A Comprehensive Review of the Present and Future Antibiotic Susceptibility Testing (AST) Systems

Abstract

Tools and instruments available in the clinical microbiology labs for analysis of patient samples and diagnosis are constantly evolving. The main impetus behind this is to decrease the overall time taken to obtain the results from the instruments, enhance the ease of sample processing, increasing the sample turn-around time with the ultimate goal of earlier patient treatment and better recovery rates. This is especially true in the case of antibiotic susceptibility testing (AST), where every hour saved in obtaining the results leading to an earlier switch to targeted antibiotic therapy will have a direct influence on improving clinical outcomes. Reduction in the time to obtain AST results reduces the duration of use of broad-spectrum antibiotics, which in turn decreases the emergence of antibiotic resistance among bacteria. Many of the traditional methods available for AST are labor intensive and slow despite being precise in obtaining results. Thus, there is a trend towards development and use of automated diagnostic devices which are rapid and easy to use. This review article provides a detailed summary of traditional AST methods, currently used automated methods, and focuses on some of the promising emerging and future technologies in the field of rapid antibiotic susceptibility profiling.

Nanomechanical Sensors as a Tool for Bacteria Detection and Antibiotic Susceptibility Testing

“…The LifeScale system performs rapid AST based on biomass changes, which is a growth-dependent approach. AST can be performed directly from positive blood culture and urine samples if the concentration is above 10 4 cfu mL −1 , providing AST data in 3-4 h for fast-growing bacteria but taking much longer in the case of slowly growing bacteria (Puttaswamy et al, 2018).…”

“…On the other hand, conventional AST methods used in clinical practice (e.g., broth microdilution or the disk diffusion method) are accurate but labor intensive and timeconsuming (16-24 h to obtain a result). These operational limitations generate a wide gap (days) between sample processing from patients and final results, which delay the initiation of precise targeted antimicrobial therapy while extending the administration of broad-spectrum antibiotics (Puttaswamy et al, 2018). In addition, the prolonged use of broad-spectrum antibiotics increases the chances for development of antibiotic resistance among microbial communities.…”

3D microfluidic gradient generator for combination antimicrobial susceptibility testing

“…As a result, the duration from sample collection to delivery of definitive AST results in clinical settings can take anywhere from 2 days to 1 week 10 . A standard clinical procedure while a clinician awaits AST evaluation, therefore, is to prescribe a large dose of a broad-spectrum antibiotic to stop the infection from worsening, which often contributes to the emergence and propagation of AMR in the first place [22][23][24] . Moreover, while MIC values 9,11 and CDS results 16,20,25 for specific antibiotics and bacterial strains can be found in the literature, antibiotic sensitivity can evolve over the lifetime of a bacterial colony 26 ; therefore, frequent MIC and CDS testing is recommended in clinical settings 10,27,28 , posing a considerable limitation on AST throughput and overall cost, especially for screening more than two antibiotics at one time 29,30 .…”

“…Various microfluidic-based AST platforms 23,31 have demonstrated miniaturized and multiplexed fluid handing 32,33 to increase the throughput of AST analysis 29,34,35 and decrease the mortality rate and healthcare costs 36,37 associated with treating clinical AMR-related infections 38,39 , for novel drug development 40,41 , and for pointof-care clinical dosage recommendations [42][43][44][45] . Microfluidic concentration gradient generators (µ-CGGs), the most widely adopted class of microfluidic AST technologies 46 for MIC and CDS studies, employ branching microchannel networks comprised of nodal units to produce diluted concentrations representing a gradient between input species.…”

Electrical antimicrobial susceptibility testing based on aptamer-functionalized capacitance sensor array for clinical isolates

“…For example, several microscopy-based methods have been developed to measure bacterial growth every 10 min as clonal aggregates multiply in Mueller-Hinton media, to determine antibiotic-induced morphological changes in single bacterial cells 10 , and to measure the number of bacteria in a microfluidic channel 19 . In addition, rapid AST using biochemical, optical, and isothermal measurements has been reported 21,22 .…”