2784. Rates of Susceptibility and Heteroresistance to Novel Antibiotic Combinations in Carbapenem-Resistant Enterobacterales Isolates - Emory Healthcare, 2016-2021
Authors: Lin Christina K , Page Alex M , Lohsen Sarah , Babiker Ahmed , Jacob Jesse T , Satola Sarah W , Howard-Anderson Jessica 
Published: November 2023

Abstract

Background
CRE infections are frequently treated with new beta-lactam/beta-lactamase inhibitors (BL/BLI): imipenem-relebactam (I-R), ceftazidime-avibactam (CZA), and meropenem-vaborbactam (MVB). However, the frequency of susceptibility and heteroresistance (HR), defined as the presence of an antibiotic-resistant subpopulation within a primary susceptible population, to these newer antibiotics is unknown. Here we evaluate rates of susceptibility and HR to newer BL/BLI in a convenience sample of clinical CRE isolates as potential reasons for clinical failure.

Methods
We created an antibiogram for carbapenem-resistant Enterobacter cloacae, Escherichia coli and Klebsiella pneumoniae isolates collected between 2016–2021 as part of routine clinical care from two &gt;500-bed academic hospitals. We tested the first isolate per patient for susceptibility to I-R, CZA, and MVB by broth microdilution. We used population analysis profiling (PAP) to test for HR to CZA and I-R.

Results
Of 328 CRE isolates, 74 (22%) were from sterile sites, 151 (46%) from urine, 43 (13%) from the respiratory tract, and 60 (18%) from other non-sterile sites. For E. cloacae (n=152), 93% were susceptible to I-R, 98% to CZA, and 99% to MVB. For E. coli (n=53), 89% were susceptible to I-R, 94% to CZA, and 93% to MVB. For K. pneumoniae (n=123), 90% were susceptible to I-R, 94% to CZA, and 93% to MVB (Table 1). Over time, decreases in the activity of all 3 BL/BLI were noted. Compared to 2016, the percentage of susceptible CRE isolates decreased by 11% (98% to 87%) for I-R, 7% (98% to 91%) for CZA, and 8% (98% to 90%) for MVB (Figure 1). The percentage of isolates with HR to CZA was 7.2% for E. cloacae, 1.9% for E. coli, and 4.9% for K. pneumoniae. For I-R, the percentage of HR isolates was 4.1% for E. cloacae, 9.6% for E. coli, and 10.3% for K. pneumoniae.Table 1.Proportion of carbapenem-resistant Enterobacterales isolates susceptible to new beta-lactam/beta-lactamase inhibitors in two academic hospitals. N = number of antibiotic susceptible isolates, followed by percentage (%) of susceptible isolates. Asterisk (*) indicates if not all isolates were tested against the specified antibiotic. I-R = imipenem-relebactam CZA = ceftazidime-avibactam MVB = meropenem-vaborbactam
The percent susceptibility of carbapenem-resistant Enterobacterales isolates to the specified antibiotic was graphed per year for all isolates and by individual species. The isolates from two academic hospitals were combined. I-R Sus % = Percent susceptibility to imipenem-relebactam MVB Sus % = Percent susceptibility to meropenem-vaborbactam CZA Sus % = Percent susceptibility to ceftazidime-avibactam

Conclusion
In our study on the activity of newer BL/BLI against CRE, susceptibility remains high and HR is rare. While newer BL/BLIs remain highly active against CRE, the observed decrease in susceptibility over time suggests a need for ongoing antibiotic stewardship.

Disclosures
Ahmed Babiker, MBBS, Roche: Advisor/Consultant