Abstract Background Recently, comparative phylogenetics dictated the formerly named Enterobacter aerogenes be separated from the genus Enterobacter and renamed Klebsiella aerogenes (KA); however, it remains unclear whether the genotypic differences responsible for the reclassification translate into clinical differences. We aimed to evaluate clinical characteristics and outcomes of patients colonized or infected with carbapenem-resistant (CR) Enterobacter cloacae complex (ECC) or CR KA. Methods We conducted a nested, case-control study of patients hospitalized from May 9th, 2016 until November 11th, 2019 and enrolled in The Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacterales II (CRACKLE-2). Cases were patients with an index culture with CR KA and controls were patients with an index culture positive for CR ECC, matched to each case by: 1) country, 2) anatomical source, 3) infection vs. colonization, and 4) availability/result of whole genome sequencing for the isolate. Where WGS was available the pan-genome Ortholog Clustering Tool was used to identify flexible genomic islands (FGI) associated with KA (n=65) versus ECC (n=66). Results Cases with CR KA (n=95) were matched with 95 controls with CR ECC. 49% of cultures met infection criteria. When compared with control patients, cases with KA were less likely to have liver disease (6% vs. 19%,p=0.009) but more likely to have been admitted for longer at the time of culture (median [IQR] 16[1,32] vs. 7[1,23]), have a Pitt score ≥ 4 (53% vs. 38%, p=0.041), and to have been in an intensive care unit (ICU) at the time of culture (54% vs. 45%, p=0.246) (Table 1). 30-day mortality (21% vs. 25%, p=0.492), 90-day mortality (26% vs. 35% p=0.208), and 30-day DOOR outcomes (p=0.727) did not differ between cases and controls for all patients (Figure 1, 2). There were 94 unique FGI containing 216 putative virulence factors for KA versus 77 and132 for ECC. Conclusion Despite significant differences in baseline characteristics and in the putative virulence genes present, clinical outcomes are similar in patients with CR KA and CR ECC colonization and infection (alive without events 37% vs. 36%). Disclosures Michael J. Satlin, MD, AbbVie: DSMB participant|bioMerieux: Grant/Research Support|Merck: Grant/Research Support|Selux Diagnostics: Grant/Research Support|SNIPRBiome: Grant/Research Support Keith S. Kaye, MD, MPH, Allecra: Advisor/Consultant|CARB-X: Advisor/Consultant|GSK: Advisor/Consultant|Merck: Advisor/Consultant|Shionogi: Advisor/Consultant|Spero: Advisor/Consultant Carol Hill, PhD, Glaxo SmithKline: Retirement Health, Cash Balance Plan|Glaxo SmithKline: Stocks/Bonds (Public Company) David van Duin, MD, PhD, Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Qpex: Advisor/Consultant|Roche: Advisor/Consultant|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support
Read full abstract