Imipenem/Cilastatin/Relebactam (IMI/REL) in Treatment of CRE Infections
Imipenem/Cilastatin/Relebactam (IMI/REL) in Treatment of CRE Infections
This is an observation study comparing prospective use of Imipenem/Cilastatin/Relebactam
 (IMI/REL) to retrospective data using Meropenem/Vabobactam (MVB)and Ceftazidime/Avibactam
 CZA) in treatment of Klebsiella Producing Carbapenemase Enterobacteriaceae infections at a
 tertiary care hospital. The objectives of the study are to demonstrate successful treatment
 of KPC containing Enterobacteriaceae infections with IMI/REL including in bacteremia, and to
 analyze treatment outcomes in use of IMI/REL for KPC-producing infections compared to
 historical clinical outcome data with CZA and MVB use at the same institution.
Inclusion Criteria:

 1. Adult (>18 years of age) patients with a KPC-producing CRE infection at any site
 except for isolated urinary source. Patients may be initially enrolled once identified
 with a CRE infection defined as resistance to any carbapenem. Any carbapenem
 resistance will provide an initial mechanism of identifying study eligible patients in
 accordance with our institutions definition of CRE for infection prevention purposes.
 As this study is specific for KPC-producing CRE inclusion in the study analysis will
 require confirmation of a KPC gene by molecular analysis of the isolate and subjects
 enrolled may be subsequently removed from study and excluded from analysis if
 molecular testing reveals their CRE isolate to be a non-KPC mechanism of resistance.
 Polymicrobial infections at same or different sites can also be included as long as
 additional gram-negative active agents aside from IMI/REL are not needed for
 treatment.

 2. Bacterial infection with Enterobacteriaceae excluding Morganellaceae

 3. Ability and willingness to give informed consent. A Legal authorized representative
 may be used when the patient is unable to provide informed consent.

 4. Be the first episode of a CRE infection to be treated with IMI/REL. Previously
 treatment with IMI/REL for a KPC-containing Enterobacteriaceae infection will exclude
 patients from enrollment.

 Exclusion Criteria:

 1. Receipt of more than 48 hours of effective antibiotic therapy against KPC containing
 infections (e.g. MVB, CZA) prior to first dose of IMI/REL being administered.

 2. Infections localized to urinary source alone (bloodstream infections from urinary
 source will be included)

 3. Infection with Morganellaceae

 4. Prior serious allergic reaction to carbapenem therapy

 5. Need for ongoing concomitant therapy with ganciclovir or valproic acid

 6. Need for ongoing concomitant therapy with another antibiotic active against gram
 negative pathogens. Concomitant therapy with Vancomycin, Daptomycin, Linezolid,
 Clindamycin, Fidaxomicin, Nafcillin, Metronidazole, and Rifaximin will be allowed but
 no other antibiotic agents.

 7. Pregnancy or ongoing breastfeeding. Women of childbearing age must test negative on a
 urine pregnancy test at time of screening for trial eligibility and remain either
 abstinent or use 2 forms of highly effective contraception for the duration of the
 IMI/REL administration during the study.

 8. Inability to comply with study protocol or remain hospitalized for duration of study.

 9. Life expectancy less than 72 hours in opinion of study investigators.