Evaluation of a New Culture-Based AtbFinder Test-System Employing a Novel Nutrient Medium for the Selection of Optimal Antibiotics for Critically Ill Patients with Polymicrobial Infections within 4 h

Abstract

Here, we describe the validation of a new phenotypic culture-based AtbFinder method for rapid selection of antibiotics in vitro using specimens with mono- and polybacterial infections. AtbFinder, which can be applied to any type of non-blood tissue, does not require isolation of pure bacterial cultures. The method uses a novel TGV medium that allows more rapid bacterial growth of Gram-positive and Gram-negative monoisolates compared with that achieved with conventional laboratory media, demonstrating overall sensitivity, specificity, PPV, NPV values of 99.6%, 98.1%, 98.5%, and 99.4%, respectively, after 4 h. For polymicrobial infections, AtbFinder utilized a novel paradigm of the population response to antibiotics, enabling bacterial growth in the form of a mixed microbial community and selecting antibiotics targeting not only the principal pathogen, but also those bacteria that support their growth. TGV medium allowed culturing of a more diverse set of bacteria from polymicrobial biospecimens, compared with that achieved with the standard media, and enabled, within 4 h, accurate selection of the antibiotics that completely eliminated all cultivatable bacteria from clinical samples. In conclusion, the AtbFinder system may be a valuable tool in improving antibiotic selection, and enabling targeted empirical therapy and accurate antibiotic replacement, which is especially important in high-risk patients.

Biofilm antimicrobial susceptibility testing: where are we and where could we be going?

“…Alternative culture-based approaches for AST are also being developed. An example of such an approach is the AtbFinder system, in which a medium is used that supports growth of many different bacteria (TGV medium) (69,70). The system is based on direct plating of clinical specimens on TGV agar, with or without antibiotics added at a concentration that can be achieved at the infection site;…”

AtbFinder Diagnostic Test System Improves Optimal Selection of Antibiotic Therapy in Persons with Cystic Fibrosis

“…The persistence of P. aeruginosa in patients with CF is the result of not only the high antibiotic resistance profile of this pathogen but also the specificity of its behavior in polymicrobial communities that are not accounted for by routine ASTs ( 2 , 14 ). We recently tested the efficacy of AtbFinder, a novel, culture-based test system developed to address the shortcomings of existing ASTs, including the issue of combined antibiotic resistance ( 32 , 33 ).…”

“…It is comprised of a multiwell plate filled with a novel TGV medium, with each well individually supplemented with antibiotics for the treatment of certain diseases. TGV medium was shown to allow culturing of a more diverse set of bacteria from polymicrobial biospecimens in the form of mixed biofilm, compared with that achieved with the standard media ( 32 ). Thus, antibiotics are selected based on their ability to modulate polybacterial cooperative interactions at the site of infection.…”

AtbFinder Diagnostic Test System Improves Optimal Selection of Antibiotic Therapy in Persons with Cystic Fibrosis

“…The persistence of P. aeruginosa in patients with CF is the result of not only the high antibiotic resistance profile of this pathogen, but also the specificity of its behavior in polymicrobial communities that are not accounted for by routine ASTs (2,10). We recently tested the efficacy of AtbFinder, a novel, culture-based test system developed to address the shortcomings of existing ASTs, including the issue of combined antibiotic resistance (39,40).…”