Translational Infectious Disease Research Program
Antimicrobial resistance is considered by the National Foundation for Infectious Diseases to be the number one long term infectious disease problem in the U.S. Bacteria such as Pseudomonas, Klebsiella, and Acinetobacter are presently resistant to all therapy except for the polymyxins, but polymyxin resistance is now being reported as well. New antibiotics are not being rapidly developed. One approach to help combat resistance is to determine synergy with the use of two or more presently available agents but doing so would not have practical value in caring for very sick patients, unless the synergy could be determined quickly.
Dr. George Pankey
The goal of the Infectious Disease Translational Research Laboratory is to develop rapid diagnostic methods for the determination of synergy or antagonism between two or more antimicrobial agents against multidrug-resistant bacteria and fungi. We developed an Etest® methodology that is very promising in this regard. Our research also involves evaluation of rapid diagnostic testing for direct-from-blood organisms and resistance genes.
Bacterial Synergy Testing
The laboratory is equipped with a Vitek® 2 instrument (which performs rapid automated identification and antimicrobial susceptibility testing of bacteria and fungi). An Eddy Jet Spiral plater with a Sphere Flash automated colony counter are used for time-kill studies to determine interactions between antimicrobial agents, along with the Etest and checkerboard methods. Recent synergy studies include: nisin plus polymyxin B against pan drug-resistant Acinetobacter baumannii; fosfomycin plus doxycycline against linezolid-resistant, vancomycin-resistant Enterococcus faecium; fosfomycin plus meropenem against metallo-ß-lactamase producing Pseudomonas aeruginosa; and lefamulin plus doxycycline against linezolid-resistant, vancomycin-resistant E. faecium. Our laboratory is also involved in the study of how quickly bacteria are killed by antibiotics and non-antibiotics with antibacterial activity.
Thomas VM, Brown RM, Ashcraft DS, Pankey GA. 2019. Synergistic effect between nisin and polymyxin B against pandrug-resistant and extensively drug-resistant Acinetobacter baumannii. Int J Antimicrob Agents. 53:663-668. https://doi.org/10.1016/j.ijantimicag.2019.03.009
Davis H, Brown R, Ashcraft D, Pankey G. 2020. In Vitro Synergy with Fosfomycin Plus Doxycycline Against Linezolid and Vancomycin-resistant Enterococcus faecium. J Global Antimicrob Resist.;22:78-83. https://doi.org/10.1016/j.jgar.2020.01.014
Candida species are the fourth most common cause of health care-associated bloodstream infections in the US (2015), with Candida albicans predominating. However, at Ochsner since 2010, Candida glabrata has been the most common species. C. glabrata is more resistant to certain antifungals, creating a concern regarding appropriate therapy, because susceptibility studies are not routinely performed by the diagnostic microbiology laboratory. The Infectious Disease research laboratory is performing antifungal susceptibility testing on these bloodstream isolates. Specific aims of the study include determining if there is a trend in Candida species being isolated more frequently from the blood and if any antifungal resistance is developing. We will determine if there is any effect of the time of diagnosis and time of initial antifungal therapy on mortality of patients with Candida bloodstream infections. This study will provide useful information that may improve treatments for future patients. Synergy studies include fluconazole plus polymyxin B or doxycycline or tigecycline or caspofungin against C. glabrata; and fluconazole plus polymyxin B or trimethoprim-sulfamethoxazole against Candida auris.
Hooper RW, Ashcraft DS, Pankey GA. 2018. In vitro synergy with fluconazole plus doxycycline or tigecycline against clinical Candida glabrata isolates. Med Mycol. Mar:1-5. https://doi.org/10.1093/mmy/myy008
Adams EK, Ashcraft DS, Pankey GA. 2016. In vitro Synergistic Activity of Caspofungin Plus Polymyxin B Against Fluconazole-Resistant Candida glabrata. Am J Med Sciences. Mar:351(3):265-9. https://doi.org/10.1016/j.amjms.2015.12.014
Pankey G, Ashcraft D, Kahn H, Ismail A. 2014. Time-kill assay and Etest evaluation for synergy with polymyxin B and fluconazole against Candida glabrata. Antimicrob. Agents Chemother. Oct;58(10):5795-800. https://doi.org/10.1128/AAC.03035-14
The Infectious Disease research laboratory has a T2MR® instrument (T2Dx®, T2 Biosystems) that will rapidly detect Candida spp. and 90% of deadly ESKAPE pathogens (E. faecium, Staphylococcus aureus, Klebsiella pneumoniae, P. aeruginosa, and Escherichia coli) in the blood in 3-5 hrs. This will enable early and more appropriate treatment decisions, since up to 5 days are required for identification from blood culture. Our laboratory was one of 11 U.S. acute care hospitals who participated in the clinical trial for the T2Bacteria Panel, which was FDA-cleared in 2018. The T2Resistance Panel- Research use only (RUO), which can detect 13 resistance genes from both gram-positive and gram-negative pathogens directly from blood, is available for future research studies. Other products available with this T2MR technology include the T2Cauris Panel RUO, which detects the rapidly emerging multidrug-resistant Candida auris in patient skin and blood, in addition to hospital environmental samples in <5 hrs and the T2SARS-CoV-2 Panel, designed for direct detection of nucleic acid from SARS-CoV-2 in upper respiratory specimens in <2 hrs.
M. Hong Nguyen, MD; Cornelius J. Clancy, MD; A. William Pasculle, ScD; Peter G. Pappas, MD; George Alangaden, MD; George A. Pankey, MD; Bryan H. Schmitt, DO; Altaf Rasool, MD; Melvin P. Weinstein, MD; Raymond Widen, MD; Diana R. Hernandez, PhD; Donna M. Wolk, PhD; Thomas J. Walsh, MD; John R. Perfect, MD; Mollie N. Wilson, MS; and Eleftherios Mylonakis, MD. Performance of the T2Bacteria Panel for Diagnosing Bloodstream Infections. A Diagnostic Accuracy Study. 2019. Ann Intern Med. https://doi.org/10.7326/M18-2772
Voigt C, Silbert S, Widen RH, Marturano JE, Lowery TJ, Ashcraft D, Pankey G. 2020. The T2Bacteria Assay Is a Sensitive and Rapid Detector of Bacteremia That Can Be Initiated in the Emergency Department and Has Potential to Favorably Influence Subsequent Therapy. J Emerg Med May;58(5):785-796. https://doi.org/10.1016/j.jemermed.2019.11.028 Epub 2020 Jan PMID: 31982197
The Infectious Disease research laboratory continues to collect and bank bacterial and fungal isolates from blood cultures—as well as unusual or multidrug-resistant isolates from other specimen sources. Over 25,000 isolates are available for use in future studies. This research laboratory serves as a reference laboratory to the Ochsner diagnostic microbiology laboratory to expand testing capabilities on patients’ cultures and as a teaching laboratory for undergraduate and medical students, residents, and fellows interested in Infectious Disease translational research.
The laboratory also is a regional site for the collection of bacterial and fungal isolates for the SENTRY Antimicrobial Surveillance Program for USA/Core Lab, representing the SW region of the U.S. (JMI Laboratories, North Liberty, IA).
SENTRY Program Participating Sites (1997–2016)
Open Forum Infectious Diseases, Volume 6, Issue Supplement_1, March 2019, Pages S95–S102, https://doi.org/10.1093/ofid/ofz058
For more information, please contact Dr. George Pankey (firstname.lastname@example.org).