scholarly journals 1247. Molecular Epidemiology of Multi-drug Resistant Klebsiella pneumoniae and K. quasipneumoniae in Qatar

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S712-S712
Author(s):  
Clement Tsui ◽  
Fatma Ben Abid ◽  
Christi L McElheny ◽  
Muna Almaslamani ◽  
Abdullatif Al Khal ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Molecular Epidemiology ◽  
Panel Member ◽  
Research Support ◽  
Review Panel ◽  
Klebsiella Species ◽  
Carbapenem Resistant ◽  
Antimicrobial Resistance Genes ◽  
Encoding Genes ◽  
Serotype K2

Abstract Background The molecular epidemiology of carbapenem-resistant Klebsiella species is not well investigated in Qatar. The objective of this work was to characterize the genetic context of carbapenemase-producing Klebsiella isolates recovered from clinical specimens. Methods Klebsiella isolates (n=100) were collected at 7 tertiary hospitals from 2015-2017. Identification and susceptibility testing were performed using MALDI-TOF MS and BD Phoenix system, respectively. Whole Genome Sequencing was performed on the Illumina NextSeq platform. Phylogenomic analysis, screening of resistance and virulence genes, and comparison of genetic environment of carbapenemase were carried out. Results Klebsiella pneumoniae was common (80), followed by K. quasipneumoniae (16), K. aerogenes (3) and K. oxytoca (1). The most prevalent were genes encoding NDM-1 (39), OXA-48 (20), OXA-232 (10) and OXA-181 (12). KPC-2 (3) and KPC-3 (2) were also identified; no carbapenemase-encoding genes could be identified in 15 isolates. Plasmid locations of 24 carbapenemase-encoding genes were determined; blaNDM-1 was localized on IncFII replicon, while blaOXA-181 and blaOXA-232 were commonly associated with ColKP3 plasmids. pOXA-48-like plasmid was detected in 17/20 isolates harboring blaOXA-48. blaKPC-3 was located on a contig with ‘traditional’ Tn4401a mobile genetic element. Sequence types (STs) were diverse and the ‘traditional’ clonal group (CG) 258 was rare. K. pneumoniae ST147 was predominant (13), followed by ST231 (7) and ST11 (5). Nine K. quasipneumoniae isolates belonged to ST196 and were highly clonal. The virulence loci such as yersiniabactin (ybt) and rmpA were not detected within the study’s K. quasipneumoniae isolates. Amongst K. pneumoniae, there were 50 ybt+ isolates; 8 isolates had rmpA, and of these, 3 belonged to ST383. K. pneumoniae serotype K2, the capsular serotype associated with invasive liver abscess syndrome, was detected in 5 isolates. Genetic relationship of carbapenem-resistant Klebsiella pneumoniae and K. quasipneumoniae isolates in Qatar inferred from core genome SNPs. The tree is overlaid with predicted antimicrobial resistance genes and virulence factors for each isolate. Conclusion The predominant carbapenemases among clinical Klebsiella species isolates in Qatar are NDM and OXA-48 like enzymes, disseminated through various plasmids. The detection of carbapenemase-producing isolate bearing rmpA and serotype K2 reflect the presence of both multidrug resistance and hypervirulence in K. pneumoniae. Disclosures Yohei Doi, MD, PhD, AstraZeneca (Speaker’s Bureau)bioMerieux (Consultant)FujiFilm (Advisor or Review Panel member, Speaker’s Bureau)Gilead (Consultant)GSK (Consultant)Meiji (Consultant)MSD (Consultant)Shionogi (Consultant) Yohei Doi, MD, PhD, Astellas (Individual(s) Involved: Self): Grant/Research Support; AstraZeneca (Individual(s) Involved: Self): Speakers’ bureau; bioMerieux (Individual(s) Involved: Self): Consultant, Speakers’ bureau; Chugai (Individual(s) Involved: Self): Consultant; Entasis (Individual(s) Involved: Self): Consultant; FujiFilm (Individual(s) Involved: Self): Advisor or Review Panel member; Gilead (Individual(s) Involved: Self): Consultant; GSK (Individual(s) Involved: Self): Consultant; Kanto Chemical (Individual(s) Involved: Self): Grant/Research Support; MSD (Individual(s) Involved: Self): Speaking Fee; Pfizer (Individual(s) Involved: Self): Grant/Research Support; Shionogi (Individual(s) Involved: Self): Grant/Research Support, Speakers’ bureau; Teijin Healthcare (Individual(s) Involved: Self): Speakers’ bureau; VenatoRx (Individual(s) Involved: Self): Consultant

scholarly journals 158. Intra- and Inter-hospital Epidemiology of Carbapenem-resistant klebsiella Pneumoniae in US Hospitals

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S208-S209
Author(s):  
Courtney Luterbach ◽  
Liang Chen ◽  
Blake Hanson ◽  
Michelle Earley ◽  
Lauren Komarow ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Clinical Outcomes ◽  
Research Study ◽  
Scientific Research ◽  
Panel Member ◽  
Recent Common Ancestor ◽  
Research Support ◽  
Review Panel ◽  
Carbapenem Resistant ◽  
Study Investigator

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)

scholarly journals 785. Distribution and Associated Mortality in Carbapenem-Resistant Gram-Negative Bacilli in Japan: A Multicenter Study From Multi-Drug Resistant Organisms Clinical Research Network (MDRnet)

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S489-S490
Author(s):  
Sho Saito ◽  
Aki Sakurai ◽  
Kohei Uemura ◽  
Yasufumi Matsumara ◽  
Ryota Hase ◽  
...  
Keyword(s):  
Panel Member ◽  
Mortality Rates ◽  
Research Network ◽  
Drug Resistant ◽  
Survival Curves ◽  
Research Support ◽  
Review Panel ◽  
Gram Negative ◽  
Carbapenem Resistant ◽  
Kaplan Meier

Abstract Background Carbapenem-resistant gram-negative bacilli (CRGNB) are increasingly reported around the world as a cause of serious infections. However, the epidemiology and clinical course of patients with CRGNB in Japan is not well understood. Methods We prospectively collected CR cases from 4/2019 to 9/2020 in Multi-Drug Resistant organisms clinical research network (MDRnet) consisting of 5 tertiary care facilities in Japan. We looked for all CRGNB, and all unique patients with CR Enterobacterales, CR nonfermenting gram-negative bacilli (NFGNB) and CR Aeromonas sp. isolation were included. Carbapenem resistance was tested by agar dilution method and defined based on the CLSI criteria for each species. Infections were determined by NHSN protocols. Results In total, 156 patients (30 Enterobacterales, 119 NFGNB, 7 Aeromonas spp.) were included (11 Enterobacter spp., 11 Klebsiella spp., 86 Pseudomonas aeruginosa, 29 Stenotrophomonas maltophilia, 7 Aeromonas spp.). Acinetobacter sp. was not detected. Isolation sites were sputum (n = 12) and urine (n = 7) in Enterobacterales, sputum (n = 62) and blood (n = 18) in NFGNB, and blood (n = 6) in Aeromonas spp. The median age and male ratio of the patients were 68 years [IQR: 53-74] and 19 (63.3%) in Enterobacterales, 72 years [IQR: 60-79] and 70 (58.8%) in NFGNB and 78 years [IQR: 54-83] and 2 (28.6%) in Aeromonas spp. Ten (33.3%) patients with Enterobacterales, 55 (46.2%) patients with NFGNB, and 6 (85.7%) patients with Aeromonas spp. were infected cases. The others were considered as colonized. There were no patients with ICU stay or intubation in Enterobacterales, while 5 (4.2%) and 4 (3.4%) patients were in ICU and intubated in NFGNB, and 2 patients were in ICU and intubated in Aeromonas spp., respectively. All-cause 30-day mortality rates were 10% in Enterobacterales, 16.8 % in NFGNB and 28.6% in Aeromonas spp. In the infected patients, 3 patients (30%) with Enterobacterales, 12 patients (21.8%) with NFGNB and 1 patient (16.7%) with Aeromonas spp. died within 30 days after isolation. Flow diagram outlining the characteristics of the patients and species in this study. Kaplan-Meier survival curves of patients with carbapenem resistant Enterobacterales Kaplan-Meier survival curves of patients with carbapenem resistant nonfermenting gram-negative bacilli Conclusion Mortality rates were high in infected cases of CR Enterobacterales, CR NFGNB and CR Aeromonas spp. Carbapenem-resistant Acinetobacter spp. was not detected, which differed from the CR epidemiology in Europe, the United States, and other Asian countries. Disclosures Sho Saito, n/a, Shionogi (Grant/Research Support) David van Duin, MD, PhD, Entasis (Advisor or Review Panel member)genentech (Advisor or Review Panel member)Karius (Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Pfizer (Consultant, Advisor or Review Panel member)Qpex (Advisor or Review Panel member)Shionogi (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)Utility (Advisor or Review Panel member) Yohei Doi, MD, PhD, AstraZeneca (Speaker's Bureau)bioMerieux (Consultant)FujiFilm (Advisor or Review Panel member, Speaker's Bureau)Gilead (Consultant)GSK (Consultant)Meiji (Consultant)MSD (Consultant)Shionogi (Consultant) Yohei Doi, MD, PhD, Astellas (Individual(s) Involved: Self): Grant/Research Support; AstraZeneca (Individual(s) Involved: Self): Speakers' bureau; bioMerieux (Individual(s) Involved: Self): Consultant, Speakers' bureau; Chugai (Individual(s) Involved: Self): Consultant; Entasis (Individual(s) Involved: Self): Consultant; FujiFilm (Individual(s) Involved: Self): Advisor or Review Panel member; Gilead (Individual(s) Involved: Self): Consultant; GSK (Individual(s) Involved: Self): Consultant; Kanto Chemical (Individual(s) Involved: Self): Grant/Research Support; MSD (Individual(s) Involved: Self): Speaking Fee; Pfizer (Individual(s) Involved: Self): Grant/Research Support; Shionogi (Individual(s) Involved: Self): Grant/Research Support, Speakers' bureau; Teijin Healthcare (Individual(s) Involved: Self): Speakers' bureau; VenatoRx (Individual(s) Involved: Self): Consultant

scholarly journals 1219. Unfavorable Clinical Outcomes with Polymyxins Compared to Ceftolozane/Tazobactam for the Treatment of Carbapenem-Resistant Pseudomonas aeruginosa

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S699-S700
Author(s):  
Jessica Howard-Anderson ◽  
Michelle Earley ◽  
Toshimitsu Hamasaki ◽  
Chris W Bower ◽  
Gillian Smith ◽  
...  
Keyword(s):  
Adverse Events ◽  
Clinical Outcomes ◽  
Panel Member ◽  
Partial Credit ◽  
Research Support ◽  
Review Panel ◽  
Inverse Probability ◽  
Carbapenem Resistant ◽  
Credit Scores ◽  
Credit Analysis

Abstract Background Patients with carbapenem-resistant Pseudomonas aeruginosa (CRPA) have high in-hospital mortality rates. It is unknown if patients with CRPA treated with ceftolozane/tazobactam (C/T) have improved clinical outcomes compared to those treated with polymyxins. Methods The CDC-funded, Georgia Emerging Infections Program performed active population- and laboratory-based surveillance for CRPA isolated from sterile sites, urine, lower respiratory tract and wounds in metropolitan Atlanta, GA from 8/1/2016–7/31/2018. We reviewed charts of adults without cystic fibrosis who were hospitalized within 1 week of CRPA culture. Using a desirability of outcome ranking (DOOR) analysis which incorporates both benefits and risks into a single outcome, we estimated the probability that a patient treated first with C/T would have a more desirable clinical outcome at 30-days than a patient treated with polymyxins (polymyxin B or colistin). We adjusted for confounding using inverse probability of treatment weighting (IPTW) based on culture source and need for dialysis at baseline. A partial credit analysis allowed for variable weighting of DOOR ranks and calculation of differences in mean partial credit scores. Results Among 710 cases from 18 different hospitals, we identified 73 patients treated for CRPA infections with polymyxins (n=31) or C/T (n=42). Most patients were male (64%) and Black (80%), and those receiving polymyxins were more likely to have required dialysis at baseline (35% vs. 14%, p=0.03) (Table 1). At 30 days after culture, 34 (47%) were alive with no adverse events, 21 (29%) were alive with ≥ 1 adverse event, and 18 (25%) had died. Patients first treated with C/T had a lower 30-day mortality rate than those treated with polymyxins (14% vs 39%, p=0.03). Additionally, those receiving C/T had better overall clinical outcomes, with an adjusted DOOR probability of having an improved outcome of 67% (95% CI 53%–80%) compared to those receiving polymyxins (Figure 1). Partial credit analyses indicated consistent results across different patient values of survival with adverse events (Figure 2). Figure 1: Inverse probability of treatment weighting-adjusted desirability of outcome ranking (DOOR) distributions by treatment group, accounting for adverse events and survival status that occurred up to 30 days after CRPA culture. 1. Percentages are adjusted using inverse probability of treatment weighting, controlling for culture source and need for dialysis at baseline 2. Adverse events measured included: acute kidney injury, discharge to higher acuity location than previous residence, or being hospitalized 30 days after culture Figure 2: Inverse probability of treatment weighting-adjusted partial credit analysis. This displays the difference (ceftolozane/tazobactam minus polymyxin) in mean partial credit scores (black line) and associated 95% confidence bands (gray lines) as a function of the partial credit score assigned to an individual having at least one adverse event (range 0 – 100%). A score of 100% is assigned to patients alive with no adverse events and a score of 0% is assigned to patients who die. A difference in mean partial credit scores of approximately zero suggests there was no difference observed between treatment groups. Conclusion These findings support the recent Infectious Diseases Society of America guidance favoring C/T over polymyxins for treatment of CRPA infections. Disclosures David van Duin, MD, PhD, Entasis (Advisor or Review Panel member)genentech (Advisor or Review Panel member)Karius (Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Pfizer (Consultant, Advisor or Review Panel member)Qpex (Advisor or Review Panel member)Shionogi (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)Utility (Advisor or Review Panel member) Scott R. Evans, PhD, Abbvie (Consultant)Advantagene (Consultant)Alexion (Consultant)Amgen (Consultant)AstraZeneca (Consultant)Atricure (Consultant)Breast International Group (Consultant)Cardinal Health (Consultant)Clover (Consultant)FHI Clinical (Consultant)Genentech (Consultant)Gilead (Consultant)Horizon (Consultant)International Drug Development Institute (Consultant)Lung Biotech (Consultant)Microbiotix (Consultant)Neovasc (Consultant)Nobel Pharma (Consultant)Novartis (Consultant)Nuvelution (Consultant)Pfizer (Consultant)Rakuten (Consultant)Roche (Consultant)Roivant (Consultant)SAB Biopharm (Consultant)Shire (Consultant)Stryker (Consultant)SVB Leerink (Consultant)Takeda (Consultant)Teva (Consultant)Tracon (Consultant)Vir (Consultant)

scholarly journals LB15. SER-109, an Investigational Microbiome Therapeutic, Reduces Abundance of Antimicrobial Resistance Genes in Patients with Recurrent Clostridioides difficile Infection (rCDI) after Standard-of-Care Antibiotics

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S812-S813
Author(s):  
Timothy J Straub ◽  
Liyang Diao ◽  
Christopher Ford ◽  
Matthew Sims ◽  
Thomas J Louie ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Relative Abundance ◽  
Resistance Genes ◽  
Panel Member ◽  
Standard Of Care ◽  
Post Treatment ◽  
Research Support ◽  
Independent Contractor ◽  
Review Panel ◽  
Antimicrobial Resistance Genes

Abstract Background The gastrointestinal microbiota is the first line of defense against colonization with antimicrobial resistant (AR) bacteria, particularly in vulnerable hosts with frequent antibiotic exposure. In a double-blind Phase 3 trial of rCDI patients, SER-109, an orally formulated consortia of purified Firmicutes spores, was superior to placebo in reducing CDI recurrence at week 8 post clinical resolution on standard-of-care (SoC) antibiotics. Overall recurrence rates were lower in SER-109 vs placebo (12.4% vs 39.8%, respectively) relative risk, 0.32 [95% CI, 0.18–0.58; p< 0.001 for RR< 1.0; p< 0.001 for RR< 0.833]. This is a post-hoc analysis examining the impact of SER-109 on antimicrobial resistance genes (ARGs) abundance in the intestinal microbiota compared to placebo. Methods Subjects with rCDI received SoC antibiotics, then were randomized 1:1 to SER-109 or placebo at baseline. Of 182 subjects, 140 who had paired stool samples at baseline and 1-week post-treatment were included in this analysis. ARG abundances and taxonomic profiles were generated from whole metagenomic shotgun sequencing. t-tests were used to compare changes in ARG abundance from baseline; mixed linear models were used to associate ARG and taxon abundances across time points. Results ARG abundance was reduced overall by week 1, with a significantly greater decrease in SER-109 subjects vs. placebo at week 1 (Fig. 1). Proteobacteria relative abundance were positively correlated with ARG abundance across all samples (Fig. 2), with the Enterobacteriaceae family associated with the abundance of 95 ARGs (all p < 0.05). Enterococcaceae relative abundance was associated with glycopeptide AR abundance (p < 0.001). At week 1, Proteobacteria relative abundance was significantly decreased from baseline in SER-109 subjects vs. placebo (p < 0.001). Enterobacteriaceae and Enterococcaceae relative abundances were also decreased from baseline in SER-109 subjects vs. placebo (p < 0.001 and p = 0.007, respectively). Figure 1. Significant reduction in ARG abundance at week 1 from baseline in SER-109 treatment compared to placebo. Figure 2. Total ARG abundance is associated with the relative abundance of Proteobacteria in SER-109 and placebo subjects at baseline and week 1. Conclusion SER-109 was associated with significantly greater reduction of ARGs and AR bacteria abundances compared to placebo at 1 week post treatment. These findings support a potential role of microbiome therapeutics in rapid decolonization of AR bacteria with implications for infection prevention. Disclosures Timothy J. Straub, MS, Seres Therapeutics (Employee) Liyang Diao, PhD, Seres Therapeutics (Employee) Christopher Ford, PhD, Seres Therapeutics (Employee, Shareholder) Matthew Sims, MD, PhD, Astra Zeneca (Independent Contractor)Diasorin Molecular (Independent Contractor)Epigenomics Inc (Independent Contractor)Finch (Independent Contractor)Genentech (Independent Contractor)Janssen Pharmaceuticals NV (Independent Contractor)Kinevant Sciences gmBH (Independent Contractor)Leonard-Meron Biosciences (Independent Contractor)Merck and Co (Independent Contractor)OpGen (Independent Contractor)Prenosis (Independent Contractor)Regeneron Pharmaceuticals Inc (Independent Contractor)Seres Therapeutics Inc (Independent Contractor)Shire (Independent Contractor)Summit Therapeutics (Independent Contractor) Thomas J. Louie, MD, Artugen (Advisor or Review Panel member)Crestone (Consultant, Grant/Research Support)Da Volterra (Advisor or Review Panel member)Finch Therapeutics (Grant/Research Support, Advisor or Review Panel member)MGB Biopharma (Grant/Research Support, Advisor or Review Panel member)Rebiotix (Consultant, Grant/Research Support)Seres Therapeutics (Consultant, Grant/Research Support)Summit PLC (Grant/Research Support)Vedanta (Grant/Research Support, Advisor or Review Panel member) Colleen S. Kraft, MD, MSc, Rebiotix (Individual(s) Involved: Self): Advisor or Review Panel member Stuart H. Cohen, MD, Seres (Research Grant or Support) Stuart H. Cohen, MD, Nothing to disclose Mary-Jane Lombardo, PhD, Seres Therapeutics (Employee, Shareholder) Barbara McGovern, MD, Seres Therapeutics (Employee, Shareholder) Lisa von Moltke, MD, Seres Therapeutics (Employee, Shareholder) Matt Henn, PhD, Seres Therapeutics (Employee, Shareholder)

scholarly journals 1012. Efficacy, safety and tolerability of switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in HIV-1 infected virologically-suppressed older adults in a real-world setting

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S534-S535
Author(s):  
Charlotte-Paige M Rolle ◽  
Vu Nguyen ◽  
Kiran Patel ◽  
Dan Cruz ◽  
Federico Hinestrosa ◽  
...  
Keyword(s):  
Older Adults ◽  
Drug Interactions ◽  
Real World ◽  
Research Study ◽  
Panel Member ◽  
Median Number ◽  
Research Support ◽  
Review Panel ◽  
Study Investigator ◽  
Hiv 1

Abstract Background Approximately 50% of people living with HIV (PLWH) in the United States are ≥50 years old. Efforts are ongoing to identify antiretrovirals associated with fewer drug-drug interactions (DDIs) and long-term side effects in this group. Clinical trials of B/F/TAF demonstrated favorable efficacy and safety in older adults, however, data from real-word settings are needed to validate these results. Methods This retrospective analysis evaluated records from PLWH aged ≥ 50 years at the Orlando Immunology Center who were switched to B/F/TAF between 2/7/2018 and 5/31/2019. Eligible patients had baseline HIV-1 RNA< 50 copies/mL and were followed for 48 weeks post-switch. The primary endpoint was maintenance of HIV-1 RNA< 50 copies/mL at week 48. The impact of switching to B/F/TAF on DDIs, adverse events (AEs) and safety parameters were analyzed throughout the study. Results 306 patients met inclusion criteria. 62 (20%) were female, 126 (41%) were non-white, median age was 58 years (range [r] 50-81), median duration of HIV infection was 19.5 years (r 2-40), median number of chronic co-morbid conditions was 5 (r 0-20), and median number of baseline concomitant medications was 4 (r 0-23). 159 (52%) patients were switched from regimens containing ritonavir or cobicistat. The most commonly documented reason for switch was simplification (Table 1). At Week 48, 287 (94%) patients maintained an HIV-1 RNA< 50 copies/ml and 19 (6%) had an HIV-1 RNA between 50-200 copies/mL (Figure 1). 1 patient discontinued due to lack of efficacy. A total of 123 potential DDIs were identified in 104 (34%) patients taking a boosting agent or rilpivirine at baseline (Table 2). At Week 48, there was a significant median decline in total cholesterol (15.5 mg/dL, 95% confidence interval [CI]: 9.5; 21.5), LDL cholesterol (9.5 mg/dL, 95% CI: 4; 15.5) and triglycerides (20 mg/dL, 95% CI: 9.5; 32.5), and median weight increased by 2.5 pounds (95% CI: 1.5; 3.5). Treatment-related AEs occurred in 33 (11%) patients (all Grade 1-2) and led to 7 (2%) discontinuations. Table 1-Baseline demographic and clinical characteristics Table 2-Avoidance of Drug-Drug Interactions (DDIs) following switch to B/F/TAF Figure 1-Subgroup analysis of virologic outcomes at Week 48 Conclusion In this real-world cohort, switching to B/F/TAF was associated with maintenance of virologic control, improvement in lipid parameters, and avoidance of DDIs in a large proportion of patients. These data support use of B/F/TAF as a treatment option in older PLWH. Disclosures Charlotte-Paige M. Rolle, MD MPH, Gilead Sciences (Grant/Research Support, Scientific Research Study Investigator, Speaker’s Bureau)Janssen Infectious Disease (Grant/Research Support)ViiV Healthcare (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Speaker’s Bureau) Kiran Patel, PharmD, Gilead Sciences (Employee) Federico Hinestrosa, MD, AbbVie (Speaker’s Bureau)Gilead Sciences (Speaker’s Bureau)Merck (Speaker’s Bureau)Theratechnologies (Speaker’s Bureau) Edwin DeJesus, MD, Gilead Sciences (Advisor or Review Panel member)

scholarly journals 1104. Risk Factors and Outcomes of Refractory and/or Resistant Cytomegalovirus (CMV) Infection after Allogeneic Hematopoietic Stem Cell Transplantation

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S582-S583
Author(s):  
Eleni Karantoni ◽  
Yiqi Su ◽  
Anat Stern ◽  
Phaedon D Zavras ◽  
Sergio Giralt ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
T Cell ◽  
Panel Member ◽  
Multivariable Model ◽  
Research Support ◽  
Review Panel ◽  
Material Support ◽  
Advisory Boards ◽  
Research Grant

Abstract Background The epidemiology of CMV end-organ disease (EOD) after Hematopoietic Cell Transplant (HCT) in the era of preemptive therapy (PET) is defined. In contrast, less data exists on refractory and/or resistant (R/R) CMV. We report on 1) the incidence; 2) risk factors and outcomes of R/R CMV by 1-year post HCT. Methods Retrospective review of 167 CMV seropositive (R+) recipients of first marrow or peripheral blood HCT from 1/2014 - 12/2017 managed by PET. Refractory CMV was defined as failure to achieve >1 log10 decrease in CMV viral load (VL) and having VL >1,000 IU/mL after ≥14 day of PET. Resistant CMV required genotypic confirmation of resistance mutation(s) in UL54 and/or UL97 genes. End organ disease (EOD) was defined by standard criteria. Patients (pts) were followed through 1-year post HCT and were categorized in two mutually exclusive groups as R/R and no R/R. Demographics, clinical characteristics and outcomes were extracted from medical records and hospital databases. Univariable and multivariable logistic models were used to identify risk factors for R/R CMV. Results Of 167 PET recipients, 91 (54.5%) received ex vivo T cell depleted (TCD) HCT; 40 (24.0%) had mismatched donor; and 26 (15.6%) had multiple myeloma. 66/167 (39.5%) pts developed refractory CMV (6 pts also had resistant CMV). Time from HCT to CMV viremia was shorter in R/R group: median (IQR) 21.5 (17.2-27.8) days compared to no R/R group: 26 (19-32) days (p=0.031). Maximum VL was higher for R/R compared to no R/R: median (IQR) 9,118 (2,849-18,456) and 868 (474-1,908), respectively (p< 0.001). In multivariable model, risk factors for R/R included TCD HCT (p< 0.0001) and higher VL at PET initiation (p=0.0002). In contrast, CMV seropositive donor (p=0.035) was protective (Figure 1). CMV EOD developed in 28.2% of R/R and 16.2% of no R/R groups (p=0.085) (Figure 2). Overall survival at 1 year was 59.1% for R/R compared to 83.1% for no R/R group (p=0.00027) (Figure 3). Figure 1. Adjusted odds ratio (OR) and 95% confidence interval (CI) from multivariable model evaluating risk factors of refractory/resistant (R/R) CMV. Figure 2. Cumulative incidence curves of CMV end-organ disease (EOD) at 1-year post HCT Figure 3. Kaplan-Meier survival curves of overall survival (OS) at 1-year post HCT Conclusion 1) Refractory and/or resistant CMV occurred in 39,5% of PET recipients. 2) T-cell depletion and higher CMV VL at PET initiation were risk factors for R/R CMV in multivariable models. 3) R/R CMV was associated with more EOD and worse overall survival. Disclosures Sergio Giralt, MD, Amgen (Advisor or Review Panel member, Research Grant or Support, Served an advisory board for Amgen, Actinuum, Celgene, Johnson & Johnson, JAZZ pharmaceutical, Takeda, Novartis, KITE, and Spectrum pharma and has received research support from Amgen, Actinuum, Celgene, Johnson & Johnson, and Miltenyi, Takeda.) Miguel-Angel Perales, MD, Abbvie (Other Financial or Material Support, Honoraria from Abbvie, Bellicum, Celgene, Bristol-Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda.)ASTCT (Other Financial or Material Support, Volunteer member of the Board of Directors of American Society for Transplantation and Cellular Therapy (ASTCT), Be The Match (National Marrow Donor Program, NMDP), and the CIBMTR Cellular Immunotherapy Data Resource (CIDR) Committee)Cidara Therapeutics (Advisor or Review Panel member, Other Financial or Material Support, Serve on DSMBs for Cidara Therapeutics, Servier and Medigene, and the scientific advisory boards of MolMed and NexImmune.)Kite/Gilead (Research Grant or Support, Other Financial or Material Support, Received research support for clinical trials from Incyte, Kite/Gilead and Miltenyi Biotec.) Genovefa Papanicolaou, MD, Chimerix (Research Grant or Support)Merck&Co (Research Grant or Support, Investigator and received funding and consulting fees from Merck, Chimerix, Shire and Astellas)

scholarly journals 652. Comparison of fosfomycin (FOF) activity and prevalence of subpopulations between Escherichia coli (EC) and Klebsiella pneumoniae (KP) during susceptibility testing

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S384-S384
Author(s):  
Jadyn C Anderson ◽  
Amanda R Krueger ◽  
Elizabeth C Smith ◽  
Morgan L Bixby ◽  
Hunter V Brigman ◽  
...  
Keyword(s):  
Clinical Efficacy ◽  
Inhibitory Concentration ◽  
Panel Member ◽  
Colony Growth ◽  
The United States ◽  
Research Support ◽  
Review Panel ◽  
Agreement Rate ◽  
Future Studies ◽  
Agar Dilution

Abstract Background In the United States, interpretive criteria for FOF are established only for EC, yet those criteria are often extrapolated to KP. Recent studies have highlighted both inferior clinical outcomes after FOF treatment and difficulties in interpretation of inner colony subpopulations, the presence of which may affect clinical efficacy. We sought to compare FOF activity against EC and KP and to determine the prevalence of inner colony subpopulations following disk diffusion (DD) testing of the two species. Methods A convenience collection of 73 KP and 42 EC isolates from 3 U.S. institutions were included. Minimal inhibitory concentration (MIC) testing was performed in duplicate on separate days using agar dilution (AD) and DD as recommended by the Clinical and Laboratory Standards Institute guidelines, with application of EC susceptibility (≤ 64mg/L) breakpoints. The frequency and counts of inner colonies observed during DD testing was calculated, and colonies were subcultured for use in future studies. Results MIC50/90 values were 1/16 mg/L and 32/256 mg/L for EC and KP respectively. All EC isolates were considered susceptible and therefore categorical agreement was 100%. The majority of KP isolates were considered susceptible (83.6% with AD and 86.3% with DD) and categorical agreement between the methods was 84.9%. Inner colonies were observed during DD testing in 88.1% of EC isolates and 80.8% of KP isolates during at least one replicate, with 47.6% of EC isolates and 39.7% of KP isolates showing inner colony growth during both DD test replicates. More than 10 inner colonies were observed in 50% of EC isolates compared to 12.3% of KP isolates. Conclusion KP isolates demonstrated considerably higher FOF MIC values compared to EC, as evidenced by MIC50/90 values 4-5 dilutions higher than those for EC. The categorical agreement rate was higher among EC than KP, highlighting concerns regarding the practice of extrapolating FOF susceptibility breakpoints for EC to KP. The high frequency of inner colonies observed in DD for both species necessitates further studies to determine best practices for interpreting their relevance, fitness, and resistance in order to identify potential impacts to clinical efficacy of FOF. Disclosures Elizabeth B. Hirsch, PharmD, Merck (Grant/Research Support)Nabriva Therapeutics (Advisor or Review Panel member)

scholarly journals 108. Selective Decay of Intact HIV-1 Proviral DNA on Antiretroviral Therapy

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S183-S183
Author(s):  
Rajesh Gandhi ◽  
Joshua Cyktor ◽  
Ronald Bosch ◽  
Hanna Mar ◽  
Gregory Laird ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Panel Member ◽  
Plasma Viremia ◽  
Research Support ◽  
Review Panel ◽  
Proviral Dna ◽  
Hiv 1 ◽  
Over Time ◽  
Residual Plasma Viremia ◽  
Research Grant

Abstract Background HIV-1 proviruses persist in people on antiretroviral therapy (ART) but most are defective and do not constitute a replication-competent reservoir. The decay of infected cells carrying intact compared with defective HIV-1 proviruses has not been well-defined in people on ART. Methods We separately quantified intact and defective proviruses (using an intact proviral DNA assay), residual plasma viremia, and markers of inflammation and activation in people on long-term ART. Longitudinal measurements were done at three timepoints: timepoint 1 was a median of 7.1 years on ART; timepoint 2 was a median of 3.7 years later; timepoint 3 was a median of 5.5 years after timepoint 1 and a median 12 years after starting ART (Figure 1). Figure 1: Study timepoints Results Among 40 participants tested longitudinally from a median of 7.1 years to 12 years after ART initiation, intact provirus levels declined significantly over time (median half-life 7.1 years; 95% confidence interval [CI], 3.9, 18), whereas defective provirus levels did not decrease. The median half-life of total HIV-1 DNA was 41.6 years (95% CI, 13.6, 75). When we evaluated the change in proviral DNA per year, intact proviral DNA declined significantly more (p< 0.001) than defective proviral DNA (the latter did not change) (Figure 2). The proportion of all proviruses that were intact diminished over time on ART, from about 10% at the first on-ART timepoint to about 5% at the last timepoint (Figure 3). At timepoint 1, intact provirus levels on ART correlated with total HIV-1 DNA and residual plasma viremia, but there was no evidence for associations between intact provirus levels and inflammation or immune activation. Figure 2: Percent change in HIV-1 proviral DNA per year Figure 3: Total HIV-1 proviruses (grey bars) and the percentage of intact proviruses (red lines, displaying median, Q1, Q3) by timepoint. Conclusion Cells containing intact, replication-competent proviruses are selectively lost during suppressive ART. Defining the mechanisms involved should inform strategies to accelerate HIV-1 reservoir depletion. Disclosures Rajesh Gandhi, MD, Merck (Advisor or Review Panel member) Gregory Laird, PhD, Accelevir Diagnostics (Shareholder, Other Financial or Material Support, Employee) Albine Martin, PhD, Accelevir Diagnostics (Shareholder, Other Financial or Material Support, Employee) Bernard Macatangay, MD, Gilead (Grant/Research Support) Joseph J. Eron, MD, Gilead Sciences (Consultant, Research Grant or Support)Janssen (Consultant, Research Grant or Support)Merck (Consultant)ViiV Healthcare (Consultant, Research Grant or Support) Janet Siliciano, PhD, Gilead (Advisor or Review Panel member)US Military HIV Research Program (Advisor or Review Panel member) John Mellors, MD, Abound Bio (Shareholder)Accelevir Diagnostics (Consultant)Co-Crystal Pharmaceuticals (Shareholder)Gilead (Consultant, Grant/Research Support)Merck (Consultant)

scholarly journals 1465. Age-Dependent Interactions Among Clinical Characteristics, Viral Loads and Disease Severity in Young Children with Respiratory Syncytial Virus Infection (RSV) Infection

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S734-S735
Author(s):  
Helena Brenes-Chacon ◽  
Cristina Garcia-Maurino ◽  
Melissa Moore-Clingenpeel ◽  
Sara Mertz ◽  
Fang Ye ◽  
...  
Keyword(s):  
Young Children ◽  
Disease Severity ◽  
Age Groups ◽  
Panel Member ◽  
Signs And Symptoms ◽  
Research Support ◽  
Review Panel ◽  
Viral Loads ◽  
Age Dependent ◽  
Rsv Infection

Abstract Background Differences in clinical presentation and viral loads according to age in young children with RSV, and their correlation with disease severity are poorly defined. The aim of this study was to define age-dependent the differences in demographic, clinical factors and viral loads between children < 2 years of age with mild RSV infection evaluated as outpatients versus those hospitalized with severe RSV infection. Figure 1. Sign and Symptoms according to disease severity and age in infants with RSV infection. Most relevant signs and symptoms were stratified in outpatients (orange) vs inpatients (blue) by age in (A) < 3 months, (B) between 3 and 6 months, and (C) > 6 to 24 months of age. The Y axis represents the signs and symptoms in the two disease severity groups and the X axis the frequency of that specific symptom (%). Numbers next to bars represent the exact number of patients with that specific sign/symptom. Comparisons by Fisher exact test. Symbol (*) indicate significant 2-sided p values Figure 2. Viral load differences according to age in infants with RSV infection. The Y axis represents RSV loads in log10 copies/mL and the X axis differences in viral loads in outpatients (orange) and inpatients (blue) in the three age groups. Comparisons by Mann Whitney test. Methods Previously healthy children < 2 years old with mild (outpatients) and severe (inpatients) RSV infection were enrolled and nasopharyngeal swabs were obtained for RSV typing and quantitation by real-time PCR. Patients were stratified by age (0-< 3, 3-6, and >6-24 months) and multivariable analyses were performed to identify clinical and viral factors associated with severe disease. Results From 2014-2018 we enrolled 534 children with RSV infection: 130 outpatients and 404 inpatients. Median duration of illness was 4 days for both groups, yet viral loads were higher in outpatients than inpatient in the three age groups (Fig 1). Wheezing was more frequent in outpatients of older age (>3 months) than in inpatients (p< 0.01), while fever was more common in inpatients that outpatients (p< 0.01) and increased with age (Fig 2). Adjusted analyses confirmed that increased work of breathing and fever were consistently associated with hospitalization irrespective of age, while wheezing in infants >3 months, and higher RSV loads in children >6-24 months were independently associated with reduced disease severity. Conclusion Age had a significant impact defining the interactions among viral loads, specific clinical manifestations and disease severity in children with RSV infection. These observations highlight the importance of patient stratification when evaluating interventions against RSV. Disclosures Octavio Ramilo, MD, Bill & Melinda Gates Foundation (Grant/Research Support)Janssen (Grant/Research Support, Advisor or Review Panel member)Medimmune (Grant/Research Support)Merck (Advisor or Review Panel member)NIH/NIAID (Grant/Research Support)Pfizer (Consultant, Advisor or Review Panel member)Sanofi/Medimmune (Consultant, Advisor or Review Panel member) Asuncion Mejias, MD, PhD, MsCS, Janssen (Grant/Research Support, Advisor or Review Panel member)Merck (Advisor or Review Panel member)Roche (Advisor or Review Panel member)

An Important Public Health Problem "Carbapenem Resistant Enterobacteriaceae Frequency": An Example From A Training And Research Hospital

2021 ◽  
Vol 6 (14) ◽  
pp. 51-55
Author(s):  
Ülkü VERANYURT ◽  
Betül AKALIN
Keyword(s):  
Public Health ◽  
Klebsiella Pneumoniae ◽  
Klebsiella Oxytoca ◽  
Public Health Problem ◽  
Important Public Health Problem ◽  
Klebsiella Species ◽  
Research Hospital ◽  
Control Programs ◽  
Carbapenem Resistant ◽  
Training And Research

Background: Carbapenem-resistant Enterobacterales (CRE) infections are a significant threat to public health due to the limited availability of antibiotics and the effect on mortality. This study was conducted retrospectively to determine the prevalence of CRE in a teaching and research hospital in Istanbul. Materials and Methods: In 2016, 2017 and in the first half of 2018 Klebsiella species were evaluated retrospectively in culture samples that were sent to Microbiology Laboratory in an educational hospital. The typing of Klebsiella species were performed with MALDITOF-MS device (Biomerieux, France). Imipenem, merapenem, ertapenem susceptibilities of the strains were evaluated with VITEC2 Compact (Biomerieux, France) according to EUCAST (European Committee on Antimicrobial Susceptibility Testing). If the strains were found to be resistant, the results were confirmed by the antibiotic gradient test. Results: In our study, 257 samples; Klebsiella oxytoca 9 (3.49%) and Klebsiella pneumoniae 248 (96.51%) were detected. 130 endotracheal aspirates, 57 wounds, 34 blood, 15 urine, 9 sputum, 3 catheters, 4 tissue biopsies, 2 mediastinum, 2 peritoneal fluid and 1 pleural fluid strains were identified. While none of the Klebsiella oxytoca strains were resistant to carbapenems, the percentages of Klebsiella pneumoniae resistance against imipenem, merapenem and ertapenem were found to be 23.29%, 16.94% and 29.44% respectively. Conclusion: The increasing problem of carbapenem-resistant (CR) Klebsiella pneumoniae in the last decade has been observed in our hospital for the last 2 years. CR strains often show increased resistance to other antibiotics and their treatment possibilities are limited. It increases the importance of controlling this factor. The application of effective infection control programs and the use of rational antibiotics are of great importance.

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