A multiplexed microfluidic platform for antibiotic susceptibility testing.

摘要

Antibiotic susceptibility testing represents a key first step for determining therapeutic regimens to treat bacterial infections. Current technologies are slow and cumbersome, require large sample volumes for analysis, have poor detection sensitivity and limited combinatorial capabilities. These factors often preclude the timely administration of correct antibiotics, which complicates the clinical management of infections and exacerbates the escalating problem of antibiotic resistance development in pathogens. My work has focused on developing microfluidic platforms for rapid antimicrobial susceptibility testing with a future potential in point-of-care diagnostics. I have employed the platform to quantify the effects of commonly used antibiotics on E. coli cells at various concentrations (0.5-500 mug/mL) of each antibiotic as well as combinations thereof, on cellular proliferation and morphology as a proof-of-concept. I demonstrated that combinations of three or more antibiotics are not necessarily better suited to eradicating pathogens in comparison to antibiotic pairs, which is a significant result for prescribing therapeutic regimens based on antibiotic cocktails. Then, I addressed the effects of initial cell density (ranging from 108 -10 10 cells/mL) on the efficiency of antibiotic action. Finally, I extended the platform to test more clinically relevant pathogens such as P. aeruginosa and K. pneumoniae in monomicrobial and polymicrobial cultures. I demonstrated that bacteria behave significantly differently when co-cultured and individual susceptibility to antibiotics such as amikacin and tobramycin increases in co-cultures. I illustrate the advantages of using microfluidics over conventional methods for AST for precise determination of antibiotic dosing regimen, which encompass a significant potential to address the issue of antibiotic resistance.