Arias, César A.

Abstract Background Carbapenem-resistant Enterobacterales (CRE) and specifically Klebsiella pneumoniae (CRKp) are a global threat. CRE rapidly spreading in a healthcare network may infect a distinct patient cohort or have higher virulence. We determined the impact of cluster assignment of CRKp on transmission dynamics and clinical outcomes. Methods CRACKLE-2 is a multi-site, prospective, observational cohort study of hospitalized patients with a clinical CRE culture from any anatomic site. We analyzed 351 patients enrolled 4/30/2016–8/31/2017 in 42 US hospitals with clonal group 258 CRKp. Static clusters were set as ≤ 21 core single nucleotide polymorphisms (SNPs), identified by Snippy, and sharing a recent common ancestor, using a maximum likelihood phylogeny (RAxML v8.2.4). Dynamic clusters were set as > 80% probability of being within 3 transmissions by the R program transcluster (λ = 4, β = 1.6). Clinical outcome was assessed by desirability of outcome ranking with best outcome as alive without events and worst outcome as death. Events were no clinical response, unsuccessful discharge, and adverse events. We compared patients in and out of clusters. For patients in clusters, we also compared intra- vs inter-hospital clusters. Results In total, there were 49 static (median: 5, IQR: 2, 8) and 45 dynamic clusters (median: 5, IQR: 2, 20). For static clusters, 176 patients (50%) were in clusters with 82 (47%) patients in intra-hospital clusters. A higher proportion of patients in clusters, vs not in clusters, had a CRKp culture > 3 days from admission (P = 0.037). More patients in inter-hospital, vs intra-hospital, clusters had diabetes (P = 0.02). For dynamic clusters, 179 patients (51%) were in clusters with 69 (39%) patients in intra-hospital clusters. A lower proportion of patients in clusters, vs not in clusters, had CRKp isolated from urine (P = 0.04). More patients in inter-hospital, vs intra-hospital, clusters had a CRKp culture 3 days from admission (P = 0.04). Clinical outcomes were the same for patients in clusters vs not in clusters for static and dynamic clusters. Conclusion This analysis shows that clinical outcomes are independent of clustering assignment. Static clustering better represented nosocomial spread, based on a higher proportion of patients in clusters having a later CRKp culture. Disclosures Gregory Weston, MD MSCR, Allergan (Grant/Research Support) W. Charles Huskins, MD, MSc, ADMA Biologics (Consultant)Pfizer, Inc (Consultant) Jason C. Gallagher, PharmD, Allergan (Consultant)Astellas (Consultant)Merck (Consultant)Nabriva (Consultant)Qpex (Consultant)scPharmaceuticals (Consultant)Shionogi (Consultant)Spero (Consultant)Tetraphase (Consultant) Robert A. Bonomo, MD, Entasis, Merck, Venatorx (Research Grant or Support) Cesar A. Arias, MD, MSc, PhD, FIDSA, Entasis Therapeutics (Scientific Research Study Investigator)MeMed (Scientific Research Study Investigator)Merck (Grant/Research Support) David van Duin, MD, PhD, Achaogen (Advisor or Review Panel member)Allergan (Advisor or Review Panel member)Astellas (Advisor or Review Panel member)MedImmune (Advisor or Review Panel member)Merck (Advisor or Review Panel member)NeuMedicine (Advisor or Review Panel member)Qpex (Advisor or Review Panel member)Roche (Advisor or Review Panel member)Sanofi-Pasteur (Advisor or Review Panel member)Shionogi (Advisor or Review Panel member)T2 Biosystems (Advisor or Review Panel member)Tetraphase (Advisor or Review Panel member)

Plazomicin was tested against 697 recently acquired carbapenem-resistant Klebsiella pneumoniae isolates from the Great Lakes region of the United States. Plazomicin MIC 50 and MIC 90 values were 0.25 and 1 mg/liter, respectively; 680 isolates (97.6%) were susceptible (MICs of ≤2 mg/liter), 9 (1.3%) intermediate (MICs of 4 mg/liter), and 8 (1.1%) resistant (MICs of >32 mg/liter). Resistance was associated with rmtF -, rmtB -, or armA -encoded 16S rRNA methyltransferases in all except 1 isolate.

Objective Microbiome analyses now allow precise determination of the sinus microbiota of patients with exacerbations of chronic rhinosinusitis (CRS). The aim of this report is to describe the sinus microbiota of acute exacerbations in CRS clinical subgroups (with nasal polyps [CRSwNP], without nasal polyps [CRSsNP], and allergic fungal rhinosinusitis [AFRS]). Study Design Retrospective chart review. Setting Tertiary rhinology practice. Subjects and Methods A retrospective review was performed of all patients whose sinus microbiota were assayed via a commercially available microbiome technology during an acute CRS exacerbation during the 2‐year period ending December 31, 2016. All samples were sinus aspirates collected under endoscopic visualization in clinic. Results Samples from a total of 134 patients (65 CRSsNP, 55 CRSwNP, and 14 AFRS) were reviewed. The observed richness (number of taxa >2% relative abundance) ranged between 1 and 11 taxa, with an average of 3 taxa per specimen. The most common bacteria in all groups were Staphylococcal spp (including Staphylococcus aureus ), Streptococcus spp, Pseudomonas spp, and Escherichia spp. S aureus had an increased prevalence in CRSsNP and AFRS as compared with CRSwNP. Otherwise, the sinus microbiota were markedly similar among all 3 clinical subgroups. Conclusions Many bacterial types are identified during acute CRS exacerbation according to DNA‐based detection techniques. Bacterial richness was remarkably low in all samples. Few differences in the patterns among clinical subgroups were observed. Further investigation is warranted to determine the clinical significance of these observations and their role in current clinical algorithms.