiella pneumoniae carbapenemase (KPCs), AmpC, and certain oxacillinases (OXA). AVYCAZ also demonstrated in vitro activity against Pseudomonas aeruginosa in the presence of some AmpC beta-lactamases, and certain strains lacking outer membrane porin (OprD). AVYCAZ is not active against bacteria that produce metallo-beta lactamases and may not have activity against Gram-negative bacteria that overexpress efflux pumps or have porin mutations.
“AVYCAZ represents a significant advance in addressing urgent public health threats caused by difficult-to-treat Gram-negative pathogens,” Dr. Melnick said.
“Allergan looks forward to building on the 10 years of research and development the company invested in bringing this product to market and will continue to bring much-needed innovations to physicians and their patients.”
The INFORM data, presented in a poster titled, “Antimicrobial Activity of Ceftazidime-Avibactam and Comparator Agents Tested Against Gram-negative Organisms Isolated from Urinary Tract Infections (UTI): Results from the International Network for Optimal Resistance (INFORM) Program,” evaluated 7,262 unique patient organisms from patients with UTIs treated at 71 U.S. medical centers between 2012 and 2014. Susceptibility testing was performed for ceftazidime and avibactam, ceftazidime alone, meropenem and piperacillin-tazobactam by reference broth microdilution methods. Enterobacteriaceae with an ESBL phenotype were evaluated for the presence of genes encoding ESBLs, KPC, metallo and transferable AmpC enzymes using a microarray-based assay.
Ceftazidime and avibactam is co-developed with partner AstraZeneca. AstraZeneca has filed a variation to the Marketing Application in the EU seeking approval for similar indications.
Allergan about About AVYCAZTM
AVYCAZ is an antibiotic developed to treat certain serious Gram-negative bacterial infections. It consists of ceftazidime, a third-generation, cephalosporin, that is an established and respected treatment for serious Gram-negative bacterial infections, and avibactam, a non-ß lactam ß-lactamase inhibitor.
The addition of avibactam to ceftazidime protects ceftazidime from breakdown by certain ß-lactamases. AVYCAZ offers a differentiated profile in the treatment of serious Gram-negative infections through its coverage of a range of species of Enterobacteriaceae, including those that produce certain ESBL and KPC, together with activity against difficult to treat Pseudomonas aeruginosa.