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Avycaz achieves mixed results for patients infected with CRE
Avycaz achieved a clinical success rate of 59% among patients infected with carbapenem-resistant Enterobacteriaceae but was associated with troubling levels of resistance, according to a recent study in Clinical Infectious Diseases.
“Our data suggest that [Avycaz (ceftazidime-avibactam), Allergan] is an important addition to the limited antimicrobial armamentarium against [carbapenem-resistant Enterobacteriaceae (CRE)] infections, which is at least as efficacious as alternative regimens and likely to be better-tolerated,” Ryan K. Shields, PharmD, MS, assistant professor of medicine in the division of infectious diseases at the University of Pittsburgh, and colleagues wrote. “The rapid onset of ceftazidime-avibactam resistance in patients with microbiologic persistence of CRE was the most concerning finding of this study.”
Ceftazidime-avibactam was approved by the FDA in 2015, and it was hoped that it might offer a significant advance over previously developed antimicrobials used to treat CRE. The objective of the study was to describe initial clinical experience with ceftazidime-avibactam against CRE infections.
Shields and colleagues evaluated 37 patients with CRE infection who were treated with at least 3 days of ceftazidime-avibactam at the University of Pittsburgh Medical Center from April 2015 to February. Patients were given a standard dosage of 2.5 g intravenously every 8 hours, with adjustments for renal impairment.
Thirty- and 90-day survival rates were 76% and 62%, respectively. Clinical success, defined as survival, resolution of signs of infection, sterilization of site-specific cultures within 7 days of treatment initiation, and the absence of recurrence 30 days after infection, was achieved in 59% of patients. In 23% of clinical successes, infection recurred within 90 days.
Brad Spellberg
The researchers noted that the overall survival and clinical success rates were comparable to previous reports of CRE-infected patients treated with two or more in vitro active agents. Furthermore, they noted that the rate of acute kidney injury (10%) among patients treated with ceftazidime-avibactam was “considerably lower” than rates previously reported with carbapenem-colistin or aminoglycoside-based combinations.
Microbiologic failures occurred in 27% of patients. Among those failures, ceftazidime-avibactam resistance was detected in 30% patients, with resistance developing after a median of 15 days (range, 10-19) of therapy.
“The development of resistance after as few as 10 days of therapy is troubling, and treatment failures and deaths in a significant minority of patients highlight the need for more agents with activity against CRE,” the researchers concluded. “It is incumbent upon health care providers to share their clinical experiences with ceftazidime-avibactam and other new beta-lactamase inhibitors, so these agents can be used most effectively for the longest period of time.”
Robert A. Bonomo
In a related editorial, Brad Spellberg, MD, professor of clinical medicine at the Los Angeles County-University of Southern California Medical Center, and Robert A. Bonomo, MD, professor of medicine at Case Western Reserve University, wrote that the results of this study were both important and worrisome.
“It is the first meaningful clinical evaluation of the efficacy of ceftazidime-avibactam when treating CRE infections, and among a fairly large number of patients with CRE. The results are quite concerning. Mortality continues to be high, and resistance seems to emerge rapidly.” – by Sarah Kennedy
Disclosures: Shields reports no relevant financial disclosures. Spellberg and Bonomo report relationships with several pharmaceutical companies. Please see the full study for a list of all other authors’ relevant financial disclosures.