The FDA has approved Allergan's sNDA to expand the approved use of AVYCAZ (ceftazidime and avibactam), to include the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) caused by certain susceptible Gram-negative microorganisms.
The US Food and Drug Administration (FDA) has approved Allergan's supplemental New Drug Application (sNDA) to expand the approved use of their cephalosporin / beta-lactamase inhibitor combo antibiotic, AVYCAZ (ceftazidime and avibactam), to include the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) caused by the following susceptible Gram-negative microorganisms: Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, Serratia marcescens, Proteus mirabilis, Pseudomonas aeruginosa, and Haemophilus influenzae in patients 18 years of age or older. This approval is the first Gram-negative antibiotic approved in the United States to treat HABP/VABP in more than 15 years, according to a press release from Allergan.
The antibiotic was originally approved to treat complicated intra-abdominal infections (cIAI) and complicated urinary tract infection (cUTI) in February 2015 in combination with metronidazole. It was approved in 2017 for complicated urinary tract infections (cUTI), including pyelonephritis, caused by designated susceptible Gram-negative bacteria, including certain Enterobacteriaceae and Pseudomonas aeruginosa. Subsequent testing on the efficacy of the antibiotic to treat other types of infections proved positive and led to the submission of the sNDA for HABP/VABP.
As Contagion® previously reported, studies have shown a “susceptibility rate of 94.6% and an MIC90 of 8 μg/mL against Pseudomonas aeruginosa isolates for AVYCAZ, [as well as] susceptibility to 99.9% of Klebsiella pneumoniae isolates overall (MIC90 .5 μg/mL) and extended spectrum beta-lactamase-producing Klebsiella pneumoniae isolates (MIC90 2 μg/mL), 99.7% of all Enterobacter cloacae isolates (MIC90 1 μg/mL), and 92.0% of ertapenem-resistant Enterobacter cloacae isolates (MIC90 8 μg/mL).”
The combo antibiotic has also shown strong activity against, “Enterobacteriaceae isolates collected as part of the INFORM surveillance program. Susceptibility rates in this study were 99.1% overall and 94.2% against multidrug-resistant isolates. Reduced activity (78.5%) was observed against meropenem non-susceptible isolates (MIC90 >128 μg/mL) due to Class B enzymes and was improved against meropenem non-susceptible, metallo-beta-lactamase (MBL)-negative isolates (99.4%; MIC90 4 μg/mL) and colistin-resistant isolates (96.4%).”
As reported at IDWeek 2017, the outlook for the drug is good; however, resistance isolates have been seen. In addition, presenters at IDWeek noted that whether or not ceftazidime—avibactam will follow, “the oft-repeated pattern of initial drug success followed by increasing resistance remains to be seen.”