Translational Infectious Disease Research Program
Antimicrobial resistance is considered by the National Foundation for Infectious Diseases to be the number one infectious disease problem in the USA. 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 developed fast enough. One approach would be to find synergy with the use of two presently available agents but doing so would not have practical value in caring for very sick patients, unless the synergy can be determined quickly.
For more information, please contact Dr. George Pankey (firstname.lastname@example.org).
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.
The laboratory is equipped with a Vitek® 2 instrument (which performs rapid automated identification and antimicrobial susceptibility testing of bacteria and fungi). A Spiral Biotech plater and QCount automated colony counter are used for time-kill studies to determine interactions between antimicrobial agents. The Etest method and checkerboard methods are also used. Recent synergy studies include: nisin plus polymyxin B against pandrug-resistant Acinetobacter baumannii; fosfomycin plus doxycycline against linezolid-resistant, vancomycin-resistant Enterococcus faecium; and polymyxin B plus rifampin against mcr-producing Enterobacteriaceae. Our laboratory is also involved in the study of how quickly bacteria are killed by antibioticsand other non-antibiotics, such as atorvastatin, against Gram-negative bacteria and Candida. Future plans include genomics studies analyzing bacteria and yeast using next-generation sequencing technologies.
Candida species are the fourth most common cause of hospital-acquired bloodstream infections in the US (1995-2002), with Candida albicans predominating. However, in 2010-2011 at Ochsner, Candida glabrata was most common. C. glabrata is more resistant to certain antifungals, creating a concern regarding appropriate therapy because susceptibility studies are not performed by the Ochsner microbiology laboratory. Our 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, if any antifungal resistance is developing, and comparing clinical data with in vitro data. We will determine if there is any effect of 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 and caspofungin plus polymyxin B against C. glabrata; and fluconazole plus polymyxin B against Candida auris.
The laboratory has a T2MR® instrument (T2Dx®) that will rapidly (in 3-5 hours) detect Candida in the blood. 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-approved in 2018.
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. doi:10.7326/M18-2772
Our laboratory continues to collect and freeze bacterial and fungal isolates from blood cultures—as well as unusual or multidrug-resistant isolates from other specimen sources. Over 22,000 isolates are available for use in future studies. The Infectious Disease 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 research.
The laboratory also is a regional site for the collection of bacterial and fungal isolates for the SENTRY Antimicrobial Surveillance Program for USA (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
Published: 15 March 2019