Abstract
Many patients with severe infections receive inappropriate empirical treatment, and rapid detection of bacterial antibiotic susceptibility can improve clinical outcome and reduce mortality. To this end, we have developed a multiplex fluidic chip for rapid phenotypic antibiotic susceptibility testing of bacteria. A total of 21 clinical isolates of Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus were acquired from the EUCAST Development Laboratory and tested against amikacin, ceftazidime, and meropenem (Gram-negative bacteria) or gentamicin, ofloxacin, and tetracycline (Gram-positive bacteria). The bacterial samples were mixed with agarose and loaded in an array of growth chambers in the chip where bacterial microcolony growth was monitored over time using automated image analysis. MIC values were automatically obtained by tracking the growth rates of individual microcolonies in different regions of antibiotic gradients. Stable MIC values were obtained within 2 to 4 h, and the results showed categorical agreement with reference MIC values as determined by broth microdilution in 86% of the cases.IMPORTANCE Prompt and effective antimicrobial therapy is crucial for the management of patients with severe bacterial infections but is becoming increasingly difficult to provide due to emerging antibiotic resistance. The traditional methods for antibiotic susceptibility testing (AST) used in most clinical laboratories are reliable but slow with turnaround times of 2 to 3 days, which necessitates the use of empirical therapy with broad-spectrum antibiotics. There is a great need for fast and reliable AST methods that enable starting targeted treatment within a few hours to improve patient outcome and reduce the overuse of broad-spectrum antibiotics. The multiplex fluidic chip for phenotypic AST described in the present study may enable data on antimicrobial resistance within 2 to 4 h, allowing for an early initiation of appropriate antibiotic therapy.
Highlights
Many patients with severe infections receive inappropriate empirical treatment, and rapid detection of bacterial antibiotic susceptibility can improve clinical outcome and reduce mortality
Each growth chamber, flanked by two fluidic channels used for delivery of growth media and antibiotics, was designed to feature a loading port that was used to inject bacteria mixed with agarose (Fig. 1A to C)
Loading the bacterium-agarose mix filled up the growth chamber all the way to the edges of the flanking fluidic channels, which were designed to be slightly enlarged at the location of the growth chamber to tolerate slight variations in agarose gel volume without compromising fluid flow
Summary
Many patients with severe infections receive inappropriate empirical treatment, and rapid detection of bacterial antibiotic susceptibility can improve clinical outcome and reduce mortality. To this end, we have developed a multiplex fluidic chip for rapid phenotypic antibiotic susceptibility testing of bacteria. New rapid and robust methods for antibiotic susceptibility testing (AST) that can deliver data on bacterial antibiotic resistance within hours instead of days are much needed Such methods will make it possible to prescribe targeted antibiotic therapy, which will improve clinical outcome and reduce unnecessary use of broad-spectrum antibiotics, thereby minimizing the risk of adverse events and resistance development [9,10,11]. Studies show that in severe infections such as septic shock and bacterial meningitis, delayed appropriate antibiotic treatment is associated with increased mortality [10]
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