Using inkjet printing technology, researchers at Beth Israel Deaconess Medical Center (BIDMC) have found a way to quickly and accurately test multi-drug resistant bacteria for susceptibility to antibiotics in a clinical setting, according to their results, to be published in the September issue of the Journal of Clinical Microbiology, which are available online.
Currently, the gold standard of susceptibility testing involves specialized laboratories that perform microdilution susceptibility testing, a process that can lead to days of delays before therapy can be chosen and initiated.
“The time between starting empiric therapy and starting directed therapy is what we in my laboratory call the antimicrobial testing gap,” said James Kirby, MD, Director of the Clinical Microbiology Laboratory at BIDMC, and associate professor, pathology, Harvard Medical School, both in Boston, MA.
“If a doctor’s initial guess is good, patients generally do well. Physicians’ initial predictions used to be very good because the susceptibility of our pathogens was predictable; however, with the emergence of multi-drug resistance, our instincts are increasingly wrong,” he added.
Dr. Kirby and colleagues in his lab have endeavored to reduce this testing gap, and have applied and validated a novel technology that uses inkjet printer technology to print out droplets of antimicrobial compound, with the printed drops varying in size up to a million-fold. “With this technology, the assay can be set up in a minute or so, and testing multiple drugs for multiple patients requires minimal additional effort,” said first author Kenneth Smith, PhD, a postdoctoral fellow at BIDMC.
For their assessments, these researchers verified the performance of this method via testing Enterobacteriaceae for its susceptibility to ampicillin, cefazolin, ciprofloxacin, colistin, gentamicin, meropenem, and tetracycline, comparing this to a broth microdilution reference standard.
Drs. Kirby, Smith, and colleagues found an essential agreement of 96.8% and categorical agreement of 98.3%, and significantly fewer D300-based measurements that were outside ±1 dilution from the modal MIC, which suggests enhanced reproducibility.
They performed accuracy studies using a panel of 80 curated clinical isolates, and found:
- essential and categorical agreement: 94% and 96.6%, respectively;
- very major errors: 0%;
- major errors: 0%, and;
- minor errors: 3.4%.
“We believe that our methodology will bring testing for multi-drug resistant pathogens back into clinical laboratories at the site of patient care. Testing at the site of patient care will significantly decrease the antimicrobial testing gap and allow therapy to be directed in a timely fashion against multi-drug resistant pathogens,” concluded Dr. Smith.
This work was supported, in part, by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award numbers R21AI119114 and R21AI112694 to Kirby.