New combinations and repurposed antibiotics active against the pandrug-resistant Nevada CRE, NDM-1 strain early release today in AAC
Our latest manuscript: "Synergistic combinations and repurposed antibiotics active against the pandrug-resistant Klebsiella pneumoniae Nevada strain." Antimicrobial Agents and Chemotherapy early release identifies:
Highly synergistic activity of several antimicrobial combinations.
Low apramycin and spectinomycin MIC values.
CDC previously reported that none of 26 antimicrobials they tested were active against the Nevada strain. That made the strain until now pandrug-resistant.
Links to several news articles about this pandrug-resistant strain::
The Atlantic. NPR, NBC, PBS. Forbes
"3 Drug Combinations Appear Effective Against C auris" by Jared Kaltwasser discussed work presented by Thea Brennan-Krohn at ASM Microbe 2019.
Gentian violet is diluted in hollow fiber cassette with a half life of approximately 4 hours based on dilution of initial "dose" in central compartment with fresh media at flow rate selected on peristaltic pump. Next two antibiotics with different half lives. Will the bacteria outside the hollow fibers survive and for how long?
JoVE manuscript accepted on use of Inkjet Printing to perform antimicrobial susceptibility testing for single and drug combinations and follow up time-kill study methodology
Postdoctoral fellow, Thea Brennan-Krohn, recently had a manuscript accepted in the Journal of Visualized Experimentation, aka JoVE. The title of the manuscript and link to the abstract are "Antimicrobial Synergy Testing by the Inkjet Printer-Assisted Automated Checkerboard Array and the Manual Time-Kill Method." We have been fielding a lot of questions over the past two years about implementation of inkjet printing antimicrobial susceptibility testing technology and thought it would be useful to share a video of the technique as well as classic time-kill analysis to analyze antimicrobial synergy. We are excited to learn that the CDC has decided to implement the technology in the near future in their Antimicrobial Resistance Laboratory Network (ARLN), initially to test, the combination of ceftazidime-avibactam and aztreonam for activity against multidrug-resistant Gram-negatives.
BIDMC news release on Thea's antimicrobial synergy paper:
"Bacteria—especially Gram-negative strains—are becoming increasingly resistant to current antibiotic drugs, and the development of new classes of antibiotics has slowed. Faced with these challenges, investigators are studying the potential of combination therapy, in which two or more drugs are used together to increase or restore the efficacy of both drugs against a resistant bacterial pathogen. Now new research indicates that such synergy may work even when bacteria become resistant to colistin, which is considered a treatment agent of last resort.
The findings are especially promising because recent evidence indicates the potential for rapid worldwide spread of colistin resistance. “For an infected patient, if the multidrug-resistant Gram-negative bacterial pathogen is resistant to colistin, then there is a big problem,” said senior author James Kirby, MD, Director of the Clinical Microbiology Laboratory at BIDMC.
In their Antimicrobial Agents and Chemotherapy study, Kirby and his colleagues Thea Brennan-Krohn, MD and Alejandro Pironti, PhD screened 19 different antibiotics for synergy with colistin. The team discovered several combinations where synergy was present and infections with resistant pathogens could potentially be treated with the combination therapy.
Of particular interest, colistin demonstrated high rates of synergy with linezolid, fusidic acid, and clindamycin, which are protein synthesis inhibitor antibiotics that individually have no activity against Gram-negative bacteria. “It was remarkable to see two drugs, each of which is inactive on its own against these bacteria, inhibiting them in combination,” notes Brennan-Krohn. “These findings suggest that colistin retains sub-lethal activity against colistin-resistant bacteria, which may enable drugs like linezolid to reach their targets.”
“Faced with highly resistant pathogens, clinicians often currently treat with multiple antibiotics without knowing the benefit the combinations may provide,” said Kirby. “This study now provides some scientific underpinning for these choices and direction for future investigation.” He added that combination therapy may also allow clinicians to use lower effective doses of colistin and other drugs, which would help avoid toxicities associated with the medications as well as slow the development of antibiotic resistance.
This work was funded in part with Federal funds from the National Institute of Allergy and Infectious Diseases, the National Institutes of Health, and the Department of Health and Human Services."
Synergistic Activity of Colistin-Containing Combinations against Colistin-Resistant Enterobacteriaceae.
Published online today in Antimicrobial Agents and Chemotherapy! Thea Brennan-Krohn, Alejandro Pironti, and James E. Kirby. Synergistic Activity of Colistin-Containing Combinations against Colistin-Resistant Enterobacteriaceae. Antimicrob. Agents Chemother. Accepted manuscript posted online 30 July 2018 , doi:10.1128/AAC.00873-18.
Congratulations to Thea Brennan-Krohn on being awarded a five year K08 Mentored Clinical Scientist Research Career Development Award by the National Institutes of Health!
on Drug Development to Meet the Challenge of Antimicrobial Resistance, September 6-8, 2017. Posters were on apramycin, inkjet printer-based susceptibility testing methodology, and MAST rapid susceptibility technology, respectively.
.On acceptance of her manuscript by the Journal of Antimicrobial Chemotherapy:
Brennan-Krohn T, Truelson KA, Smith KP, Kirby JE. Screening for synergistic activity of antimicrobial combinations against carbapenem-resistant Enterobacteriaceae using inkjet printer-based technology. J Antimicrobial Chemotherapy. 2017 July.
Link to abstract. Link to Journal Full Text.
Our editorial titled "How inkjet printing technology can defeat multidrug-resistant pathogens" is now online in Future Microbiology
In an article posted online today in Future Microbiology titled "How inkjet printing technology can defeat multidrug-resistant pathogens", postdoctoral fellow, KP Smith, and I discuss the potential uses of inkjet printing digital dispensing technology for addressing the antimicrobial susceptibility testing gap.
Kirby Lab Blog