Read our January issue to learn about the National Institute of Allergy and Infectious Diseases (NIAID) renewal funding of up to $102.5M for the ARLG. In this issue, we also spotlight early-stage investigator, Pranita D. Tamma, MD, MHS, and highlight Robert A. Bonomo, MD, of the Louis Stokes Cleveland VA Medical Center, 2020 recipient of the Wolcott Award for Excellence in Clinical Care Leadership.
As antibiotic-resistant bacteria become more urgent threats worldwide, the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, announced today up to $102.5 million in renewed funding over seven years for the Antibacterial Resistance Leadership Group (ARLG). This funding will allow the network to continue and enhance its mission to prioritize, design, and execute clinical research to reduce the public health threat of antibacterial resistance.
Composed of more than 50 leading experts working together to innovate clinical trial design, inform guidelines, and improve clinical practice in infectious diseases, the ARLG received its initial funding in 2013.
Vance Fowler, M.D., of Duke University and Henry Chambers, M.D., of the University of California, San Francisco, will continue to serve as the ARLG principal investigators. The ARLG will include several centers that will support essential network functions:
- The Scientific Leadership Center will provide administrative guidance and oversight, prioritize the research agenda and ensure timely publication of results.
- The Clinical Operations Center will provide clinical support for studies and trials, select sites, oversee protocol teams and ensure that the trials are aligned with ARLG priorities.
- The Laboratory Center will oversee laboratory research and ensure that the specimens from clinical trials are processed, analyzed, and stored appropriately.
- The Statistics and Data Management Center will assist with study design and analysis to ensure high-quality data.
With clinical operations based at the Duke Clinical Research Institute, the ARLG’s research team has collaborations in 19 countries and has initiated more than 40 clinical research studies involving more than 20,000 patients across more than 130 sites. Its three areas of research align with the Centers for Disease Control and Prevention antibiotic resistance threats and include:
- Infections caused by Gram-negative bacteria, such as Escherichia coli;
- Infections caused by Gram-positive bacteria, such as Staphylococcus aureus; and
- Diagnostics such as rapid point-of-care tests to detect drug resistance, guide antibacterial therapy, and support clinical trials.
“The renewal support from the NIAID will allow the ARLG to continue its collaborative work to advance science in antibacterial research, and to provide funding opportunities for the next generation of researchers dedicated to addressing this public health threat,” said Vance Fowler, M.D., ARLG co-principal investigator, member of the DCRI, and professor of medicine at the Duke University School of Medicine.
“We are delighted to be able to continue to support efforts to fight antibiotic resistance by generating data that is used to inform dosing guidelines and developing diagnostic testing for better detection and timely treatment,” Fowler said.
The ARLG is funded through grant UM1AI104681.
Our September 2019 newsletter includes information about the MASTER-GC Study and the Pharmacokinetics Special Emphasis Panel. We also provide a spotlight on early-career trialist, Thomas L. Holland, MD, MSc of Duke University. ARLG’s presence at IDWeek2019 is included as well as recent announcements and publications.
Are you attending IDWeek 2019? Connect with your ARLG colleagues at the following sessions, oral presentations, and posters.
|Day||Time||Session Title||Presentation Title||Moderators||Speakers|
|10/2/2019||1:30-1:55 pm||What’s Hot in ID and HIV||What’s Hot in ID Clinical Science||Cesar Arias||Helen Boucher|
|10/2/2019||3:45-5:15 pm||Opening Plenary Session: From Outbreaks to –Omics: Revolutionizing the Infectious Diseases Landscape in the Age of Big Data||Cesar Arias|
|10/3/2019||8:05-8:20 am||The Big Idea: Making the Case to Policymakers for ID and HIV Priorities||The Big Idea IDSA-HIVMA Advocacy Hill Day: Lessons Learned||Sarah Doernberg, Buddy Creech (panelists)|
|10/3/2019||9:15-10:00 am||Edward H. Kass Lecture: Epidemic Infectious Diseases and Creation of the Infectious Diseases Discipline.||Cesar Arias|
|10/3/2019||10:30-11:45 am||Diagnostic Clinical Cases||Kimberly Hanson (interactive moderator)||Robin Patel (panelist)|
|10/3/2019||10:30-11:45 am||We’re Part of the Problem: How ID Killed Antibiotic Development||Helen Boucher, Vance Fowler||Helen Boucher|
|10/3/2019||10:30-11:45 am||Behavioral Approaches to Antibiotic Stewardship||Ebbing Lautenbach|
|10/3/2019||10:55-11:20 am||Clinical Trials that Might Change your Practice||Clinical Trials in Bacterial Diseases that Might Change your Practice||David van Duin|
|10/3/2019||11:20-11:45 am||Help or Hype? Update on Biomarkers in Management of Adult and Pediatric Infectious Diseases||The Next Generation of ID Host Response Biomarkers||Ephraim Tsalik||Ephraim Tsalik|
|10/3/2019||12:15- 12:45 pm||Rapid Fire Poster Session: Antimicrobial Resistance||Pranita Tamma|
|10/3/2019||12:15- 12:45 pm||Rapid Fire Poster Session: Diagnostics||Patricia Simner|
|10/3/2019||1:45-2:10 pm||Antimicrobial Stewardship in Compromised Hosts||Antimicrobial Stewardship in Solid Organ Transplant Patients||Judith Anesi|
|10/3/2019||1:45-3:00 pm||Applying Contact Precautions: What’s the Best Approach to Reduce Transmission?||Ebbing Lautenbach|
|10/3/2019||2:35-3:00 pm||Head Scratching Cases of MDR Gram-Negatives Other than Enterobacteriales||Acinetobacter baumannii||Yohei Doi,
|10/3/2019||2:35-3:00 pm||Who Owns Sepsis Anyway?||Sepsis and Antimicrobial Stewardship: Right Drug, Right on Time||Deverick Anderson|
|10/3/2019||3:15-4:30 pm||Clinical Controversies||Oral Therapy for Uncomplicated S.aureus Bacteremia||Vance Fowler|
|10/4/2019||8:00-9:00 am||Meet the Professor
Cefazolin vs Nafcillin for MSSA Infections: Pro- Con Debate
|Cefazolin vs Nafcillin for MSSA Infections: Pro- Con Discussion||Sarah Doernberg|
|10/4/2019||10:30-11:45 am||Phages to the Rescue||Yohei Doi,
|10/4/2019||10:30-11:45 am||Tackling the Big Beasts of Healthcare Epidemiology||Ebbing Lautenbach|
|10/4/2019||10:30-11:45 am||Pathogenesis and Inflammatory Response||Robert Bonomo|
|10/4/2019||1:45-3:00 pm||Big Beasts I||Samuel Shelburne|
|10/4/2019||1:45-3:00 pm||Emergent Mechanisms of Resistance and How to Prevent Them||Amy Mathers|
|10/4/2019||1:45-3:00 pm||Innovative Diagnostics||Robin Patel|
|10/4/2019||1:45-2:04 pm||Hot Topics in Pediatric Infectious Diseases||Hot Topics in Pediatric Infectious Diseases-Speaker 1||Ritu Banerjee|
|10/4/2019||3:15-4:30 pm||Challenging Cases in Infectious Diseases||Henry F. Chambers|
|10/4/2019||3:15-4:30 pm||Cutting Edge in Pediatric Osteomyelitis: Basic Scientist, ID Clinician, and Orthopedist||Pranita Tamma|
|10/5/2019||8:00-9:00 am||Meet the Professor
Registration Trials versus Clinical Practice: Challenges Associated with Newly Approved Antimicrobials
|10/5/2019||10:30-11:45 am||Novel Antimicrobials and Approaches Against MDR Organisms||Jose Munita|
|10/5/2019||2:10-2:35 pm||The Etiology of Community Acquired Pneumonia: How Appropriate are Current Guidelines?||New Diagnostic Platforms and Antibiotic Use in Community Acquired Pneumonia||Sara Cosgrove|
|10/5/2019||3:15-4:30 pm||This Year’s Innovations in Pediatric Infectious Diseases||Buddy Creech|
|10/5/2019||3:15-4:30 pm||Diagnosis and Management of Cryptococcal Meningitis||Jose M. Miro|
|10/5/2019||3:15-4:30 pm||Mechanistic Basis of Action and Resistance of B-lactam/B-lactamase Inhibitors||Yohei Doi|
|10/5/2019||3:15-4:30 pm||Opportunistic Infections in the ICU: From Pathophysiology to Practical Approaches||Samuel Shelburne|
|10/5/2019||3:15-4:30 pm||Fungi: Blood, Sweat, and Genes||Cornelius Clancy|
|10/5/2019||4:45-5:15 pm||Maxwell Finland Lecture||Prosthetic Joint Infection: Bedside to Bench, Bath Sonication and Beyond||Robin Patel|
|10/6/2019||8:00-9:00 am||Hot Topics in Outpatient Antimicrobial Therapy of Infective Endocarditis||Jose M. Miro|
|10/6/2019||9:15-10:45 am||Closing Plenary Session: All About Vaccines: The Individual, the Community, the World||Cesar Arias
|10/3/2019||2:45-3:00 pm/144ABC||841-Implications of C. difficile Treatment on Environmental Contamination: A Randomized, Controlled Trial with Microbiologic, Environmental, and Molecular Outcomes||Nicholas A Turner, Maria Gergen, William A Rutala, Daniel J Sexton, Vance G Fowler, Rachel Addison, Deverick J Anderson|
|10/4/2019||3:30-3:45 pm/147AB||1878-Impact of Antibiotic Stewardship Rounds in the Intensive Care Setting: a Prospective Cluster-Randomized Crossover Study||Jessica Seidelman, Nicholas A. Turner, Rebekah Wrenn, Christina Sarubbi, Deverick J. Anderson, Daniel J. Sexton, Rebekah Moehring|
12: 35 – 12:40 pm: A brief oral presentation will be given in the Poster/Exhibit Hot Zone area.
|640-Randomized clinical trial evaluating clinical impact of RAPid IDentification and antimicrobial Susceptibility testing for Gram Negative bacteremia (RAPIDS-GN)||Ritu Banerjee, Lauren Komarow, Abinash Virk, Nipunie Rajapakse, Audrey Schuetz, Brenda Dylla, Michelle Earley, Judith Lok, Peggy Kohner, Sherry Ihde, Nicolynn Cole, Lisa Hines, Katelyn Reed, Omai Garner, Sukantha Chandrasekaran, Annabelle de St. Maurice, Meganne Kanatani, Jennifer Curello, Rubi Arias, William Swearingen, Sarah Doernberg, Robin Patel, and the Antibacterial Resistant Leadership Group|
|10/3/2019||12:15-1:30 pm||636-Genome Epidemiology of Carbapenem-Resistant Acinetobacter baumannii in the United States||Alina Iovleva, Mustapha M Mustapha, Eric Cober, Sandra Richter, Cesar Arias, Jesse Jacob, Robert Salata, Michael Satlin, Darren Wong, Robert Bonomo, David van Duin, Yohei Doi|
|10/3/2019||12:15-1:30 pm||498-High burden of CRO colonization and its association with infection among patients transferred to a tertiary care hospital in India||Smita Sarma, Matthew Robinson, Yatin Mehta|
|10/3/2019||12:15-1:30 pm||625-Genomic Epidemiology of Carbapenem-Resistant Enterobacteriaceae from Colombia: A Prospective Multicenter Study||Jinnethe Reyes, Lorena Díaz, Lina P. Carvajal, Rafael Rios, Lina V. Millán, Aura M. Echeverri, Angie K. Hernandez, Sandra Vargas, Soraya Salcedo, Adriana Marin, Laura Mora, Karen Ordoñez Diaz, Edilberto Cristancho Quintero, Sandra Valderrama, Beatriz Elena Ariza, Gloria Cortes, Laura Rojas, Henry F. Chambers, Vance G. Fowler, Barry Kreiswirth, Maria V. Villegas, Robert Bonomo, Blake Hanson, David van Duin, Cesar A. Arias|
|10/3/2019||12:15-1:30 pm||508-Gentamicin Non-susceptibility is Associated with Persistence of Carbapenem-Resistant Klebsiella pneumoniae in the Urinary Tract||Courtney L. Luterbach, Heather Henderson, Eric Cober, Sandra Richter, Robert Salata, Keith Kaye, Yohei Doi, Richard Watkins, Robert Bonomo, David van Duin|
|10/04/2019||12:15-1:30 pm||1330-Evaluation of Multiple Host Response-Based Strategies to Classify Acute Respiratory Illness||Melissa Ross, Ricardo Henao, Thomas Burke, Micah McClain, Geoffrey Ginsburg, Christopher Woods, Ephraim Tsalik|
|10/5/2019||12:15-1:30 pm||2276-Clinical Epidemiology of The Carbapenem-Resistant Enterobacteriaceae Epidemic in Colombia: A Multicenter Prospective Study||Sandra Valderrama-Beltran, Lauren Komarow, Soraya Salcedo, Laura Mora, Adriana Marin, Karen Ordoñez Diaz, Edilberto Cristancho Quintero, Beatriz Helena Ariza, Gloria Cortes, Alejandro de La Hoz, Jose Oñate, Elsa Yasmin Vente, Viviana Mendez, Jairo Figueroa, Luz M. Osorio, Carlos Moreno, Jinnethe Reyes, Luis Dulcey, Christian Pallares, Henry Chambers, Vance G. Fowler, Scott Evans, Barry Kreiswirth, Maria V. Villegas, Robert Bonomo, David van Duin, Cesar A. Arias|
Chair, Pharmacokinetics Special Emphasis Panel
Thomas Lodise, Pharm D, PhD
Albany College of Pharmacy and Health Sciences
Professor, Department of Pharmacy Practice
The Pharmacokinetics Special Emphasis Panel (PK SEP) is dedicated to enhancing our current understanding of antimicrobial exposure-response relationships in patients with invasive infections. Similar to other ARLG special emphasis panels and committees, the PK SEP supports the mission of the ARLG by reviewing proposals, assigning scientific merit scores, and serving as a resource in prioritizing the network’s scientific agenda. The panel’s purpose is to ensure that state-of-the-art pharmacokinetic/pharmacodynamic (PK/PD) methods are used to design innovative pharmacologic strategies that optimize the utility of the existing antibacterial agents in our armamentarium for implementation into clinical practice.
The PK SEP concentrates on development of innovative dosing regimens for antibacterial agents prioritized by the U.S. Centers for Disease Control and Prevention (CDC), U.S. Food and Drug Administration (FDA), and the National Institutes of Health (NIH) to combat antibacterial resistance. In addition, the PK SEP is most interested in identifying optimal dosing schemes for patient populations typically underrepresented in Phase III clinical trials, but likely to be encountered in clinical practice.
With support from the PK SEP, the ARLG is pioneering practice-changing research. Panel chair, Tom Lodise, PharmD, PhD, highlights three studies below:
PROVIDE: Prospective Observational Evaluation of the Association between Initial Vancomycin Exposure and Failure Rates among Adult Hospitalized Patients with MRSA Bloodstream Infection.
Recently published in Clinical Infectious Diseases, PROVIDE was a multi-center prospective study to evaluate the relationship between day-2 vancomycin exposure profiles and outcomes in patients infected with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia.Vancomycin is the most commonly administered antibiotic in United States hospitals and has been a mainstay for treatment of MRSA infections for decades, yet optimal dosing of vancomycin is unclear. For serious MRSA infections, current guidelines recommend targeting an area under the concentration time curve to minimum inhibitory concentration ratio (AUC/MIC) ≥400. Despite widespread clinical adoption of these recommendations, optimal exposure targets remain controversial.
The study took place in 14 hospitals across the United States. The primary outcome was treatment failure, defined as 30-day mortality or a positive blood culture at ≥7 days. Secondary outcomes included acute kidney injury (AKI), defined as a ≥1.5-fold increase in serum creatinine. Of the 265 eligible patients, treatment failure occurred in 18% and AKI in 26% of patients. Overall, higher day-2 vancomycin exposures for patients with MRSA bacteremia were not associated with a lower incidence of treatment failure but were associated with higher rates of AKI. Patients with day 2 area under the curve (AUC) exposures ≤515 experienced the best global outcomes (no treatment failure and no AKI).
The results from PROVIDE have important implications for clinical practice and indicate that clinicians should reassess the balance of benefits and risks of targeting higher day-2 exposures for patients with MRSA bacteremia. Most importantly, the findings suggest that vancomycin dosing should be guided by the AUC and day-2 AUCs should be maintained below 515 to maximize efficacy and minimize risk of AKI. Moving forward, further study is needed to define the lower bound of the therapeutic range
PROVIDE results heavily informed the draft vancomycin consensus guidelines by the American Society of Health-System Pharmacists ASHP. Based in large part on PROVIDE, the guidelines now recommend monitoring vancomycin AUCs vs. troughs in clinical practice.
ACUMIN: Acute Care Unit Minocycline
The ACUMIN study is examining the PK of intravenous (IV) minocycline in critically-ill patients with Gram-negative infections in the intensive care unit (ICU). Minocycline is a tetracycline derivative first approved in the United States as both oral and IV formulations in the 1970s. A new IV formulation of minocycline became available in 2015 and is approved by the FDA for the treatment of patients with infections due to Gram-positive and Gram-negative pathogens, including Acinetobacter baumannii.
A. baumannii is a healthcare-associated pathogen and a major cause of pneumonia, bacteremia, and wound infection among critically ill patients. A. baumannii is intrinsically resistant to many commercially available antibiotics. It also has a remarkable capacity to develop resistance to commonly used antibiotics like carbapenems, aminoglycosides, and fluoroquinolones. As a result, the terms ‘multi-drug resistant (MDR)’ and ‘extensively drug resistant’ are often used to characterize the different patterns of resistance exhibited by A. baumannii. Infections due to MDR A. baumannii is a growing world-wide problem and is classified as a serious public health threat by the CDC. Fortunately, minocycline is highly active against A. baumannii, including MDR strains, and is well tolerated, making it a potential treatment option for MDR A. baumannii infections.
While there is longstanding clinical use experience with minocycline in patients, PK studies are limited and were conducted in the 1970s in healthy volunteers. In addition, no published minocycline PK data exists in critically ill patients staying in the ICU.
ACUMIN is designed to address this PK knowledge gap by developing a population PK model to describe the plasma exposure profile of minocycline in ICU patients following a single 200-mg IV infusion over 60 minutes. Results of ACUMIN will inform optimal dosing of minocycline in the critically ill patient population. More importantly, this study will determine if dosing adjustments for the approved FDA minocycline dosing regimen are needed based on weight and estimated renal function. ACUMIN enrollment is complete and data analyses will start in fall 2019.
COMBINE: Efficacy and Safety of Ceftazidime-Avibactam in Combination with Aztreonam
COMBINE focuses on the use of ceftazidime-avibactam in combination with aztreonam (ATM) for patients with metallo-β-lactamase (MBL) – producing Gram-negative infections. Metallo-β-lactamases are carbapenemases and have the ability to inactivate all β-lactams except ATM. Infections due to MBL-producing Gram-negative bacteria (GNB) are increasing worldwide and are a major public health concern as there are limited treatment options available. Furthermore, none of the recently approved antibiotics have notable activity against MBL-producing GNB. Several antibiotics with activity against MBL-producing GNB are being developed, but none are anticipated to be available until at least 2021. This underscores the demand of redeploying our existing agents in innovative ways to meet the needs of patients today.
One strategy that is serving as a “bridge” treatment for MBL-producing GNB infections is ceftazidime-avibactam (AVYCAZ) combined with ATM. Although the precise mechanism of improved bacterial killing activity with AVYCAZ combined with ATM is not completely understood, it is likely attributable to maximal saturation of the diverse penicillin binding proteins present in GNB, flooding of periplasm with β-lactams, and maximal binding of available β-lactamases. Aztreonam is not inactivated by MBLs but many MBL-bearing GNB co-harbor extended spectrum beta-lactamases (ESBLs) that inactivate ATM. In the combination of ATM with AVYCAZ, AVI inhibits the ESBLs and other beta-lactamases that are often present in MBL-producing GNB, allowing ATM, which is unaffected by MBLs, to effectively bind to its target site of action (i.e., bacterial penicillin binding proteins).
Before uniform adoption of this treatment, it is critical to identify the optimal combination of AVYCAZ with ATM regimens associated with maximal efficacy and safety due to the potential of cumulative toxicity from use of two beta-lactam antibiotics simultaneously. To identify the optimal treatment regimens, an in-vitro PK/PD study using the hollow fiber infection model (HFIM) system was conducted to determine the optimal AVYCAZ combined with ATM treatment regimens that result in maximal bacterial kill and resistance suppression. The HFIM studies were selected to determine optimal combination regimens as they are an integral part of the drug development process and are used to inform dose and schedule selection for Phase III clinical trials. They are particularly useful in situations when there are limited clinical data available to define optimal therapy, especially when there is interest in studying humanized drug exposure profiles, treatment durations, and starting bacterial burdens that mirror clinical practice.
In these HFIM experiments the two combination regimens that showed maximal bacterial killing and resistance suppression over 7 days were:
- AVYCAZ 2.5 g IV as a 2-hour infusion every 8 hours combined with ATM 2g IV as a 2-hour infusion every six hours, and
- AVYCAZ combined with ATM, each administered as a continuous infusion (CI) (AVYCAZ 7.5 g/day CI combined with ATM 8g/day CI).
The ARLG, in consultation with the PK SEP, believe it is of paramount importance to establish the safety and PK of these regimens in humans. Although AVYCAZ and ATM appear to be safe and well-tolerated, there are no available data on safety when these antibiotics are used in combination. Mild-to-moderate elevations in liver enzymes are common with ATM; however, these elevations are usually self-limiting and do not require ATM discontinuation. It is unclear if AVYCAZ combined with ATM will further exacerbate liver enzyme elevations or lead to other adverse events due to the potential of cumulative toxicity from dual-β-lactam treatment. There are also no published PK data of these antibiotics when administered concurrently, and it is therefore unknown if use of these agents in combination will lead to an altered PK profile of each agent due to inhibition of renal or other compensatory clearance mechanisms. Therefore, a Phase I study using healthy volunteers was launched to assess the safety and PK profile of AVYCAZ combined with ATM relative to its standalone counterparts.
This Phase I study is currently underway at the Duke Early Phase Clinical Research Unit. It is an open-label, single center study in 48 healthy adult male and female participants age 18-45 years old. Eligible subjects are admitted to the Phase I unit and assigned into one of six dosing cohorts. Four treatment cohorts are single-agent dosing cohorts and include AVYCAZ per label dosing, AVYCAZ as a CI, ATM per label dosing, and ATM as a CI. Single-drug treatment cohorts are being conducted to collect baseline safety and PK data. The remaining two cohorts are the two optimal AVYCAZ combined with ATM regimens identified from the HFIM experiments. Participants will stay in the study unit for a minimum of one week. Cohorts 1-4 will be completed prior to Cohorts 5 and 6.
Safety is being closely monitored using daily assessments of adverse events, vital signs, and clinical laboratory safety tests. Serial blood and urine samples are being collected for PK evaluation. The target completion for enrollment is December 2019 with data analysis completed in early 2020.
As ARLG moves forward, the PK SEP will continue to support the mission of the ARLG by reviewing proposals, assigning scientific merit scores, and serving as a resource in prioritizing the ARLG scientific agenda. The panel will continue to ensure that the best PK/PD methods are used to derive optimal treatment strategies with maximal efficacy and safety for implementation into clinical practice. The SEP will also work to ensure the populations most likely to be encountered in clinical practice are included when designing future studies.
Congratulations to the ARLG’s co-principal investigators, Vance Fowler, MD, MHS, Duke University, and Henry “Chip” Chambers, MD, UCSF, as well as a number of other ARLG investigators who have been recognized as world experts in Staphylococcus aureus by Expertcape.
In addition, Dr. Fowler was recognized as the number one world expert in bacteremia by Expertscape. Other ARLG leaders, such as Robert Bonomo, MD, David Paterson, MD, Ralph Corey, MD, and Tom Holland, MD, ranked high on the list.
Congratulations to Robert Bonomo, MD, ARLG Laboratory Center Co-Director, who was named a Distinguished University Professor at Case Western Reserve University (CWRU) during its fall convocation on August 28, 2019. CWRU awards the title of “Distinguished University Professor”— a permanent, honorific title, to acknowledge contributions of full-time, tenured faculty with exceptional records of research, scholarship, teaching, and service.
Bonomo, a professor of medicine, pharmacology, molecular biology, and microbiology at the CWRU School of Medicine, has dedicated his research career to addressing the mounting problem of antibiotic resistance. “Infections previously brought under control can resurface in resistant and more virulent new forms,” he said, “allowing disease to proliferate — potentially unchecked.”
Among his investigations, Bonomo works to uncover the genetic and amino acid determinants of bacterial enzymes that create multi-resistance to such widely used antibiotics as penicillins and cephalosporins. Nailing down these sequences and using an integrated approach can lead to new medications that overcome the antibiotic resistance, and his work is paying off. Because of his collaboration with colleagues at CWRU and elsewhere, five new antimicrobials have been approved to date. “We’re always trying to stay a step ahead of the bacteria,” he said. “Evolution rewards organisms that adapt to their environments, including those that fend off antibiotics, so there is a fundamental natural mechanism that we have to overcome.” Bonomo said his teaching and mentoring are as meaningful to him as his research. “Providing intellectual prep for the next generation helps ensure that future patients live longer, healthier lives,” he said. “Nothing can be more crucial than that.”
Read the complete article from CWRU.
Support your ARLG colleagues who will be presenting at the 29th European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Amsterdam, Netherlands from April 13-16, 2019.
|Date/ Time||Session Title||Presenter (Chair or Moderator noted)||Topic (if presenter)||Place|
|Saturday, April 13 13:30 – 14:30||Antibacterial activity of unusual combinations||Barry Kreiswirth||Multifactorial treatment approaches targeting carbapenem-resistant and hypervirulent Klebsiella pneumoniae||Arena 2|
|Saturday, April 13 14:45 – 15:45||Clinical Trials with recently approved or late- stage development antibiotics||Thomas Holland||An efficacy analysis by lesion size of iclaprim versus vancomcin in patients with acute bacterial skin and skin structure infections: pooled phase III REVIVE trials||Arena 5|
|Saturday, April 13 14:45 – 15:45||Beta-lactamase inhibitors: the “second generation” meets the “first generation” problems||Robert Bonomo||Imipenem-relebactam efficiently inhibits D179 variants of the KPC-2 beta-lactamase||Arena 2|
|Saturday, April 13
10:00 – 12:00
|Management of chronic bone and joint infections||Robin Patel (Chair)||Hall D|
|Sunday, April 14 11:00 – 12:00||Pathogenetic profiling to fight antimicrobial resistance||Robert Bonomo (Chair)||Hall K|
|Sunday, April 14 14:45 – 15:45||Antibodies in the flight against multidrug-resistant Gram-negative bacterial infection||Robert Bonomo (Chair)||Hall H|
|Sunday, April 14
11:00 – 12:00
|Possible impact of new immunomodulators on infection and infection management||David van Duin (Chair)||Hall B|
|Sunday, April 14
14:45 – 15:45
|US experiences||Bettina C. Fries||Antibody-mediated killing of multidrug-resistant Gram-negative bacteria: what’s the future?||Hall H|
|Monday, April 15 07:30 – 8:30||How to use Point-of-Care tests in microbiology? European vs.||Robin Patel (Chair)||Robin Patel (Rochester, United States)||Hall J|
|Monday, April 15 16:00 – 18:00||Phage therapy’s coming of age: Progress towards the application of bacteriophages in the treatment of infectious diseases||Robin Patel (Chair)||Hall J|
|Tuesday, April 16 08:45 – 10:45||MRSA, VRE and beyond||Cesar Arias (chair)||Hall H|
|Tuesday, April 16 11:00 – 12:00||Recent Clinical Trials||Vance Fowler||Exebacase (Lysin CF-301) Improved clinical responder rates in methicillin-resistant Staphylococcus aureus bacteraemia including endocarditis compared to standard of care antibiotics alone in a first-in patient phase 2 study||Hall N|
|Tuesday, April 16
11:00 – 12:00
|Infection in immunocompromised hosts||David van Duin (Chair)||Hall J|
|Tuesday, April 16
12:15 – 13:15
|Networks for Clinical Research – no other way||David van Duin (Moderators)||Arena 4|
|Tuesday, April 16
12:15 – 13:15
|Networks for Clinical Research – no other way||Sarah Doernberg||ARLG in the USA||Arena 4|
|Tuesday, April 16
13:30 – 15:30
|Interventions to reduce morbidity and mortality of bloodstream infection||Thomas Holland||Patients’ experiences with Staphylococcus aureus and Gram-negative rod bloodstream infections: a qualitative study to inform development of a quality of life measure||Hall N|
|Tuesday,April 16 13:30 – 15:30||Bacterial resistance: evolution, plasmids and fitness||Barry Kreiswirth||Processes driving the evolution of antibiotic resistance||Hall E|
Consortium on Resistance against Carbapenems in Klebsiella Pneumoniae and other Enterobacteriaceae
An observational study that utilizes an existing CRKP consortium consisting of 20 hospitals that are part of 9 different health care systems. The primary objectives were:
1) To determine whether CRKP strain type is associated with outcomes in CRKP infections
2) To evaluate the constellation of clinical and microbiologic factors associated colistin and tigecycline non-suspectibility
3) To explore variation in treatment and outcomes of CRKP infections in various anatomical sites.
Collection of Rectal and Oropharyngeal Swabs from Healthy Volunteers
Collection of rectal and oropharyngeal swabs from healthy controls for the development of an assay