Outcomes with ceftazidime/avibactam in patients with carbapenem-resistant Enterobacteriaceae (CRE) infections: a multi-center study

Background: Ceftazidime-avibactam (CAZAVI) is a cephalosporin-beta-lactamase inhibitor combination that is active against Enterobacteriaceae and Pseudomonas aeruginosathat is resistant to other agents, including carbapenems and late-generation cephalosporins. This purpose of this study is to describe the outcomes of patients receiving ceftazidime-avibactam for CRE infections.

Methods: A retrospective chart review was completed from March 2015 through April 2016 at 9 hospitals in the United States for adult patients who received ceftazidime/avibactam for a CRE infection. Patients were included if they received CAZAVI for at least 24 hours for a carbapenem-resistant Enterobacteriaceae. Dosage was chosen by providers at individual sites. The primary outcome was in-hospital mortality. Microbiologic and clinical outcomes were also evaluated. Microbiological success required a negative culture at the end of therapy. Clinical success was judged by improved symptoms, improved imaging where relevant, and defervesence.

Results:

Characteristic	Results (N=47)
Male gender, n(%)	28 (60)
Age (median, IQR)	59 (51-71)
Charlson Comorbidity Index (median, IQR)	5 (3-8)
Pitt Bacteremia Score (median, IQR)	2 (0-5)
ICU, n(%)	30 (64)
Moderate-severe renal disease	18 (38)
Moderate-severe liver disease	7 (15)
Primary organism, n(%) Klebsiella pneumoniae Enterobacter aerogenes Escherichia coli Providencia stuartii Serratia marcescens	40 (85) 3 (6) 3 (6) 1 (2) 1 (2)
Primary infection, n(%) Bacteremia Pneumonia Urinary tract Wound Intra-abdominal Bone/joint	19 (40) 16 (34) 11 (23) 5 (11) 2 (4) 2 (4)
Hospital day CRE infection diagnosed (median, IQR)	2 (1-16)
Hospital day CAZAVI started (median, IQR)	8 (5-23)
Patients receiving concomitant therapy for index pathogen, n(%)	25 (53)
Isolates susceptible to CAZAVI, n/N (%)	27/28 (96)
In-hospital mortality, n(%)	17 (36)
Microbiologic cure, n(%)	24 (51)
Clinical success, n(%)	31 (66)

Conclusion: In this severely ill population, 51% of patients had microbiological cure, 66% had clinical success, and 64% were alive at the end of their hospital stay. Ceftazidime/avibactam is a potential option for patients with multi-drug resistant organisms causing Enterobacteriaceae infections, including those in intensive care.