1055. Epidemiology and Mechanisms of Carbapenem Resistance in Recurrent Extended-Spectrum β-lactamase- Producing Enterobacteriaceae Bacteremia
Session: Poster Abstract Session: Bacteremia and Endocarditis
Friday, October 5, 2018
Room: S Poster Hall
Posters
  • Aitken - CRE in ESBL Bacteremia.pdf (450.2 kB)
  • Background: Carbapenems are the treatment of choice for bacteremia caused by extended spectrum β-lactamase producing Enterobacteriaceae (ESBL-E). The emergence carbapenem resistance (CR) in ESBL-E isolates has been described, however, the rate of such resistance in clinical settings are unknown. We describe the frequency and mechanisms of CR in recurrent ESBL-E bacteremia at an NCI-designated cancer center.

    Methods: We performed a prospective whole genome sequencing (WGS) study and retrospective cohort review of adult (age ≥ 18 years) patients with ESBL-E bacteremia between January 2015 and July 2016. Recurrent bacteremia was defined as identification of the same organism in blood culture at any time following initial successful treatment. CR was defined as resistance to meropenem. Carbapenemase production was assessed in the microbiology laboratory using Carba-NP. Available paired isolates underwent WGS via Illumina HiSeq for assessment of clonality and identification of CR mechanisms.

    Results: 116 patients with ESBL-E bacteremia were identified. E. coli was the most common organism (86%), followed by K. pneumoniae (12%), and K. oxytoca (2%). Recurrent bacteremia was identified in 17 (15%) patients (E. coli [n=15], K. pneumoniae [n=2]). Of these, 6 (35%) were CR and 5/6 (83%) were Carba-NP negative. All 6 recurrent CR isolates occurred in patients with leukemia. 5 isolate pairs were available for WGS. In 4 of 5 pairs (3 E. coli, 1 K. pneumoniae), CR emerged from the same strain causing the original infection; 1 recurrence was caused by a distinct E. coli with a OXA-48-like gene. Compared to parental strains, CR E. coli contained deletions in porin-encoding genes and had increased mapping depth for genes encoding CTX-M ESBLs. The K. pneumoniae was Carba-NP negative with no identifiable CR mechanism.

    Conclusion: Emergence of CR following treatment for ESBL-E bacteremia was seen only in leukemia patients and was primarily due to porin loss and amplification of ESBL genes, rather than acquisition of exogenous carbapenemases. These are the first clinical data describing the molecular mechanism of ESBL-E transformation to CR. These data serve as the basis for future studies of antimicrobial stewardship interventions to limit the emergence of CR in ESBL-E.

    Samuel L. Aitken, PharmD1,2, Micah Bhatti, MD, PhD3, Pranoti Sahasrabhojane, MS4, Jessica Galloway-Pena, PhD4, Xiqi Li, MS5, Frank P. Tverdek, PharmD2, Cagney Reeves, PharmD2, Patrick McDaneld, PharmD2, David Greenberg, MD, FIDSA6 and Samuel Shelburne, MD, PhD, FIDSA7, (1)Center for Antimicrobial Resistance and Microbial Genomics (CARMiG), UTHealth McGovern Medical School, Houston, TX, (2)Division of Pharmacy, The University of Texas MD Anderson Cancer Center, Houston, TX, (3)Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, (4)The University of Texas MD Anderson Cancer Center, Houston, TX, (5)Department of Infectious Diseases, University of Texas MD Anderson Cancer Center, Houston, TX, (6)Infectious Disease, University of Texas Southwestern Medical Center, Dallas, TX, (7)Infectious Diseases, MD Anderson Cancer Center, Houston, TX

    Disclosures:

    S. L. Aitken, Shionogi: Scientific Advisor , Consulting fee . Medicines Company: Scientific Advisor , Consulting fee . Merck & Co.: Scientific Advisor , Consulting fee .

    M. Bhatti, None

    P. Sahasrabhojane, None

    J. Galloway-Pena, None

    X. Li, None

    F. P. Tverdek, None

    C. Reeves, None

    P. McDaneld, None

    D. Greenberg, None

    S. Shelburne, None

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 3rd with the exception of research findings presented at the IDWeek press conferences.