Ceftazidime–avibactam Susceptibility Patterns in Carbapenem-Resistant Enterobacteriaceae in the USA: Results from the Consortium on Resistance against Carbapenems in Klebsiella and Other Enterobacteriaceae (CRACKLE-2)

Abstract

Background. Cefazidime-avibactam (caz-avi) is a new treatment option for car-bapenem-resistant Enterobacteriaceae (CRE). Methods. The Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE-2) is a multi-center, prospective, observational study of 60 hospitals in all five regions of the USA. Hospitalized patients with CRE isolated from clinical cultures are enrolled in CRACKLE-2. CRE was defined per CDC guidelines. Pitt Bacteremia score (PBS) and Charlson comorbidity score (CMS) were calculated. caz-avi susceptibility was tested as clinically indicated in participating clinical laboratories. Results. From June 1, 2016-April 4, 2017, 568 unique patients with 591 admissions and 681 culture episodes (42% infection, 58% colonization) were included. The distribution of 252 first CRE infections per unique patient was 78 (31%) blood, 67 (27%) urine, 37 (15%) respiratory, 34 (13%) intra-abdominal, 30 (12%) wound, and 6 (2%) other. Patients with CRE infections were chronically ill (CMS median [IQR] 3 [1,5]) and acutely ill (PBS median [IQR] 3 [2,6]). Outcomes were available for198 patients with infections; all-cause mortality was 29/198 (15%) at14 days, and 55/198 (28%) at 90 days. K. pneumoniae (62%), E. cloacae (17%), and E. coli (13%) were the top three CRE species. A total of124 isolates were tested for carbapenemase genes; 62/124 (50%), and 29/124 (23%) were positive for blaKPC-2, and blaKPC-3, respectively. Within 96 tested CR K. pneumoniae (CRKP) isolates, 22/96 (23%), 36/96 (38%), 38/96 (40%) were ST258-1, ST258-2, and non-ST258 clades, respectively. Antibiotic data were available for 224 patients with infections. In various combinations, 37/224 (16%) patients received polymyxins, 74/224 (33%) aminoglycosides, 111/224 (49%) carbapenems, 47/224 (21%) cefazidime/avibactam, and 26/224 (12%) tigecycline. A total of 111 CRE were tested for caz-avi susceptibility; 32/111 (29%) were non-susceptible. All-cause mortality by caz-avi susceptibility did not difer among 62 patients with outcomes (P = 0.74). Conclusion. In this national sample of hospitalized patients with CRE, 29% of tested isolates were caz-avi non-susceptible. Results need to be confirmed by central laboratory testing. [Figure Presented].