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."
Kirby Lab Blog