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

Outbreak of Klebsiella pneumoniae Carbapenemase-Producing Citrobacter freundii at a Tertiary Acute Care Facility in Miami, Florida

OBJECTIVE To describe the investigation and control of a rare cluster of Klebsiella pneumoniae carbapenemase-producing Citrobacter freundii in a hospital in southern Florida. METHODS An epidemiologic investigation, review of infection prevention procedures, and molecular studies including whole genome sequencing were conducted. RESULTS An outbreak of K. pneumoniae carbapenemase-3-producing C. freundii was identified at a tertiary hospital in Florida in 2014. Of the 6 cases identified, 3 occurred in the same intensive care unit and were caused by the same clone. For 2 of the 3 remaining cases, the isolates had low carbapenem minimum inhibitory concentrations and were unrelated by whole genome sequencing. As a response to the outbreak, supplementary environmental cleaning was implemented, including closure and terminal cleaning of the unit where the 3 cases clustered, in addition to the infection control bundle already in place at the time. No further cases were identified after these additional interventions. CONCLUSIONS Although C. freundii is not a species that commonly demonstrates carbapenem resistance, our findings suggest that carbapenemase-producing C. freundii may be underdetected even when active surveillance is in place and has a potential to cause hospital outbreak. Infect Control Hosp Epidemiol 2017;38:320-326

Carbapenem-Resistant Acinetobacter baumannii

OBJECTIVETo concomitantly determine the differential degrees of air and environmental contamination by Acinetobacter baumannii based on anatomic source of colonization and type of ICU layout (single-occupancy vs open layout).DESIGNLongitudinal prospective surveillance study of air and environmental surfaces in patient rooms.SETTINGA 1,500-bed public teaching hospital in Miami, Florida.PATIENTSConsecutive A. baumannii–colonized patients admitted to our ICUs between October 2013 and February 2014.METHODSAir and environmental surfaces of the rooms of A. baumannii–colonized patients were sampled daily for up to 10 days. Pulsed-field gel electrophoresis (PFGE) was used to type and match the matching air, environmental, and clinical A. baumannii isolates.RESULTSA total of 25 A. baumannii–colonized patients were identified during the study period; 17 were colonized in the respiratory tract and 8 were colonized in the rectum. In rooms with rectally colonized patients, 38.3% of air samples were positive for A. baumannii; in rooms of patients with respiratory colonization, 13.1% of air samples were positive (P=.0001). In rooms with rectally colonized patients, 15.5% of environmental samples were positive for A. baumannii; in rooms of patients with respiratory colonization, 9.5% of environmental samples were positive (P=.02). The rates of air contamination in the open-layout and single-occupancy ICUs were 17.9% and 21.8%, respectively (P=.5). Environmental surfaces were positive in 9.5% of instances in open-layout ICUs versus 13.4% in single-occupancy ICUs (P=.09).CONCLUSIONSAir and environmental surface contaminations were significantly greater among rectally colonized patients; however, ICU layout did not influence the rate of contamination.Infect Control Hosp Epidemiol 2016;37:777–78

Contamination of Ambient Air with Acinetobacter baumannii on Consecutive Inpatient Days

Acinetobacter-positive patients had their ambient air tested for up to 10 consecutive days. The air was Acinetobacter positive for an average of 21% of the days; the rate of contamination was higher among patients colonized in the rectum than in the airways (relative risk [RR], 2.35; P = 0.006). Of the 6 air/clinical isolate pairs available, 4 pairs were closely related according to rep-PCR results

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

Multicenter Evaluation of Ceftolozane/Tazobactam for Serious Infections Caused by Carbapenem-Resistant Pseudomonas aeruginosa

A multicenter, retrospective study of patients infected with carbapenem-resistant Pseudomonas aeruginosa who were treated with ceftolozane/tazobactam was performed. Among 35 patients, pneumonia was the most common indication and treatment was successful in 26 (74%). Treatment failure was observed in all cases where isolates demonstrated ceftolozane-tazobactam minimum inhibitory concentrations ≥8 μg/mL

Impact of Cytomegalovirus Viral Load on Probability of Spontaneous Clearance and Response to Preemptive Therapy in Allogeneic Stem Cell Transplantation Recipients

•Self-resolved viremia is uncommon when CMV DNA levels reach the ≥150 IU/mL cutoff.•Duration of viremia is shorter when starting CMV preemptive therapy at <350 IU/mL.•Starting preemptive therapy at <350 IU/mL does not increase the risk of cytopenias.•Eradication of CMV viremia by treatment day 35 is associated with reduced NRM.•Refractory CMV viremia is associated with a high mortality rate after HCT. The optimal viral load threshold at which to initiate preemptive cytomegalovirus (CMV) therapy in hematopoietic cell transplantation (HCT) recipients remains to be defined. In an effort to address this question, we conducted a retrospective study of 174 allogeneic HCT recipients who underwent transplantation at a single center between August 2012 and April 2016. During this period, preemptive therapy was initiated at the discretion of the treating clinician. A total of 109 patients (63%) developed CMV viremia. The median time to reactivation was 17 days (interquartile range, IQR, 7-30 days) post-HCT. A peak viremia ≥150 IU/mL was strongly associated with a reduced probability of spontaneous clearance (relative risk, .16; 95% confidence interval, .1-.27), independent of established clinical risk factors, including CMV donor serostatus, exposure to antithymocyte globulin, and underlying lymphoid malignancy. The median time to clearance of viremia was significantly shorter in those who started therapy at CMV 350 IU/mL (44% versus 57%; P = .42). Unresolved CMV viremia by treatment day 35 was associated with increased risk of therapeutic failure (32% versus 0%; P = .001). Achieving eradication of CMV viremia by treatment day 35 was associated with a 74% reduction in 1-year nonrelapse mortality (NRM) (adjusted hazard ratio [HR], .26; 95% confidence interval [CI], .1-.8; P = .02), whereas therapeutic failure was associated with a significant increase in the probability of 1-year NRM (adjusted HR, 26; 95% CI, 8-87; P 80% reduction in the probability of spontaneous clearance independent of ATG administration, CMV donor serostatus, and lymphoid malignancy, and is a reasonable cutoff for preemptive therapy. Delaying initiation of therapy until a CMV value ≥350 IU/mL is associated with more protracted CMV viremia, and unresolved viremia by treatment day 35 is associated with a significant increase in NRM