339. Ceftazidime/avibactam Susceptibility Patterns in Carbapenem-Resistant Enterobacteriaceae in the US: Results from the Consortium on Resistance against Carbapenems in Klebsiella and Other Enterobacteriaceae (CRACKLE-2)
Session: Poster Abstract Session: Emerging Resistance - Epidemiology and Mechanisms
Thursday, October 5, 2017
Room: Poster Hall CD

Background:

Ceftazidime-avibactam (caz-avi) is a new treatment option for carbapenem-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 5 regions of the US. 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 6/1/2016-4/17/2017, 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 for 198 patients with infections; all-cause mortality was 29/198 (15%) at 14 days, and 55/198 (28%) at 90 days. K. pneumoniae (62%), E. cloacae (17%) and E. coli (13%) were the top 3 CRE species.  124 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 was 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%) ceftazidime/avibactam, and 26/224 (12%) tigecycline.  111 CRE were tested for caz-avi susceptibility; 32/111 (29%) were non-susceptible.  All-cause mortality by caz-avi susceptibility did not differ 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.

David Van Duin, MD, PhD1, Romney Humphries, PhD2, Jesse T. Jacob, MD3, Eric Cober, MD4, Sandra S. Richter, MD5, Yohei Doi, MD, PhD6, Keith S. Kaye, MD, MPH7, Sorabh Dhar, MD8, Cesar Arias, MD, PhD, FIDSA9, Angela Kim, MD10, Julia Garcia-Diaz, MD, FIDSA11, Jennifer H. Han, MD, MSCE12, Michael Satlin, MD13, Samit Desai, MD14, Gregory Weston, MD, MS15, Belinda Ostrowsky, MD, MPH, FIDSA, FSHEA16, Bettina Fries, MD, FIDSA17, Robert Salata, MD18, Darren Wong, MD19, Glenn Wortmann, MD20, Robert Kalayjian, MD21, W. Charles Huskins, MD, MSc, FIDSA, FSHEA, FPIDS22, Deverick J. Anderson, MD, MPH, FIDSA, FSHEA23, Brandon Eilertson, MD24, Lauren Komarow, MS25, Michelle Earley, MS26, Scott R. Evans, PhD27, Steve H. Marshall, MS28, Susan D. Rudin, BS29, T. Nicholas Domitrovic, MS30, Andrea Hujer, BS29, Kristine M. Hujer, BS30, Robert A. Bonomo, MD31 and Antibacterial Resistance Leadership Group (ARLG), (1)Division of Infectious Diseases, University of North Carolina, Chapel Hill, NC, (2)Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA, (3)Emory University School of Medicine, Atlanta, GA, (4)Department of Infectious Diseases, Cleveland Clinic, Cleveland, OH, (5)Department of Laboratory Medicine, Cleveland Clinic, Cleveland, OH, (6)University of Pittsburgh Medical Center, Pittsburgh, PA, (7)Department of Internal Medicine, Division of Infectious Diseases, University of Michigan Medical School, Ann Arbor, MI, (8)Detroit Medical Center, Detroit, MI, (9)Infectious Diseases, University of Texas Medical School at Houston Molecular Genetics and Antimicrobial Resistance Unit, Universidad El Bosque, Bogota, Colombia., Houston, TX, (10)North Shore-LIJ Health System, Manhasset, NY, (11)Infectious Diseases, Ochsner Clinic Foundation, New Orleans, LA, (12)Department of Medicine, The University of Pennsylvania School of Medicine, Philadelphia, PA, (13)New York-Presbyterian, New York, NY, (14)Hackensack University, Hackensack, NJ, (15)Montefiore Medical Center, Bronx, NY, (16)Division of Infectious Diseases, Department of Medicine, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY, (17)Albert Einstein College of Medicine, Bronx, NY, (18)University Hospitals Case Medical Center, Cleveland, OH, (19)USC, Los Angeles, CA, (20)Infection Prevention and Infectious Diseases, MedStar Washington Hospital Center, Washington, DC, (21)Department of Medicine, MetroHealth Medical Center, Cleveland, OH, (22)Mayo Clinic, Rochester, MN, (23)Duke Antimicrobial Stewardship Outreach Network (DASON), Durham, NC, (24)Infectious Diseases, SUNY Downstate, Brooklyn, NY, (25)Statistical and Data Analysis Center, Harvard School of Public Health, Boston, MA, (26)Harvard, Boston, MA, (27)Harvard School of Public Health, Boston, MA, (28)Louis Stokes Cleveland VA Medical Center, Cleveland, OH, (29)Case Western Reserve University, Cleveland, OH, (30)Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH, (31)Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH

Disclosures:

D. Van Duin, Astellas: Scientific Advisor , Consulting fee
Achaogen: Scientific Advisor , Consulting fee
Allergan: Scientific Advisor , Consulting fee
MedImmune: Scientific Advisor , Consulting fee
Shionogi: Scientific Advisor , Consulting fee

R. Humphries, None

J. T. Jacob, None

E. Cober, None

S. S. Richter, bioMerieux: Investigator , Research support
BD Diagnostics: Investigator , Research support
Roche: Investigator , Research support
BioFire: Investigator , Research support
OpGen: Investigator , Research support

Y. Doi, None

K. S. Kaye, Xellia: Consultant , Consulting fee
Merck: Consultant and Grant Investigator , Consulting fee and Research support
The Medicines Company: Consultant and Grant Investigator , Consulting fee and Research support

S. Dhar, None

C. Arias, Bayer Global: Consultant and Speaker's Bureau , Consulting fee and Speaker honorarium
Medicines Company: Consultant , Grant Investigator and Speaker's Bureau , Consulting fee , Grant recipient and Speaker honorarium
Merck: Consultant , Grant Investigator and Speaker's Bureau , Consulting fee , Grant recipient and Speaker honorarium
Pfizer: Consultant and Speaker's Bureau , Consulting fee and Speaker honorarium
Theravance: Consultant , Grant Investigator and Speaker's Bureau , Consulting fee , Grant recipient and Speaker honorarium
Allergan: Consultant , Grant Investigator and Speaker's Bureau , Consulting fee , Grant recipient and Speaker honorarium

A. Kim, None

J. Garcia-Diaz, None

J. H. Han, None

M. Satlin, None

S. Desai, None

G. Weston, None

B. Ostrowsky, None

B. Fries, None

R. Salata, None

D. Wong, None

G. Wortmann, None

R. Kalayjian, None

W. C. Huskins, None

D. J. Anderson, None

B. Eilertson, None

L. Komarow, None

M. Earley, None

S. R. Evans, None

S. H. Marshall, None

S. D. Rudin, None

T. N. Domitrovic, None

A. Hujer, None

K. M. Hujer, None

R. A. Bonomo, None

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