A Prospective Randomized Clinical Trial to Assess Antibiotic Pocket Irrigation on Tissue Expander Breast Reconstruction

Bacterial infection is the most common complication following staged post-mastectomy breast reconstruction initiated with a tissue expander (TE). to limit bacterial infection, antibiotic irrigation of the surgical site is commonly performed despite little high-quality data to support this practice. We performed a prospective randomized control trial to compare the impact of saline irrigation alone to a triple antibiotic irrigation regimen (1 g cefazolin, 80 mg gentamicin, and 50,000 units of bacitracin in 500 mL of saline) for breast implant surgery. The microbiome in breasts with cancer

Liax Is a Surrogate Marker For Cell Envelope Stress and Daptomycin Non-Susceptibility in Enterococcus Faecium

Daptomycin (DAP) is often used as a first-line therapy to treat vancomycin-resistan

Contemporary Clinical and Molecular Epidemiology of Vancomycin-Resistant Enterococcal Bacteremia: A Prospective Multicenter Cohort Study (VENOUS I)

Background Vancomycin-resistant enterococci (VRE) are major therapeutic challenges. Prospective contemporary data characterizing the clinical and molecular epidemiology of VRE bloodstream infections (BSIs) are lacking. Methods The Vancomycin-Resistant Enterococcal BSI Outcomes Study (VENOUS I) is a prospective observational cohort of adult patients with enterococcal BSI in 11 US hospitals. We included patients with Enterococcus faecalis or Enterococcus faecium BSI with >= 1 follow-up blood culture(s) within 7 days and availability of isolate(s) for further characterization. The primary study outcome was in-hospital mortality. Secondary outcomes were mortality at days 4, 7, 10, 12, and 15 after index blood culture. A desirability of outcome ranking was constructed to assess the association of vancomycin resistance with outcomes. All index isolates were subjected to whole genome sequencing. Results Forty-two of 232 (18%) patients died in hospital and 39 (17%) exhibited microbiological failure (lack of clearance in the first 4 days). Neutropenia (hazard ratio [HR], 3.13), microbiological failure (HR, 2.4), VRE BSI (HR, 2.13), use of urinary catheter (HR, 1.85), and Pitt BSI score >= 2 (HR, 1.83) were significant predictors of in-hospital mortality. Microbiological failure was the strongest predictor of in-hospital mortality in patients with E faecium bacteremia (HR, 5.03). The impact of vancomycin resistance on mortality in our cohort changed throughout the course of hospitalization. Enterococcus faecalis sequence type 6 was a predominant multidrug-resistant lineage, whereas a heterogeneous genomic population of E faecium was identified. Conclusions Failure of early eradication of VRE from the bloodstream is a major factor associated with poor outcomes. Failure to eradicate enterococci from the bloodstream in the first 4 days after the index blood culture was the most consistent factor associated with increased risk of mortality. The association of vancomycin resistance with mortality changed throughout the course of the hospitalization

Multisite Detection of Tn1549-Mediated vanB Vancomycin Resistance in Multidrug-Resistant Enterococcus faecalis ST6 in Texas and Florida

In the United States, vanB-mediated resistance in enterococci is rare. We characterized three sequence type (ST) 6, vancomycin-resistant Enterococcus faecalis isolates causing bacteremia in unique patients in spatiotemporally distinct settings. In the United States, vanB-mediated resistance in enterococci is rare. We characterized three sequence type (ST) 6, vancomycin-resistant Enterococcus faecalis isolates causing bacteremia in unique patients in spatiotemporally distinct settings. Isolates were recovered between 2018 and 2020 in two cities in the United States (Houston, TX; Miami, FL). The isolates harbored the vanB operon on a chromosomally located Tn1549 transposon, and epidemiological data suggested multiple introductions of the vanB gene cluster into ST6 E. faecalis

242. Evaluation of PBP4 promoter variation and clinical outcomes in patients with Enterococcus faecalis bacteremia

Abstract Background Penicillin-binding protein 4 (PBP4) is a low affinity PBP that has been associated with decreased susceptibility to penicillins in Enterococcus faecalis (Efs). Changes in the promoter region leading to increased expression of the pbp4 gene contribute to this phenotype. There is limited data on the clinical outcome of patients infected with these strains in the U.S. We investigated the clinical outcomes of patients with Efs bacteremia stratified by PBP4 promoter type and piperacillin MIC. Methods Index Efs bloodstream isolates from 167 patients were selected from the VENOUS cohort (2016-2021). Whole genome sequencing was performed on all isolates and changes in the promoter region (200 bp upstream of the start codon) were identified, using Efs JH2-2 as reference. β-lactam susceptibility (ampicillin, penicillin, and piperacillin [PIP]) was performed on all isolates by broth microdilution. Clinical outcomes (in-hospital mortality, microbiologic failure, and recurrence) were collected on all patients. Results The median age for the cohort was 65 years (IQR: 56-72), and 63.5% were male. The median length of hospitalization was 13 days (IQR: 8-22). The duration of bacteremia was 3 days (IQR: 2-4) and 8.98% of patients had prolonged bacteremia (≥ 7 days). Among 167 isolates, 4 major primary promoter variants were identified: reference JH2-2 (n=66), ΔA88 (n=43), A175C (n=35), and insA192 (n=20). All strains were susceptible to ampicillin and penicillin. A PIP MIC ≥ 16 mg/L (non-susceptible) was found in 74.4% of strains with the ΔA88 promoter, as compared to 22.7% of reference, 17.1% of A175C, and 10% of insA192 (p < 0.001). Clinical outcomes of the 167 patients are shown in Table 1. PIP non-susceptibility was associated with immunocompromise state (49.09% vs 23.85%, p=0.001), history of hematological cancer (40% vs 16.51%, p=0.002), and recurrence (7.27% vs 0.92%, p=0.044). There was no statistical difference in mortality or microbiologic failure. Conclusion Isolates with ΔA88 PBP4 promoter variants were associated with PIP non-susceptibility. While in-hospital mortality and microbiologic failure were similar between all patients, those who were infected with a PIP non-susceptible strain were more likely to experience a recurrence. Disclosures Marcus Zervos, MD, Contrafect: Advisor/Consultant|GSK: Grant/Research Support|Johnson and Johnson: Grant/Research Support|Pfizer: Grant/Research Support Lilian M. Abbo, MD, MBA, Ferring: Advisor/Consultant|Pfizer: Advisor/Consultant|Regeneron: Grant/Research Support|Shionogi: Advisor/Consultant William R. Miller, M.D, Merck: Grant/Research Support|UpToDate: Honorari

622. The Accessory Genome in Enterococcal Bacteremia: Results from the Vancomycin-Resistant Enterococcal Bacteremia Outcomes Study (VENOUS)

Abstract Background Vancomycin-resistant enterococci (VRE) are a major cause of nosocomial bloodstream infections. Enterococci exhibit remarkable genomic plasticity and can recombine through the acquisition of genetic material via mobile genetic elements (MGEs), including resistance genes. The accessory genome plays a major role in the evolution of enterococci within the human host. Thus, dissecting the entire genome (pan-genome) is of paramount importance to characterize the population structure of enterococci causing disease. Methods VENOUS is an ongoing prospective, observational study of adults with enterococcal bacteremia. From September 2016 to March 2018, E. faecalis (Efs) and E. faecium (Efm) were collected in 14 hospitals of a single hospital system and a major cancer center in Houston, TX, and a general hospital in Detroit, MI. Short- and long-read genomic sequencing were performed with Illumina MiSeq and Oxford Nanopore Technologies GridION X5, respectively. A proprietary bioinformatics pipeline was utilized for genome assembly and further analyses. Results 156 Efs and 98 Efm isolates from single patients were analyzed. The average proportion of core genes in each genome was 64.6% (53.0–74.1) and 49.1% (45.2–51.0) for Efs and Efm, respectively. The vanA gene cluster was identified in 5.1% (8/157) of Efs and 57.1% (56/98) of Efm. The plasmid-encoded aac(6′)-Ie-aph(2″)-Ia gene conferring high-level resistance to aminoglycosides was found in 37.6% (59/157) Efs, seven of which also possessed vanA. Long-read sequencing of vanA-harboring plasmids from a subset of VRE revealed that the vanA cluster was carried in plasmids ranging from 31.7 to 132.3 kb. Although the vanA operon was fairly conserved, insertions of MGE were identified in the intergenic regions of vanS/vanH and vanX/vanY. Furthermore, a variety of MGE insertions mediated integration of the vanA operon, including IS1216 and IS256 (figure). Conclusion Accessory genes, including AMR genes, comprise a significant proportion of the enterococcal pan-genome, indicating major genetic plasticity within these organisms. Acquired resistance genes seem to have a high degree of recombination and play a substantial role in the expansion of the genomic repertoire in clinical isolates. Disclosures Samuel L. Aitken, PharmD, Melinta Therapeutics: Grant/Research Support, Research Grant; Merck, Sharpe, and Dohme: Advisory Board; Shionogi: Advisory Board