Treatment of Carbapenem-Resistant Enterobacterales (CRE)

Although guidances are available for the treatment of infections caused by carbapenem-resistant Enterobacterales (CRE), variation in provider practice may exist with respect to certain “gray areas” such as: preferences when multiple treatment options are reasonable, preference for “older” versus “newer” antibiotics, and barriers to use that affect being able to follow the guidance documents.

The objective of this survey is to understand current management of CRE infections in the context of new therapeutics.
Abbreviations: TMP/SMX = trimethoprim/sulfamethoxazole
AST = antimicrobial susceptibility testing
UTI = urinary tract infection

Please answer the entire survey regardless of whether you have recently treated infections caused by CRE. a. Within the last year, have you treated any patients infected with CRE as defined by AST alone (i.e. resistant to ≥1 carbapenem antibiotic)? Yes     No     Not sure b. If yes, were any infected with carbapenemase-producing CRE? Yes, at least 1 No, all carbapenemase-negative Not sure as isolates were not tested for carbapenemases Not sure; do not recall a. Within the last year, which of the following best describes how frequently carbapenem resistance mechanism testing was available to you: Automatically performed and available on all CRE isolates Performed on select CRE isolates or on request to the lab Available only through a reference or state laboratory and not timely to inform treatment decisions Not available Not applicable / I have not treated patients with CRE Not sure; do not recall b. If mechanism testing is available, which of the following best describes the carbapenem resistance mechanism testing usually performed? Only phenotypic carbapenemase production results (e.g., CarbaNP, mCIM, etc.) Only genotypic results indicating which carbapenemase is present (e.g., from PCR or WGS) Both phenotypic and genotypic results Other Not sure; do not recall Please answer case questions based on your primary inpatient facility’s formulary. CASE 1: A 57-yo female with a history of recurrent UTIs (otherwise healthy with good renal function) presented to the hospital with UTI symptoms. A urine culture grew Klebsiella pneumoniae resistant to meropenem, ertapenem, nitrofurantoin, TMP/SMX, and ciprofloxacin. a. Indicate which antibiotic you would most realistically choose to treat this patient with cystitis, assuming susceptibility to all of the following (colistin MIC≤2 mcg/ml (I)): amikacin, single dose amikacin, >1 dose cefiderocol ceftazidime-avibactam colistin eravacycline oral fosfomycin imipenem-relebactam meropenem-vaborbactam b. Which of the following 2 factors most influenced your choice? Availability of drug Clinical infection severity Effort to preserve antibiotic activity Familiarity with drug Cost compared to other options Desire to minimize adverse drug events Treatment guidelines Efficacy in primary literature CASE 1 UPDATE: the same patient instead presented with K. pneumoniae pyelonephritis (same susceptibilities). a. Indicate which regimen you would most realistically choose to treat this patient: amikacin, full treatment course cefiderocol ceftazidime-avibactam colistin imipenem-relebactam meropenem-vaborbactam b. Which of the following 2 factors most influenced your choice? Availability of drug Clinical infection severity Effort to preserve antibiotic activity Familiarity with drug Cost compared to other options Desire to minimize adverse drug events Treatment guidelines Efficacy in primary literature CASE 2: A 64-year-old ICU patient with a new fever has peritonitis and an intra-abdominal abscess. Peritoneal fluid culture grows E. coli resistant to meropenem and ertapenem. Blood cultures are negative and carbapenemase testing is pending. Past medical history does not indicate international travel. a. Indicate which regimen you would most realistically choose to treat this patient with intra-abdominal infection, assuming susceptibility to all of the following (colistin MIC≤2 mcg/ml (I)): cefiderocol ceftazidime-avibactam ceftazidime-avibactam + aztreonam eravacycline imipenem-relebactam meropenem-vaborbactam meropenem (extended infusion) + amikacin meropenem (extended infusion) + colistin tigecycline b. Which of the following 2 factors most influenced your choice? Availability of drug Clinical infection severity Effort to preserve antibiotic activity Familiarity with drug Cost compared to other options Desire to minimize adverse drug events Treatment guidelines Efficacy in primary literature CASE 2 UPDATE: The lab reports that carbapenemase testing detects the presence of blaNDM for this isolate. a. Indicate which regimen you would most realistically choose to treat this patient with an NDM intra-abdominal infection: cefiderocol ceftazidime-avibactam + aztreonam colistin eravacycline tigecycline b. Which of the following 2 factors most influenced your choice? Availability of drug Clinical infection severity Effort to preserve antibiotic activity Familiarity with drug Cost compared to other options Desire to minimize adverse drug events Treatment guidelines Efficacy in primary literature What are the main reasons you would NOT use the antibiotics below for CRE? Cefiderocol Ceftazidime-avibactam Eravacycline The clinical evidence is not sufficient or is concerning The clinical evidence is not sufficient or is concerning The clinical evidence is not sufficient or is concerning Concern about resistance to this drug Concern about resistance to this drug Concern about resistance to this drug Cost Cost Cost Not on formulary Not on formulary Not on formulary On formulary, but not stocked On formulary, but not stocked On formulary, but not stocked AST for this drug not available to me AST for this drug not available to me AST for this drug not available to me N/A - I do use this drug N/A - I do use this drug N/A - I do use this drug N/A - No/limited experience treating CRE N/A - No/limited experience treating CRE N/A - No/limited experience treating CRE Any final comments about management of CRE infections:

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