177. Distinctive Features of Ertapenem Mono-Resistant Carbapenem-Resistant Enterobacterales in the United States: A Cohort Study

Abstract Background Carbapenem-resistant Enterobacterales (CRE) are highly antibiotic-resistant bacteria. Whether CRE resistant only to ertapenem among carbapenems (ertapenem mono-resistant) represent a unique CRE subset with regards to risk factors, carbapenemase genes, and outcomes is unknown. Methods We analyzed laboratory- and population-based surveillance data from nine sites participating in CDC’s Emerging Infections Program (EIP). We defined an incident case as the first isolation of Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, K. oxytoca, K. pneumoniae, or K. variicola resistant to doripenem, ertapenem, imipenem, or meropenem (determined at clinical laboratory) from a normally sterile site or urine identified from a resident of the EIP catchment area in 2016-2017. We compared risk factors, carbapenemase genes (determined via polymerase chain reaction at CDC), and mortality of cases with ertapenem “mono-resistant” to “other” CRE (resistant to ≥ 1 carbapenem other than ertapenem). We additionally conducted survival analysis to determine the effect of ertapenem mono-resistant status and isolate source (sterile vs. urine) on survival. Results Of 2009 cases, 1249 (62.2%) were ertapenem mono-resistant and 760 (37.8%) were other CRE (Figure 1). Ertapenem mono-resistant CRE cases were more frequently ≥ 80 years old (29.1% vs. 19.5%, p< 0.0001), female (67.9% vs 59.0%, p< 0.0001), and white (62.6% vs. 45.1%, p< 0.0001). Ertapenem mono-resistant isolates were more likely than other CRE to be Enterobacter cloacae complex (48.4% vs. 15.4%, p< 0.0001) but less likely to be isolated from a normally sterile site (7.1% vs. 11.7%, p< 0.01) or have a carbapenemase gene (2.4% vs. 47.4%, p< 0.0001) (Figure 2). Ertapenem mono-resistance was not associated with difference in 90-day mortality (unadjusted odds ratio [OR] 0.82, 95% confidence interval [CI] 0.63-1.06) in logistic models or survival analysis (Figure 3). Figure 1. Flow diagram of carbapenem-resistant Enterobacterales cases included in analysis, 2017-2018. CRE, carbapenem-resistant Enterobacterales; MIC, minimum inhibitory concentration. Ertapenem mono-resistant CRE are only resistant to ertapenem (among carbapenems). Other CRE are resistant to ≥1 carbapenem other than ertapenem. We excluded isolates that (1) had no interpretable MICs for any carbapenem, (2) were only tested against ertapenem, (3) had unknown death status, or (4) were not associated with patient’s first incident case. Figure 2. Proportion of ertapenem mono-resistant carbapenem-resistant Enterobacterales (CRE) vs. other CRE isolates with specific carbapenemase genes. KPC, Klebsiella pneumoniae carbapenemase; NDM, New Delhi metallo-ß-lactamase; OXA, oxacillinase. Ertapenem mono-resistant carbapenem-resistant Enterobacterales (CRE) are only resistant to ertapenem (among carbapenems). Other CRE are resistant to ≥1 carbapenem other than ertapenem. Testing via reverse transcriptase polymerase chain reaction. Figure 3. Survival analysis comparing patients with carbapenem-resistant Enterobacterales (CRE) that are ertapenem mono-resistant to other CRE (i.e., resistant to ≥1 carbapenem other than ertapenem), either total (A) or stratified by isolate site (B). Ertapenem mono-resistant) isolates were not associated with decreased mortality, and sterile isolate source (i.e., non-urinary isolates) was associated with increased mortality regardless of ertapenem mono-resistance. Conclusion Ertapenem mono-resistant CRE rarely have carbapenemase genes and have distinct clinical and microbiologic characteristics compared to other CRE. These findings may inform antibiotic choice particularly when testing for carbapenemases is not readily available. Disclosures All Authors: No reported disclosures

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Distinctive Features of Ertapenem Mono-Resistant Carbapenem-Resistant
Methods. We analyzed laboratory-and population-based surveillance data from nine sites participating in CDC's Emerging Infections Program (EIP). We defined an incident case as the first isolation of Enterobacter cloacae complex, Escherichia coli, Klebsiella aerogenes, K. oxytoca, K. pneumoniae, or K. variicola resistant to doripenem, ertapenem, imipenem, or meropenem (determined at clinical laboratory) from a normally sterile site or urine identified from a resident of the EIP catchment area in 2016-2017. We compared risk factors, carbapenemase genes (determined via polymerase chain reaction at CDC), and mortality of cases with ertapenem "mono-resistant" to "other" CRE (resistant to ≥ 1 carbapenem other than ertapenem). We additionally conducted survival analysis to determine the effect of ertapenem mono-resistant status and isolate source (sterile vs. urine) on survival.
Conclusion. Ertapenem mono-resistant CRE rarely have carbapenemase genes and have distinct clinical and microbiologic characteristics compared to other CRE. These findings may inform antibiotic choice particularly when testing for carbapenemases is not readily available.
Disclosures. Background. Carbapenem-resistant Enterobacterales (CRE) have become endemic and cause significant morbidity and mortality globally. The metallo-beta-lactamase gene bla IMP-4 is a key CRE resistance determinant in Australia and Asia but its genomic context remains unknown. We aimed to determine the genomic epidemiology of bla IMP-4 in clinical and environmental isolates from 2008 -2020 at our institution.
Methods. We performed whole genome sequencing on 219 bla IMP-4 -carrying isolates from 134 patients (219 short-read and 75 long-read). Multi-locus sequence types (MLSTs), resistance determinants and plasmid replicons were assessed. High-quality de novo hybrid assemblies were used to identify location of bla IMP-4 gene. We conducted phylogenetic analysis for key MLSTs and plasmids.
Results. Bla IMP-4 was noted on a class I integron also harboring aminoglycoside, sulfamethoxazole, chloramphenicol and quaternary ammonium compound resistance genes. This integron was able to migrate over time to 10 bacterial species (42 STs) and 6 different plasmid types (Figure 1 and Figure 2). From 2008-2020, bla IMP-4 was present on IncC plasmids in Serratia marcescens and Klebsiella pneumoniae. We noted small outbreaks of Pseudomonas aeruginosa ST111 with chromosomal integration of bla IMP-4 from 2008IMP-4 from -2018 and Enterobacter cloacae complex ST114 with bla IMP-4 on IncFIB(K)/ IncFIA(HI1) plasmids from 2011-2020 (19 isolates). From 2016-2020, there was an explosion of diverse IncHI2 plasmids carrying bla IMP-4 . This was driven by clonal expansion of E. cloacae complex ST93/ST190 (79 isolates), with spillover of IncHI2 plasmids to Klebsiella spp (13 isolates), Citrobacter spp (2 isolates), S. marcescens (1 isolate), Escherichia coli (4 isolates). In addition to bla IMP-4 , these plasmids carried mcr-9.1, a colistin resistance gene, and resistance determinants to nearly all key classes of Gram-negative antimicrobials. BlaIMP-4 was noted in diverse bacterial species over the study period. Serratia marcescens and Klebsiella pneumoniae were present throughout. Outbreaks of Enterobacter cloacae complex ST114, ST190 and ST93 and Pseudomonas aeruginosa ST111 were noted. Presence of blaIMP-4 on diverse plasmids that varied through the study period was noted. Plasmids were charaterised by analysing de novo hybrid assembly data and co-location of blaIMP-4 and plasmid replicons on the same contigs.
Conclusion. Bla IMP-4 spread on a class I integron was responsible for endemic carbapenem resistance at our institution. This mobile genetic element was able to persist due to both clonal spread and entry into diverse plasmids. Concerningly, we noted a large outbreak driven by IncHI2 plasmids harboring colistin resistance genes with spread to multiple bacterial species.
Disclosures. All Authors: No reported disclosures