788. Enterobacter cloacae Infection Characteristics and Outcomes in Military Personnel who Sustained Trauma in Iraq and Afghanistan

Abstract Background Enterobacter cloacae is a Gram-negative rod with chromosomally-induced Amp-C β-lactamase with multidrug-resistant potential. Joint Trauma System guidelines for treating combat wounds include prophylaxis with cefazolin and ertapenem, potent inducers of Amp-C. We evaluated clinical characteristics, antibiotic utilization, and outcomes associated with battlefield-related E. cloacae infections. Methods All initial solitary (those with single isolates) and serial E. cloacae isolates (≥24 hours from initial isolate from any site) were collected from the Trauma Infectious Disease Outcomes Study (6/2009-12/2014). Inclusion required E. cloacae isolation from a clinical infection. Amp-C-inducing β-lactams were classified based on induction potential and lability to the Amp-C β-lactamase as Amp-C induction levels. Results Of 653 E. cloacae isolates, 253 met inclusion criteria – 64 patients had only initial isolates, 54 patients had serial isolates. Patients were largely male (99%), median age 23 years (IQR 21-27), with injury severity score of 34 (IQR 24-45). Initial isolates were wound (70%), respiratory (22%), blood (7%), urine (1%), and other (1%). Patients commonly had blast injuries (89%), required ICU admission (95%), and had a median hospital stay of 57 days (IQR 39-82). Patients with serial isolates showed a trend towards earlier clinical infection (5 vs 8 days, P = 0.07). They were also less likely to receive carbapenems prior to E. cloacae isolation compared to those with only initial isolates (4% vs 38%) and more likely to receive 1st generation cephalosporins (79% vs 58%, P = 0.01). The serial isolate group received more days of 1st generation cephalosporins (median 6 days vs 2.5 days, P = 0.01). Cumulative antimicrobial therapy trended towards significance and was greater with the serial isolates (median 100 days vs 74 days, P = 0.08). There was no difference in number of surgical interventions between those with and without serial isolates (P = 0.54). Overall, 6 patients died. Conclusion E. cloacae infections after battlefield trauma were frequently encountered and associated with exposure to 1st generation cephalosporins. Serial infections did not correlate to worse patient outcomes but displayed a trend towards an overall greater duration of antibiotic use. Disclosures William N. Bennett, V, MD, Abbvie (Shareholder)Amgen (Shareholder)Nabriva (Shareholder)


Clinical and Genomic Epidemiology of mcr-9 Containing Carbapenemresistant Enterobacterales
Background. Colistin is a last-resort antibiotic for multidrug resistant gram-negative infections. Recently, a new allele of the mobile colistin resistance (mcr) gene family designated mcr-9, has been reported. However, its clinical and phenotypic significance remains unclear.
Methods. The Centers for Diseases Control and Prevention-funded Georgia Emerging Infections Program (EIP) performs population-and laboratory-based surveillance for CRE isolated from sterile sites or urine in metropolitan Atlanta, GA including standardized chart abstraction. We queried genomes of carbapenem-resistant Enterobacterales (CRE) for mcr-9 from a convenience sample of Georgia EIP clinical isolates between 2012-2017. Isolates underwent phenotypic characterization by broth microdilution and population analysis profiling. Nine available E. cloacae (two mcr-9 positive, seven mcr-9 negative) genomes from the National Institutes of Health were included in downstream genomic analysis. Fastq files underwent de novo assembly, annotation and AMR and virulence gene prediction, pan-genome association analysis, pairwise comparisons of average nucleotide identity and phylogenetic tree construction based on core genes. We compared characteristics and outcomes of mcr-9 positive and negative CRE cases.

Figure
Legend 1: Phylogeny and average nucleotide identity heatmap of mcr-9 positive (n=13) and mcr-9 negative (n=14) E. cloacae from Georgia Emerging Infection program in addition to 9 available E. cloacae (two mcr-9 positive, seven mcr-9 negative) from the National Institutes of Health. A phylogenetic tree based on a core gene alignment containing 1,904 genes defined using Roary v3.13.0. was generated using IQtree v2.0.3. A maximum likelihood tree was generated by running 1,000 bootstrap replicates under the generalized time-reversible model of evolution. The tree was visualized and annotated using Interactive Tree of Life (iTOL) v4. Pairwise comparisons of average nucleotide identity on the assembled genomes were performed with the Mashmap method using fastANI v1.32. Abbreviations: GA EIP: Georgia Emerging Infection Program, NIH: National Institutes of Health, Background. Enterobacter cloacae is a Gram-negative rod with chromosomally-induced Amp-C β-lactamase with multidrug-resistant potential. Joint Trauma System guidelines for treating combat wounds include prophylaxis with cefazolin and ertapenem, potent inducers of Amp-C. We evaluated clinical characteristics, antibiotic utilization, and outcomes associated with battlefield-related E. cloacae infections.
Methods. All initial solitary (those with single isolates) and serial E. cloacae isolates (≥24 hours from initial isolate from any site) were collected from the Trauma Infectious Disease Outcomes Study (6/2009-12/2014). Inclusion required E. cloacae isolation from a clinical infection. Amp-C-inducing β-lactams were classified based on induction potential and lability to the Amp-C β-lactamase as Amp-C induction levels.
Conclusion. E. cloacae infections after battlefield trauma were frequently encountered and associated with exposure to 1 st generation cephalosporins. Serial infections did not correlate to worse patient outcomes but displayed a trend towards an overall greater duration of antibiotic use.

Susceptibility of Phenotypic Subsets of Pseudomonas aeruginosa Isolates to Cefiderocol and Comparator Agents from SIDERO-WT 2014-2019
Results. The different phenotypic subsets and susceptibility of tested compounds are shown in the table. Among 7700 PsA isolates, 47.7% and 23% were from respiratory and gastrointestinal sources of infection. CFDC inhibited 97.5% and 99.9% of all PsA at its FDA-S and CLSI-S MIC breakpoint of ≤1 and ≤4, respectively. CFDC had the lowest MIC 90 of all tested agents and >99% S at an MIC ≤4 for all phenotypic subsets. At a MIC ≤1, CFDC displayed high susceptibility rates against all subsets including ≥88% S against CZA-NS, C/T-NS, I/R-NS, and MEM+I/R-NS isolates. Against MDR subsets, comparator agents consistently demonstrated lower activity than CFDC; 88% of MEM+C/T-NS and MEM+CZA-NS isolates had a CFDC MIC≤1 while 15.6% and 20.3% were S to I/R, respectively. 86% of MEM+CZA+C/T-NS and 80.4% CZA+C/ T+I/R-NS isolates were S to CFDC. CFDC inhibited 98.1% and 99.4% of PsA isolates from NA (n = 3548) at a MIC of ≤1 and ≤4, respectively. In NA isolates that were MEM+C/T-NS; 85.7% of PsA isolates had a MIC ≤1 to CFDC and 33.3% and 28.6% were S to CZA and I/R, respectively. Background. Carbapenemase-producing Enterobacteriaceae (CPE) poses a great challenge in infection control in healthcare settings. A screening and contact precautions are recommended to prevent the spread of CPE among patients. However, screening strategies differ among countries and healthcare facilities.
Methods. In September 2018, we launched a CPE screening program at a 660bed hospital in South Korea, which targeted previously colonized patients, patients with history of admission < 1 month or transferred patients or ICU-admitted patients. Once patients were identified to have CPE, they were isolated in a single room. After a CPE outbreak in July-Aug 2019, the enhanced screening program was implemented, which included patients with additional risk factors (exposure to hospitals in the past 6 months, receipt of hemodialysis or invasive procedures or rehabilitation) combined with weekly screening in ICU-admitted patients. Screening methods changed from two consecutive rectal screening swabs with chromogenic agar to initial screening with Xpert-Carba-R PCR, followed by one or two consecutive tests with chromogenic agar. We compared the CPE incidence in screening and clinical cultures before and after the enhanced screening program introduction (Sep 2018-Nov 2020. Results. A total of 14,318 (2,178 vs. 12,140) were screened among 49,980 admitted patients and screening compliance increased from 18.6% to 94.5%. The number of CPE detection increased from 44 to 154 cases and the proportion of CPE-positive screening per 1000 admissions increased 0.6 to 2.2. However, the number of clinical CPE cultures decreased from 11 to 3 (Figure). Among screened patients, time-to-positivity was markedly reduced by 1.9 days (2.96 vs. 1.02 days) during the post-period. Additional 70 patients were detected: 36 due to serial screening in the ICUs and 34 due to enhanced on-admission screening. Factors significantly associated with positive screening were previous exposure to hospital (OR 3.5; 95% CI 1.7-7.1) and receipt of hemodialysis (OR 4.3; 95%CI 1.9-9.2). CPE isolates and carbapenemase genes were diverse (Figure). Trends in CPE detection in screening and clinical samples (upper), and bacterial species with detected carbapenemase genes (lower).