scholarly journals 200. Prospective Evaluation of the GenMark Dx ePlex® Blood Culture Identification Gram Positive Panel

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S208-S208
Author(s):  
Jeremy Meeder ◽  
Derek Moates ◽  
Hannah Pierce ◽  
Jamie Hutchinson ◽  
Cameron White ◽  
...  
Keyword(s):  
Blood Culture ◽  
Resistance Genes ◽  
Antimicrobial Therapy ◽  
False Negative ◽  
Meca Gene ◽  
Standard Of Care ◽  
Gene Detection ◽  
Research Support ◽  
Coagulase Negative Staphylococci ◽  
Material Support

Abstract Background The ePlex BCID Gram-Positive (GP) panel utilizes electrowetting technology to detect the most common causes of GP bacteremia (20 targets) and 4 antimicrobial resistance genes in positive blood culture bottles. Rapid detection of intrinsic vancomycin resistance and acquired resistance genes (mecA, mecC, vanA, vanB) enables early optimization of antimicrobial therapy whereas early detection of common contaminants decreases unnecessary antibiotic utilization and hospitalizations. Methods In this prospective study, we evaluated the performance of the BCID-GP panel compared to traditional standard of care culture and susceptibility testing with organism identification using the BioMerieux Vitek MS Matrix Assisted Laser Desorption Ionization (MALDI) Time of Flight mass spectrometry. Samples submitted for standard of care testing in Biomerieux BacT/Alert resin FA/FN blood culture bottles on the BacT/Alert VIRTUO automated blood culture system with GP bacteria on direct exam (n=100) were included. Results All GP bacteria were represented on the BCID-GP panel, most tests 97/100 (97%) yielded valid results, 53 common skin contaminants (50 coagulase negative staphylococci (CNS), 2 Bacillus, 1 Corynebacterium) were identified, and 7/7 coinfections with Gram negative (GN) bacteria were detected by the Pan GN target and identified by the BCID-GN panel. Discordant analyses revealed a positive percent agreement (PPA) of 96/97 (99%) with 1 false negative CNS and a negative percent agreement (NPA) of 92/97 (94.8%) with 5 false positives for either S. epidermidis or Corynebacterium. Detection of vanA yielded a PPA of 4/4 and NPA of 9/9. mecA gene detection exhibited a PPA of 14/14 and NPA of 14/14 for S. aureus and a PPA of 31/32 (97%) and NPA of 16/16 for coagulase negative staphylococci with 1 false negative methicillin resistant S. epidermidis. Conclusion Detection of acquired vancomycin resistance (n=4) and absence of mecA gene detection in Staphylococcus species (n=30) represent opportunities for early optimization of antimicrobial therapy in 34/100 (34%) of samples. The BCID-GP panel provides rapid accurate detection of resistant isolates and common contaminants enabling high quality data driven optimization of antimicrobial therapy. Disclosures Todd P. McCarty, MD, Cidara (Grant/Research Support)GenMark (Grant/Research Support, Other Financial or Material Support, Honoraria for Research Presentation)T2 Biosystems (Consultant) Sixto M. Leal, Jr., MD, PhD, Abnova (Grant/Research Support)AltImmune (Grant/Research Support)Amplyx Pharmaceuticals (Grant/Research Support)Astellas Pharmaceuticals (Grant/Research Support)CNINE Dx (Grant/Research Support)GenMark Diagnostics (Grant/Research Support, Other Financial or Material Support, Honoraria- Research Presentation)IHMA (Grant/Research Support)IMMY Dx (Grant/Research Support)JMI/Sentry (Grant/Research Support)mFluiDx Dx (Grant/Research Support)SpeeDx Dx (Grant/Research Support)Tetraphase Pharmaceuticals (Grant/Research Support)

scholarly journals 214. Prospective Evaluation of the GenMark Dx ePlex® Blood Culture Identification Gram Negative Panel

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S215-S215
Author(s):  
Jeremy Meeder ◽  
Derek Moates ◽  
Hannah Pierce ◽  
Jamie Hutchinson ◽  
Pia Cumagun ◽  
...  
Keyword(s):  
Blood Culture ◽  
Antimicrobial Therapy ◽  
Standard Of Care ◽  
Quality Data ◽  
Resistant Bacteria ◽  
M Gene ◽  
Research Support ◽  
Gram Negative ◽  
Material Support ◽  
Percent Agreement

Abstract Background The ePlex BCID Gram-Negative (GN) panel utilizes electrowetting technology to detect the most common causes of GN bacteremia (21 targets) and 6 antimicrobial resistance genes from positive blood culture bottles. Rapid detection of extended spectrum β-lactamases (ESBL; CTX-M), carbapenemases (KPC, NDM, IMP, VIM, OXA 23/48), and highly resistant bacteria such as Stenotrophomonas maltophilia enables early optimization of antimicrobial therapy. Methods In this prospective study, we evaluated the performance of the BCID-GN panel compared to traditional standard of care culture and susceptibility testing with organism identification using the BioMerieux Vitek MS Matrix Assisted Laser Desorption Ionization (MALDI) Time of Flight mass spectrometry. Samples submitted for standard of care testing in Biomerieux BacT/Alert resin FA/FN blood culture bottles on the BacT/Alert VIRTUO automated blood culture system with GN bacteria on direct exam (n=108) were included. Results All but two GN bacteria identified by MALDI were represented on the BCID-GN Panel (106/108, 98.1%) and most tests (107/108, 99.1%) yielded valid results. Discordant analyses revealed a positive percent agreement (PPA) of 102/105 (97.2%) with 3 false negatives (2 pan-susceptible Enterobacterales, 1 ESBL E.coli) and a negative percent agreement (NPA) of 105/105 (100%). Consistent with alternative resistance mechanisms, only 8/12 (66.7%) of Enterobacterales with resistance to 3rd generation cephalosporins harbored the CTX-M gene. In contrast, 8/8 (100%) of isolates from samples harboring the CTX-M gene were resistant to 3rd generation cephalosporins. Conclusion Detection of 1 S. maltophilia, 1 Acinetobacter baumannii expressing OXA 23/48, and 8 Enterobacterales expressing CTX-M represent opportunities for early optimization of antimicrobial therapy in 10/108 (9.3%) of samples. The BCID-GN Panel provides rapid accurate detection of resistant gram negative bacteria enabling high quality data driven optimization of antimicrobial therapy. Disclosures Todd P. McCarty, MD, Cidara (Grant/Research Support)GenMark (Grant/Research Support, Other Financial or Material Support, Honoraria for Research Presentation)T2 Biosystems (Consultant) Sixto M. Leal, Jr., MD, PhD, Abnova (Grant/Research Support)AltImmune (Grant/Research Support)Amplyx Pharmaceuticals (Grant/Research Support)Astellas Pharmaceuticals (Grant/Research Support)CNINE Dx (Grant/Research Support)GenMark Diagnostics (Grant/Research Support, Other Financial or Material Support, Honoraria- Research Presentation)IHMA (Grant/Research Support)IMMY Dx (Grant/Research Support)JMI/Sentry (Grant/Research Support)mFluiDx Dx (Grant/Research Support)SpeeDx Dx (Grant/Research Support)Tetraphase Pharmaceuticals (Grant/Research Support)

scholarly journals 1027. Earlier Is Better: Progress Toward Decreased Time to Optimal Therapy and Improved Antibiotic Stewardship for Gram-positive Bloodstream Infections Through Use of GenMark Dx ePlex system

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S604-S605
Author(s):  
Cameron White ◽  
Jeremy Meeder ◽  
Derek Moates ◽  
Hannah Pierce ◽  
Todd P McCarty ◽  
...  
Keyword(s):  
Antimicrobial Therapy ◽  
Susceptibility Testing ◽  
Acquired Resistance ◽  
Meca Gene ◽  
Bloodstream Infections ◽  
Final Analysis ◽  
Research Support ◽  
Coagulase Negative Staphylococci ◽  
Gram Positive ◽  
Material Support

Abstract Background The ePlex BCID Gram-Positive (GP) panel utilizes electrowetting technology to detect the most common causes of GP bacteremia (20 targets) and 4 antimicrobial resistance (AMR) genes in positive blood culture (BC) bottles. Rapid detection of intrinsic vancomycin resistance and acquired resistance genes (mecA, mecC, vanA, vanB) enables early optimization of antimicrobial therapy whereas early detection of common contaminants is expected to decrease unnecessary antibiotic utilization and hospitalizations. Methods In this prospective study, aliquots of BC bottles with GP bacteria detected on Gram stain (GS) (n=101) received standard of care (SOC) culture and antimicrobial susceptibility testing (AST). Additionally, samples were evaluated with the BCID-GP panel but only SOC results were reported in the EMR and available to inform clinical decisions. Patients were excluded if the sample was a subsequent culture in a persistent episode of bacteremia (n=17) or if the assay failed (n=4). Chart review was performed to evaluate the expected impact of the BCID-GP panel on the time to organism identification, AST results, and optimization of antimicrobial therapy. Results A total of 80 patients were included in the final analysis (Table 1). S. epidermidis was the most common bacteria identified, followed by S. aureus, and other coagulase-negative staphylococci. Thirty-nine patients with staphylococci (48.8%) had the mecA gene detected and 2 patients with E. faecium had the vanA gene detected. The BCID-GP panel saved a mean of 24.4 hours (h) to identification and 48.3h to susceptibility testing compared to standard methods across all patients. In 38 patients (47.5%), the BCID-GP panel result could have enabled an earlier change in antibiotic therapy. Table 2 highlights opportunities to optimize antimicrobial therapy 53.4h earlier for 16 (20%) patients with organisms expressing AMR genes, 29.2h earlier for 8 (10%) patients infected with organisms, such as streptococci, with very low resistance rates, and to stop antimicrobial therapy 42.9h earlier for 14 (17.5%) patients with contaminated blood cultures. Conclusion The BCID-GP panel could have enabled earlier optimization or stopping of antibiotics in many patients with significant time savings compared to standard laboratory methods. Disclosures Todd P. McCarty, MD, Cidara (Grant/Research Support)GenMark (Grant/Research Support, Other Financial or Material Support, Honoraria for Research Presentation)T2 Biosystems (Consultant) Sixto M. Leal, Jr., MD, PhD, Abnova (Grant/Research Support)AltImmune (Grant/Research Support)Amplyx Pharmaceuticals (Grant/Research Support)Astellas Pharmaceuticals (Grant/Research Support)CNINE Dx (Grant/Research Support)GenMark Diagnostics (Grant/Research Support, Other Financial or Material Support, Honoraria- Research Presentation)IHMA (Grant/Research Support)IMMY Dx (Grant/Research Support)JMI/Sentry (Grant/Research Support)mFluiDx Dx (Grant/Research Support)SpeeDx Dx (Grant/Research Support)Tetraphase Pharmaceuticals (Grant/Research Support)

scholarly journals 1368. The Clinical Impact of BioFire BCID2 Compared to BCID in a U.S. Pediatric Hospital

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S694-S694
Author(s):  
Kelly E Graff ◽  
Claire Palmer ◽  
Toraj Anarestani ◽  
Darcy Velasquez ◽  
Stacey Hamilton ◽  
...  
Keyword(s):  
Blood Culture ◽  
Enterococcus Faecalis ◽  
Resistance Genes ◽  
Antimicrobial Therapy ◽  
Enteric Bacteria ◽  
Species Level ◽  
Effective Therapy ◽  
Research Support ◽  
Standard Culture ◽  
Culture Identification

Abstract Background Multiplex PCR panels, particularly BioFire FilmArray Blood Culture Identification (BCID), have been shown to decrease time to pathogen identification and time to effective and optimal antimicrobial therapy. BioFire Blood Culture Identification 2 (BCID2) has an additional 17 targets and resistance genes compared to BCID. There is limited data on the impact of these expanded targets in pediatric populations. Methods We performed a head-to-head comparison between BioFire BCID2 with BCID when compared to standard culture. From January 2020- May 2020, we ran BCID2 simultaneously as a research use only prototype with the current standard of care on all blood culture specimens at Children’s Hospital Colorado. Percent agreement was calculated with BCID2 compared to standard culture and BCID compared to standard culture. Time to positivity, time to optimal therapy, and time to effective therapy were also calculated. Results We performed an interim analysis halfway through the study with 86 unique positive blood cultures. We found equal organism detection rates between BCID and BCID2 when compared to standard culture (88% each). BCID2 correctly identified 100% of target organisms. There were 10 (12%) isolates that only grew in culture that were not BCID or BCID2 targets. Compared to BCID, BCID2 was able to detect to the species level on 23 additional isolates. Most notably, 3 Enterococcus faecalis isolates were detected on BCID2, which would have resulted in a theoretical decrease in time to optimal antimicrobial therapy. Three CTX-M genes were detected on the resistance panels for Enteric bacteria, which could have resulted in a theoretical decrease in time to effective therapy. Conclusion BioFire BCID2 had equal rates of detection when compared to BCID in pediatric patients. It has the additional advantage of detecting more organisms at the species level, with clinical significance for Enterococcus faecalis specifically. With the additional resistance genes, it also has the potential to impact care with early identification of ESBL-producing Enteric pathogens. Disclosures Kelly E. Graff, MD, BioFire Diagnostics, LLC (Grant/Research Support) Claire Palmer, MS, BioFire Diagnostics, LLC (Grant/Research Support) Toraj Anarestani, MT(ASCP), BioFire Diagnostics, LLC (Grant/Research Support) Darcy Velasquez, MS, MB (ASCP)CM, BioFire Diagnostics, LLC (Grant/Research Support) Stacey Hamilton, MT(ASCP)SM, BioFire Diagnostics, LLC (Grant/Research Support) Kristin Pretty, n/a, BioFire Diagnostics, LLC (Grant/Research Support) Samuel Dominguez, MD, PhD, BioFire (Consultant, Research Grant or Support)

scholarly journals 1022. Evaluating the Impact of GenMark Dx ePlex® Blood Culture Identification (BCID) on Gram-negative Bloodstream Infections

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S602-S603
Author(s):  
Pia Cumagun ◽  
Jeremy Meeder ◽  
Derek Moates ◽  
Hannah Pierce ◽  
Todd P McCarty ◽  
...  
Keyword(s):  
Blood Culture ◽  
Antimicrobial Therapy ◽  
Resistant Bacteria ◽  
Research Support ◽  
Gram Positive ◽  
Negative Spectrum ◽  
Gram Negative ◽  
Material Support ◽  
Organism Identification ◽  
The Impact

Abstract Background The GenMark Dx ePlex BCID Gram-Negative (GN) panel utilizes electrowetting technology to detect the most common causes of GN bacteremia (21 targets) and 6 antimicrobial resistance (AMR) genes from positive blood culture (BC) bottles. Rapid detection of extended spectrum β-lactamases (ESBL: CTX-M & carbapenemases: KPC, NDM, IMP, VIM, OXA 23/48), and highly resistant bacteria such as S. maltophilia should enable early optimization of antimicrobial therapy. Methods In this prospective study, aliquots of positive BC bottles with GN bacteria detected on Gram stain (GS) (n=108) received standard of care (SOC) culture and antimicrobial susceptibility testing (AST). Additionally, samples were evaluated with the BCID-GN panel but only SOC results were reported in the EMR and available to inform clinical decisions. Chart reviews were performed to evaluate the impact of the BCID-GN panel on the time to organism identification, AST results, and optimization of antimicrobial therapy. Results A total of 108 patients are included in the analysis (Table 1). Escherichia coli was the most common bacteria identified followed by Klebsiella pneumoniae, Pseudomonas aeruginosa, and Enterobacter species (Table 2). There were 11 (10.2%) polymicrobial bacteremias. Repeat BCs were obtained in 68 (63%) patients of which 13 (19%) were persistently positive. Eight (7%) patients had evidence of additional gram-positive (GP) pathogens. Organism identification occurred 26.7 hours faster than culture. In conjunction with GS, negative pan-GP marker data could have helped providers make the decision to remove GP antibiotic coverage in 63 (58%) patients. Narrowing from empiric meropenem could have occurred in 5 patients. Of 10 individuals infected with resistant isolates (1 S. maltophilia, 1 OXA 23/48, and 8 CTX-M) empiric therapy was ineffective in 4 (40%) cases. Optimization of antimicrobial therapy for 9 (8.3%) patients could have occurred an average of 52.4 hours earlier than standard methods. Table 1. Patient demographics and co-morbidities. Table 2. Gram-negative bacteria frequency. Conclusion The BCID-GN panel enabled earlier time to optimal treatment of highly resistant bacteria as well as multiple opportunities for narrowing gram negative spectrum and a higher degree of certainty in cessation of broad-spectrum gram-positive antibiotics Disclosures Todd P. McCarty, MD, Cidara (Grant/Research Support)GenMark (Grant/Research Support, Other Financial or Material Support, Honoraria for Research Presentation)T2 Biosystems (Consultant) Sixto M. Leal, Jr., MD, PhD, Abnova (Grant/Research Support)AltImmune (Grant/Research Support)Amplyx Pharmaceuticals (Grant/Research Support)Astellas Pharmaceuticals (Grant/Research Support)CNINE Dx (Grant/Research Support)GenMark Diagnostics (Grant/Research Support, Other Financial or Material Support, Honoraria- Research Presentation)IHMA (Grant/Research Support)IMMY Dx (Grant/Research Support)JMI/Sentry (Grant/Research Support)mFluiDx Dx (Grant/Research Support)SpeeDx Dx (Grant/Research Support)Tetraphase Pharmaceuticals (Grant/Research Support)

scholarly journals Comparison of Pharmacist-Directed Management of Multiplex PCR Blood Culture Results with Conventional Microbiology Methods on Effective and Optimal Therapy within a Community Hospital

2018 ◽  
Vol 63 (1) ◽  
Author(s):  
Allison M. Porter ◽  
Christopher M. Bland ◽  
Henry N. Young ◽  
David R. Allen ◽  
Sabrina R. Croft ◽  
...  
Keyword(s):  
Blood Culture ◽  
Multiplex Pcr ◽  
Positive Blood Culture ◽  
Antimicrobial Therapy ◽  
Community Hospital ◽  
Intervention Group ◽  
Standard Of Care ◽  
Pharmacist Intervention ◽  
Coagulase Negative Staphylococcus ◽  
Optimal Therapy

ABSTRACT Multiplex PCR combined with a pharmacist-driven reporting protocol was compared to the standard of care within a community hospital to evaluate initial changes after notification of a positive blood culture. The intervention group demonstrated decreased times to changes in antimicrobial therapy (P = 0.0081), increased changes to optimal antimicrobial therapy (P = 0.013), and decreased vancomycin use for coagulase-negative staphylococcus contaminants (P < 0.01) with multiplex PCR implementation and pharmacist intervention.

Staphylococci among Wild European Rabbits from the Azores: A Potential Zoonotic Issue?

2020 ◽  
Vol 83 (7) ◽  
pp. 1110-1114 ◽  
Author(s):  
MARGARIDA SOUSA ◽  
VANESSA SILVA ◽  
ADRIANA SILVA ◽  
NUNO SILVA ◽  
JESSICA RIBEIRO ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Resistance Genes ◽  
Meca Gene ◽  
Diffusion Method ◽  
Coagulase Negative Staphylococci ◽  
Spa Typing ◽  
Disk Diffusion Method ◽  
Genetic Lineages ◽  
Antimicrobial Resistance Genes ◽  
European Rabbits

ABSTRACT The prevalence and diversity of Staphylococcus species from wild European rabbits (Oryctolagus cuniculus) in the Azores were investigated, and the antibiotic resistance phenotype and genotype of the isolates were determined. Nasal samples from 77 wild European rabbits from São Jorge and São Miguel islands in Azores were examined. Antibiotic susceptibility of the isolates was determined using the Kirby-Bauer disk diffusion method, and the presence of antimicrobial resistance genes and virulence factors was determined by PCR. The genetic lineages of S. aureus isolates were characterized by spa typing and multilocus sequence typing. A total of 49 staphylococci were obtained from 35 of the 77 wild rabbits. Both coagulase-positive (8.2%) and coagulase-negative (91.8%) staphylococci were detected: 4 S. aureus, 17 S. fleurettii, 13 S. sciuri, 7 S. xylosus, 4 S. epidermidis, and 1 each of S. simulans, S. saprophyticus, S. succinus, and S. equorum. The four S. aureus isolates showed methicillin susceptibility and were characterized as spa type t272/CC121, Panton-Valentine leukocidin negative, and hlB positive. Most of the coagulase-negative staphylococci showed resistance to fusidic acid and beta-lactams, and multidrug resistance was identified especially among S. epidermidis isolates. The mecA gene was detected in 20 isolates of the species S. fleurettii and S. epidermidis, associated with the blaZ gene in one S. epidermidis isolate. Five antimicrobial resistance genes were detected in one S. epidermidis isolate (mecA,dfrA,dfrG,aac6′-aph2′′, and ant4). Our results highlight that wild rabbits are reservoirs or “temporary hosts” of Staphylococcus species with zoonotic potential, some of them carrying relevant antimicrobial resistances. HIGHLIGHTS

scholarly journals 639. Time to Recurrence of Clostridioides difficile Infection (rCDI) is Rapid Following Completion of Standard of Care Antibiotics: Results from ECOSPOR-III, a Phase 3 Double-Blind, Placebo-Controlled Randomized Trial of SER-109, an Investigational Microbiome Therapeutic

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S422-S422
Author(s):  
Thomas J Louie ◽  
Matthew Sims ◽  
Richard Nathan ◽  
Steven O'Marro ◽  
Princy N Kumar ◽  
...  
Keyword(s):  
Panel Member ◽  
Standard Of Care ◽  
Oral Microbiome ◽  
Research Support ◽  
Independent Contractor ◽  
Review Panel ◽  
Material Support ◽  
Time To Recurrence ◽  
Study Population

Abstract Background The natural history of CDI recurrence after antibiotics may be helpful to understand the window of opportunity for microbiome repair. ECOSPOR III evaluated the efficacy of SER-109, an investigational microbiome therapeutic, compared to placebo with rates of rCDI as the primary endpoint. SER-109 was superior to placebo in reducing the rate of rCDI following standard-of-care antibiotics at 8 weeks (12.4% vs 39.8%, respectively; P &lt; 0.001). Herein, we describe results from the secondary endpoint, time to recurrence, in this well-characterized study population. Methods A total of 182 C. difficile toxin+ adults with ≥ 3 CDI episodes and symptom resolution on CDI antibiotics were randomly assigned to SER-109 (4 capsules orally x 3 days) or placebo. Recurrence for this analysis was defined as ≥ 3 unformed stools/day for ≥ 48 hours, ± C. difficile stool toxin test, and an investigator decision to treat. Time to CDI recurrence was analyzed using observed data and Kaplan-Meier methods. Data were not imputed for subjects lost to follow-up or discontinued from study. Subjects who did not have a CDI recurrence were censored on the date of study completion, study discontinuation or death. Results Through 24 weeks, 11/89 (12.4%) SER-109 and 36/93 (38.7%) placebo subjects had rCDI (P &lt; 0.001). Of all recurrence events in the study population, 16/47 (34.0%) were observed within 1 week; 30/47 (63.8%) within 2 weeks; and 34/47 (72.3%) within 4 weeks after randomization, highlighting the rapid onset of recurrence. On the other hand, 12/47 (25.5%) recurrences occurred between 4 and 12 weeks, highlighting late onset of recurrence in a subset of patients (Table). Significantly lower rates of recurrence in patients on SER-109 compared to placebo was maintained throughout the 24-week follow-up (Figure). Time of rCDI K-M Plot Conclusion SER-109, an investigational oral microbiome therapeutic, maintained significant efficacy in reducing rCDI vs placebo through 24 weeks. About two-thirds of all recurrences occurred within 14 days of antibiotic completion highlighting the need for rapid repair of the disrupted microbiome. However, the significant number of late recurrences in the placebo arm also highlights that rCDI trials limited to 4 weeks of follow-up after treatment completion may underestimate recurrences. Disclosures 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) 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) Richard Nathan, DO, none (Other Financial or Material Support, I am PI on several clinical trials. If you need that information, I would be happy to supply it.) Princy N. Kumar, MD, AMGEN (Other Financial or Material Support, Honoraria)Eli Lilly (Grant/Research Support)Gilead (Grant/Research Support, Shareholder, Other Financial or Material Support, Honoraria)GSK (Grant/Research Support, Shareholder, Other Financial or Material Support, Honoraria)Merck & Co., Inc. (Grant/Research Support, Shareholder, Other Financial or Material Support, Honoraria) Elaine E. Wang, MD, Seres Therapeutics (Employee) Elaine E. Wang, MD, Seres Therapeutics (Employee, Shareholder) Robert Stevens, PharmD, Seres Therapeutics (Employee, Shareholder) Kelly Brady, MS, Seres Therapeutics (Employee, Shareholder) Barbara McGovern, MD, Seres Therapeutics (Employee, Shareholder) Lisa von Moltke, MD, Seres Therapeutics (Employee, Shareholder)

A multicentre outbreak of ST45 MRSA containing deletions in the spa gene in New South Wales, Australia

2020 ◽  
Vol 75 (5) ◽  
pp. 1112-1116 ◽  
Author(s):  
Alicia G Beukers ◽  
Peter Newton ◽  
Bernard Hudson ◽  
Kimberly Ross ◽  
Thomas Gottlieb ◽  
...  
Keyword(s):  
Methicillin Resistance ◽  
New South ◽  
New South Wales ◽  
False Negative ◽  
Meca Gene ◽  
Gene Detection ◽  
Diagnostic Assays ◽  
South Wales ◽  
Recent Emergence ◽  
Spa Gene

Abstract Background Early identification of MRSA by diagnostic medical microbiology laboratories enables improved antimicrobial choice and outcomes. The Cepheid Xpert® MRSA/SA BC test rapidly identifies Staphylococcus aureus bloodstream infections through spa gene detection and methicillin resistance via mecA gene detection. Recent emergence of S. aureus with deletions in the spa gene has resulted in false-negative results for this test, leading to misidentification of infections with this organism, particularly MRSA ST45. Objectives To investigate the emergence and prevalence of ST45 MRSA in New South Wales (NSW), Australia. Methods WGS read data from six NSW hospitals were collected for 131 ST45 MRSA isolates and analysed. Results Of the 131 ST45 MRSA investigated, 88.5% (116/131) contained a deletion in the spa gene that appeared to have arisen once in approximately 2010 followed by clonal expansion. Given the successful establishment of this ‘spa-deletion’ MRSA clone, the Cepheid Xpert® MRSA/SA BC test became unreliable for confirming S. aureus bacteraemia in NSW. Subsequently, the algorithm used by this test has been updated and evaluated to take into account the presence of S. aureus with either a spa deletion or SCCmec target variations. Conclusions This study highlighted the applied use of WGS for assessing diagnostic assays and informing necessary changes to ensure the viability of the Cepheid Xpert® MRSA/SA BC test in the context of the new ‘spa-deletion’ MRSA clone. It demonstrated how continued surveillance through WGS can reveal evolutionary events that may impact diagnostic assays, allowing corrective modifications to be made in real time.

scholarly journals 1602. Comparative Activity of Ceftolozane-Tazobactam (C/T) and Ceftazidime-Avibactam (CZA) against Pseudomonas aeruginosa (PSA) from Patients with Cystic Fibrosis (CF)

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S797-S797
Author(s):  
Maxwell J Lasko ◽  
David P Nicolau ◽  
Joseph L Kuti
Keyword(s):  
Treatment Options ◽  
Standard Of Care ◽  
Research Support ◽  
Current Standard ◽  
Material Support ◽  
Standard Of Care Treatment ◽  
Hospital Systems ◽  
Support Research ◽  
Research Grant

Abstract Background Acute pulmonary exacerbations (APE) are a frequent cause of hospitalization for patients with CF. PSA is among the most common pathogen implicated in CF APE. Due to repetitive antibiotic courses, multidrug resistance (MDR) must be considered leaving few available intravenous antibiotic options. CZA and C/T are newer anti-PSA antibiotics that have been used to treat CF APE, but little data are available to compare their in vitro activity. Methods Non-duplicate, contemporary, clinical PSA (n=105) isolates were acquired from 85 patients during CF APE from 3 US hospital systems. MICs were assessed in at least triplicate by reference broth microdilution for C/T, CZA, aztreonam (ATM), cefepime (FEP), ceftazidime (CAZ), ciprofloxacin (CIP), levofloxacin (LVX), meropenem (MEM), piperacillin/tazobactam (TZP), and tobramycin (TOB). Current CLSI breakpoints were used to define susceptibility. Activity was further assessed in MDR, CAZ and MEM non-susceptible (NS) phenotypes. Results The mean patient age at isolate retrieval was 31 years (IQR: 21-43), and 20% were under 18 years. Mucoid morphology was observed in 48 (46%) isolates, and MDR defined in 41 (39%). Rates of susceptibility (MIC50/MIC90/%S) were: C/T (1/4/92%), CZA (2/8/90%), CAZ (4/64/68%), TZP (8/256/67%), TOB (2/32/63%), MEM (1/32/58%), ATM (8/64/57%), FEP (8/≥128/50%), CIP (2/8/27%), and LVX (4/16/24%). A mucoid phenotype did not alter %S (non-mucoid vs. mucoid) for C/T (93 vs. 92%) or CZA (91 vs. 88%). Among the 41 MDR PSA, activity was 2/16/83% and 4/16/76% for C/T and CZA, respectively. C/T, CZA, and MEM %S was 77, 69, and 23% for the 35 CAZ-NS isolates. C/T, CZA, and CAZ %S was 84, 77, and 39% for MEM-NS isolates. Conclusion These contemporary PSA from patients with CF displayed low susceptibility rates to most β-lactams, fluoroquinolones, and tobramycin, and MDR was common. C/T and CZA retained similarly high susceptibility against these isolates, including MDR strains and CAZ-NS/MEM-NS phenotypes. These data justify that both CT and CZA may be considered for CF APE due to PSA non-susceptible to current standard of care treatment options. Disclosures David P. Nicolau, PharmD, Cepheid (Other Financial or Material Support, Consultant, speaker bureau member or has received research support.)Merck & Co., Inc. (Consultant, Grant/Research Support, Speaker’s Bureau)Wockhardt (Grant/Research Support) Joseph L. Kuti, PharmD, Allergan (Speaker’s Bureau)bioMérieux (Research Grant or Support, Other Financial or Material Support, Speaker Honorarium)Melinta (Research Grant or Support)Merck & Co., Inc. (Research Grant or Support)Paratek (Speaker’s Bureau)Summit (Other Financial or Material Support, Research funding (clinical trials))

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&lt; 0.001 for RR&lt; 1.0; p&lt; 0.001 for RR&lt; 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 &lt; 0.05). Enterococcaceae relative abundance was associated with glycopeptide AR abundance (p &lt; 0.001). At week 1, Proteobacteria relative abundance was significantly decreased from baseline in SER-109 subjects vs. placebo (p &lt; 0.001). Enterobacteriaceae and Enterococcaceae relative abundances were also decreased from baseline in SER-109 subjects vs. placebo (p &lt; 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)

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