Randomized Trial Evaluating Clinical Impact of RAPid IDentification and Susceptibility Testing for Gram-negative Bacteremia: RAPIDS-GN

Abstract

Background Rapid blood culture diagnostics are costly and of unclearbenefit for patients with Gram-negative bacilli (GNB) bloodstream infections (BSIs). We conducted a multicenter, prospective, randomized controlled trial comparing outcomes of patients with GNB BSI who had blood culture testing with standard of care (SOC) culture and antimicrobial susceptibility testing (AST) versus rapid organism identification (ID) and phenotypic AST using the Accelerate Pheno™ System (RAPID). Methods Patients with positive blood cultures with Gram stains showing GNB were randomized to SOC testing with antimicrobial stewardship review (AS) or RAPID with AS, at two medical centers between 10/2017-10/2018. The primary outcome was time to first antibiotic modification within 72 hours of randomization. Results Of 500 randomized subjects, 448 were included (226 SOC, 222 RAPID). Mean (S.D.) hours to results was faster for RAPID than SOC for organism ID [2.7 (1.2) vs 11.7 (10.5), p < 0.001] and AST [13.5 (56) vs. 44.9 (12.1), p<0.001]. Median (IQR) hours to first antibiotic modification was faster in the RAPID vs. SOC arm for overall antibiotics [8.6 (2.6, 27.6) vs. 14.9 (3.3, 41.1), difference 6.3, p=0.02] and Gram-negative antibiotics [17.3 (4.9, 72) vs. 42.1 (10.1, 72), difference 24.8, p<0.001]. Median (IQR) hours to antibiotic escalation was faster in the RAPID vs. SOC arm for antimicrobial-resistant BSIs [18.4 (5.8, 72) vs. 61.7 (30.4, 72), difference 43.3, p=0.01]. There were no statistically significant differences between the arms in patient outcomes including mortality and length of stay. Conclusion Rapid organism ID and phenotypic AST led to faster changes in antibiotic therapy for Gram-negative BSIs. (Funded by the U.S. NIH UM1AI104681; ClinicalTrials.gov number, NCT03218397.)

Impact of Rapid Antimicrobial Susceptibility Testing in Gram-Negative Rod Bacteremia: a Quasi-experimental Study

“…Nonetheless, the secondary clinical outcomes were considered important to include, given that they may reveal trends that warrant further assessment in future studies. The lack of clinical impact is consistent with that seen in previous studies (24,25,38). Third, ASP intervention was only performed during regular weekday working hours, which may contribute to the prolonged time to appropriate antibiotic change.…”

Rapid Antimicrobial Susceptibility Testing Methods for Blood Cultures and Their Clinical Impact

“…The recently completed RAPIDS GN trial evaluated the impact of a rapid phenotypic AST method for Gram-negative bacilli bloodstream infection and addresses some of the limitations of the BCID trial (19). This multicenter study evaluated the impact of the Accelerate PhenoTest TM BC Kit, performed on the original FDA-cleared Accelerate Pheno TM System, compared with standard of care (SOC) MALDI-TOF and BMD or agar dilution for AST.…”

“…The arm with rapid testing had faster time to antibiotic change and optimal antibiotic therapy but did not have any benefit in terms of mortality, length of stay, adverse events, or cost. Notably, the impact on antibiotic utilization varied by resistance profile of the blood isolate; compared with the SOC arm, in the rapid testing arm, time to any Gram-negative antibiotic change occurred 24 h faster for all patients, and antibiotic escalation occurred 43 h faster for patients with drug-resistant isolates (19). Lastly, a recent small study from Korea evaluated the impact of a rapid phenotypic AST method based on a microscopic imaging and microfluidic chip technology called dRAST (QuantaMatrix) (76).…”

“…However, most RCTs do not demonstrate that rapid AST methods result in significant reductions in mortality, hospital length of stay, or adverse events, perhaps because larger studies are required to detect differences in these rare events. It is also notable that with the exception of the study by Kim et al, most of these trials were conducted in areas with low rates of antimicrobial-resistant bacteria, and it is possible that more clinical benefit would be observed in areas with higher rates of resistant infections (19,20). Additionally, most of the studies demonstrate the importance of pairing rapid blood culture diagnostics with antibiotic stewardship team review, as has been emphasized by many others (20,68,69,73,(77)(78)(79)(80).…”

“…In a Swiss prospective population-based study, blood culture-proven pediatric sepsis accounted for 66% of all pediatric hospital admissions for sepsis (18). Knowledge of the antimicrobial susceptibility profile of a blood isolate as soon as possible is often critical for optimal management and outcomes of patients with sepsis, enabling de-escalation or escalation of antibiotics to appropriate definitive therapy (19)(20)(21)(22). While standard turnaround time for clinical microbiology laboratories to isolate, identify, and perform antimicrobial susceptibility testing (AST) of bacterial isolates is 48-96 h from the time a blood culture turns positive (23), many rapid testing methods provide results within 6-24 h (24,25).…”