Clinical Validation of Innovative Optical-Sensor-Based, Low-Cost, Rapid Diagnostic Test to Reduce Antimicrobial Resistance

Abstract

The antibiotic susceptibility test determines the most effective antibiotic treatment for bacterial infection. Antimicrobial stewardship is advocated for the rational use of antibiotics to preserve their efficacy in the long term and provide empirical therapy for disease management. Therefore, rapid diagnostic tests can play a pivotal role in efficient and timely treatment. Here, we developed a novel, rapid, affordable, and portable platform for detecting uropathogens and reporting antibiogram to clinicians in just 4 h. This technology replicates the basic tenets of clinical microbiology including bacterial growth in indigenously formulated medium, and measurement of inhibition of bacterial growth in presence of antibiotic/s. Detection is based on chromogenic endpoints using optical sensors and is analyzed by a lab-developed algorithm, which reports sensitivity to the antibiotic's panel tested. To assess its diagnostic accuracy, a prospective clinical validation study was conducted in two tertiary-care Indian hospitals. Urine samples from 1986 participants were processed by both novel/index test and conventional Kirby Bauer Disc Diffusion method. The sensitivity and specificity of this assay was 92.5% and 82%, respectively (p < 0.0005). This novel technology will promote evidence-based prescription of antibiotics and reduce the burden of increasing resistance by providing rapid and precise diagnosis in shortest possible time.trial-and-error treatment and over-prescription, v) shorten the time before treatment begins, and vi) decrease the length of hospital stays. Appropriate diagnosis can improve the effectiveness of treatments and avoid long-term complications for the infected patient. India harbors the world's largest burden of drug-resistant pathogens. Easy access, availability, and higher consumption of medicines have led to a disproportionately higher incidence of inappropriate use of antibiotics and greater levels of antimicrobial resistance (AMR) compared to developed countries [1]. It has been shown that the health sector in India suffers from gross inadequacy of funds, which will further result in conditions favorable for the development of drug resistance [2]. The high resistance of pathogens in the country, even to newer antibiotics, has led to the emergence of superbugs like New Delhi Metallo-beta-lactamase (NDM-1) [3]. By 2050, 2 million Indians are projected to die as a result of AMR [3]. Indians are the largest consumers of antibiotics worldwide, despite a decline in communicable diseases [3], due to a liberal policy for over-the-counter sale of antibiotics and irrational prescription of antibiotics. A study by Ganguly et al. highlighted the importance of rationalizing antibiotic use to limit AMR in India [4]. Irrational prescription happens due to a lack of fast point-of-use tests for evidence-based prescription, lack of infrastructure for bacterial culture and antibiotic susceptibility test (AST), and lack of awareness worldwide. Selective pressure from inappropriate use of antibiotics can lead t...

Effectiveness of antenatal screening of asymptomatic bacteriuria in reduction of prematurity and low birth weight: Evaluating a point-of-care rapid test in a pragmatic randomized controlled study

“…Whereas, pregnant women enrolled in intervention arm were additionally screened for ASB with the novel rapid test [ 18 , 23 , 24 ]. The rapid test utilized a proprietary medium to promote growth of uropathogens; chromogens to impart color to the medium; a pre-functionalized identification strip; two pre-loaded antibiotic strips; and a reader machine with optical sensor to detect chromogenic and nephelometric endpoints, and a proprietary indigenous lab-developed statistical algorithm-based software.…”

“…The machine provided at the same time, the results of bacterial load; direct quantitative detection of common UTI-causing bacteria found in human urine, namely Escherichia coli, Klebsiella, Pseudomonas, Enterococcus, Proteus, and Staphylococcus sp. ; and phenotypic antibiotic sensitivity of the causative bacteria to Amoxicillin, Gentamicin, Amikacin, Cefepime, Ofloxacin, Ciprofloxacin, Ceftriaxone, Piperacillin-Tazobactum, Cefotaxime, Cefuroxime, Tobramycin, Levofloxacin, Cefazolin and Imipenem [ 18 , 23 , 24 ]. The sensitivity and specificity of the rapid test was found to be 92.5% and 82% respectively as compared to the gold standard urine culture [18] .…”

“…; and phenotypic antibiotic sensitivity of the causative bacteria to Amoxicillin, Gentamicin, Amikacin, Cefepime, Ofloxacin, Ciprofloxacin, Ceftriaxone, Piperacillin-Tazobactum, Cefotaxime, Cefuroxime, Tobramycin, Levofloxacin, Cefazolin and Imipenem [18,23,24]. The sensitivity and specificity of the rapid test was found to be 92.5% and 82% respectively as compared to the gold standard urine culture [18].…”

“…Several tests have been tried to screen ASB but none of them provided identification of bacteria and antimicrobial sensitivity (ID & AST) or possessed characteristics like rapidity, validity, user-friendliness, and affordability [16] . The rapid test employed in this study is based on optical sensors and provides results of ID & AST within four hours at the point-of-testing [18] . This novel test has been clinically validated in around 2000 patients suffering from UTI [18] .…”

“…The rapid test employed in this study is based on optical sensors and provides results of ID & AST within four hours at the point-of-testing [18] . This novel test has been clinically validated in around 2000 patients suffering from UTI [18] .…”