First Report of Ceftazidime-Avibactam Resistance in a KPC-3-Expressing Klebsiella pneumoniae Isolate

Abstract

b Ceftazidime-avibactam is the first antimicrobial approved by the U.S. FDA for the treatment of carbapenem-resistant Enterobacteriaceae. Avibactam, a non-␤-lactam ␤-lactamase inhibitor, inactivates class A serine carbapenemases, including Klebsiella pneumoniae carbapenemase (KPC). We report a KPC-producing K. pneumoniae isolate resistant to ceftazidime-avibactam (MIC, 32/4 g/ml) from a patient with no prior treatment with ceftazidime-avibactam.

Clinical and laboratory considerations for the rapid detection of carbapenem-resistant Enterobacteriaceae

“…However, this drug does not have activity against the class B metallo-b-lactamases (such as NDM), 72 and resistance in at least one KPC-producing K. pneumoniae has been described. 73 A few publications propose potential algorithms for treatment of CRE infection based on molecular detection of specific carbapenemases 74 and carbapenem MIC. 75,76 Infection control implications of rapid detection of CP-CRE Timely identification of individuals who are infected or colonized with CP-CRE would enable prompt implementation of infection control interventions, including patient cohorting and isolation, precautions during invasive procedures and patient transport, and appropriate environmental disinfection.…”

Pharmacodynamic and pharmacokinetic considerations in the treatment of critically Ill patients infected with carbapenem-resistant Enterobacteriaceae

“…109 In addition, the first case report of a ceftazidime-avibactam resistant KPC-3-expressing K. pneumoniae isolate was recently reported; however the exact mechanism of resistance has yet to be elucidated. 110 Pharmacokinetic properties of ceftazidime and avibactam are very similar. The protein binding is low (<10 % ceftazidime, 8% avibactam) and the Vd is relatively small (17 L for ceftazidime, 22 L for avibactam).…”

Ceftazidime/Avibactam: Who Says You Can’t Teach an Old Drug New Tricks?

“…Unfortunately, this resistance pattern is not isolated to laboratory observations. The first instance of a ceftazidime/avibactam resistant KPC-3 Klebsiella pneumoniae clinical isolate has been reported in a patient with no prior drug exposure (20). Further exploration of KPC subtypes shows that the MIC of ceftazidime/avibactam against KPC-3 is significantly higher than against KPC-2 variants (21).…”

“…Lastly, a single report of ceftazidime/avibactam was published with minimal patient information for an off-label indication of a 62 year old female with a complicated past medical history presenting with vomiting and fever two weeks after a pylorus preserving pancreaticoduodenectomy (20). Admission blood cultures were positive for Citrobacter freundii and a carbapenem-resistant K. pneumoniae.…”