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."
Our inoculum effect manuscript in the journal Antimicrobial Agents and Chemotherapy highlighted in BIDMC news release.
The laboratory has been fortunate to participate in Harvard Catalyst Reactor Program through the "Big Ideas, Small Features” Pilot Grant Award. A description of the program was recently published last week in Harvard Medical School news titled "Catalyzing Research Innovation."
A description of the supported work can be found at: "Reactor Program Awards Eight New Pilot Grants: Supports researchers with novel solutions to major clinical challenges."
See discussion of our work on Microscopy-Based Antimicrobial Susceptibility Testing as part of the Harvard Catalyst Reactor Pilot Program.
I was selected as a SLAS 2017 Innovation Award Finalist and will be speaking at the SLAS Annual Meeting with a presentation titled: "Inkjet Printing Technology for Facilitated At Will Antimicrobial Susceptibility Testing (FAST) in Under 5 Hours: Addressing the Needs of a So-Called 'Post-Antibiotic Era'.
BIDMC issued a press release on our manuscript on at-will antimicrobial susceptibility testing performed using a digital dispensing method. "Simple Method Quickly Tests Hard-to-Treat Bacteria’s Susceptibility to Different Antibiotics".
The original article is now available online at: http://www.ncbi.nlm.nih.gov/pubmed/27335151
There has been a lot of attention paid recently to plasmid-borne colistin resistance. The presence of MCR-1 gene has now been examined in large collections of clinical bacterial isolates obtained during the past few years. Perhaps not surprisingly the MCR-1 gene was present at low frequency.
Here is a link to the CNN interview about MCR-1. I also indicated in my discussion with the CNN the need for improved diagnostics, but that did not make it into the article.
Kirby Lab Blog